The Peter Attia Drive - #259 - Women's sexual health： Why it matters, what can go wrong, and how to fix it ｜ Sharon Parish, M.D.

00:00:00.000 Hey everyone, welcome to the drive podcast. I'm your host, Peter Atiyah. This podcast,

00:00:15.500 my website and my weekly newsletter all focus on the goal of translating the science of longevity

00:00:19.840 into something accessible for everyone. Our goal is to provide the best content in health and

00:00:24.780 wellness full stop. And we've assembled a great team of analysts to make this happen.

00:00:28.920 If you enjoy this podcast, we've created a membership program that brings you far more

00:00:33.320 in-depth content. If you want to take your knowledge of this space to the next level,

00:00:36.940 at the end of this episode, I'll explain what those benefits are. Or if you want to learn more now,

00:00:41.760 head over to peteratiyahmd.com forward slash subscribe. Now, without further delay,

00:00:47.800 here's today's episode. My guest this week is Dr. Sharon Parish. Sharon is a prominent sexual 1.00

00:00:55.100 medicine specialist and professor of medicine in clinical psychiatry and clinical medicine at

00:01:00.560 Weill Cornell Medicine. Throughout her career, she has become a leading expert in sexual medicine,

00:01:06.420 focusing her work on helping patients overcome sexual dysfunction. She has published numerous

00:01:11.880 articles and book chapters on sexual health and is a sought after speaker and educator on the topic.

00:01:17.620 In this episode, we focus the entire conversation around women's sexual health. So for folks who are

00:01:24.700 curious about men's sexual health, not to worry, next week we'll be launching the complimentary

00:01:30.720 podcast to this that focuses exclusively on men's sexual health. In this episode, we review the female 0.76

00:01:37.100 physiology and anatomy in order to better understand some of the potential problems and treatments

00:01:41.480 available to women that we cover throughout the interview. We speak about how sexual health and

00:01:45.640 sexual dysfunction can affect a woman's well-being and how childbirth and metabolic health can affect

00:01:50.580 women's sexual health. From there, we cover a variety of issues a woman may face throughout her

00:01:56.080 life by looking at three different case studies. Using these case studies, we differentiate and tease

00:02:02.760 apart the differences between desire and arousal. We talk about different classes of drugs that are

00:02:07.860 available for women as it relates to desire and arousal. We talk about the impact of birth control.

00:02:13.420 We talk about treatments for women who are having difficulty achieving orgasm, including testosterone and DHEA.

00:02:18.760 And we, of course, talk about the role of hormone replacement in addition to many other things.

00:02:23.420 One final point. I learn something with every podcast I do. In other words, every time I finish

00:02:29.700 interviewing somebody, regardless of how well I know the subject matter beforehand, I always come away

00:02:34.980 learning something. But it might be the case that this episode in particular taught me more that I

00:02:40.800 didn't know relative to any other podcast I can recall. So I think it's safe to say that whether you're a man

00:02:46.760 or a woman, you will learn a lot from this episode that will improve the quality of your life. So 0.95

00:02:52.980 without further delay, please enjoy my conversation with Dr. Sharon Parrish.

00:03:02.700 Hey, Sharon, thank you so much for making time to meet with me today. This is a topic that is

00:03:07.980 incredibly applicable to more than half our population, because while we're going to be talking

00:03:12.400 about sexual function in women, of course, women have partners. And so by extension, I would argue 1.00

00:03:17.440 this is a topic that is applicable to our entire listening population. It's also a topic where there

00:03:23.140 seems to be a lot of misunderstanding, a lot of asymmetry in attention. We're going to talk about a bunch

00:03:29.760 of those things as we get going. Before we do, though, I just kind of want to give people a sense of your

00:03:34.200 background and how you arrived where you did. So you went to medical school, you did your residency in

00:03:39.080 internal medicine and primary care, correct? That is right. And primary care, meaning with a focus

00:03:44.640 on ambulatory medicine and being sort of a general medical physician with a focus on primary care and

00:03:51.060 academic general medicine. But what point during that process did you realize that your interest

00:03:56.660 was in sexual health? I think when I was in med school, really, I was always struggling. It seems

00:04:02.760 like a little bit of a strange union, but always struggling between deciding whether I wanted to be a

00:04:07.540 general internist, a psychiatrist, or a gynecologist. You know, this interface, particularly, although I

00:04:13.200 do, as an internist, I do take care of men's sexual health as well. This interface between women's

00:04:18.360 health, the mind and the body, behavioral issues, and comprehensive, or for lack of a better word,

00:04:24.640 holistic care for all sort of was always tugging at me in three different directions. And somehow,

00:04:30.260 when I eventually found my way to sexual medicine, it just kind of brought it all together.

00:04:33.560 I did some projects on women's health and then in residency also on various women's health issues

00:04:39.540 and reproductive issues. I worked, for example, in a contraception clinic, an adolescent medicine

00:04:44.720 program, STD program. So I did a lot of work in that area. I did a fellowship afterwards at NYU

00:04:51.540 Bellevue in psychosocial and behavioral medicine in the general medical field. And I worked with then

00:04:56.820 some sexual medicine experts in some projects. And that's when I really moved more deliberately toward

00:05:01.700 the field. And so how does the field stand today? How many physicians are there in the United States,

00:05:07.760 if you had to estimate, that have your degree of training and clinical focus?

00:05:11.940 The field of men's sexual health is a little more clearly defined. Like there's many psychiatrists,

00:05:18.080 urologists, and even men's health internists who have like a clear distinction. I think women's

00:05:23.080 sexual health, it's less clear, but again, gynecologists, some internists, family medicine

00:05:28.140 physicians, a few psychiatrists, and then there's psychological therapists. It goes across disciplines

00:05:33.560 that's a little hard to define, but I can say that there's many fewer who clearly identify.

00:05:38.340 I went to the International Society for the Study of Women's Sexual Health annual meeting a couple

00:05:41.940 weeks ago, and there were 600 attendees, five to 600, and that probably represents most people who work

00:05:48.100 in the field. There's sex therapy meetings and pelvic floor physical therapy meetings that have

00:05:52.160 others. But if you're looking at the field of sexual medicine, it's not robust. If you go to the AUA,

00:05:57.300 I think everybody there, 20,000 people, think they could probably handle male ED problem. So if that

00:06:03.420 gives you a point of comparison. That's sort of in line with what my expectations were. Let's also just

00:06:09.400 maybe by way of background, perhaps start with what is encompassed in this field. So you've already kind

00:06:14.880 of alluded to it a little bit. There's clearly a supratentorial component to this. There's also an

00:06:20.700 anatomic component to this or physiologic component to this. How does it make sense to maybe walk

00:06:27.060 me and the listeners through the background knowledge of this physiology anatomy so that

00:06:34.200 we can better kind of go into what some of the problems are and what some of the treatments are?

00:06:38.620 With any issue where you're looking at the mind, the body, a genital response, a hormonal response,

00:06:44.860 you know, the integration, I always take people back to the concept of the biopsychosocial model.

00:06:49.440 I guess you're asking when it comes to sexual response, what are the bio, what is the psycho,

00:06:53.200 and what is the social, and what's the contextual. Maybe just for sexual health problems, the brain

00:06:59.160 is a really active organ, as I'm sure you can imagine. We have thinking and feeling, and that

00:07:04.620 probably on a biologic or neurophysiological level translates into neurotransmitters and the

00:07:09.300 interaction with hormones and pathways, brain neural pathways, neural networks. And there's the

00:07:15.440 psychological concepts of conditioning and learning and unlearning. Reward and disappointment,

00:07:20.620 et cetera, all plays a role. And it's fascinating how that might all interact. There's the general

00:07:25.440 medical state, our vascular system, nervous system, and like systemic medical issues that might impact

00:07:31.200 those. And there's hormones, and they get stimulated by the master glands in the brain,

00:07:37.100 our genitals that make sex steroids, and our adrenal glands and thyroid. So there's a collection of 0.68

00:07:42.140 hormonal locuses that play a role potentially in sexual health. And then there's the local genital

00:07:47.520 milieu. And that might include the vascular system, the nervous system, small nerves,

00:07:53.180 the mucosa, the surface, and then there are muscles and soft tissue. So all in the genital

00:07:58.100 tract. And then there's a bladder in the rectum, the breasts, which play a role in stimulation. So 0.68

00:08:02.660 I think that that's the big picture. How does this all come together in a three-dimensional concept

00:08:07.440 where you integrate experience, relational issues, culture, and time is really the fascinating part of

00:08:14.460 this field? So how do these things change during a woman's life? Obviously, puberty is a very 1.00

00:08:20.760 important milestone, but I suspect also menopause is an equally important transition that is much more

00:08:28.200 abrupt, at least from an endocrine standpoint, than men would experience at the same age.

00:08:33.940 Yeah. So I think there are times when hormones play a more master role in sexuality and sexual

00:08:40.320 response. You know, what's tricky about this is, and I guess the body's kind of programmed and smart,

00:08:46.200 is that there's a lot of life cycle and life stage things happening. And those are prime times as well,

00:08:50.760 whether one commands the other or not, it's hard to know. Menopause is kind of a longer process than

00:08:55.480 people think. There's perimenopause, there's menopause, there's postmenopause, and there's a lot

00:08:59.740 of life cycle stuff going on. You know, that's probably the most defining moment for women in that it 1.00

00:09:05.440 interfaces with no longer being able to reproduce. There are significant changes in hormone levels

00:09:10.340 like estrogen that affect vaginal, global vaginal comfort. And at the same time, androgens decline

00:09:15.600 that affects desire. And when you're starting up with puberty, that's probably all roaring up and

00:09:19.900 getting going. And you're also developing the cognitive skills of relational issues and sexual

00:09:25.220 relationships. So those are two peak times. I have worked with adolescents. I have more experience

00:09:30.620 with midlife women. That's the focus in my, often in my practice. And those are the people that,

00:09:34.600 this is a good time to mention this point. The data suggests, and my experience with this field

00:09:39.980 suggests, that the time when women are most interested in looking into it is in those 0.93

00:09:44.360 perimenopausal, late reproductive perimenopausal and early postmenopausal years.

00:09:49.500 When you say looking into it, do you mean looking into-

00:09:52.160 For themselves. So it might be that they have a problem. It might be they want to understand it

00:09:55.860 better. It might be they want to be proactive and preserve their sexuality. It usually is that

00:10:01.580 something's changing and they weren't expecting it and want to know why, or they want it to be

00:10:05.700 better. People have a little trouble sorting out, like, is it the relationship at this point? Is it

00:10:10.860 the menopausal changes overall? Is it the sexual function or is it sort of all of it? And I think

00:10:15.940 that's what makes the midlife sexual medicine challenges the most complex and challenging, but

00:10:20.420 also the most interesting and the most rewarding. I think there's also the most likelihood where women 1.00

00:10:25.860 are, midlife women are youthful. They're young, they're active, they're connected. They're not 0.98

00:10:30.260 like, you know, some other time in our universe where they're becoming the wise woman sitting in

00:10:35.120 the tent, you know, retiring from childbearing and everything else. I mean, often women are peaking in 1.00

00:10:40.040 their career. If they're having, you know, these trends vary a little bit. Children later, you know,

00:10:44.640 they've got teenage children, college children, aging parents, big careers, bodies changing,

00:10:49.940 and wanting partners. And there's a lot going on. So they're the most likely to seek attention,

00:10:53.680 actually. We can say a lot about helping them today. I also would like to talk a little bit

00:10:58.740 about how the anatomy changes post childbirth. And does that have anything to do with sexual

00:11:04.440 function? And I guess I want to kind of also at some point soon define some of the problems.

00:11:10.300 I can think of three off the top of my head, right? One would be low sexual desire or hypoactive

00:11:15.360 sexual desire. One would be inability to have an orgasm. And a third would be discomfort or pain. 0.71

00:11:21.320 Clearly a big problem for women post menopause due to vaginal atrophy. So those are three things I

00:11:26.780 think we must address today. Do you think there are others that are important enough that to a

00:11:32.200 non-expert audience, we should also present? I never want the forgotten, we'll call her sister,

00:11:37.460 the forgotten sister to desire as arousal. And having women understand that when they come to me, 0.66

00:11:42.920 they're like, I no longer get turned on. And I mean, is it about wanting? Is it about mental or

00:11:48.420 subjective or cognitive excitement? Is it that bridge between desire and thinking and actually

00:11:55.440 being in a moment and being excited? Or is it their genitals are no longer responding? And then 0.70

00:12:00.100 that sometimes is uniquely or can be tied to orgasmic difficulty.

00:12:03.760 I see.

00:12:04.300 And I think it's really in the field, it's an area of discussion and sometimes even controversy.

00:12:09.940 I think for women, it's hard to separate what they're asking for. Sometimes women come to me and 1.00

00:12:14.600 they say like, I no longer want sex, but everything works okay. Sometimes they say like, I love this

00:12:19.880 person or I want to have sex with myself. That's not the problem, but nothing's turning on. Like 0.96

00:12:24.400 I'm not feeling anything and learning about that for one's body and being able to articulate that.

00:12:29.280 And I think it gets commonly tied to orgasmic changes. We could certainly discuss whether they're

00:12:34.460 the same process or different. Okay.

00:12:37.060 You know, childbirth, I don't know if you want to talk about that now.

00:12:39.280 Yeah. Let's talk about it just because I think we've already established there are these two

00:12:43.640 enormous hormone swings, right? There's the swing on, which is reasonably quick. And then there's

00:12:49.420 the swing off, which is relatively abrupt. But as you point out, it's occurring over years,

00:12:54.560 not months. It's also worth mentioning, it's the estrogen and progesterone that are coming off

00:12:59.600 really quickly. The testosterone is kind of coming off not as quickly. We can maybe come back to that

00:13:04.720 in a moment. Let's talk about anatomy in a minute, because I'm guessing that women have 1.00

00:13:10.540 very different experiences with childbirth and presumably a vaginal delivery is different from

00:13:16.180 a C-section in terms of the impact it has on the pelvic floor. By the way, that's something we

00:13:20.920 should define for people so they understand the anatomy of the pelvic floor. But anyway, yes,

00:13:24.680 let's talk a little bit about how that might impact any of the elements of sexual health in a

00:13:29.560 woman's life. You know, it's not the time typically where the sexual problems that people 1.00

00:13:34.740 come to me for, I'm also not a gynecologist, kick in and stay. They tend to be for some women 1.00

00:13:40.420 relatively transient, postpartum, but it also depends on like how many kids and what age and

00:13:45.320 all of that. So let's talk about the pelvic floor for a moment, because that's where that might

00:13:48.740 impact with childbirth. So the pelvic floor is kind of a mysterious concept, but if I had to give it

00:13:53.760 one concept, it's the idea that it's a basket of muscles. And they attach from various parts of the

00:14:00.880 inner pelvis. So like onto the pupus ramus, onto the ischial spine, onto the bones in the, around our

00:14:08.640 pelvis, internally and into the walls, and then also into the organs. And they create a basket around

00:14:14.940 the uterus, around the urethra. Like for example, there's a sling around the urethra and the anus that

00:14:20.020 holds it up and also holds up the uterus. And they also provide motion during childbirth. They

00:14:26.440 allow for the childbirth process. They're quite active during sexual activity. They contract and

00:14:31.640 release. They help us with urination, with defecation and so forth. And it'd be easier if we

00:14:37.480 had like the opportunity to show people a diagram, but I think the best way to understand it is-

00:14:42.300 We'll include diagrams in the show notes.

00:14:43.960 That would be wonderful. The best way to understand is it's a basket of muscles that hold things up

00:14:48.000 and help things move. And when they're not working properly, they can result in, for example,

00:14:53.080 difficulty with urination or incontinence or sometimes pain during sexual activity or changes

00:14:58.400 in orgasmic function. That's sort of the broadest concept. We can get into the nitty gritty of

00:15:02.560 disorders, but I guess you were asking about childbirth. So with pregnancy, those muscles stretch a lot.

00:15:06.880 Things are expanding. Sometimes women will notice improvements actually in their sexual function

00:15:12.060 because if they've had tight pelvic floor muscles that are causing changes in sexual response or even

00:15:16.380 pain, it sometimes gets better. Sometimes with deliveries, they get stretched, they get irritated,

00:15:21.460 they get torn. It's rare that any of those things I find persist unless there was really a birth trauma.

00:15:28.380 It often gets confused with what happens with other things during childbirth. For example,

00:15:32.500 episiotomies, lacerations, suturing, where there can be scarring, there can be inflammation around a

00:15:38.840 suture line, there can be et cetera. So I think the general process of muscles stretching during

00:15:44.140 childbirth is one thing. During pregnancy, it's different. And any other related injuries or

00:15:49.760 trauma during the actual birthing process of vaginal delivery is another. The only other thing

00:15:54.160 about C-section versus vaginal delivery, this could be a whole nother topic, but in general,

00:15:59.280 vaginal deliveries are better for women. Yeah. Say more about that. Again, I'm very

00:16:03.060 ignorant of most of these topics. I think people have this idea that they're going to preserve

00:16:07.280 the size of their vaginal canal or prevent their pelvic floor muscles from stretching, et cetera. And

00:16:11.980 the truth is that most of that goes back. It's not all that unusual for women to just have a transient 0.83

00:16:17.940 difficulty for four to six weeks and things improve. But having surgery, an abdominal surgery,

00:16:23.960 you're opening your abdominal wall, there are muscles, there's scarring. It sometimes leads to

00:16:28.880 other kinds of later difficulties that people don't anticipate. And it's also safer for the mother and

00:16:33.100 the baby not to have surgery. What is the, for lack of a better word, incidence of C-section versus

00:16:39.160 vaginal birth today in the United States? Do you know? I don't know that number. We could easily

00:16:43.600 find it. I don't have it offhand. I'm not an obstetrician. I don't deliver babies. But the

00:16:47.860 biggest concern that I hear in sexual medicine discussions is that people have this idea that

00:16:51.640 it's better for their sexual health not to deliver babies vaginally. Maybe that's the most important 0.99

00:16:55.740 message. And that the number of C-sections has been going up and is alarming. And that routine

00:17:00.880 scheduled C-sections to preserve sexual health for a whole number of reasons isn't really better for

00:17:05.620 women. And that might be a myth. I'm not an expert in childbirth or in delivery because I'm not an 0.94

00:17:09.920 obstetrician or gynecologist. But if someone asks my opinion, I say like, have your baby vaginally and 0.61

00:17:16.020 most people preserve their sexual function. That's not a peak time. The bigger problem actually is 0.83

00:17:21.980 postpartum that comes up in my practice. You know, people are breastfeeding. They're essentially like

00:17:27.980 postmenopausal women and they may experience, because their hormones are dipping way down, they're not, 0.99

00:17:32.820 they're still keeping ovulation off by breastfeeding. And they're experiencing vaginal

00:17:36.760 dryness, irritation, sometimes changes in sex drive. And they're not aware of the effects of

00:17:42.940 breastfeeding on sexual function on a vulva vaginal changes and sexual response. And there's easy things 0.59

00:17:48.640 to do for that, especially the vulva and vaginal symptoms. Can you give me a sense of how high the

00:17:53.460 FSH and LH are during breastfeeding? You're asking, are they organically comparable to a

00:17:59.760 postmenopausal woman, I guess is the question. Yeah. And is estradiol sufficiently low as well?

00:18:05.040 Like, yeah, I'm trying to understand how low estradiol is, how high FSH is. I think there's so

00:18:09.020 much variability. So it depends on like, if you're completely breastfeeding, completely an

00:18:13.440 ovulatory, women can look postmenopausal. Wow. That's defined as over, an FSH over 35. Most women 0.94

00:18:19.420 aren't fully an ovulatory. They're having irregular cycles. They're ovulating intermittently.

00:18:24.940 So I think the numbers are all over the board. Interesting. But you can have estradiols as low

00:18:29.360 as like 20 or 30, right? Wow. Yeah. Might as well be in menopause.

00:18:32.860 Yeah. And everybody's like HPA axis and sensitivity to lactation is a little bit different. And sometimes

00:18:39.000 women aren't breastfeeding completely. And the correlation with how much milk they're making 1.00

00:18:44.360 and whether they're ovulating isn't clear cut either. What I would say is if you're breastfeeding 0.96

00:18:48.720 and you're not having menses for six months, the likelihood that you're hormonally similar to a

00:18:53.640 postmenopausal woman is higher and that you're completely an ovulatory. And that if you're 1.00

00:18:58.160 having dryness and difficulty and pain and low sexual function, that you should talk to your

00:19:02.680 doctor because there are things that we would do some of the same things that we'll probably get

00:19:06.420 into in a little while. We're going to talk about that because I guess you could make the case that

00:19:10.540 if there's one thing we want listeners to take away from this program, it's that there's really no

00:19:16.120 reason for any woman of any age to be struggling with vaginal dryness, regardless of how far she is into 0.97

00:19:22.700 menopause or whatever. We have the technology to solve that problem all day long, right?

00:19:26.460 There's a number of approaches and that is the most treatable or the most manageable amongst these

00:19:31.140 conditions. And the algorithm or the options for that are the most clear cut. So I'm a general

00:19:35.940 internist by heart. You know, I'm a card carrying general internist, although I've gotten quite

00:19:40.020 specialized in my work. So some of the, my colleagues say to me, well, you know, you're not doing

00:19:44.780 procedures. You're not a gynecologist. You know, what's the big deal? You just call me, hand them a 0.93

00:19:48.500 lubricant, a moisturizer, maybe some vaginal hormones. What's the complexity of the concept

00:19:53.020 or the consult? And what it comes down to is women really, really don't understand the whole thing. 1.00

00:19:58.420 What's happening in their body, the difference between the things that we can offer them and

00:20:02.360 how to put them together and use them and then how to integrate that into their sex life. And that's

00:20:07.300 what I would say, like the number one concept that I get or referral that I get is to help a woman 0.94

00:20:11.820 walk through that. So one other thing I want to talk about before we leave the sort of basics and the

00:20:17.340 foundational stuff is the role of metabolic health slash systemic vascular health. So again, in men,

00:20:24.620 this is really clear. So for example, higher incidence of ASCVD, higher incidence of ED,

00:20:31.680 similar concept to endothelial damage, higher incidence of type 2 diabetes, microvascular disease,

00:20:38.300 higher incidence of erectile dysfunction. How clear is that relationship in women? In other words, 1.00

00:20:44.360 do the things that drive glycosylation of proteins and microvascular disease in other parts of the

00:20:53.000 body, do they contribute to sexual health in women as they do in men through the ED pathway?

00:20:59.000 So I'm glad you brought this up because this is really an emerging discussion in the field. For

00:21:03.780 those that are not aware in men, there's kind of a really clear literature and guidance that if a man

00:21:09.280 is having ED, it may be a mirror to small vessel cardiovascular or cerebrovascular disease. And we

00:21:15.480 can use surrogate markers like looking at Doppler studies in the urologist's office of penile and

00:21:21.480 genital blood flow, and then send them for a coronary calcium score, even a coronary CT, right? And look

00:21:27.380 and see if we can see those correlations. And there's good evidence supporting that they mirror one

00:21:31.420 another. And so if a man has erectile dysfunction and sexual dysfunction associated, they should have a

00:21:35.980 cardiovascular assessment. That's sort of the emerging, those are discussions.

00:21:39.800 Just so folks know, a Doppler study is a study that uses waves to look at blood flow through

00:21:45.660 blood vessels. And it's very helpful when you're looking through these sort of smaller blood

00:21:49.780 vessels that you wouldn't otherwise be able to get a good look into.

00:21:52.240 And so I think before we got started, I was telling you, I was just at a two-day meeting where this was

00:21:56.460 the depth of the discussion. Where are we with understanding the presentation of erectile dysfunction as a

00:22:02.200 market for cardiovascular disease? And if someone has cardiovascular disease,

00:22:05.000 what kind of recommendations should we make about asking men about sexual function?

00:22:09.360 And then what do you do about it? Do vasodilators to medications that, PD-5 inhibitors that dilate

00:22:15.240 the small vessels work? And my participation in this particular conference was about the discussion

00:22:20.720 of, do we have similar measures in women? So first of all, if someone comes to me and says, 0.99

00:22:24.320 like, I have no genital sensation, does that mean that she has vascular disease? I mean,

00:22:28.280 there's also nerves there, but it's really not as clear cut. Like a man comes in and says,

00:22:32.160 you know, I don't have an erection. Women's like, I don't feel, you know, I can't be sure that 1.00

00:22:36.500 exactly what it is. There's been some research looking at using something called clitoral cutler 0.61

00:22:41.260 doppler ultrasound or CDU with assessment of like the blood flow, which is called the pulsatile index,

00:22:47.320 looking at resistance to blood flow as an objective measure of how to assess arousal in women.

00:22:52.900 So right now it's just that the level of the lab or research, it's not really being used clinically,

00:22:57.780 except in a very few selected practices who also research this. If someone comes in and says,

00:23:02.820 I don't feel, can I put a clitoral doppler on and look and see, yes, that's the explanation. 0.97

00:23:08.380 That's one thing. The second thing is how well does this correlate with the risk factors

00:23:11.900 that we have seen in men, things like metabolic syndrome, hyperlipidemia, diabetes. And if someone

00:23:19.080 has those things, should I then be asking her about clitoral sensation and doing testing, 0.98

00:23:23.260 both to understand her sexual function and also as a mirror for her systemic blood vascular risk. 0.93

00:23:29.300 Again, we're starting to study that, but we don't have clear information. There's this concept called

00:23:34.000 the female genital vascular district. And does that whole area, the larger vessels and the small 0.98

00:23:40.640 vessels, does that give us a correlate or a window? You know, can we use that again as markers for small

00:23:46.940 vessel disease? And then vice versa, like if someone says to me, you know, I have a patient with

00:23:51.300 metabolic syndrome and a high A1C, obesity, diabetes, hyperlipidemia, et cetera. Is that a

00:23:58.060 high risk patient that I should be really counseling and talking to about sexual medicine? And then using

00:24:02.800 that as a reason, managing those issues to preserve sexual health. And I think we need to define,

00:24:08.700 first of all, what is the role of clitoral doppler testing? There's no research on carnea calcium

00:24:13.460 scores or carnea CTs on women and their correlate with sexual function. And can we use these both as

00:24:19.380 mirrors of sexual function and predictors of other issues, other vascular issues for women?

00:24:23.820 I feel like this is the most important growing field that it needs to catch up. You know,

00:24:28.380 that we can't just look at like, oh, she's complaining she's postmenopausal. I think I'll

00:24:32.000 hand her a lubricant because she's not feeling things. That's very crude compared to what we

00:24:36.280 have available for understanding men at this point. So that's a long discussion, but it's an area of

00:24:41.040 great fascination. But practically speaking, we don't have a lot to offer women in the office yet, 1.00

00:24:46.160 but we need to. But it sounds like we're moving in the same direction that we kind of have a clear

00:24:52.900 sense of what's going on with men, which is, and by the way, this is something I do see in my practice

00:24:57.900 quite often, which is you have a guy that shows up with a hemoglobin A1c of 5.9. So he doesn't

00:25:03.100 have type 2 diabetes, but he clearly has too much blood glucose and dyslipidemia. A year later,

00:25:08.260 when you've got all those biomarkers improved, he also notices he doesn't need his Cialis anymore.

00:25:13.520 That's a very obvious, clear, repeatable, common story. So I don't think it's a huge stretch to

00:25:22.280 assume that women could experience the same thing. I like to, when I talk about this with my patients

00:25:27.040 and my colleagues, I like to say there's the motivator and there's the mirror. That's obvious

00:25:30.700 when you're talking about a man. They're like with these parameters. And then you say, so tell me about

00:25:35.760 your sexual function. How's it going? Any difficulty with erections? They report it. And you say, well, 0.79

00:25:40.480 they can sometimes go hand in hand or, and that's a good motivation overall for many men, right? They

00:25:46.560 want to improve everything. And that might be sometimes even the biggest motivation that's

00:25:50.560 important to them. So that's a reason to lose weight. I think we need to have the same way to

00:25:55.360 think about women. And I think the other thing for all people is that we don't do enough to teach

00:26:01.760 that prevention and lifestyle and disease management is important for sexual health and validate how

00:26:07.480 important that is for quality of life. Like there's all these reasons you don't want to have

00:26:10.680 heart disease. You know, we should be saying you don't want to have sexual dysfunction.

00:26:13.740 There's not enough education when people, before they have issues.

00:26:17.380 How clear is that, Sharon? Again, empirically, it just makes sense. But what can we say about sexual

00:26:22.860 health and general health? What I mean by that is overall wellbeing as a function of sexual health.

00:26:29.400 We've already established the causality in the other direction, meaning when your metabolic health is

00:26:33.800 poor and your vascular health is poor, it can impact sexual health. But what I'm saying

00:26:37.360 is even independent of that, if a person is otherwise healthy physically, but still having

00:26:42.860 sexual dysfunction, how does that translate into the rest of their life? There's a couple ways to

00:26:49.020 look at this. One thing is most of the research, I guess we're talking about women today. Most of the

00:26:54.460 research is association research. So it's sometimes a little hard to tell. I think you understand the

00:26:59.880 difference between really risk factor and cause and effect. We know which lifestyle and health factors

00:27:05.620 seem to be associated with better sexual function, better satisfaction, better sexual activity.

00:27:11.060 And most of the research is actually in desire when it comes to that. For example, I'll give you a few

00:27:15.020 examples. In women, there's interesting research that being resilient, having a positive attitude, 1.00

00:27:20.800 for women, especially as they get older, having a partner, being connected socially, having support,

00:27:26.220 normal BMI. The funny one is Mediterranean diet, actually. It probably has to do with overall health

00:27:31.480 and well-being and the other benefits. All those things are associated with good sexual function.

00:27:35.460 And whether people who do those things preserve their sexual function or those things preserve

00:27:40.680 sexual function is still, it's association. I sort of think it doesn't matter. You know, you want,

00:27:45.320 they're both are good. Where it matters as a motivator is that validating the importance of sexual

00:27:50.260 function to quality of life is critical for people feeling that they have permission. Like, that's a good

00:27:55.000 reason for me. Because sometimes it's like an afterthought, like, oh, okay, it's okay. I could prevent heart

00:27:58.840 disease, but do I have to preserve my sexual function? That's a little indulgent. Why should

00:28:02.320 I go to the gym just to have better sexual function? My kids need me to help with their homework. But if

00:28:06.520 it's like, okay, I can't have heart disease, I have to go to the gym. So I think part of it is validating

00:28:10.780 that for people that probably there's strong association. On the other hand, we know what the

00:28:15.660 heavy hitters are in terms of overall sexual function and biological medical conditions and psychiatric 0.89

00:28:21.760 disorders. I'm not sure if this is exactly what you asked me, but it's at a point that I think is

00:28:25.380 important to make. We could go back and clarify if you wanted to hear anything different. So the heavy hitters,

00:28:30.180 we could talk about categories. There's what we've already been talking about. There is associative data

00:28:34.880 that metabolic syndrome in women, obesity, particularly, interestingly, hypertriglyceridemia, which probably

00:28:40.920 makes sense to you, and then coronary artery disease and diabetes. But what's interesting about the last two is

00:28:47.100 that the condition itself isn't as clearly correlated as the psychological adaptation or relationship to the

00:28:53.320 disorder is for women. So for example, if someone had a heart attack or has heart disease and they're

00:28:58.220 female, it's more about how they see themselves and their interest or enthusiasm in becoming reengaged

00:29:04.240 with activity than clearly the severity of cardiac disease. And that might just be we don't have good

00:29:08.580 research, or it might be different in women. And same thing is too with diabetes. Like in men, it's

00:29:13.080 clear, like the higher A1C, the more sexual dysfunction, neurovascular disease, et cetera. But in women,

00:29:18.480 it's more about the impact of diabetes so far in the research. Are they depressed because they have

00:29:24.640 diabetes? They don't like wearing the monitor, so they're embarrassed to have sex or like things like 0.90

00:29:28.920 that, or their feet are numb and it just makes them negative rather than their blood sugar control.

00:29:33.560 But I think that part of the problem is that we don't have as good research. And then there's the

00:29:36.760 whole bucket of genital urinary symptoms, menopausal symptoms, and cancer. We haven't even talked about

00:29:41.660 cancer yet. Breast cancer, gynecologic cancer, cervical and urinary cancer, ovarian cancer. So those are the

00:29:47.280 categories, all those things I just mentioned that are associated with lower sexual function and

00:29:51.460 sexual problems in women. And then there's the whole bucket of depression, anxiety, and their

00:29:56.840 treatments that also clearly interacts with sexual function in women and can be problematic.

00:30:02.320 And I'm kind of curious about both of those in both directions. So for example, like if you take

00:30:06.740 two women who are identical in all ways, but one of them is sexually active and sexually healthy, 0.70

00:30:11.980 and the other one is having sexual dysfunction for whatever reason. And let's assume it's not

00:30:17.360 a physiologic reason. So let's assume it is a supratentorial reason. And as a result of that,

00:30:23.660 she's just not sexually active. Do we have a sense of their quality of life, their well-being as a

00:30:29.220 result of that? In other words, what I'm really trying to understand is how important is sexual health

00:30:34.660 for overall well-being, in particular, in this case, for women?

00:30:39.480 There's a kind of a collection of different buckets of research looking at this. Probably

00:30:43.260 the strongest and most consistent research comes out of the desire literature and looking at the

00:30:48.960 impact of hypoarchasexual desire disorder, which is more like a diagnosable condition or distressing low

00:30:53.880 desire on overall quality of life. And there's, I could quote you studies, but there's a number of

00:30:58.540 well-done both survey studies, which are like in the community and population studies,

00:31:03.740 and clinical data studies collected in clinical settings, suggesting that there's a strong

00:31:08.780 correlation with impaired desire and overall quality of life. The problem, I think, with this research is

00:31:14.540 the dichotomy or distinction you're making that it's purely supratentorial or psychological

00:31:19.180 relational lifestyle is sometimes so hard to tease out.

00:31:23.140 I'm sure.

00:31:23.540 Because no one person has zero biology impacting sexual function. But I will say something that

00:31:29.960 does support that point of view. Practically speaking, you look at the, if you're a clinician,

00:31:34.980 let's say, or someone comes to you, you look at the biology, you look at the psychological factors.

00:31:40.180 Maybe it's sometimes even past sexual function or sexual trauma or religious upbringing or how they

00:31:47.280 saw themselves as a sexual being from the time they were young. Even as a physician, I ask those

00:31:51.640 questions. Then you look at the relationship, you know, and how that is or the culture. And then

00:31:57.800 you look at the things that you think are contributing and those that are amenable to

00:32:00.760 intervention. And you do get to the idea sometimes that it is the psychology. You can reach that,

00:32:07.760 but you'd want to be careful not to assume that you thought about everything in their biology until

00:32:11.680 you have. But that said, you were asking me the condition of someone who has like a psychological

00:32:16.160 sexual dysfunction. And what is the level of distress like? When people identify it and they

00:32:21.600 want it to be different, it's extremely distressing and quite impairing to quality of life. And it can

00:32:27.380 be a mirror for very distressing feelings. There are studies that look at the level of distress and

00:32:32.420 the qualities, and they show things like, for example, loss of sexual desire, despairing, hopeless,

00:32:38.380 feel old, feel ugly, don't feel connected, feel sad, feel hurt. You know, there's a whole collection of

00:32:45.280 emotions associated with it. And typically in this research, they also look at discrepancy.

00:32:50.440 And when they look at the discrepancy between, for example, a clinician's perspective or perception

00:32:54.940 and the patients, when they're asked by like someone else, like an independent reviewer,

00:32:59.560 usually it's way underestimated how distressing or impairing it is to quality of life. We don't do a

00:33:05.840 great job of understanding this. Part of it is legitimizing this. And that's what we're doing here

00:33:10.500 today is like really legitimizing. Like this is a real thing for you. It infects your quality of

00:33:15.680 life. It's okay to tell me, and it's okay to want this to be different. And when women are given that 1.00

00:33:20.900 permission, either because they're being interviewed in a study or somewhere in a doctor's office or

00:33:25.240 they embrace it because it is something that they're feeling. They're feeling impaired quality

00:33:30.580 of life. I think that's what you're sort of getting at. This is worth emphasizing, giving this

00:33:35.140 audience permission to understand that you can seek assistance or understanding or even treatment

00:33:40.300 for these things, for different sexual assumptions. And we can get into defining them a little more

00:33:44.300 specifically soon. And that's good. It's not something you should put as like an afterthought

00:33:49.420 in your life. Because first of all, it's good for quality of life. It's good for your relationship.

00:33:54.100 And there's also some, I don't know if you've quite asked me this, but there is some research

00:33:58.260 supporting the idea that it improves overall health. That's not a stretch, right? I mean,

00:34:02.320 whether or not that turns out to be true, we would only know with more rigorous study.

00:34:07.280 But there's plausibility to that based on other things that we understand about the relationship

00:34:13.880 between hypercortisolemia, HPA dysfunction, stress, all sorts of things that we know do directly impact

00:34:22.540 physical health. So my way of thinking about these things is they may or may not impact the length of

00:34:28.440 your life, but the quality of your life is at least as important, if not more important. And it's very

00:34:34.080 hard to argue it doesn't impact the quality of life, especially if, as you say, it is being perceived

00:34:38.060 that way. So I'm going to preface my next question with an assertion, which is just because evolution

00:34:44.920 didn't care about something doesn't mean we shouldn't. And the example I would use is atherosclerosis.

00:34:50.720 So evolution had no interest in preventing atherosclerosis. If it did, it would have got

00:34:57.100 rid of ApoB hundreds of thousands of years ago because we didn't need it. I mean, we would have

00:35:02.420 got rid of it in the last thousand years, I think, and we wouldn't have atherosclerosis today. But

00:35:07.040 given that it didn't interfere with our reproductive fitness, it's of no concern to Darwin. That said,

00:35:14.060 now that we can live longer, we have every reason to care about it, and we've taken great pains

00:35:19.400 to reduce our risk of dying from it. Okay, so put that aside for a moment as I ask a very

00:35:25.260 naive, potentially, question, but one that I've often thought about, which is, do women have it 0.60

00:35:31.400 harder when it comes to sexual health because evolution didn't necessarily care about their 0.84

00:35:39.460 sexual function post-childbearing years, whereas in theory, evolution might care if men could reproduce

00:35:47.220 through the length of their life. You know, absolutely. This is a really important topic

00:35:52.660 and area for discussion. So let me start with a point that I make often. I mean, women who are

00:35:57.380 perimenopausal, menopausal, and postmenopausal aren't sick. And so sometimes people talk about it,

00:36:02.320 and when you have postmenopausal vulvovaginal atrophy, right? Like, that's a horrible term.

00:36:06.960 Talk about evolutionary terms that make people feel bad.

00:36:09.560 It needs a whole PR firm to come in and just come up with better terminology here.

00:36:14.220 As an aside, I think you've heard this terminology, is that the North American Menopause Society and

00:36:18.640 International Society for the Study of Women's Sexual Health, about, I guess it's almost a decade

00:36:22.980 ago at this point, and I was involved with this process, we got together and had a whole panel on

00:36:27.960 what to do about this name, vulvovaginal atrophy, for a whole variety of reasons. And it concluded that

00:36:33.980 it is what happens, you know, things atrophy, but it's not what we want women to think about. So we came up

00:36:40.820 with the terminology genital urinary syndrome of menopause. So vulvovaginal atrophy can lead to

00:36:46.460 genital urinary symptoms during and after menopause and the syndrome of menopause. So it took away the

00:36:51.960 disease state. It's not really an illness. It's a syndrome which could be thought about in many

00:36:57.440 other ways. I mean, happiness is a syndrome. And so we were really trying to neutralize it. I don't

00:37:01.700 know how well it stuck. It does speak to this idea, first of all, a few concepts. One is when people

00:37:06.560 talk about symptoms or treatments, are we talking about a disease? I guess when we're talking about

00:37:10.500 atherosclerosis and aging, we're talking about a disease. So on the one hand, you could put them

00:37:15.500 as parallels, right? There's hormonal changes, the ovary stops making things, the brain does other

00:37:20.440 things to the sex steroid hormones, testosterone declines in both ovarian and adrenal production,

00:37:24.540 et cetera. And we have physiologic changes which lead to aging, lead to decreased sexual function,

00:37:30.000 and even complete loss of good sexual function. Pain doesn't allow women to, you know, engage in 1.00

00:37:35.880 quality of life, improving sexual activities, relationship building activities. So evolution

00:37:40.260 has not been kind to women in a whole collection of ways. I think that's what you're asking me.

00:37:44.700 And although women aren't sick, our position in the field, and certainly mine, is that we have the 0.73

00:37:50.800 skills, the tools, and the sophistication to manage it and to reverse it and to have a very different

00:37:56.660 outcome than evolution would command. I'll speak not too personally, but I'm a midlife woman. I'm not

00:38:01.360 ready to turn in the towel. And I can tell you that most of my colleagues and friends and family

00:38:06.140 members have the same attitude. And so the challenge in the area is, first of all, not medicalizing this

00:38:12.320 too much and making someone feel sick or give them things that make them sicker. And to balance that,

00:38:18.320 for lack of a better word, lethality therapy balanced to the point where you're optimizing without

00:38:23.980 giving people other problems. Like you give a hormone, you don't want to give breast cancer or

00:38:28.320 endometrial cancer, or you give estrogen, you don't want to cause cardiac disease. And so that's the

00:38:34.300 work that we do in this field, is learning how to trick mother nature or evolution safely, but optimize

00:38:41.760 all of these things, sexual function, quality of life, longevity, even. We could get into the

00:38:46.420 discussion about whether hormone therapy improves longevity. I know that's an area of interest of

00:38:49.760 yours. Okay. This has been an excellent foundation for us to now go through some of these various

00:38:55.640 things. So let's start with sexual dysfunction, and I'll leave it to you which one you want to

00:39:01.660 start with. So do you want to talk about arousal and desire separately and kind of walk through that?

00:39:07.560 Sometimes I find this helpful, Sharon, with other podcast guests where we do actual case studies. So

00:39:12.480 I can make some up, but you can feel free to adjust them and say, okay, so a 35-year-old mother of two 0.93

00:39:20.500 married comes into your office and says, I love my partner. I just don't want to have sex. I'm just

00:39:31.560 not in the mood. So tell me, what's your workup? That's basically all she says on presentation.

00:39:36.160 Let's just pretend that the kids are old enough now that she's not sleep deprived, 0.96

00:39:40.520 waking up every 10 minutes. So her kids are 10 and 12 or something like that.

00:39:45.160 And let's make her 39 if her kids are 10 and 12. Okay, perfect. So she's 39. Her kids are 10 and

00:39:51.560 12. Or 41, right? Where things may be starting to change. Yeah, yeah. Perfect. So the point is-

00:39:56.240 I have reasons for that. She's premenopausal is the point I'm really just trying to get at. 0.77

00:40:00.480 Right. And that's it. And she doesn't have tiny kids waking her up in the middle of the night.

00:40:03.680 She's out of the difficulties of child rearing. Okay. Well, how do you want to work her up and how do we

00:40:07.960 help her? Let me just give you the categories and tell you how I would think about her.

00:40:11.480 Who have you seen Masters of Sex? So the whole concept or how to organize sexual dysfunction was

00:40:17.320 based on the work really first of Masters and Johnson, that there was a response cycle that

00:40:21.660 had an order. They looked at both men and women. They were actually really quite progressive.

00:40:26.280 And the idea was that people started with getting aroused. And I think in their concept,

00:40:31.260 it was all physiologic because they mostly just looked at physiologic parameters. They understood

00:40:34.840 the psychology of things to some extent. That there was this idea that people get physically

00:40:39.320 and mentally excited. They reach some sort of escalation and maybe even a peak or a plateau.

00:40:46.580 And that can be variable. And there's some models that for women, there's more variability in 1.00

00:40:51.820 plateaus. And then the classic response cycle is it results in an orgasm, climax, peak, lots of

00:40:58.360 different words get used, but we're just going to use the word orgasm, keep it simple. And that there's

00:41:02.680 different patterns for that too, right? Like, so-

00:41:05.120 Can I ask a question that goes before that? So what comes first, desire or arousal? Desire comes

00:41:12.080 first, does it? Or do you have to have some arousal to then trigger desire?

00:41:16.200 I'm going to talk about desire in a moment because that's an interesting question. But in their model,

00:41:20.580 they kept it simple. You engaged in sex and you got aroused. And so maybe they thought like

00:41:25.680 the interest in having sex was about being turned on or being aroused. They didn't really get

00:41:30.040 distinguished about it. And then you have an orgasm. And for women, like there's different 0.93

00:41:34.700 patterns. It could be happened in different ways with clitoral stimulation, vaginal stimulation, 0.75

00:41:38.820 et cetera. And sometimes multiple orgasms, which is more characteristic for the variability in women. 0.98

00:41:43.980 And then there's this idea of the like refractory or resolution phase. And that's kind of for like

00:41:49.260 many decades since their work in the late fifties, early sixties, that's how people organize their

00:41:53.760 thinking. A few people came along, notably Helen Singer Kaplan in the seventies. And she happened to be

00:41:59.760 a psychologist at Cornell and has like a whole discipline and following, some of which are my

00:42:03.780 colleagues still, there are a few around and added this idea of wanting or desire and felt that it

00:42:08.460 was really distinct. Thinking about it, anticipating willingness to engage. And that if you didn't

00:42:14.040 separate it, you were missing something about what could be a problem for someone. Like, so that 35

00:42:19.920 year old or that 39 year old we're talking about. I think she's 41 now, but yeah. No, we made her

00:42:23.740 fool because her kids were 10. I wasn't letting her have kids at 25, but some do. Her kids, 0.99

00:42:28.220 if you said they were 10 and 12, I made, I was just trying to be realistic. The other thing is,

00:42:32.660 I feel like it comes up in that if it's not late reproductive post-menopausal, it's like 38 to 41.

00:42:38.900 I don't know why, but I hear that a lot. There's sort of timeframes that come up. We can talk about

00:42:43.320 why that one is, but that's why I picked it. But she might say to me, like, you know, I'm exhausted.

00:42:49.040 I have these kids, I have this job, but I agree. And I'm always kind of like, it's still even to this

00:42:54.620 day, surprised to hear. But I said, do you get turned on? Well, yeah. I mean, it feels fine.

00:42:59.980 Do you have an orgasm? Oh, yeah. And is it satisfying? Yeah. But I don't want sex. If you 0.96

00:43:04.160 get rid of the idea that desire is separate, you miss that. You know, there's a lot of variation

00:43:09.180 on that. We could talk about a different patient where they say, like, theoretically, I really want

00:43:13.100 to be with this person, but I know that, like, things aren't going to work. I'm not going to feel

00:43:16.580 anything. I'm not going to get wet. I'm going to have pain. So that I avoid, and that I don't want

00:43:22.060 because of that reason. Like, there's variations on that. So it's really helpful to keep these

00:43:25.540 concepts separate. There's some work coming out. I don't know if you want to get into this. It's

00:43:30.500 come out over the last decade, actually, in some sort of lay press books that are smushing them

00:43:34.460 together, saying that they're indistinguishable for women. But I feel they shouldn't be. I feel 1.00

00:43:39.040 they need to be separated. And that's based on, first of all, vast clinical experience that you

00:43:43.920 need to walk people through this to understand the problem by separating them. Secondly, that the

00:43:48.940 available treatments target different things. And the physiologic plausibility for separation is

00:43:54.980 strong in terms of risk factor and response to treatment intervention and the opportunity for

00:44:00.340 future direction in improving sexual function. If we keep them together, we're going to lose that. 0.96

00:44:04.360 And to get very granular about this, the psychiatric compendiums has now combined them,

00:44:08.860 desire and arousal, as one thing called female sexual interest in arousal disorder. Whereas the 0.99

00:44:13.740 sexual medicine societies have put out strong position statements as well as nomenclature papers

00:44:18.360 suggesting that we have to have these categories be separate. And the upcoming ICD or the International

00:44:23.680 Classification of Diseases is going to maintain separate coding for desire and arousal for both

00:44:28.160 men and women. And yet you're saying the DSM combines them? The DSM-5, which came out, now it's almost 10

00:44:34.120 years ago, interestingly. They just put out a revision, which I worked on actually as a medical

00:44:38.240 reviewer. They insisted on keeping it the same. They told me that at the onset, you can review this,

00:44:42.820 but we're not separating them. And they wanted me to look at sort of the medical piece of this.

00:44:46.960 Again, it's based on the idea, and I think this is fair for the kinds of people that show up in

00:44:52.280 psychological and psychiatric offices, that for women, it often is interchangeable, like it can 0.55

00:44:57.640 be. It is still separate for men. Do you want to digress for this for a moment? Because it's

00:45:01.420 interesting. I think it resonates for people. And then we'll come back to how we would evaluate

00:45:05.760 your 39-year-old or 41, whatever she is now. So Rosemary Besson is sort of the mother of this model.

00:45:12.240 And there've been others that have written about this, primarily the professional literature,

00:45:15.660 but there's some books out right now, some lay press books about this. And the idea is that

00:45:20.500 instead of this linear response cycle, that a better model for many women or for some women 0.99

00:45:26.040 is something more circular. It's called the circular incentive model. And it's the idea that

00:45:30.980 what drives sexual response isn't linear. Women go, I want to have desire. I want sex. I'm going to go 1.00

00:45:36.340 find my partner. I'm going to initiate or I'm going to receive, and then I'm going to be turned on,

00:45:40.320 and then I'm going to have an orgasm. It's going to be great. And that when you say that to people, 0.98

00:45:43.780 lots of people are going to say that I must be abnormal because I don't feel that way.

00:45:47.160 And that their normal is more something like this. Like they're not particularly feeling

00:45:50.980 spontaneous sexual desire, but the circle starts with the motivation and the incentive to be close,

00:45:57.240 to drive toward intimacy. They're mostly neutral, but because they are close to their partner,

00:46:04.060 or even we should make sure we understand that sex with oneself fits in here too. They like

00:46:08.460 want to feel the benefits that come from a sexual encounter with either a partner or oneself. And

00:46:14.080 they're receptive or seek the stimuli, but not because they're feeling like sex hunger,

00:46:19.000 the classic desire, but because of that motivation. And if everything's intact,

00:46:23.900 psychological and biological influences that govern arousability are intact, they're going to have

00:46:28.540 all of that arousal. Their brain's going to turn on, their body, your heart rate's going to go up,

00:46:32.960 your nipples become erect. You're going to feel the genital sensations, 0.97

00:46:35.580 and that will trigger engagement or arousal. That'll make you feel more invested and then

00:46:41.540 more desire and then more arousal. And that will lead to satisfaction and maybe an orgasm.

00:46:45.760 So that's a chain reaction there, sort of.

00:46:47.780 Right. It's modeled as a circle, but it's the idea that that satisfaction, knowing it's good,

00:46:54.600 knowing you're going to feel close. One of my favorite expressions from one of my own

00:46:58.460 longstanding patients is the afterglow is what motivates it. How you feel together with how she feels

00:47:03.260 connected, not just herself good, but in the relationship. And that if you don't normalize

00:47:09.020 that thing where desire and arousal kind of smoosh together, when everything works, you're going to

00:47:14.140 make people think there's something wrong with them, that they don't have spontaneous sexual desire.

00:47:18.500 So there's a book out there, for example, Emily Nogosu wrote a book called Come As You Are.

00:47:22.400 Some of the work of Lori Brado, these are live press books, looks at this, that we want to make it

00:47:27.060 okay that you can be motivated by other reasons. But where this model gets confusing is that it

00:47:33.880 doesn't normalize low sexual desire where you can't make it work. So let's go back now. Let's

00:47:39.320 go back to your example. So if she says to me, everything works fine, but I still, even though

00:47:44.720 I have a good experience, I still come back to this and I don't want to have sex. Then that model 1.00

00:47:49.020 doesn't apply to her and she's not normal. And where that model misses is they forget that 0.98

00:47:54.280 we have to make sure that people who don't feel reinforcement, don't feel motivated to re-engage,

00:48:00.300 don't have the desire, the willingness, or the interest, it isn't normal. Where I do find this

00:48:04.880 idea works the most, where people are kind of neutral, but they engage to be closest in long-term

00:48:08.460 relationships because they know what makes the relationship work. So this person comes to you,

00:48:13.580 what I'll do is I'll walk her through. I'll say, you know, do you feel sex hunger? Do you initiate? 0.85

00:48:18.660 Are you receptive? No, no, I avoid it. I finally give in because I know he's grouchy or she or whatever.

00:48:24.660 How does everything work? Does your brain turn on? Do you get breast sensations? Does your body get

00:48:30.120 general arousal? Do you get genital sensations? Do you feel engorged? Do you get lubricated?

00:48:35.800 The degree to which I ask specific questions is variable. Sometimes I ask more general questions,

00:48:39.720 like, do your genitals get turned on? And do you peak? Do you climb? I've tried to find the language. 0.99

00:48:44.820 Usually I just say, do you have an orgasm? And sometimes, you know, that's a whole nother discussion. 0.95

00:48:48.900 Women aren't sure. So I try to help them understand what it is they're experiencing. And there's a lot

00:48:53.580 of variability in the female orgasmic response, but women orgasm. 1.00

00:48:57.000 Can we put a pin in that and come back to that? I want to make sure we cover that,

00:49:00.320 but let's continue with this patient.

00:49:01.540 And then I always ask, this gets forgotten often, is do they have pain? Now, this is a

00:49:07.000 premenopausal woman, right? Likelihood, she's no longer breastfeeding. She's probably ovulating 1.00

00:49:12.800 regularly, having regular menstrual cycles. So I interweave those of the gynecologic history,

00:49:16.840 like what's the menstrual history. A 39-year-old could be having an early menopause. I make sure

00:49:21.940 that I'm not missing that. Emerging dryness, pain, discomfort. You can't always assume you know

00:49:27.340 someone's age, you know what's happening. So it's regular cycles. Are they having dryness, pain?

00:49:32.220 Are they, in this case, she's no longer ovulating? Are they taking some other medication? Are they on

00:49:37.520 an antidepressant? So then I look at factors. Things like medications can affect multiple different

00:49:42.080 phases. But so I collect that information for a variety of reasons. Someone with low desire,

00:49:47.180 I would collect medication information. Someone with arousal difficulty.

00:49:50.160 What are some of the worst offenders there? I know that SSRIs certainly wreak havoc in men. Do 1.00

00:49:55.600 they also do so in women? So if you're talking about general sexual dysfunction that can affect a

00:49:59.800 variety of phases, antidepressants, but all psychotropics, all categories of psychotropics.

00:50:05.740 And these days, people aren't just on antidepressants. The SSRIs and SNRIs are probably

00:50:09.480 most well-known to cause multi-phase dysfunction. There's differences though. I mean, that's one

00:50:14.960 of the areas that I consult with a lot because I work closely with psychiatry here, is that not all

00:50:19.000 drugs are the same. It is a class effect, but there are better drugs. And then there are other

00:50:22.960 categories. Like for example, bupropion, which is more dopaminergic, is a different choice for a

00:50:28.160 variety of reasons. That's Welbutrin?

00:50:30.060 That's the brand name for that is Welbutrin. The generic is bupropion.

00:50:33.420 Within that class of drugs, what are the ones that are more likely to reduce desire?

00:50:39.960 So the classic SSRIs, most of them fit in that. And the bundle together, or they cluster together

00:50:45.440 somewhere around 35 to 40% of what we call treatment-emergent sexual dysfunction. But I want

00:50:50.640 to make a really strong caveat in a moment about this because there's actually some new research

00:50:54.600 kind of debunking some of this a little bit. But that said, so the SSRIs, do you want me to use

00:50:59.940 brand names because people know that better, or generics? So Prozac, Fluoxetine, I'll use both

00:51:04.700 being mindful of this. Prozac, Fluoxetine, Sertraline, Zoloft, Paxil, Paroxetine, those

00:51:12.140 are the SSRIs, and probably Eschatolopram, Lexapro, and Sotolopram. They're probably similar.

00:51:18.800 That said, I have patients who say like, I develop low desire on Prozac, or I have difficulty

00:51:23.500 with orgasm on Sertraline, on Paxil, but not on Prozac. So we sometimes try a few, if I think

00:51:29.780 an SSRI is the best choice. That's definitely been our experience clinically is that, yeah,

00:51:35.780 there's a class effect, but at the end of the day, it's kind of drug specific. And I always tell

00:51:40.960 patients, we're not the ones that are prescribing those. We're not psychiatrists. But if your doctor

00:51:44.920 is prescribing you an SSRI or an SNRI, I always say the probability that you're going to get it right

00:51:51.520 on the first one in terms of efficacy and side effects is actually not that high. So you have to

00:51:57.160 be willing to switch drugs to find that right combination of efficacy and avoidance of side

00:52:02.580 effects. And you'll be able to stay within the same class usually, but there seem to be non-trivial

00:52:08.780 effects. So again, we're talking about the condition that you're treating it for. Usually it's depression

00:52:13.060 or anxiety or both. And then there's the side effects, which amongst them is sexual dysfunction.

00:52:18.640 So then there's another category, the SNRIs, the serotonergic norepinephrine drugs, which I know

00:52:23.220 you're familiar with. There's more variability in the data on that. So there's duloxetine,

00:52:29.540 there's venlafaxine, which is a faxor, which is probably the most commonly used one. And then

00:52:34.100 there's Pristique, which is desvenlafaxine. They're probably, all of them are probably similar

00:52:40.120 to the SSRIs. But venlafaxine is interesting. At a low level, low dose, it functions more like an SSRI.

00:52:47.040 And that is you kick in above, like 75 is up to 75 is probably low, somewhere over 100 to 150

00:52:52.960 functions more like an SNRI. And so teasing out the sexual dysfunction and the dose dependency is

00:52:58.500 a little tricky on that one, but just keep that in mind. And then desvenlafaxine has some data

00:53:04.280 suggesting it's less likely to cause sexual dysfunction. It probably has to do with the

00:53:08.080 chemical composition and how it's different than venlafaxine. Then there's some new drugs. I guess

00:53:12.360 they're not so new anymore. Velazodone and vortioxetine, which have very unique and different

00:53:18.260 mechanisms, and they seem to be better. They're complex serotonergic, dopaminergic transporters.

00:53:25.360 They're a little complicated in their mechanism, but the bottom line is they work both with serotonergic

00:53:29.780 transporters as well as dopaminergic drugs. So it's the multi-receptor factors that when you're

00:53:36.000 looking at the sexual dysfunction component, that's why the theory is that they're better. The best data is

00:53:41.180 actually with velazodone. Though I have some- Best data for fewest sexual side effects.

00:53:46.560 Lack of sexual dysfunction. The problem with the research on the three newest that seem to be the

00:53:51.280 better, that is desvenlafaxine, vortioxetine, and velazodone, is that the studies weren't perfect.

00:53:56.900 There was a lot of high pretreatment sexual dysfunction. So when they separate from placebo

00:54:02.140 and not having treatment emergent, it may be the effect of just treating disease state of depression

00:54:07.600 and improving sexual function, which speaks to the point that I told you I wanted to make in a minute

00:54:11.460 about what some of the newer research says about this in general. The other drug is metazapine,

00:54:16.480 which is kind of an atypical SSRI. It is very low in sexual dysfunction compared to the other SSRIs,

00:54:23.740 but it has some other problems with side effects. It can be sedating, which is good for people who don't

00:54:27.400 sleep, and there's some weight gain that people report with that and why that is is a little unclear,

00:54:31.440 but probably the dopaminergic component. Let's assume that this woman is not taking any of those

00:54:37.240 psychotropic meds. Would her being on an oral contraceptive sway? Yes. Yes. Thank you. Okay.

00:54:42.780 So what's the role of oral contraceptives in this? Yeah. So I was going to tell you about that in a

00:54:47.060 minute when we talk about hormones in this age, premenopausal women. Let me make my point though,

00:54:51.060 because I don't want to forget. So there's some research that's come out both in menopause for

00:54:55.680 menopausal women and in general, that the best thing to do for a depressed person for sexual 1.00

00:55:01.660 function is to treat their depression. I still am having trouble teasing this out,

00:55:06.820 that probably the best thing to do is pick the best drug for them, for their depression,

00:55:11.420 and that it's more important to get them undepressed in terms of sexual function,

00:55:16.020 and that a small percentage, even though the numbers in other studies say 30 to 40 percent,

00:55:20.640 will get what's called treatment emergent sexual dysfunction.

00:55:22.840 But one of my colleagues who I admire greatly, who does a lot of work in this area, said something

00:55:27.980 to me the other day. We're working on a project, a paper that relates to this. She said, look,

00:55:32.160 the bottom line is, here's the simple answer. If you treat their depression, most likely their

00:55:36.960 sexual function is going to get better. If it doesn't, it's due to the drug. And I thought if

00:55:42.620 they don't want to, it's not because their depression is not better, because depression is

00:55:46.100 associated with sexual dysfunction. And then that's when you start to say, well, if this is important

00:55:50.160 to that person, you switch the drug around. And this is where we can come in, is where we can say,

00:55:54.620 look, this is an important reason to switch meds. But some people say to me, I don't care. I just am

00:55:59.920 so happy I'm feeling good. And I sometimes say, great. Or sometimes I say, well, you could feel

00:56:03.740 good on something else and still have good sexual dysfunction. Don't dismiss that. So it depends on 0.91

00:56:07.920 the patient. So the other big category, so we talked about psychotropics, and they're less commonly

00:56:12.700 prescribed in ordinary situations. But antipsychotics, anxiety meds, they all have some issues around

00:56:17.800 sexual function. And should that be relevant, we could discuss that. So the other categories, like

00:56:23.520 not so much for this woman, blood pressure meds, there's some discussion about how to think about 0.96

00:56:28.000 those, a collection of pain medications are another big bucket, hormone suppressing drugs, like if

00:56:33.760 someone's on an aromatase inhibitor for cancer, prophylaxis, et cetera. But the thing that we really

00:56:39.660 want to make sure we talk about in this age group, and you're bringing this up, is combined hormonal

00:56:43.300 contraception. I'm glad you raised this, Peter. So confusing area also. There's like, people are

00:56:49.580 very polar on this and very opinionated. But I think it's important not to recognize, not just

00:56:54.560 oral contraceptives, it's combined systemic hormonal contraception. So people take birth

00:57:00.300 control pills, which have estrogen and progesterone. They also use patches, like the OrthoEver patch and

00:57:05.940 the ring, like the NuvaRing, right? And those combine, and there's a whole bunch of different

00:57:10.420 types of these. But the idea here, what are you doing when you give hormonal contraception?

00:57:15.220 You're turning off the brain and that feedback loop that makes you ovulate, you know, make a

00:57:19.920 lining, shed it, and be able to have a pregnancy and then shed it if you don't. And you're turning

00:57:24.040 it all off by giving super high doses of hormones. So what happens, the short answer is with combined

00:57:30.200 contraception, it's probably most noted in the research, is that a small percentage of women 0.95

00:57:35.100 get that high level of estrogen, but the vulval vaginal mucosa doesn't recognize it. 0.98

00:57:40.540 And you can develop a vestibulodynia, a vestibulitis, that the vestibule is that tissue around

00:57:47.080 the entrance to the vagina. Not so much inside the vagina, but that surrounding tissue called 1.00

00:57:51.700 the vestibule is very sensitive to the drop in these endogenous estradiol, and the synthetic

00:57:58.900 estrogens sometimes don't do their trick. And they can develop a vestibulodynia, meaning pain

00:58:04.680 and dryness, and almost look like a postmenopausal woman when it comes to that. That's one issue 1.00

00:58:09.300 with contraception. It's probably that number, you want to number, the work of some of my colleagues

00:58:14.540 in this area who do like sexual pain and vestibulodynia work, say it's somewhere around 10%.

00:58:19.240 Meaning 10% of women that are receiving systemic-

00:58:22.620 Of users.

00:58:23.260 Okay, who are receiving systemic birth.

00:58:24.700 And that it's probably similar with rings and patches, but it's not as well documented. And then

00:58:30.740 there's some variability, like higher dose oral contraceptives have been more likely,

00:58:36.220 low, I'm sorry, the very low dose have been more likely implicated. And people do better if they

00:58:39.720 have like more robust high dose, like sort of more standard 35-microgram pills, as opposed to these

00:58:44.700 ultra-low, like the 20-micrograms.

00:58:47.160 Like is low-loestrin considered low?

00:58:49.360 Yes, that's an example. So the ultra-low ones tend to be the biggest culprits.

00:58:53.020 That said, the experts in the field feel this is very important for us to understand.

00:58:56.780 And the ordinary gynecologic community thinks it's relatively insignificant,

00:59:01.060 whether they're under-detecting this particular piece of it or not is something that needs more

00:59:05.500 development. The other issue with birth control pills is that it can have an effect on neurotransmitters.

00:59:10.380 And sometimes women will develop mood issues with, as you probably know, with like high-dose

00:59:14.100 oral contraceptives. And that may have an impact on the neurotransmitter milieu and the mix that

00:59:20.160 leads to sexual dysfunction and low sex drive. Then finally, and this is probably more important as

00:59:25.620 when we get a little older, and it might lead us into the discussion about testosterone,

00:59:29.100 is that, so three things. One is they can have an effect on the local vulvar tissue if we have

00:59:34.200 this issue, particularly the lowest dose estrogen. The other thing is it depends on the androgenicity

00:59:39.080 of the birth control pill. That's yet another issue. And there are androgen receptors in the vulvovaginal

00:59:44.820 tissue. So that may change sensitivity or even lead to pain, that piece of it. The second thing is that

00:59:50.840 intersection with brain neurotransmitters and mood and that effect on sexual function could also be

00:59:55.880 clinically important. And then finally, and this is like a whole nother thing, what do you do when

01:00:02.060 you send all that hormone into someone's body? You increase the production of SHBG.

01:00:05.980 So you're binding up more of the hormone as well.

01:00:08.960 The easiest way to think about it is you need something to carry it around with. And that SHBG goes

01:00:13.160 up in other states like pregnancy. You might ask me like the same with birth control pills in pregnancy or

01:00:18.080 when you take thyroid hormone. There are other things that make that production of that go up.

01:00:23.300 The data across situations is like, you could say, okay, it's like around a hundred such with this or

01:00:29.440 is not so clear. I think it's best just to say it makes it go up. Now that is a hundred percent of

01:00:35.660 women. Like I get asked this question, like, does it matter? A hundred percent of women have a higher 1.00

01:00:39.480 SHBG if they take, for example, let's just say high dose birth control pills. Let's just stick to that

01:00:43.680 for now. Everybody who takes it has that. And what does that do? So it helps carry it around,

01:00:50.160 but it also, fortunately or unfortunately, whatever you want, the fellow traveler is

01:00:53.740 androgens or testosterone gets carried by SHBG. So because you're increasing SHBG, there's some

01:01:00.600 thinking that you're binding up the circulating testosterone and you may be lowering free

01:01:05.800 testosterone in those women. And that might be another potential contributor to low desire.

01:01:10.620 Now we get into testosterone, we can talk about that, but has testosterone affect desire?

01:01:14.380 Probably at the level of brain receptors and turning on those pathways of desire. And there's

01:01:18.220 some genital changes too in the metabolites of the androgens that change sensitivity and that

01:01:23.520 might impact desire, but that's a secondary state. And we're also going to, when we talk about

01:01:28.040 testosterone, we were talking about how it doesn't like abruptly change so much like ovarian hormones

01:01:32.480 with menopause, that it's more of a gradual decline. So the intersection between contraception and

01:01:38.320 women in their late 30s and early 40s and testosterone is interesting. So if you look 0.96

01:01:43.200 at my arm, when you're 18 to 24, that's when we start to study reproductive, your testosterone is 0.92

01:01:48.060 like up here in the 40s for women, right? And then it kind of goes down, like, I wish I could do it

01:01:53.120 better, but it declines. And by the time you're in like those late 30s, early 40s, it's about half.

01:01:59.180 Like if you look at normal ranges, studies that have tried to, of what you were when you were 18.

01:02:03.320 And then it levels off at somewhat lower in your 40s and 50s, and actually goes up a little bit

01:02:08.580 past 60 and kind of levels off down there. So if you're on birth control pills, that curve is way

01:02:15.020 down. A woman at 40 might be much more sensitive to that effect than she was if she was on a birth

01:02:19.500 control pill at 25. And that difference in her testosterone or free testosterone may be significant

01:02:25.620 in that she'll come and say, like, I have no sex drive or I have no general sensitivity.

01:02:29.060 That's a kind of an important thing that most people don't tell their patients when they put

01:02:34.680 them on a birth control pill or a combined contraception for 20 years. Now, the other

01:02:38.540 thing, and I think it was in, we get some notes in advance. It was one of the questions you asked,

01:02:42.000 what happens? Believe it or not, even though people say it doesn't come back, like let's say

01:02:45.840 you take a birth control pill from 20 to 40, and then you have, you know, you decide to switch to an

01:02:50.180 IUD after your second baby or your third baby, which happens a lot. What happens to my SHBG?

01:02:54.900 There's really only, believe it or not, really one good study that was done by Claudia Panzer in

01:03:00.240 like 2000, something like that. And we need more. There's some other data, but not a good study.

01:03:05.060 And she looked at current users, never users, and stopped users who stopped six months ago.

01:03:10.460 And the bottom line was at six months, the stopped users, the previous users, were in the middle of

01:03:15.660 the other two. They hadn't gone down to normal. Now, no one ever studied them out to three or four

01:03:19.800 years. But I can tell you, and my colleagues can say that if that woman walked in and she'd been on

01:03:23.860 birth control pills, and I checked her SHBG, even if she had stopped it, it's always going to be

01:03:28.100 higher than the person who ever used them. I just see that all the time. So does that mean that her

01:03:32.300 free testosterone at 40 is lower than it would have been if she hadn't used birth control pills for 20

01:03:37.080 years? Well, that's the theory. Wouldn't it have to be unless her testosterone has gone up? I mean,

01:03:41.260 because SHBG is doing the lion's share of the binding. I mean, albumin is a relatively small

01:03:46.880 contributor to this process. So isn't it about 85% of the androgen binding is coming through SHBG?

01:03:53.860 It depends a little on how much you have, but that's roughly the idea. To answer your question,

01:04:00.480 it depends a little bit on how much SHBG you have, but most of the binding is through SHBG and a small

01:04:05.420 percentage is through albumin. There's one more point, which before we go back to talking about

01:04:10.560 binding in a second, is part of the controversy is it's not clear that free testosterone is the

01:04:15.520 bioactive component to what makes desire happen, both in the cells and in the brain.

01:04:20.840 So the naysayers are saying, well, okay, but that's not necessarily the active component.

01:04:27.340 And like looking at SHBG and free tea might not be what we need to be doing anyway.

01:04:33.940 And sorry, just let's go down that rabbit hole a little bit further, because this is something

01:04:37.060 that fascinates me endlessly is at least in men, the way I think about this, but I would think that's

01:04:44.220 parallel in women. The one thing that's missing from all biomarkers that we can measure. So let's

01:04:50.600 just make sure people understand the lingo you and I are throwing around. Testosterone is a measurement

01:04:55.800 assay. When you go and measure, when you ask what's a person's testosterone level, there's an assay that

01:05:02.380 breaks apart and separates testosterone from albumin from SHBG. And you actually measure in

01:05:08.360 nanograms per deciliter, the concentration of testosterone in that plasma. When people talk

01:05:13.720 about free testosterone, that is not measured. That is calculated. It's estimated based on the

01:05:20.420 measured testosterone, the measured SHBG, and the measured albumin. But there's a whole other issue

01:05:26.500 here, which I don't think gets enough attention. I do plan to explore this in subsequent podcasts,

01:05:31.800 because I find the topic really fascinating, which is androgen receptor saturation. I'll give you a very

01:05:37.080 clear clinical example I see in men, but I know it applies to women, which is you take two guys that

01:05:43.440 both have a total testosterone of 500. And let's just assume that their free testosterone are estimated

01:05:49.040 to be roughly the same. And you give them both testosterone. So now they both have a total

01:05:54.560 testosterone of a thousand. One of them feels significantly better. The other one says, I don't

01:06:00.640 really notice a difference. There's an argument that says that the guy who doesn't feel any different

01:06:05.500 already had his androgen receptors saturated. So yes, you drove up his testosterone. And yes,

01:06:11.540 more of it is free, but it doesn't matter because where it matters most in the nucleus at the androgen

01:06:17.380 receptor, you haven't increased it. Whereas the guy who says, oh my God, you've changed my life.

01:06:23.260 My libido is higher. I'm recovering from workouts better. I'm putting on muscle. Everything feels better.

01:06:28.960 He was probably under saturated. So this is something, I mean, to my knowledge, Sharon,

01:06:33.480 we don't have a way to measure this clinically. You know, I know that there are people in the lab

01:06:37.300 who can do this, but... Right. So this is part of all of that emerging understanding and lack of

01:06:42.980 clarity is now being brought to the question of female testosterone too. And even less is understood

01:06:47.720 about the role of the circulating actual measurable testosterone, what we think is free or bioavailable,

01:06:56.520 and how that's interacting with the androgen receptor, both in non-genomic and through genomic

01:07:01.980 mechanisms. And then all of that, what cells do we even mean in a woman? Is it her brain? Is it her 1.00

01:07:08.060 genitals? Is it her nipples? Like we don't even know. But the theory is that the most important 1.00

01:07:14.060 place that testosterone acts is in the brain. So like, is it, where is that happening at a cellular

01:07:18.920 level in the brain? If you look at like the most general concepts is that testosterone is the hormone

01:07:23.780 of desire, testosterone in its metabolites, and that it interacts with brain neurotransmitters to turn

01:07:29.420 on pathways of desire. And when it drops, it's sensitive. Like if you look at the early work

01:07:34.080 of Helen Singer Kaplan, who was a psychologist, I love reading her work because she actually talked

01:07:38.020 a lot about this and said, the goal, and this is like my mantra. I have it like in a couple of slides,

01:07:43.020 which is to fine tune that just the right amount of giving exogenous testosterone safely to turn the

01:07:50.780 brain back on to where she was when she was satisfied, meaning like pre-menopausal satisfied,

01:07:55.820 but not invoking lethality and keeping her safe. And that titration is the work of desire,

01:08:02.980 you know, the desire treatment, right? When you're using pharmaceuticals. So the argument is,

01:08:07.840 first of all, do we know what's actually happening? And then do we know what we want to fix?

01:08:11.340 Getting back to our original discussion, this woman, let's say she was on birth and total 1.00

01:08:14.880 puzzle, and it's been 20 years. And like she stopped them on and off for her kids, but she still is

01:08:19.320 taking them. And her SHPD is high and her free tea measures low. And then she has low desires.

01:08:24.120 Are we confident enough to say, that's why? And then the answer question is, will stopping her

01:08:29.640 birth and total pills solve the problem if her SHPD doesn't come down? Or am I going to give her 1.00

01:08:33.100 doomsday prognosis? Because women will say to me, well, what if it doesn't come down? Will I be like 0.98

01:08:37.380 this forever? And then it gets into this whole question of like, is she a candidate for exogenous

01:08:42.640 testosterone? She's pre-menopausal and she's still menstruating. So we could go on and on with where 1.00

01:08:46.600 this leads us. I think we want to talk about like, what do we know? What don't we know? And what

01:08:50.700 are the pragmatic or practical implications of what we do understand and how we counsel patients

01:08:55.660 ultimately? Well, I think this is as good a time as any to go a little further down the testosterone

01:08:59.240 hole, because I think we're making this up as we go along vis-a-vis this case. I think where we're

01:09:03.400 arriving organically is actually quite a common phenomenon. You know, I've made this point on a

01:09:07.660 previous podcast. I think when I was on Andrew Huberman's podcast a long time ago, I made this

01:09:11.260 point. It's worth making again, which is we think of testosterone as the man's hormone, estrogen,

01:09:17.600 progesterone as the woman's hormone, not entirely correct. In fact, one of the challenges is the way

01:09:24.460 the labs report the units of estrogen and testosterone are different. Testosterone is

01:09:29.800 typically reported in nanograms per deciliter, whereas estrogen is reported in picograms per

01:09:36.900 milliliter. So when you convert these to the same units, so you can do an apples to apples comparison,

01:09:42.920 you realize that testosterone is much higher in a woman than estrogen is. Let me repeat that.

01:09:50.280 Yes, absolutely. Thank you for saying that.

01:09:52.640 A woman has much more testosterone in her body than she has estrogen. This is a staggering thing 1.00

01:09:59.580 that surprises most women and most men alike. And to me, at least the implication is,

01:10:05.380 given that testosterone is the most abundant sex hormone in a woman's body, both pre and post 0.96

01:10:12.240 menopause. And by the way, post menopause, the gap is even bigger because of the reasons we've

01:10:16.100 already discussed. It is not a surprise that changes in testosterone, a hormone that is

01:10:22.880 largely responsible for desire, can be just as important in women as they are in men. So this 0.95

01:10:27.860 brings me to this asymmetry. Such an important point is like really people just have such a hard

01:10:34.160 time wrapping their brain around it. They think that the only hormone they should be talking about is

01:10:37.660 their estrogen. And then there's this idea that estrogen supplementation improves sexual function,

01:10:42.300 and that's like a whole nother discussion. But it's so poorly understood how important testosterone

01:10:47.740 is to the functioning of women, particularly when it comes to sex organs and sexual desire or sexual 1.00

01:10:53.140 function. So this is where I think there are lots of places we can fault the medical system,

01:10:58.100 and we're going to line those up and stack them here in a minute. But let's start with one of

01:11:02.260 them, which is the double standard and frankly, the lack of scientific rigor around evaluating

01:11:08.520 testosterone replacement for women. So there recently was, there were two trials actually

01:11:12.960 looking at a, if I'm not mistaken, a gel and a transdermal testosterone product for use in women.

01:11:20.300 I believe the gel didn't find a benefit. I can come up with several reasons why not. But the

01:11:26.280 transdermal testosterone, it began with an I, I don't remember the name.

01:11:29.580 Intrinza. Yeah, Intrinza. It was a Johnson & Johnson patch, 300 microgram. So even trickier

01:11:34.200 when you think about these numbers, it was a 300 microgram patch. People are always like

01:11:38.520 struggling with the numbers. But here's the thing. It raised testosterone,

01:11:42.320 it improved sexual function, and the side effect profile was not of concern. This was a drug that

01:11:49.000 should have been approved. Why did the FDA not approve it? There was more than one trial.

01:11:54.540 There's a wonderful paper. It was in Lancet, I think in 2019. That's a meta-analysis of

01:11:59.520 over like 50-something studies. There are some that are sort of most well-known because they

01:12:03.700 resulted in presentations of campaigns toward the FDA. But there have been a number of randomized

01:12:09.180 controlled trials using patches. The Intrinza brand by Johnson & Johnson was a particular

01:12:15.100 campaign that was brought to the FDA based on their randomized trial. That study was, I think it

01:12:21.380 was also, I'm using the 2000 a lot, it approximates it. It was actually Jan Schiffrin in the New

01:12:25.720 Lincoln Journal. And the first study that she looked at was the equivalent of the 300 microgram

01:12:30.240 patch in ophorectomized women, young women who had low desire. They had distressing low desire. And 0.58

01:12:36.380 the estimation for the 300 micrograms is that's the physiologic amount. This is also a little

01:12:41.460 complicated, but that's the physiologic amount that approximates what you would get in a mid-reproductive

01:12:47.860 or late reproductive age to bring you back to that level, somewhere around, let's say, 30-ish,

01:12:53.740 27 to 38, something like that. It's based on the reference range for normals for women. And that

01:12:59.480 when you gave that patch, they looked at outcomes. The outcome of interest was hyperactive sexual

01:13:04.540 desire disorder or sex driver libido. And it showed positive improvements. And it was based on both

01:13:10.960 self-report, satisfying sexual events, et cetera, as well as other phased responses, arousal,

01:13:16.140 orgasm, overall satisfaction. And it showed really no adverse effects in the short run,

01:13:22.220 but they looked that and other data looking at longer-term safety studies. And we can talk about

01:13:26.680 some of the other trials and data too, but it looked at intermediate cardiovascular outcomes,

01:13:31.940 cancer outcomes, and metabolic outcomes. And there were no hits, but it was a 24-week trial,

01:13:38.080 six months. And the main thing in small percentage of women was what's called hirsutism. So it was a 0.92

01:13:42.660 little hair growth, like on the face, along the nipple. It was about 18% and a little acne,

01:13:48.820 but women didn't get virilized. Hirsutism is kind of a scary word. They had a little extra hair. I like 0.99

01:13:53.160 hair growth, a little hair growth, easily handled by depilation strategies that women use anyway. 1.00

01:13:58.020 And the acne was relatively mild. And women did well, and they liked it. And it was brought to the 0.53

01:14:03.500 FDA at that time. And the issue wasn't efficacy. It was lack of long-term safety data. There was a lot

01:14:08.980 rancoring. I know some of my colleagues were very, very upset about it at the time. And it did get

01:14:15.820 approved in Europe for some time for that indication. O for rectumized women with low

01:14:21.220 desire. And it was used off-label in other post-menopausal women. It went off the market

01:14:25.560 for reasons other than efficacy or safety, and it's no longer available in Europe as a 300 microgram patch.

01:14:30.780 So no patch is available anywhere in the world for women. 1.00

01:14:33.380 So let's just level set for people so they understand something. There's an undercurrent

01:14:38.200 of bad science here, which was one of the reasons given for the fear around this use of topical

01:14:48.360 testosterone was extracted from the incorrect and erroneous fear that still lingered from the

01:14:56.700 women's health initiative. So that's kind of problem one here. I think problem two is the double 0.94

01:15:02.220 standard, which is how many topical, injectable, transdermal testosterone products are approved

01:15:11.060 for men right now in the United States? We can say at least two dozen, like depending on how you look

01:15:16.380 at the indication, whether it's for, you know, hypogonadism versus sexual dysfunction, you know this,

01:15:20.960 right? So let's just say two dozen. Okay. So those products get approved on biochemical efficacy.

01:15:28.680 Do they or do they not raise testosterone? And also outcome, like the outcome of, you know,

01:15:33.580 that you're looking for, the target outcome of the study. They don't require the five-year

01:15:37.680 safety window because we've already established over decades that exogenous testosterone at

01:15:44.680 physiologic doses is safe. So again, you could make the point, well, Peter, why do you care about

01:15:50.460 this? I mean, you can prescribe it off-label to women, which of course we do. Oh no, there's a huge

01:15:55.320 reason to care. So let's talk about why does this matter? There's been a lot of feeling that the

01:16:01.620 standard, just to emphasize this clearly, applied to the first drug. The Libigel, you asked me about

01:16:07.320 that. It never made it to the FDA. They withdrew their applications and so forth. I'll talk about

01:16:11.360 why. It didn't have efficacy, correct? Right. It was called Libigel. They looked at the data for

01:16:15.480 out to five years and had like seven years of women patient data research. And it didn't show any

01:16:21.360 hits for being unsafe. And it was loaded for women with cardiovascular risk factors. There was no

01:16:27.000 increased rates above baseline rates of cardiovascular disease, of breast cancer, of

01:16:30.940 intermediate markers for metabolic or cardiovascular risk, like A1c lipids, inflammatory markers.

01:16:36.760 And they reached the therapeutic level in the blood. So they felt that they could clearly state

01:16:42.500 that this represented safety data, but the efficacy hit wasn't met. And so they did not take

01:16:48.360 it further to the FDA, unfortunately. And that's been the last effort since then.

01:16:52.280 But just going back. So the problem is that you're saying like, why do they approve these

01:16:55.500 testosterone products? Because the concept has already been proven, right? That we know

01:16:58.280 the FDA makes this assumption that it's safe. But when this was taken to the division that looks at this,

01:17:03.400 it's really the hormone and reproductive end. There's no precedent. But the lack of approval

01:17:07.920 doesn't then permit the precedent, the history, the knowing, the expert consensus in the field that it's safe.

01:17:14.880 So you never can get there if you don't approve something at 24 weeks. So this is the conundrum

01:17:20.360 that we face. Like this is the problem. There's only one place in the world that has a government

01:17:25.160 approved product of testosterone. It's the continent of Australia. They have a product that is now

01:17:31.180 available that you can get. It's called Androfem. And it's five milligrams. This is the dose. You can go

01:17:37.340 up to 10 milligrams of the item, the testosterone that gives you this physiologic amount of testosterone.

01:17:42.060 People get confused because the patch was 300 micrograms. But it is available in Australia.

01:17:46.880 It's government approved. It's based on the same research, the same numbers, the same blood levels,

01:17:52.160 the same outcomes. There's a way for practitioners and from other countries by sending their licensing

01:17:56.900 information to actually order it for patients. But it's not done very much. So no other place in

01:18:02.740 the entire world has approved a testosterone for women. So you're asking me like, why does it matter?

01:18:06.340 We've just prescribed it off label. The problem is there's no regulation to it. So let me say

01:18:11.240 something else that I think was implied, but you're mentioning the study about the 300 microgram patch

01:18:16.200 that went to the FDA. There've been a number of randomized controlled trials looking at similar

01:18:20.820 doses, mostly in patches, looking at women on and off estrogen, pre and post-menopausal,

01:18:27.580 surgical and natural menopause that have shown the same efficacy with the outcome of HSDD,

01:18:34.360 hyperoptic sexual desire, being the primary outcome and showing other parameters with improvement,

01:18:39.780 like arousal, orgasm, satisfaction, et cetera. And based on that, consensus papers that have come

01:18:44.940 out in the last couple of years really say that this is indicated and probably late reproductive age,

01:18:50.060 there's two different guidances, and definitely post-menopausal women based on this efficacy 0.99

01:18:53.460 and safety data and these numbers of randomized trials. And this large meta-analysis that looked

01:18:57.980 at efficacy and safety of numerous studies demonstrates this. So you can prescribe it.

01:19:02.060 It's off label, but it's supported by all of this data. The problem is it's impossibly hard to

01:19:08.020 prescribe it. And with the precision, unless you're in Australia, that we should command for our

01:19:15.220 patients. So yeah, it's really imprecise and it's a problem. And let's explain this because I want

01:19:21.000 to talk about it, which is because you have to basically rely on one of three methods. One is

01:19:27.040 using a man, sort of a male topical product, but then their doses are wrong. You're stuck using like

01:19:34.580 androgel, which by the way, I think is a suboptimal product even for men. So you're now taking a product

01:19:39.820 that I don't think is very good for men trying to apply it to women. You can cut patches into tiny 0.77

01:19:45.420 little areas. So take an FDA approved patch and cut it. You cannot use the FDA approved injectable

01:19:52.820 because the concentration is too high. Those are 200 milligrams per milliliter and you can't get enough

01:19:59.960 into a neat, like it's basically, you just need what's in the needle, let alone in the syringe.

01:20:03.960 So you're basically left with three options. None of them are an FDA approved product. One is a

01:20:12.780 compounded cream. One is a compounded injection. So they can compound it at 20 milligrams per milliliter

01:20:22.100 of testosterone. Which is one tenth. So just to be clear, we want to give about one tenth of the male

01:20:26.360 dose. That's right. And then the third is compounded pellets, which again, you can get an FDA certificate

01:20:32.360 for the raw ingredient, but it is not an FDA approved product. The way, for example, your

01:20:38.720 Viveldot is FDA approved as top glycerin. So therein lies the rub. That's the crux of it as I see it.

01:20:45.480 I think it's good to explain this to people. So we said earlier that testosterone was the most,

01:20:50.120 in a little more depth, was the most robust circulating hormone in women. That said,

01:20:54.400 there are normal ranges for women. They're sort of broken down by decade and quartile. So like 1.00

01:20:59.420 18 to 25, 25 to 35, 35 to 45, and sort of 45 to 50 and up. And there's been a couple of good

01:21:07.980 studies, particularly by Andrew Gay and Erwin Goldstein was involved with this work, looking

01:21:12.080 at like creating normal ranges. So the idea is when you treat a woman, you want to go to the 0.98

01:21:16.560 physiologic range for mid to late reproductive age women. So therefore you're not like overshooting

01:21:23.040 and you're not undershooting. And probably that's the time that, like that's the best range. So

01:21:28.200 somewhere like, for example, 28 to 35 or 28 to 37 with a standard direct total testosterone

01:21:35.500 assay. We didn't talk about like what you should measure and follow. We can come back to that.

01:21:39.380 And that was what they found was safe and efficacious in these studies was that physiologic

01:21:44.360 range for mid reproductive age women based on normal ranges in studies. By the way, I want to

01:21:50.660 correct myself. The data I just have it in front of me is that it was 46 studies looking at 36 of

01:21:56.800 the trials were randomized and like 8,500 women, close to 8,500 women. There's lots of data. It's

01:22:01.860 not lacking. There's probably even more that didn't get into this analysis and it didn't meet the

01:22:06.460 criteria. We have lots of data. It's not based on lack of data. And we do have decent outcome data,

01:22:12.060 meaning it's extension trial data for up to four to five years and randomized trial data,

01:22:16.800 clearly up to 24 weeks, but certainly in some trials up to even two years. So it's not any

01:22:21.920 different than what we have for men. We just have long-term use with FDA approved products

01:22:25.800 because they've approved them that you were speaking about.

01:22:28.200 So it's a little bit of a cart horse problem, which is we're stuck in this paradigm where

01:22:32.420 unless we get some approval, we can't get out of it to do the longer studies that you'll see

01:22:37.120 post-market.

01:22:37.940 That are carefully done and will satisfy future approvals, right?

01:22:41.980 Effectively the phase four trial.

01:22:43.740 Right. So you need to use one-tenth of the male dose because that's probably what gets you to this

01:22:48.560 physiologic range that I was talking about. Now, the Australian approved government product does

01:22:53.540 do that. It starts there and then you monitor levels and there's no cut point for saying this

01:22:59.400 testosterone is the one. You don't treat a testosterone, you treat a syndrome. That's the

01:23:03.620 first thing. You treat HSTD. And I usually check baseline levels to make sure they're not high

01:23:08.020 because if someone comes to me and they're 52 and their testosterone is surprisingly high,

01:23:12.180 they're not in that later quartile. I might say to them, I don't think this is the solution to

01:23:16.060 your problem. But if it's low as I expect it to be, they're not abnormal, they're not deficient,

01:23:20.440 they're just normally what they should be. Then I shoot to treat them to that reproductive 1.00

01:23:24.720 physiologic level. So you want to use one-tenth of the male dose. The position papers that I've been 0.87

01:23:29.800 involved with state that because it's so hard to get the concentrations consistent, we recommend using

01:23:36.560 transdermal male products at female doses as opposed to compounding. And if you're going to

01:23:43.200 compound, you're probably better off with transdermal than a pellet or an injection because

01:23:47.380 of the peaks and the difficulty in not getting into the... The key thing is you don't want to get into

01:23:52.020 that super physiologic level, which hasn't been demonstrated to be safe in women. And so the trick 0.99

01:23:57.920 is really, it's so hard to use one-tenth of a male dose. So here's what I tell someone. And it's a

01:24:04.460 joke. I prescribe a year, 30-day supply, for example, of the tubes, the 1% testosterone tubes.

01:24:10.540 They go to the pharmacy. The pharmacist rejects the prescription. They're not covered by insurance.

01:24:15.080 The pharmacist calls me and says, do you know it's a woman? I'm like, I write it on the prescription. 0.90

01:24:18.760 Didn't I say the patient is a woman? Hypoandrogenism is the diagnosis, HSDD. And yes,

01:24:24.740 she's going to pay for it. I tell them to look at a cost-saving app and find the cheapest place.

01:24:28.380 It's usually $200. They buy 30 days. They have to hope it works because they have to waste the $200.

01:24:32.980 Then I say, take a tube and waste one, divide it into 10 little piles, and then figure out what

01:24:39.080 you're going to do to get that amount onto your body every day. And then we'll do a blood test

01:24:42.220 in three to four weeks. That is not the kind of medicine I want to practice. So one strategy is

01:24:48.760 to tell them that you can buy them in the pharmacy, five cc syringes, and squirt the thing in and use

01:24:52.820 half a cc a day. If it's a tube, it's easier to squirt in than a packet. I have a patient. She's my

01:24:58.460 most brilliant patient. She's a baker. So she discovered that the cooking spoon, somewhere

01:25:03.200 between a pinch and a smidge, was a tenth of her packet. And then when her level's a little high,

01:25:08.280 she's like, okay, I'll level the spoon a little differently. This is crazy. There's no better

01:25:13.340 solution. Yeah, it's total alchemy. Tell me, what's the instruction you give women for how and 1.00

01:25:18.960 when to apply? Do you say, I want you to do this right after the shower? I want you to exfoliate your

01:25:23.620 inner thigh. I want maximum absorption. How are you making this as consistent as possible?

01:25:27.620 A relatively hairless area, a buttock and outer thigh, the back of the calf, just so it gets

01:25:33.400 absorbed. You obviously don't want to wash within a couple of hours. It doesn't matter the time of

01:25:38.780 day if you want to make sense to do it the same time of day. The other thing to really herald is

01:25:44.020 it can transfer. So if you have children that you're holding, or if you have a female partner and

01:25:49.380 it's skin to skin contact, it actually can transfer. And it's not thought to be insignificant.

01:25:54.080 There are two important points for us to all know. It can transfer. So you want to put it

01:25:57.900 somewhere, it won't transfer if that's going to be an issue, even though the amounts are much

01:26:01.240 smaller. And everyone knows that about male. Like if you squeeze one of those tubes out on a male 0.99

01:26:05.580 shoulder, you know this, it's like a whole big surface area. It's much smaller in women, but still. 1.00

01:26:10.200 And if you're going to get a blood test, don't put it where you're going to draw it, or don't

01:26:14.180 try to wait some hours so that you still get a little bit of a peak, even though with daily use of

01:26:18.540 transdermal, it's more of a steady state. The other caveat is if there's a potential for getting

01:26:22.400 pregnant, they really have to be on good contraception. So who might that be? So there is 0.99

01:26:27.860 a biological plausibility and the guidance in the clinical guidelines says that you can consider this

01:26:32.000 in later reproductive age women. And so every now and then a menstrual cycle peaks in and all of us

01:26:37.940 have heard of an unexpected pregnancy in those women. Probably by the time you discover you're 0.96

01:26:42.400 pregnant, the testosterone is not going to do much harm to the fetus because it's usually only a few

01:26:45.780 weeks, but we don't want people using testosterone and getting pregnant. That's one of the big reasons, 1.00

01:26:50.800 I mean, and we didn't get back to this with the oral contraceptive patient. The solution isn't to

01:26:54.680 leave her on a birth control pill and give her testosterone. First of all, it's not indicated 0.75

01:26:57.840 for premenopausal women. Second of all, that's not what you do, right? You try to correct the hormonal 0.83

01:27:01.880 imbalance. If this is the woman we're talking about. Going back to her, right. Going back to our 0.77

01:27:05.360 hypothetical case, yeah. Let's just say that that's the path we're going down. You would remove her from the 0.99

01:27:09.560 OC, probably switch to an IUD. If SHBG levels were still sufficiently high and free testosterone,

01:27:16.920 well, let's just say total testosterone was kind of 40th percentile. You'd say, look, we're going to

01:27:21.300 bring that up higher. Given that your SHBG is so high, it's going to bring your free testosterone

01:27:25.700 right up to about the 50th percentile. And again, you're using that as a guidepost, but it's ultimately

01:27:31.200 symptoms that you're treating. You're managing symptoms. So let's say that's what I decided. I look

01:27:36.600 at the biological, psychological, and social factors in this woman. I decide like, that's

01:27:40.120 the thing that's amenable to intervention. I'm going to change her contraception. So it's not 0.94

01:27:44.160 just women who are already on these that I tell. I'm a little birth control pills, combined

01:27:48.640 contraception. I want to make this disclaimer. Patches and rings are extremely effective and

01:27:54.540 most women don't have a problem. So if you ask me, what should I take? You have to talk to your 1.00

01:27:59.120 doctor. Should I use an IUD to start with? I can tell you how I counsel my own daughter,

01:28:03.180 but that's my college age daughter, but that's different than what I would tell patients.

01:28:06.500 They're incredibly effective worldwide. They prevent unwanted pregnancies. They protect

01:28:12.380 against birth fatalities, et cetera, worldwide. They liberate women all across the world. We don't 1.00

01:28:16.880 want to say nobody should take birth and child pills. But for this discussion, if somebody has

01:28:21.540 a problem, that's something you can change. And if it's one of the problems we talked about,

01:28:26.080 what you should tell a 20-year-old about whether you use birth neutral pills or put in an IUD is like

01:28:29.580 a whole nother conversation. To be preventive, again, this is a small percentage of people who

01:28:34.620 develop these issues. Some women aren't sensitive to it. Everyone gets a change in their SHPG. Some 1.00

01:28:39.100 women aren't sensitive to it. Some women aren't sensitive to the non-endogenous estradiol in 1.00

01:28:43.760 their vestibules. Some aren't. So I can't tell you who that's going to happen to. Again, the decision

01:28:48.740 about what to use over time is a discussion with your doctor. I think more gynecologists need to offer

01:28:53.200 informed consent so women can choose more carefully at the onset. And this is an important campaign that

01:28:59.720 gets missed. There's no informed consent. They just hand people a prescription at 21. You should

01:29:04.440 give women choice. But anyway, so getting back to testosterone. So I think the challenges then,

01:29:10.740 we weren't going to use it on this page, but let's go back to this for a minute, is that you're going

01:29:14.080 to then have to do that, one-tenth of the male dose. But you do have to follow levels because women 1.00

01:29:18.960 are all over the place. Like how well they get one-tenth, how that one-tenth of a product that wasn't...

01:29:24.180 Well, also how variable the absorption is. Not all people have the same skin.

01:29:27.860 These were not designed for women. I can tell you that the data in Australia is very positive. 0.77

01:29:32.720 For example, I work very closely with one of the main researchers there, a woman named Susan Davis,

01:29:36.960 who's done a lot of the work in this field, both in Australia and worldwide. And a first author on

01:29:42.000 a number of really important testosterone consensus papers. She impresses me by what she tells me about

01:29:46.840 the clinical outcomes and the ability to get kind of steady state good blood levels because it's a

01:29:51.500 controlled product designed for women, regulated and formulated. We need that. 1.00

01:29:56.240 That said, you do have to follow levels mainly to make sure that you're achieving safe doses.

01:30:03.660 So like if you said to me, well, like let's say someone has a level that it's too low and they're

01:30:09.220 not getting benefit, would you go up? And I'd say, sure, because we haven't achieved the physiologic

01:30:14.080 range and I know it's still safe. So I am like checking it to make sure that if they're not having

01:30:19.020 symptoms that are improving to see that we're giving them enough. But the most important reason for

01:30:23.640 monitoring blood levels and I monitor because of what you explained, the smartest thing is just

01:30:28.600 a matter of total T. We didn't go through this in elaborate detail. It's not clear that that's the

01:30:33.840 best marker for knowing whether that's the way to tell whether testosterone is helping a patient in

01:30:38.520 their cells and in their brain, their genital cells, their brain and some other body cells too.

01:30:42.720 But that's probably the grossest best measure we have. Free T is calculated and we don't even know if

01:30:47.120 that's the bioactive component. Testosterone, it's a very complex, what now is called intracrinology.

01:30:53.360 It hits the cells. It gets converted into metabolites, androgenion DHT. It enters the

01:30:59.300 cell through the androgen receptor and has both genomic and non-genomic effects. Non-genomic means

01:31:04.080 direct action. Genomic means it causes gene translation, other protein development, which then has

01:31:09.660 trophic effects. And so all of that's happening. Probably the total T is the best measure of both not being

01:31:14.980 too toxic and also probably targeting. Now you asked me, what's the best type of total T? So most

01:31:20.980 people have direct assays in their lab. If you send your patient to your hospital lab or quest or lab

01:31:25.400 core, they're imprecise when you use them for women. They're not the best measure, but they're good 1.00

01:31:30.600 enough for what we're doing and what we're talking about. The mass spectrometry testing, which has fancy

01:31:35.380 names, is used in research and in clinical labs. And I believe you can specifically order that. So we do

01:31:40.180 order LCMS when we send our patients. I don't know if people know what that is. When we

01:31:44.880 order estrogen levels, testosterone levels, we actually request LCMS because we've seen how, believe

01:31:51.100 it or not, supplements that you're taking can dramatically impact the readings. And we noticed

01:31:55.180 this actually first in men. We were getting men who would get estrogen levels back that were, you know,

01:31:59.880 normally a male estrogen level might be 25 to 40. We'd see guys with like 200. That'd be like,

01:32:05.580 that's impossible, right? First of all, he has no symptoms of having an estrogen of 200. Come to realize

01:32:09.900 he's on some supplement for, I don't know what, and that's impacting with the assay. You send him

01:32:15.780 to get an LCMS and it comes back normal. So all of this stuff gets very complicated very quickly.

01:32:21.980 Just quickly, I want to talk about one other hormone before we leave this and go to our next

01:32:26.420 topic. And that is the role of DHEA. For folks who might not be familiar, DHEA is a precursor to

01:32:32.460 testosterone. DHEA is actually not regulated in the United States. It's a hormone you can buy over the

01:32:38.420 counter, which is odd. I don't really understand why it's unregulated, but that's another story.

01:32:43.420 What is the role of oral or topical DHEA in female sexual health? 0.99

01:32:49.320 Testosterone, its metabolites and its precursors are also like an area of confusion. The simple

01:32:53.720 version, which is good right now, is the DHEA is a precursor. So why not use that and then make

01:32:58.560 testosterone? So testosterone gets metabolized to things, for example, like 5-alpha-DHEA, which is

01:33:03.980 probably the most potent metabolite and aromatase to estradiol. So when we're talking about throwing

01:33:08.940 all these things out, we're talking about do we want to look at a precursor or a metabolite and

01:33:13.760 then what's actually working in the body or in the cell? So the short answer is there have been

01:33:19.360 some trials looking at oral DHEA for the outcomes of interest that we're talking about here, for

01:33:23.800 example, low sexual desire, and they have not been convincingly positive. Safety has not been

01:33:30.680 really well studied to the extent to which I just told you there's all these randomized trials of

01:33:34.900 efficacy and safety for testosterone for women using the product, the 300 microgram or gel products,

01:33:41.700 right? 300 microgram patch. And again, that's different than the blood level, which we're

01:33:45.560 measuring in picograms per ml. Picograms per ml is what we measure for one, but we'll come back to

01:33:51.560 the measurement in a second. But the oral DHEA, which is administered in milligrams, some outcome

01:33:57.760 studies have been done. They've been small. They've been problematically designed. All the criteria for

01:34:02.940 good randomized trials haven't been met. And there's no good safety data really looking at this. But the

01:34:07.600 biggest thing is that efficacy has not been demonstrated. So we don't recommend oral DHEA

01:34:13.120 for the indication of HSDD. I know people use it, whether it helps some patients and whether

01:34:19.140 we're doing anything problematic to the way we're measuring different things is impossible for me to

01:34:23.380 tell you because we don't have good control data on this. That said, there is very good data

01:34:29.080 supporting the use of a vaginal, intravaginal DHEA. The chemical is called Prosterone. The brand is

01:34:36.180 called Intrarosa. Basically, it's like a little suppository. It's used for vulvovaginal atrophy

01:34:42.920 resulting in genital urinary symptoms of menopause. And the indication is just for when you're

01:34:47.100 pain, post-menopause. And it has very good efficacy and safety data with very little systemic absorption

01:34:53.580 for that indication. And the rationale for it, instead of using an estrogen local product,

01:35:00.360 and maybe we'll have a few minutes to get into that, is that there are mixed receptors in the

01:35:05.640 genitals that need both estrogen and androgen. So it gets metabolized into both androgens and then

01:35:12.840 eventually to estrogens at the intracellular level. That's the theory of it, right? Because

01:35:17.500 again, remember DHEA is a precursor. How do you decide, Sharon, for a woman who's presenting with

01:35:22.920 a pretty common presentation? Whether to give estrogen. Whether you're going to use an estrogen

01:35:27.580 suppository or whether you're going to use a DHEA suppository? The data suggesting differences in

01:35:33.620 efficacy isn't there. So you really could offer, we can get into like, how do I even, even among the

01:35:39.000 estrogen products, there's a whole bunch of choices. There's creams, there's rings, there's inserts,

01:35:44.240 and then there's tablets. They're all local vaginal estrogen products that help with dryness and pain

01:35:49.100 and sexual activity. And then DHEA, the Intrarosa product, is an option. And so the standard

01:35:56.060 practitioner will start with an estrogen product. And if it doesn't work, switch to Intrarosa. I think

01:36:01.500 it works really well. So I offer it as an option. And there's some, I have some educated patients who

01:36:06.200 that's what they want. The other thing is that it doesn't have a black box. Any distinct pros and

01:36:10.460 cons? Yeah. So it doesn't have a black box warning, which we'll also have to get into. And so some

01:36:15.320 people like, just like not seeing that warning. And the black box warning with the estrogen is around

01:36:21.160 breast cancer or clots? So it has to do with both endometrial and breast cancer and vascular

01:36:28.960 thromboembolism. And there are a few other things thrown in there. The idea is that they're applying the

01:36:33.940 risk factor data, primarily from the WHI actually, for systemic estrogen therapy. It's a class labeling

01:36:42.200 requirement that has to go on these low-dose products, which haven't demonstrated any of

01:36:46.480 the same negative outcomes. Even the systemic hormone therapy, that could be dissected.

01:36:51.940 So some practitioners prefer not having a black box. Some patients prefer not having a black box.

01:36:57.700 Sometimes it's someone like, my mother had breast cancer. I don't want any hormones. I won't use

01:37:01.840 estrogen, but they'll use this. And there's no real rationale. There's no proof that it's any more

01:37:06.180 or less likely to cause any cancer at all. The other issue is that in cancer survivors,

01:37:10.740 it doesn't have a black box. So sometimes oncologists, and again, that's a whole discussion

01:37:14.180 we could have whether they're worried unnecessarily. And I think there's some people where I feel they're

01:37:19.800 quite androgen deficient, and it might be a better choice to start with. So for example,

01:37:24.700 like I have a 40-year-old who had an ophorectomy and doesn't want to go on systemic hormone

01:37:28.360 therapy. And I know that her testosterone levels and her androgen levels have plummeted 0.99

01:37:33.380 overall because over the ovary, about half of the circulating testosterone, even though she

01:37:38.100 lost some of it since she was 25, you've now taken out half of what she has. We didn't talk about this.

01:37:43.880 So in every woman, about half of your androgens are made in your adrenal glands and half in your 0.91

01:37:48.420 ovary. And the part that goes down like in later reproductive years and through the menopausal 0.68

01:37:53.960 transition is the ovarian component. The androgen component stays about the same. There is some

01:37:57.880 decline in that. So when you take someone's ovaries out at a young age, you're lopping off, 0.52

01:38:02.200 especially the younger, the worse. Those are the people that are the most likely to have what I

01:38:06.040 think is physiological, organic, sexual desire difficulties from low testosterone, from

01:38:10.000 testosterone removal or androgen removal abruptly. So that's someone I might say like, and they're not

01:38:15.280 using systemic hormones. I might say, let's think this might be a better direction. That's like not

01:38:19.940 based on any really systematic research. It's just experience.

01:38:23.060 Okay. Let's come back to something you mentioned earlier in the discussion of our first patient

01:38:29.660 as we now talk about our second patient. So our second patient, let's say she is younger. Let's

01:38:38.240 say she's 30. She has no kids, been sexually active for 12 years, and she comes to you complaining 1.00

01:38:47.380 of inorgasmia. So she says, I have desire, but, and I do get aroused somewhat, but I have never been

01:38:59.740 able to either alone or with a partner achieve what I think I'm told an orgasm is. I'm really teeing

01:39:06.500 this up so that you can explain what an orgasm is because in a male, it tends to be somewhat more

01:39:12.440 binary. I'm curious as to how you would counsel this woman. And if you think that this is a

01:39:18.080 reasonable example to use to explain that. Sure. What I thought you were going to tell me

01:39:22.460 is that nothing else is going on. She has no sex drive. And are there FDA approved drugs for low 0.69

01:39:26.620 desire, which we didn't talk about for women, but that's not the question you're asking me. Let's

01:39:31.720 come back. Let's turn her into someone who has a different problem after that. Cause I think we 0.91

01:39:35.020 don't want to forget to mention there are two drugs. We're talking about all this testosterone

01:39:38.480 that's not approved. We should make sure before we include that we let people know there are two

01:39:42.920 drugs, FDA approved for low sexual desire and pre-menopausal women, but let's go to orgasms. 0.85

01:39:48.440 So one of the biggest things when someone comes to me, this is not an uncommon clinical scenario. You

01:39:53.260 picked a good one, Peter, because youngish women, but old enough to start realizing like, Hey, I'm 30 1.00

01:39:59.000 by now, like this should have happened, you know, or is there something wrong with me? Sometimes they

01:40:03.660 don't care, but they think there might be something wrong with them. Sometimes they're like,

01:40:06.560 you know what? It's enough. I want one of these, you know, or there's a lot of reasons why people

01:40:11.400 seek it. But first thing I do is try to figure out if it's primary anorgasmia, meaning they've never

01:40:16.020 had an orgasm or secondary, meaning they had one and now suddenly it's gone. The scenario I think

01:40:22.780 you're telling me is someone who has really never really felt like an orgasm. And now, so one of the

01:40:28.860 first things I asked them is like, why are you now coming here to talk to me about this? What is

01:40:32.600 different? Well, let's just say it. I'm really with a amazing sexual partner and everything is

01:40:38.720 perfect. And he or she is wondering if there's something wrong with them. And this inability to

01:40:48.020 have an orgasm is actually interfering with our relationship because it's now creating a stress 0.68

01:40:54.000 where my partner feels inadequate. I'm making this up, but I would assume that this is a,

01:40:58.720 it's a classic presentation. Yeah, no, it's a common reason. So the most common reason that

01:41:04.300 women suddenly decide to come to me for anorgasmia is that they are now in a relationship. And it may 1.00

01:41:09.300 be that they themselves want to have a more satisfying experience or the partner wants to.

01:41:13.980 Sometimes they lose relationships because they, it's not so much a partner isn't willing to work

01:41:18.740 it through, but they feel uncomfortable about having this problem and letting a partner see that they

01:41:24.160 can't solve it. It's usually contextual, but not always. Sometimes women just sort of come to this 1.00

01:41:29.280 realization that this is something they want to explore. So you asked me what an orgasm is. I mean,

01:41:33.700 I think the idea that it's a peaking, you become interested, you feel a sense of, we've talked

01:41:39.860 some about arousal. You feel like mentally excited, your body feels turned on, there are physical

01:41:43.880 changes that you notice. And then there's sort of a sensation that feels it's throughout you that

01:41:50.600 you're peaking and maximal pleasure. And it's an overall sense of like an escalation to something.

01:41:56.960 In the genitals, what's actually happening is first, there's what we can talk about what happens 0.74

01:42:01.000 when you get stimulated. There's sensory input. You get a stimulation to the sensation. It causes

01:42:07.360 a response that heads to the spinal cord. It can trigger the autonomic nervous system. First,

01:42:13.520 the parasympathetic nervous system to cause vasodilatation. Here's where the pelvic muscles

01:42:17.960 sometimes can relax during sexual activity. You get muscle relaxation, vasodilatation,

01:42:22.760 and then it triggers eventually as you become more and more aroused. Interestingly,

01:42:26.640 the sympathetic nervous system gets triggered and that's what triggers an orgasm. And in women, 1.00

01:42:31.220 it can be a sensation of pleasure in the brain. And it's really interesting to talk about what's

01:42:35.980 going on. Like fMRI studies have actually looked at this, but generally it's pelvic floor,

01:42:40.360 the pelvic floor muscles contract, blood vessels become maximally dilated,

01:42:43.940 and nerve stimulation results in the local release of some neurotransmitters, which cause

01:42:49.960 secretions and lubrication. So it's, for example, vasoactive intestinal polypeptide.

01:42:55.600 There's some involved nitric oxide in CMP, like in men, contributing to both vasodilatation,

01:43:01.320 secretion, and so forth. So you get like, again, you get this stimulation, parasympathetic

01:43:06.680 nervous system, then sympathetic nervous system, then muscle contraction, local hormones,

01:43:10.980 brain chemistry, local hormones, secretions, and people get this sense both of well-being,

01:43:16.820 pleasure, pelvic floor contraction. They may get secretions and then they feel they have an orgasm.

01:43:22.660 So there's a lot of variability. That's the full Monty. There's a lot of variability. Some people

01:43:26.680 just feel like an intense sensual or mental pleasure. Others feel a warm, intense sensation

01:43:32.180 in their genitals, but don't notice lubrication. Sometimes people will come to me and it's like a part 0.88

01:43:36.040 of it isn't there. Like, how come I don't squirt? That term comes up sometimes. And that's a whole

01:43:40.280 other discussion. Like, is that supposed to happen? So first of all, what proportion of women have 1.00

01:43:45.240 that sort of ejaculatory response with an orgasm? It's hard to say. Some of my colleagues believe that

01:43:51.100 it's part of every sexual response and that it's just not being perceived. I would say about 20% of

01:43:56.260 people are aware of it and that's sort of what's written. But again, so there's this whole other

01:44:00.500 theme going on in the sexual medicine literature about whether women have the prostate function in

01:44:05.960 the local genital milieu that results in the squirting of fluid. What I can say is it's

01:44:11.860 controversial and probably more commonly what I hear in when people are having sort of a more

01:44:16.980 normal orgasmic or arousal and then orgasmic response is that the lubrication from the mucosal

01:44:22.240 surface becomes robust. And that's probably the interaction between vasodilatation, the nervous

01:44:28.440 system, and the local hormones such as VIP and nitric oxide. Where the squirting of fluid

01:44:34.620 and where the female prostate actually resides structurally is an area of controversy. I think

01:44:40.220 that's the simplest answer. And I don't think that's the biggest piece of orgasm, getting back

01:44:43.920 to that. I don't know if you have other thoughts or... No, I find this to be a totally fascinating

01:44:48.860 topic. As any male would, who's seen all extremes of this, it's not consistent either. So you wonder,

01:44:55.940 is that a super orgasm? Some women have that every single time. I mean, it's a... 1.00

01:45:00.300 So I think a more interesting question. I mean, I think it's a good one because that's not really

01:45:05.300 what people are bothered by. It's that they don't feel like they're getting that overall

01:45:09.520 like sensation and peaking sensation, both in their brain and in their genitals. It's that sensory

01:45:15.060 experience and the intensity and the muscle contraction that they're probably not experiencing.

01:45:19.200 It's not so much they're worried about the lubrication or so to speak, the squirting. That's

01:45:23.140 not like the big... Some are and some aren't, but the biggest issue is your scenario is like that thing

01:45:29.420 doesn't seem to be happening to me. This woman that we're presenting with, this is clearly not

01:45:34.020 the issue that's germane to her. I'm trying to think where to go with this. But the first thing

01:45:37.860 I would do is make sure I understand whether this was something she used to have or she never did.

01:45:43.320 Let's assume the answer is no. This is primary. So the thing about secondary and he asked me to know

01:45:47.900 is that if a woman has the capacity for orgasm and she loses it, one of two things have happened,

01:45:53.380 like some kind of significant psychological impact that you need to find out about. Could it be

01:45:58.900 trauma, relationship struggle, something happened and you want to understand that? Or there's a

01:46:05.540 physiologic factor like a medication or neurologic condition or something. And it could be things like

01:46:11.120 one of my colleagues is really into like the nerve damage from spinning classes. Now that doesn't

01:46:16.160 mean don't go out and get rid of your peloton, but like in men, nerve damage can blunt sensation and

01:46:21.360 may interfere. So like I look for those things, but we're not talking about that right now.

01:46:24.860 So the first thing I do is find out like why and look at the context and make sure like somebody's

01:46:30.680 not pressuring her. Like, you know, there are people who are like, I don't really care, but my

01:46:34.340 partner wants me to have an orgasm. This is why I just fake it and he's bugging me and I'm coming here 0.92

01:46:37.500 to see if I can have a real one. You know, I've heard that. And, you know, sometimes I explore it

01:46:41.860 further. I never accept the answer at face value. I'm big on like finding out more is like, have they just

01:46:47.520 given up or they really don't worry about it? And there are some people in the field who feel like

01:46:52.680 saying, well, not having an orgasm can be normal for some women. So I avoid that. Like, is it not

01:46:58.380 having an orgasm normal? I sort of say, okay, well, like, is this important for you to have this and

01:47:02.740 find out about it? And let's learn techniques or strategies for seeing if you can reach this

01:47:08.280 experience. I don't know what to say. Like, don't worry, it's normal. Go away. Like, you know,

01:47:12.620 someone's come to me. So we look to see, are there strategies they could do to have it? So there

01:47:17.080 are multiple kinds of orgasms. The big buckets are clitoral, vaginal, or both. This is where there's 0.89

01:47:22.360 maybe some numbers. About 30% of women, maybe, if you want to go with rough numbers, reach orgasm 1.00

01:47:27.940 through clitoral stimulation, about 30 through vaginal, and 30 have flexibility. Now, what

01:47:33.060 techniques for reaching orgasm vary widely across women? Some women can have orgasms just thinking 0.93

01:47:38.620 about it. Some nipple stimulation. Some women report it with even breastfeeding or like the shower 1.00

01:47:44.180 water hitting their nipples. Some women need direct clinical stimulation, manual, oral. Some women 1.00

01:47:49.100 like vibrators. Other women through the thrusting of the intercourse. And like, there's, again, 0.98

01:47:54.120 the question, where's the G-spot fit in, right? This spot that's a spongy spot just inside the

01:47:58.640 vaginal canal on the roof. That's an area of sensitivity. The bottom line is there's lots of 1.00

01:48:03.420 nerve bundles in lots of places, and a lot of them can be stimulating enough to trigger this whole

01:48:07.760 mechanism. That's what I tell women. And the big thing for you is to figure out whether you've learned 0.98

01:48:12.840 where you can be most stimulated to have a more intensified response. That's where I kind of

01:48:18.220 start with. So like, whether it's clitoral, vaginal, through intercourse or not, it's more about what

01:48:22.480 the stimulation patterns are and how much they've explored learning about that. That's sort of the

01:48:27.060 short answer. Do we have a sense of the correlation between the number of women who would present as this

01:48:35.140 patient has, a woman who is young in her reproductive years, who is anorgasmic, who also does not 0.93

01:48:41.760 masturbate? Is that a high correlation? In other words, is part of the problem in this situation, 0.94

01:48:47.060 she is unaware of what her sensations are or what her mechanisms are, and therefore, A, can't reach 0.99

01:48:55.420 that threshold on her own, and then secondly, isn't able to communicate that with her partner? Or is there

01:48:59.640 no association between that? I mean, I think the data is a little hard to tease out. What I will tell

01:49:05.060 you, first of all, is primary anorgasmia versus secondary, it does somewhat correlate with age. So

01:49:13.080 younger women are more likely to have primary anorgasmia, whereas other sexual dysfunctions get 0.60

01:49:16.940 more marked with age, you know, desire and arousal problems due to some of the factors we've been

01:49:21.900 talking about. Primary anorgasmia tends to get better with age when women can learn more about their

01:49:26.280 orgasmic response. So that's how I'll answer that differently. In large population-based studies, it's the

01:49:31.620 least common reported sexual dysfunction, either primary or secondary. But it may be that we just

01:49:37.660 don't know how to ask about it. Like, for example, there was this large population-based study that

01:49:41.920 many people in the field have heard of called the PRESIDE study. It was like sort of the largest

01:49:46.180 population-based study. It was 31,000 women, a 50,000 survey, 31,000 women reported. It was self-report

01:49:52.520 of distressing sexual problems. So overall, sexual dysfunction desire was somewhere around 10% to 15%,

01:49:58.760 and orgasmic problems were like 3% to 6% of the women reporting those problems.

01:50:02.980 What was the age range on that study?

01:50:04.960 18 to like 100, to like 99.

01:50:07.300 So all women, effectively. 0.93

01:50:08.820 But midlife, all orgasmic disorders, midlife women were the most likely to report it,

01:50:12.460 but primary anorgasmia tends to be the most likely reported in younger women.

01:50:15.180 In younger women.

01:50:15.900 So I think once a woman learns, another point is that once a woman learns about her orgasmic response, 0.96

01:50:20.400 she doesn't usually lose it unless an organic or psychological factor, like I mentioned, intervenes.

01:50:25.140 So let's go back to this woman. How are you going to do the workup? 1.00

01:50:27.760 So it's pretty quick, workup-wise. Mostly it's the story. Tell me about your sexual function.

01:50:33.500 It's a history. I check the other phases, right? I want to make sure she's not a birth control 0.91

01:50:37.200 person having pain, and like that is a negative. And so I'll ask her to tell me like her story.

01:50:42.540 Does she have sex with herself? Has she tried masturbating? Does she have a partner? What 1.00

01:50:46.580 does she do with her partner? You know, what does she know about being able to stimulate herself?

01:50:50.260 Does she know the structure? Does she know? I might show her a picture. Does she know where

01:50:53.840 her labia are? Does she know where her clitoris is? Has she tried nipple stimulation? 1.00

01:50:57.760 What have they used as a couple? Has she tried using vibrator? You know, like I'll get into what 1.00

01:51:03.660 her knowledge about and what techniques for stimulation have she used herself? What has

01:51:08.740 her partner tried and what's she able to do in terms of communicating with her partner?

01:51:12.580 So the real question is, does she know what stimulates her? And can she teach or train or

01:51:18.780 ask her partner to do that for her if it's in partnered sex? There are two problems. There's one 0.96

01:51:22.880 women don't really know yet. And so the prescription might be learning more about that. And there are a

01:51:27.340 number of ways to do that. The other issue is communication between partners. Like they

01:51:30.920 aren't sure how to teach their partner to do what they know works. This is not this patient,

01:51:36.100 but it's one thing that happens as women get older that we haven't really talked about this, that

01:51:39.880 you do need more stimulation with age, even if you don't have any pathology. So if you don't have

01:51:44.380 diabetes or vascular disease, many women need more stimulation with age because the sensitivity 0.99

01:51:49.000 goes down. And so I really normalize the use of vibratory stimulation because it helps a lot.

01:51:54.300 But sometimes it also helps for younger women. This is less the case sometimes for young women

01:51:58.760 because they don't need quite as much stimulation. But I ask them, like, have they tried techniques

01:52:03.720 for improving or enhancing stimulation? The biggest factor is that women kind of don't know their 1.00

01:52:08.360 structures. The actual clitoris isn't the most sensitive. It's the sides of the clitoral, 0.99

01:52:12.860 the flanks of it, the side, for example, around the vestibule, the sides of the clitoral hood, 0.97

01:52:17.160 just inside where some people call the G-spot. These are where the neurovascular bundles are

01:52:21.880 concentrated. That top of the clitoral hood is actually very easily irritated and not doesn't

01:52:26.900 like being rubbed very much. I'm like, some partners are sitting there rubbing, rubbing,

01:52:30.760 you know, like as an example. I mean, not to be too graphic. And so some education about vaginal

01:52:37.160 vulvar and clitoral stimulation, techniques for stimulation. So I send people to books.

01:52:41.340 There's a number of books and we could talk about those. So that's where bibliotherapy,

01:52:45.120 looking at some really responsible lay press literature on like a book called Becoming

01:52:50.980 Orgasmic. The Joy of Sex has been republished and published and published, and it's still a great

01:52:54.880 book. What year was the first version of that book? I think it was in the, that's a good question. I

01:52:59.960 should have checked that for you, but could it be the 70s? It might be even be soon. You know,

01:53:03.880 it was some decades ago. Good question to find out. Call it 50 years ago. Okay. So The Joy of Sex.

01:53:08.760 So rattle off the names of the books that you would use as reference here.

01:53:11.960 So these are some books that I like. For Yourself, Becoming Orgasmic, The Joy of Sex.

01:53:18.940 Sandra Lieblum has a couple of different books. She's a sex therapist who's no longer with us.

01:53:23.600 She had an unfortunate accident, but she's written several different books. More of her work is on

01:53:27.840 desire. Lori Brado on mindfulness, and it talks a lot about learning how to stimulate yourself.

01:53:35.020 So there's books available. There's also a website. I have no commercial investment in any of this.

01:53:40.600 I just want to make sure people know that, that I sometimes send people to. It's called

01:53:44.420 OMG, OMG, Y-E-S. I'm like, oh my God, yes, I guess. 1.00

01:53:50.580 So sorry, the website is just www.omgyes.com.

01:53:56.740 I just Google it and it pops up. OMG, Y-E-S. Oh my God, yes. I mean, we'll just say it. That's 0.83

01:54:01.480 what I think it is. And it's a very responsibly produced website that has a lot of education for

01:54:07.560 women. So there's a small amount of money for a subscription. I think the standard program's

01:54:11.280 like around $40. And then there's a larger fee for a more involved program. It's not free,

01:54:16.440 but they have some demos on it. And it has a lot of educational videos, including very explicit

01:54:22.460 videos on showing techniques for splitteral and other kinds of stimulation. And really teaching

01:54:27.020 people to learn how to stimulate themselves and become orgasmic.

01:54:30.160 Is this a site that is also just as helpful for men?

01:54:33.100 To learn about their partners.

01:54:34.080 Or female partners of other women? 1.00

01:54:35.680 Right. It's designed for female stimulation, but it could be for the partner and- 0.92

01:54:40.060 It could be for the partner just as much for the individual.

01:54:41.800 And sometimes it's easier for someone to sit and watch a video with their partner than to

01:54:45.040 have to show them themselves. So it's not uncommon that they'll say, well, you could start by yourself

01:54:49.200 and figure out which videos you might want to watch with your partner. You know, so that's another

01:54:53.580 example. There's some other resources, but those are some common things that I would do with that

01:54:57.320 patient. You can send the person to a sex therapist too. And I'm not a sex therapist. I counsel. We

01:55:04.300 haven't talked a lot about psychological therapies. There is some data for using mindfulness-based

01:55:08.920 therapy and cognitive therapy for an array of sexual disorders. For anorgasmia, the sex therapists

01:55:15.480 use much more explicit techniques. So they use things like directed masturbation. So you could send them 0.98

01:55:20.640 to a sex therapist. I make the distinction. I counsel and I give advice and I'm a medical physician who 0.99

01:55:25.980 does kind of a multifaceted analysis and intervention. But if I think they need more work, I might suggest

01:55:31.180 that patient go to a sex therapist. And so the techniques for learning about orgasm with a sex therapist

01:55:37.480 might be, for example, directed masturbation. It's kind of some of what we're talking about, but they might

01:55:41.800 instruct them more. These sex therapists these days, it's not like if you saw, again, Masters and Johnson,

01:55:46.240 they don't go behind a room with a glass window and like have sex in front of the sex therapist.

01:55:50.760 There are surrogates. That's not what I'm talking about. But they'll discuss very, you know, in more

01:55:55.980 detail about technique and they'll give homework assignments. There may be advice or guidance about

01:56:01.780 positioning. So they might bring the partner in and discuss positioning. They might use something

01:56:07.260 called sensate focus. So a lot of times people, in addition to that, we didn't kind of get into this

01:56:11.980 yet, but people develop a lot of anxiety. So, and that makes the problem worse. They develop like

01:56:16.840 what's called spectatoring and performance anxiety. So there's a technique that works for any sexual

01:56:21.800 dysfunction, but can be used here where you gradually introduce levels of sexual and partner

01:56:28.720 communication. And you start with very non-threatening things. Like you sit, you hold hands,

01:56:32.840 you hug. And a couple is given gradual, especially when people become very anxious that like, am I going

01:56:37.960 to have an orgasm? What's going to happen? So the sensate focus prescription can be done by sex

01:56:42.080 therapists. And then sometimes more so with distraction and low desire, mindfulness and

01:56:49.000 cognitive therapy can be introduced by certain people who specialize in this. And then the other

01:56:53.800 thing we didn't mention is sometimes I discover like a really deep seated and important psychological

01:56:58.360 issue that's linked to this. Like an unfortunate scenario would be someone who's sexually traumatized.

01:57:03.380 And like every time they get into a, or they develop even a genital aversion, right? There used to be

01:57:08.060 something called sexual aversion disorder that's been kind of removed from the DSM for a variety of

01:57:11.660 reasons, but every time they enter a sexual encounter, they'll have an intrusive thought

01:57:15.780 or maybe there's mixed in with PTSD or there was very strong religious prohibition or cultural

01:57:21.280 prohibition. And then if I pick that up, I really send them right to a psychological person to work

01:57:27.140 with that because it's something that's now they understand or come to realize may be interfering with

01:57:31.900 their sexual quality of life and their happiness. So we didn't say that, but at the onset that that's

01:57:36.920 much more primary. Let's go back to the two drugs that we didn't talk about besides testosterone,

01:57:42.640 just to make sure we close the loop on that. Yeah, I think I'm glad you raised the whole point

01:57:47.740 about office counseling. So a lot of what we're talking about before we move to the drugs is that

01:57:51.620 there's office counseling like I would do looking, and we didn't get into this so explicitly, but I

01:57:56.480 look at like, what's the relationship? What's the timing? What's the lifestyle factor? So I was

01:58:03.120 thinking we were going to go there with that 39-year-old or however old we decided she was. 0.53

01:58:06.820 I call it the rant. So she'll come in and she'll say, I'll say, well, tell me what's going on.

01:58:11.080 They'll be like, well, I have two kids. There's homework. There's dinner. I work all day. There's

01:58:16.360 the house. There's the laundry. Then I have to answer my email at 12 o'clock. And then it's one in

01:58:20.760 the morning and the partner wants to have, whatever partner it is, wants to have sex like I'm too tired. 0.68

01:58:26.920 You know? Sometimes they're not helping me. It gets thrown in there. And so a lot of what I do

01:58:32.460 is dissect this back. I'm sure you do this too in your work, is help people look at how their

01:58:36.200 lifestyle is. So that's that. So when someone comes to me with low desire and I look at these

01:58:42.180 lifestyle factors, we look at some of the other medication factors, we look at whether there's

01:58:45.920 another sexual dysfunction like contributing to low desire, and they have hypoactive, meaning

01:58:51.840 distressing low desire that's clinically diagnosed. And I don't see another modifiable factor.

01:58:57.660 That's where in post-menopausal women, I might think, okay, do we need to add androgens? We should 0.99

01:59:02.340 say like, first you do a biopsychosocial assessment before you use a pharmaceutical. And you look at

01:59:07.040 these factors. You look for relationship counseling factors. You look at referrals for psychotherapy or

01:59:11.620 sex therapy. And you look at modifiable medications, other things you can change. And then if you reach

01:59:16.640 the point where you're like, I want to use something explicitly for sexual desire, in post-menopausal

01:59:21.760 women, you can use testosterone. Like that's an option. We didn't talk about who the candidates 1.00

01:59:25.620 are and when you would use that. The biggest hitters are people who've had ophrectomies at a

01:59:29.380 young age, early menopause, post-menopausal women with distressing low desire. And then you have to,

01:59:35.500 of course, do informed consent when you do that. Now, for pre-menopausal women who we reach the same

01:59:40.900 conclusion, like there's nothing I can modify or nothing obvious, we do have two FDA-approved products

01:59:47.200 for this. And strangely, they're around and they're available. And very few people, when I,

01:59:52.520 either they know about it and they come to me for a prescription, because they've already been

01:59:55.860 through everything else, when I tell them they're shocked to hear that that's available. Have you

01:59:59.720 heard of these? Like many people have. I have not. No. Yeah. Interesting, right? So the first one,

02:00:04.920 I'll briefly tell you about them and feel free to ask me questions. Would you like me just to explain

02:00:08.760 what they are at this point? Sure. Yes, please. So there's flabanserin. The brand name is Addy,

02:00:14.740 A-D-D-Y-I. And it was like a lot of these drugs. It's a centrally acting drug. It acts on serotonergic

02:00:24.100 and dopaminergic receptors. And it has a complicated mechanism, which is actually not fully understood.

02:00:28.480 It's mixed serotonergic, agonist, and antagonist. It's actually 5H2TA. And 5H2, 1A and 2A,

02:00:38.900 one's agonist, one's antagonist. It's mixed agonist, antagonist, and has activity at D4,

02:00:43.520 which is dopamine receptors with moderate affinity for some other serotonergic receptors,

02:00:48.500 2B and 2C. And that region-specific effect seems to be pro-sexual. It was studied for depression,

02:00:54.320 but discovered to be helpful for low desire.

02:00:57.560 Kind of like Viagra was studied for blood pressure and found to...

02:01:00.920 Right. But this is a centrally acting drug. So that's not to say that women who respond to this

02:01:05.960 are getting it because they're depressed, but one wonders. There may be a spectrum of why people have

02:01:10.860 no libido specifically as a presenting complaint and why a centrally acting drug could be helpful.

02:01:15.420 It's FDA approved. You're supposed to kind of rule out this other stuff and manage all the

02:01:19.500 biocycle social factors before you consider it. That said, you use the same criteria used for any

02:01:24.740 decision to use a drug. It's not so fancy.

02:01:27.120 Is it a drug that a woman takes every single day, or is it one that she takes... 1.00

02:01:30.980 So it's daily, on demand, centrally acting. It's a single dose. There's only one dose. There's no

02:01:36.600 titration. 100 milligrams. It's taken at bedtime. It's been FDA approved since 2019. It's been around.

02:01:43.600 There was a long road at the FDA. I was part of that more so than the testosterone. I was there.

02:01:48.740 I happened to be the president of ISWISH during the few years it was approved. So I

02:01:52.780 spent a lot of time at the FDA trying to advocate for its approval. I can tell you what that struggle

02:01:57.540 was like more personally. It is administered at bedtime. Initially, they did a lot of research

02:02:03.980 looking at hypotension and syncope and its interaction with alcohol. And for some time,

02:02:08.880 it had a REMS, meaning there was a risk mitigation strategy where doctors had to actually take a test

02:02:14.840 before they could prescribe it. There's other drugs like that around. And patients had a sign

02:02:19.480 a form that they wouldn't drink alcohol at the pharmacy, and pharmacists had a sign that they

02:02:23.140 counseled patients. It was relooked at that it was really no different than any drug in class. Like

02:02:27.960 SSRIs give hypotension if you take them and drink alcohol or make you feel woozy or sedated. And so

02:02:34.760 it's drug in class advice now. There is still black box because the FDA wouldn't go all the way.

02:02:39.480 It's similar in class to SSRIs. The side effects are similar. Anyway, you take it at night,

02:02:44.080 and most people, you take it and you go to sleep. It can cause a little sedation. It's

02:02:47.600 sort of like mirtazapine. I tell people, take it and go to sleep. Most people tell me they sleep

02:02:51.500 better and they're not drowsy. You take it, probably you see the maximum effect about four

02:02:56.440 weeks, but usually they say, give it eight to 12 weeks. If it works, you continue it. If it doesn't,

02:03:01.280 you stop it. It generally is about as effective as an SSRI is for depression. The measurements in the

02:03:08.100 studies are a little complicated, and we can come back to questions about that. But it looked at

02:03:11.080 both desire ratings on a validated scale called the FSFI and satisfying sexual events. And it was

02:03:16.620 found to be moderately effective, but in responders, it was quite effective. Again, what we don't know,

02:03:22.040 like when you're depressed, you say, take it for six to 12 months, and then we stop and we see how

02:03:25.740 they do. There's been some neuroplasticity and brain rewiring, and you probably know some about this.

02:03:30.760 We don't have that research. It's young about how long we treat for, whether we stop, and I can answer

02:03:35.540 questions about that. Again, the side effects are similar to SSRIs. About 10 to 12% of people get

02:03:40.740 dizzy or tired, but that's fine if you take it at night. Dry mouth on a handful. It's as safe as any

02:03:47.260 central acting drug that people prescribe routinely. There are some contraindications. It can interact

02:03:52.300 with CYP3A4 inhibitors and can worsen the side effects of SSRIs, although it's not contraindicated

02:03:58.460 to prescribe them together. Are they contraindicated with?

02:04:00.500 No. Interestingly, it is being looked at, and it is sometimes used as a remedy for SSRI-induced

02:04:05.980 side effects, but SSRI-induced treatment of emergent sexual dysfunction. But the issue is that you may

02:04:10.500 have augmented side effects, and the patient just has to watch for that. I've used it in a handful

02:04:15.100 of patients. It's not my first strategy, actually. That's a whole other discussion about what to do

02:04:19.460 with treatment of emergent sexual dysfunction. We talked a little bit about just changing drugs

02:04:22.580 or switching or adding bupropion. I don't do this first. So that's one drug. I don't know if you want

02:04:27.860 to just make sure we have time to talk about the other, or I can answer more questions.

02:04:31.220 Yeah. Let's spend a second on the other one.

02:04:32.780 So the other drug's completely different. It's bremelanotide is the chemical. The brand is called

02:04:38.720 Vilesi, V-Y-L-E-E-S-I. These are both the only drugs available. There's no generics out there.

02:04:46.060 Their websites have good information for patients. This one is the complicated one, but I'll tell you

02:04:51.340 about it. It's a cyclic 7-aminoacid melanocortin receptor agonist with a high affinity for what's

02:04:58.260 called the type 4 melanocortin receptors. It's an analog of MSH, which is melanocyte-stimulating

02:05:02.860 hormone. And what it does in the end is it acts in brain pathways that stimulate dopaminergic

02:05:07.780 pathways. So it's a direct hit for desire, right? The other one is a little more complicated

02:05:12.580 in like cooking, you know? You're like sprinkling a little of this receptor and that receptor.

02:05:16.520 This one hits the dopaminergic pathways. It's given on demand as a self-injected treatment.

02:05:24.820 Injected?

02:05:25.440 Yeah. So it looks like an EpiPen a little bit. You have to look at a picture on the website. I

02:05:29.140 wish I could hold one up. I actually should have held a trainer up. And you stab your thigh. It has

02:05:33.320 a fine little needle. When you stab, it releases it. It's very painless. I can tell you I've tried

02:05:39.240 dummies and patients tell me it feels less than like a finger stick and less than a PPD.

02:05:43.400 And how long does it take to...

02:05:45.260 So you inject 1.57 milligrams, which is 0.3 mLs of a solution, subcutaneously with this

02:05:51.200 auto-injector into like your abdomen or your thigh, like a thick muscle. And it takes about

02:05:55.720 five seconds to go in. So you say one, two, three, four, you know, and then you pull it

02:06:00.440 out. You can also see that the liquid's gone down. You can look down and see it. It's a little

02:06:04.280 scary for women, but you don't feel anything at first. 0.96

02:06:07.140 I'm sorry. You only take this drug when you want to have sex.

02:06:10.240 So it's done on demand. So what's the theory?

02:06:12.780 So you should take it about 45 minutes before and it's considered on demand, one-time use,

02:06:19.860 self-injected, and it lasts in your body presumably about 24 hours. That's the theory.

02:06:25.340 What happens is that women will say like after a little while, they just feel more like the idea 0.99

02:06:31.000 seems more interesting. Their brain, this is where this bridge between desire and arousal comes.

02:06:35.120 They start to feel like, hey, you know, I'm feeling kind of interested and turned on. And then when

02:06:38.700 they engage in the activity, the arousability is more intensified. So it's supposed to be intra-event

02:06:44.300 improvements and overall sense of satisfaction. And that fits into that idea that it fuels the

02:06:50.660 future. Like they know like, hey, I might be neutral or not even interested, but if I do this,

02:06:55.420 I'm going to feel more turned on and the experience is going to be more pleasurable because I'm going

02:06:58.960 to feel more into it, both mentally desirous and probably arousal.

02:07:02.920 How much does this drug cost?

02:07:05.060 Fulbanserin is available everywhere. Brevillanotide has a specialty pharmacy that you can see on their

02:07:10.000 website. Put it this way, if your insurance doesn't cover it, both of them have guaranteed

02:07:14.000 maxes between $40 and $90 per month. For Fulbanserin, you get a 30-day supply. For this,

02:07:19.640 you get a four-week supply from the specialty pharmacy. And it depends, like many insurance

02:07:25.640 companies don't cover this, but they guarantee a maximum. You have to-

02:07:29.160 Does it need to be refrigerated?

02:07:30.300 No. You keep it on the shelf. I think just in a cool, dry place.

02:07:34.380 The outcomes on this, there's one thing to know about this. The outcomes on this have been pretty

02:07:38.340 much, there's no head-to-head studies between the two, but pretty good. And they've looked at both

02:07:44.600 improvements in this desire rating scale, the FSFI, as well as clinical events,

02:07:49.460 like satisfying sexual events. And clinical meaningfulness has been good. Good, moderate to

02:07:54.720 solid outcomes. I can give you numbers if you want for all of this. But

02:07:58.060 the main thing with this is that the first couple of dose or two, people get nauseous.

02:08:03.120 It's about 45% of people. The nausea lasts about two hours, about 40% of people. And that tolerates

02:08:08.800 out by the second time it's down, the data suggests it's down by about somewhere around 20%, 40%. It's up

02:08:15.760 to 40. And then it's down to about 8%. And then most people don't mention that they feel nauseous.

02:08:20.120 So do you advise that women maybe use it a couple of times without trying to have sex 0.62

02:08:25.400 so that they get over the nausea?

02:08:27.340 Or you can go to sleep. Because most people, if they're sleeping, and then like in the mornings,

02:08:31.700 people notice it does sort of last for at least 12 to 15 hours, maybe even 24. Or just lay down.

02:08:38.020 Some people prescribe like a dose of anti-nausea pill with it for the first dose,

02:08:42.280 or for a couple of doses. I don't find the nausea is that clinically problematic. But if people have

02:08:47.900 it there, like it's over in a couple of hours, and it didn't happen the second time.

02:08:50.660 If you put aside sort of cost, insurance, or hesitancy with an injectable versus a pill,

02:08:56.120 if you put all those things aside as non-issues, how do you decide which of these two drugs might

02:09:01.040 be more appropriate?

02:09:02.320 So one thing is patient preference. There's no head-to-head trials, but they're probably equally

02:09:06.440 effective. Do they want it on demand? So the other thing about this I want to mention was a rare

02:09:11.920 occurrence of focal hyperpigmentation, about 1% in the clinical trial, when they used it more than

02:09:17.280 eight times a month. But we tell people probably to stick to four a month to limit that risk.

02:09:22.940 And sorry, hypopigmentation at the injection site, or just in general?

02:09:26.140 No. Face, gingiva, breasts, like melanocortin, melanoreceptor, sensitive tissue.

02:09:31.280 Wow.

02:09:31.820 And it was in the clinical trial, and it was seen in 1% of people. It's not clear if it goes away if

02:09:39.220 you stop it, but if you don't use it beyond, it's not thought to occur if you don't use it beyond

02:09:44.060 the recommended guidance. They say that backwards. Use it less than eight times a month, and it

02:09:49.220 probably isn't going to happen. But we have to tell people that. So the two contraindications

02:09:53.540 for this are uncontrolled hypertension or known cardiovascular disease, because there was small

02:09:57.940 increases in blood pressure, about eight to 10 millimeters of systolic and diastolic. It's

02:10:02.080 probably not. It's probably overkill. It was originally studied as an intranasal, and it did raise

02:10:06.740 blood pressure, intranasal squirt, and it did raise blood pressure more. So they switched to the

02:10:12.100 injectable. And there were some trials on this in men, and some of my male colleagues think about

02:10:16.820 how this might be used off-label for an array of male sexual dysfunctions. So the other point I want

02:10:21.720 to make is there are a couple of at least one good large RCT in postmenopausal women. You should 1.00

02:10:26.800 have asked me, why is this not approved for postmenopausal women? So this has to do with the FDA

02:10:31.520 again. The FDA required that the companies go for indication of a category, because this goes to

02:10:37.040 the reproductive group of the FDA. And they required either that they put in an application for either

02:10:41.720 pre or post. So they started with pre, so they didn't have to deal with all the hormonal complications

02:10:46.680 of like hormonal status, hormonal replacement, and never went back for post.

02:10:51.500 Is it typically given or prescribed off-label for post?

02:10:54.880 So here's what I say. There's good RCT data for postmenopausal women that's very strong. That

02:10:59.920 suggests there's no difference, both in outcomes and risk and safety. And no RCTs in... That's for

02:11:05.680 for Lancerin. I'm sorry. There's no RCTs for Vilisi, for ADDIE. There's postmenopausal data for ADDIE.

02:11:11.080 None for Vilisi. So you're in no man's land if you're prescribing this off-label for postmenopausal

02:11:16.720 women, but there's no physiologic plausibility for the risk. 0.99

02:11:20.240 But you could give ADDIE and testosterone to postmenopausal women without contraindication.

02:11:25.360 Well, if you're doing off-label for both, right?

02:11:28.060 Off-label, yes.

02:11:28.820 And I don't usually start with two. I'm a purist. I start with one thing and either layer or switch.

02:11:34.820 That's clinical skill, really. It was clinical art. I have multiple. They tend to be younger

02:11:39.680 postmenopausal women who are on ADDIE and understand that. I have them clear, informed

02:11:44.700 consent and understand it's off-label that there's research supporting it. I have not used

02:11:49.180 Vilisi in postmenopausal women. Some of my colleagues have because I'm just nervous that

02:11:53.780 there's no data. There's no biological possibility that should be harmful.

02:11:57.400 Are these Schedule 4? Are they controlled or uncontrolled?

02:11:59.740 They're not controlled. Testosterone is.

02:12:01.540 Yes, testosterone is, yeah.

02:12:02.780 You have to have a DEA number. It's controlled. You can only give a month at a time,

02:12:05.700 which is easy for women because you give them a box of 30. That's no man's land. They get 10 1.00

02:12:10.960 months. So these were, again, they were approved for premenopausal women purely because the FDA

02:12:15.760 in their reproductive group required that they go for one indication. The companies didn't go back.

02:12:20.920 The other thing, how do I pick? So one thing is patient preference. The other one is any

02:12:23.860 contraindications. So the CYP3A4 inhibitor issue is a problem for flubanserin. Someone's on other

02:12:30.600 psychotropic drugs and I'm worried about over-sedation. I might not choose that. If they have to be on,

02:12:35.020 like, they're on HIV drugs, for example, like CYP3A4 inhibitors, they're taking a lot of antibiotics

02:12:39.700 or diflucan. You have to wait. There's guidance about how long to wait in between all the CYP3A4s.

02:12:44.220 And that's a nitty gritty we probably don't want to get into at the moment. Liver disease is another

02:12:48.160 relative or strong contraindication for flubanserin because of the metabolism. So

02:12:53.300 vileci would be a good choice in those cases. If someone has high blood pressure or they have

02:12:59.120 like aversion to getting nauseous for the first time, I mean, it's a discussion. Some people are

02:13:04.300 terrified of injecting themselves in it. It's really one, like people do it. They're like,

02:13:08.860 it's no big deal. You just have to know that and tell people that. It's not hard to do it.

02:13:13.600 You know, what's interesting to me is I'm known to prescribe these. I don't get a lot of requests.

02:13:18.600 I'm the only person in my institution, I'm at Weill Cornell, that I know that routinely would

02:13:22.580 offer this to people. I'm a referral source. I work both in medicine and psychiatry. And when I talk

02:13:28.180 about it in meetings, like people are not writing a lot of prescriptions for these drugs. I don't know

02:13:31.740 whether, why? I was going to ask you that because I'd never heard of these drugs. You could argue,

02:13:36.520 well, I don't take care of women with respect to sexual health. But what you're just saying

02:13:40.700 seems to suggest that these are potentially underutilized? Possibly. So I'm a little bit,

02:13:45.400 I think it depends a little on setting, right? I'm based at Weill Cornell. I have a faculty practice

02:13:50.800 that people refer to me from the institution from outside, but I see people from the community.

02:13:55.640 I have colleagues who have sexual medicine practices that are purely private and community-based

02:13:59.940 who write lots of prescriptions every month for this. So it might be how and what people are

02:14:06.080 seeking in certain settings. I don't know if they're underutilized. Well, there's one other

02:14:10.220 point I want to make in a second, but they're certainly under, not known about or under-recognized.

02:14:16.540 I guess the biggest question I take away from all of this, or the biggest, sorry, observation I would

02:14:20.540 take away from all of this is, I think that there are probably a lot of women out there who don't 0.99

02:14:25.940 know what tools are available to them or their doctors with respect to the entire spectrum of

02:14:35.120 sexual dysfunction.

02:14:36.220 Right. So I think there's a lot of misunderstanding, just back to these drugs. There's a lot of

02:14:40.340 confusion, like I was telling you earlier, about what is normal. That's where this whole idea of

02:14:44.380 blending those iron rails, like if I don't ever want to have sex, but I can get an orgasm, why should

02:14:48.920 I take a drug for desire? That's what a doctor might say. But a person might then not feel like

02:14:53.120 legitimized and saying, well, you know what? I want to want. It's not good enough that I'm 39.

02:14:58.600 I can get stimulated, get an orgasm, but that I still don't want to want. Maybe that person,

02:15:03.760 maybe they're not on birth control pills or they stopped their birth control pills at six months

02:15:07.000 later. They still have no desire. Why not try Addy? They need to be validated. Like it's okay to want

02:15:11.960 to want. So that's part of the problem is that there's still a taboo. We could have a whole discussion

02:15:18.180 about a woman wanting to want. That's part of the issue. Like it's, it's okay. If I have pain, 0.98

02:15:24.100 we didn't have a lot of discussion about treating vulvovaginal atrophy causing GSM. There's the

02:15:29.060 options for like lots of things. List them. Lubricants for comfort, moisturizers for moisture,

02:15:34.480 topical hormones for resurfacing. There's a whole range of options. They're safe. They're not

02:15:38.460 systemically absorbed. They're erroneously worried about in terms of like the black box and other,

02:15:43.220 it's easy to treat. And we started, I think, talking about this a little bit. There's low

02:15:47.560 recognition and lack of uptake. At least it's normalized. I go, women should not have to be 0.99

02:15:52.620 in pain. Like that's more normalized. That said, I can't tell you how many women soldier on either 1.00

02:15:57.200 avoiding sex or in pain because they don't either know or feel validated to seek treatment for GSM.

02:16:03.140 But take desire. That's like even lower than where people feel like legitimized and validated. Like

02:16:09.660 I should go to the doctor or to my clinician and get a treatment for my low desire and take a

02:16:14.720 medicine every day. That's an indulgence. I have so many other priorities that people think I should

02:16:19.040 have. And do you think that that's generational, Sharon, or do you see just as much of that in

02:16:24.460 younger women as you do older women? This drug is available. People could come get a prescription 0.89

02:16:28.480 for me and they're premenopausal and they're not banging down the door. So I think there's a whole

02:16:34.000 other phenomenon going on in the younger people. To me, it feels like the connection to sexuality

02:16:40.660 and quality of life is sort of delayed. I don't know what's going on. Yeah, it's funny. I hear

02:16:45.940 Bill Maher talk a lot about this. He's one of my favorite commentators on all things. He often

02:16:51.580 talks about the literature and the statistics around sexuality in young people. And he kind of

02:16:57.500 seems to make the same comment. Obviously, this is something you're observing in your practice as well.

02:17:01.380 My most common age group is midlife women. And for the reasons we've been talking about.

02:17:06.600 And I also do work in menopause too. So that's probably why they come to me for the mixture of

02:17:11.460 things. Like my most common patient would be like menopausal symptoms, soft flashlight, night sweats,

02:17:16.940 sexual function changes, relationship issues, mood. Like that's my busy day. So it may be my referral

02:17:22.860 source, but I do get young patients. And what I'm seeing, I guess I've been around a while. I've been

02:17:29.340 in practice for a while. At this point, 30 years, I guess at this point. And it seems like people like

02:17:35.260 having boyfriends and girlfriends and partners in their 20s and like wondering about the quality of

02:17:41.220 the relationship and thinking about the sexual relationship has gone down some and even a lot.

02:17:46.560 And it seems to be where people are seeking help at older ages. And that the concerns of people in

02:17:53.740 their 20s, for example, has more to do with STD prevention. Or the other thing you'll see in this

02:17:59.720 age group, we haven't talked about. It's not exactly a sexual dysfunction. Sometimes they have pain in

02:18:04.780 sexual dysfunction as vulvodynia, vestibulodynia. And that tends to be more of a referral issue.

02:18:11.380 Herpes, sort of how to deal with that. Not so much like quality of sex, quality of life,

02:18:17.020 connecting and relating. I'm not seeing that in the 20s. I don't know. It's sort of a little bit

02:18:21.720 ill-defined and hard to explain. And certainly the college and young, funny-year-olds that I know

02:18:28.100 aren't having partners. They're just floating around. And they're not engaging in meaningful

02:18:33.440 discovery about sexuality in a way that I think sets them up as well as maybe at other times for

02:18:40.040 future relationships. That's what I wonder about. Yeah, the observations you've heard.

02:18:44.160 No, I've heard these observations in multiple channels. It begs the question, why? And of course,

02:18:49.960 the other question, which is, is there anything pathological about that? Does that produce a state

02:18:54.780 later in life or down the line that in some way diminishes happiness, sense of purpose,

02:19:00.480 quality of interaction? So I guess it's all TBD at this point. Before we wrap everything up,

02:19:05.340 I just want to make sure we address effectively the third patient in this sort of hypothetical visit to

02:19:12.280 Sharon's office, which is the woman who is two years since her last period. There's no ambiguity

02:19:19.100 about the fact that she's in menopause. She hasn't appeared in two years.

02:19:22.120 Or post-menopausal. Like being in menopause, that's such a vague concept.

02:19:26.000 Yeah, post-menopausal, right. Biochemically, it's also unambiguous. Her estradiol level is, 0.98

02:19:31.140 you know, 10. Her FSH is 75. She is, let's just say for the sake of argument, having some vasomotor 0.94

02:19:40.840 symptoms. So she still gets hot flashes and night sweats. She's also starting to experience

02:19:46.100 vaginal dryness and discomfort. And as a result of that, her sexual desire, she has some hesitancy.

02:19:52.840 Let's just put it that way. She's saying, yeah, this is uncomfortable. I don't really want to do

02:19:55.840 this. But she says, you know, my mom had breast cancer and hormones are obviously the worst thing

02:20:02.940 in the world. So I hate waking up with my sheets soaked at night. Oh, by the way, I also, turns out

02:20:08.720 I've got osteopenia. So anyway, take it away. The first thing I sort of try to do is break it down

02:20:14.680 a little bit. You talked about, I guess there were several buckets. One is what we'll attribute to the

02:20:19.080 menopausal transitional symptoms. So typically those symptoms are a collection of things. You

02:20:25.240 rinse in some of them. Hot flushes or hot flashes resulting in sometimes sweating and sometimes at

02:20:30.720 night. The reason people call it night sweats is because it wakes people up. And it can be bothersome

02:20:35.000 and intrusive both day and night. It can lead to fatigue because people are waking up. You have a

02:20:40.240 hot flash, they sweat, they wake up, they worry, they can't get back to sleep. And so you can get

02:20:45.040 some difficulty with sleeping. You can get some independent insomnia. People report cognitive

02:20:51.180 fogginess and sometimes a little bit of mood instability. I'm careful to say that like a

02:20:56.260 significant mood disorder shouldn't be attributed to menopause. It's a vulnerable time because of

02:21:01.060 everything else that's also going on. So I watch carefully for mislabeling mental health issues in

02:21:06.800 this timeframe, which is, it's also a vulnerable time. And it may have to do with the hormonal

02:21:10.520 changes too, actually. The brain is, the neurotransmitters are sensitive to fluctuations

02:21:14.240 in hormones. So there may be mood changes and there may be concomitant mental disorders that

02:21:18.260 sometimes emerge. That's a caveat. But the stuff we're talking about, it has to do with these.

02:21:23.180 And then as you proceed through menopause, the menopausal transition and become post-menopausal,

02:21:27.680 some of that can still continue for a while. On average, the stuff lasts three to five years,

02:21:32.380 up to five to seven, worse one to two, typically worse like right before and right after the years

02:21:38.160 that you cessate your menses. It wouldn't be unusual for her to be going on like for a year or two.

02:21:44.440 The sum of the teaching is she'll probably on the other side of it. And this, some of this might get

02:21:47.860 better, the flashing and the, you know, the symptoms. But you also mentioned there were some

02:21:53.220 hormonally related potential disease progression things like bone density, which is systemic

02:21:58.920 levels and then the effect on the vulvovaginal tissue and possibly discomfort with sexual

02:22:04.040 activity. And then on top of it, you mentioned changes in sexual enthusiasm or interest, which

02:22:09.300 could be due to the discomfort or it could be due to this whole other phenomenon we were talking about,

02:22:14.480 about declines in androgens that sort of parallel this timeframe.

02:22:17.840 So I kind of like help people break it down and say, okay, let's figure out which things we want

02:22:23.240 to start with. We want to do it all at once. And what can we address like with a single intervention

02:22:28.380 of addressing multiple things? Like, I think that's what you're kind of getting at. So it depends like

02:22:33.600 who they are and how much I want to do at once with them and what else is going on. I know you've heard

02:22:39.680 me repeatedly say this. I'm really looking at, this is like a prime lifestyle time. So the reporting of

02:22:45.300 distress around this is probably to some extent influenced by any of this, particularly like

02:22:50.440 the menopausal symptoms in the context of everything else going on for these people.

02:22:54.520 So let's take like people that are heavier body weight, exercise less, have already have sleep

02:22:59.540 difficulties, have other medical problems, may be more likely to have symptoms, lower body weight,

02:23:03.560 exercising. People that have relationship stress may be more likely to be sensitive to the changes in

02:23:10.080 like their partner being upset that there's decreased frequency because they're more tired or maybe they

02:23:14.100 can't communicate with their partner and can't teach them to use a lubricant because they're afraid to

02:23:17.680 ask. Like, so you have to get some of this too. Like, tell me about your relationship. Tell me

02:23:21.620 what's going on. Are you working? Do you have kids? Do you have older parents? And then that frames how

02:23:27.060 I see or what is their health status in terms of metabolic disease and other factors, how I look at

02:23:32.340 what to do and how much to do at once and where to start. So there is lifestyle stuff and there's

02:23:36.900 counseling and relationship stuff. Let's take that out for now. I think you want to go to the

02:23:40.420 question of hormones. So the single best treatment for disruptive vasomotor and collection of symptoms

02:23:48.020 is combined estrogen progesterone therapy and no progesterone if someone doesn't have a uterus

02:23:54.900 to treat those symptoms. For example, you can decrease hot flashes by 80%, 75 to 80%, even more,

02:24:04.160 at least 50%. And so if someone tells me like, I'm having a hot flash every two hour or two,

02:24:08.520 I'm waking up, I can't get any sleep. And they're opening the window and using a fan and taking a

02:24:13.840 bag of frozen peas on the back of their neck and wearing the most expensive like menopausal pajamas 0.91

02:24:18.000 they could find on the internet and nothing is helping. I'm like, you need to go on hormones.

02:24:23.680 I can't. My mother had breast cancer. Okay, let's look at whether that's really true. So using hormones 0.61

02:24:29.180 for a period of time, the lowest dose that treats the symptoms the most effectively is not going to

02:24:36.220 give you breast cancer most likely. I can't promise that you won't get breast cancer because one in 0.95

02:24:41.520 eight or nine women get it anyway. And you might be genetically more likely, but not from a short 0.99

02:24:45.760 term use of the lowest dose possible to suppress your symptoms. That's the important distinction

02:24:49.540 there, right? Of course, you have no idea if a woman's going to get breast cancer given that it's 1.00

02:24:53.040 so prevalent. But what we can say with an absurdly high degree of certainty is even under the worst

02:25:00.300 conditions possible, which was the conditions of the Women's Health Initiative, where for all reasons

02:25:06.320 I'm not going to go into now because I'll have a dedicated podcast that will focus exactly on all

02:25:10.520 the issues around the WHI. Yes, we should. You should. Even saw in that situation only an absolute

02:25:18.640 increase in risk of 0.1%. And that was only in the incidence of breast cancer in the women receiving

02:25:26.820 conjugated equine estrogen and MPA, both products that we are not using today. Secondly, there was

02:25:33.640 no increase in breast cancer mortality, which by the way, that effect lasted till today. We still

02:25:40.920 follow those women and we can see that no more of them have died of breast cancer than their

02:25:46.720 counterparts. So glad to hear that you're going to dedicate a full podcast to this because there's a

02:25:50.880 lot of layers to this. But the short version is the WHI used oral synthetic estrogens and

02:25:56.540 oral progesterones, which you could use them, but nobody does. There are oral therapies available.

02:26:02.260 They're bioidentical. Usually people are using oral estradiol and oral progesterone that are

02:26:06.160 bioidentical. The doses are different and lower. There's also now transdermal products available.

02:26:10.780 The problem is that there's never been as large an RCT for the length of time. So the shortage from

02:26:15.820 data showing that there's other ways to have even better outcomes and maybe even no outcomes. And

02:26:20.620 there's also been extensive reanalyses of both the actual data and subgroups. So first of all,

02:26:27.580 women 50 to 59 are very different than people who started hormones. But WHI wasn't for symptoms. It 0.86

02:26:33.160 was for disease prevention. It was osteoporosis and cardiovascular.

02:26:36.000 The women were actually asymptomatic. 1.00

02:26:37.560 Right. They were older when they started and it doesn't apply to this patient at all.

02:26:41.720 And the data also, I think, are unambiguously clear that if there's any negative effect

02:26:47.140 of the combined hormone therapy in the WHI, it had to be due to the MPA because the conjugated

02:26:53.880 equine estrogen group alone got better. They had no more breast cancer or heart disease.

02:26:58.360 Not only that, they almost achieved statistical significance by 0.2 of a p-value for a reduction

02:27:05.540 in the incidence of breast cancer, an effect that also has persisted for over 20 years. This is looked

02:27:12.480 at in every subanalysis. So I think you're making the strong point that the reanalysis of subgroup by

02:27:18.700 age, and they were never looked at by symptom indication, and then teasing out the effects

02:27:23.860 of each of the components have even debunked the things that people think are scary or risky.

02:27:29.260 And that said, we also have similarly researched, but not as large groups and not as long,

02:27:33.880 other types of products that are both oral, bioidentical, and transgeneral.

02:27:38.040 So what I would say to this patient then is like, I mentioned like in a sort of a slew,

02:27:42.320 some of the lifestyle things, and there are also some over-the-counter stuff like

02:27:45.240 black cohosh, and there's using soy. None of that works as well as systemic estrogen and potentially

02:27:52.420 with progestin therapy. And the reason for the progestin is it protects the uterus against

02:27:55.880 endometrial hyperplasia. And I think you need to use it even maybe very short-term you don't,

02:28:00.280 but for this indication, you do. So the venothromboembolism risk is probably,

02:28:05.420 no matter what you do, it's probably a little higher, probably better with transdermal.

02:28:10.460 And I tend to almost never put people on oral, although there's oral products available,

02:28:13.840 and there's actually a combined oral product. You can probably obviate that to some extent,

02:28:18.300 but it's a low-risk issue, and I haven't seen it happen with transdermal clinically,

02:28:22.100 although it's not proven that it doesn't. So these are like patches or gels that are available

02:28:26.940 for these products for both estrogen. There's an estrogen progestin patch, and then you can use

02:28:31.900 an estrogen with an oral progesterone. And it comes in different types of gels. And there's

02:28:35.600 also a ring that you can use called a fem ring. In women who struggle with systemic progesterone, 0.87

02:28:41.820 do you find yourself sometimes using systemic estrogen with a progesterone-coated IUD to provide...

02:28:48.480 Sorry, I didn't mean to interrupt you. I was just so enthusiastic that you reminded me of that.

02:28:51.860 So it's not a labeled indication, but you can use a progestin IUD for endometrial protection.

02:28:57.880 Clinically, there's some prevalence studies or risk studies looking at this, I should say.

02:29:02.560 Their perspective is the best word I could use for them. And they're really looking at the outcomes

02:29:06.980 of the number of people who have the adverse outcomes when they use the IUD, and they don't

02:29:09.780 point to a signal, although it hasn't been randomized. So there are many clinicians feeling

02:29:15.080 like there's good data to justify using an IUD for endometrial protection. Usually it's the higher

02:29:19.240 dose, the Mirena. And it's good for five to seven years, although some feel that you could leave it in

02:29:24.520 longer and still get the protection because the levels stay present for some time. And that's a

02:29:28.840 strategy used by many, whether you put it in before they don't tolerate the progestin or you just decide

02:29:33.840 that... And the theory is that also that it's an alternative. It also might provide overall less

02:29:38.180 progestin exposure, although the oral progestin is bioidentical, but the levonorgestrel isn't.

02:29:43.880 So there's back and forth about it, but that's a strategy. Now, remember, this is for hot for all these

02:29:48.400 symptoms. Now, the decision to continue or treat... It's also a very good treatment for osteoporosis,

02:29:53.440 but that's a different conversation. So beyond this, if you're just going to do symptoms you

02:29:57.500 tried for a year or two, then tape or see how they did. If you want to continue for bone protection,

02:30:02.920 it's a very good drug. So it's bone protective. It's not considered a treatment for osteoporosis.

02:30:07.780 It's a preventative measure, but it probably also prevents further fracture. Like, we can get into

02:30:11.840 that data too, but... I've done the back of the envelope math just to get on my soapbox here.

02:30:17.000 And first of all, prevention is everything when it comes to bone loss. We don't really want to

02:30:22.000 wait until someone has osteoporosis to whip out the bisphosphonates, which frankly don't necessarily

02:30:28.920 have an enormous impact on fracture risk because while they're increasing bone mineral density,

02:30:34.540 it doesn't necessarily come with some of the torsional qualities of bone that we might want

02:30:39.500 to see in a healthy bone that hasn't gone through that period of degradation. But let's put that aside

02:30:44.700 for a moment and just acknowledge that if you do the math, far more women will die as a result of 1.00

02:30:52.420 fractures of femur, hip, pelvic bones later in life that could be ameliorated by the use of

02:31:00.460 judicious hormone replacement therapy to prevent them from getting there than will ever die from

02:31:06.700 breast cancer as a result of hormones. And by the way, it's not even close. We're talking

02:31:11.000 orders of magnitude difference. And this is what I find most frustrating in the HRT discussion,

02:31:17.000 frankly, is even if you discount symptoms, and I don't know how you can, I mean, symptoms is

02:31:22.100 everything in medicine, but even if you didn't care about symptoms, simply on the basis of bone health,

02:31:29.020 it's a real tragedy to me that there is an entire generation of women for the past 20 years that have

02:31:33.520 been largely deprived this therapy on the basis of very bad science and far worse reporting and

02:31:40.780 interpretation of said science. I couldn't agree with you more that there's a lot of misconceptions

02:31:46.380 about the importance of preventing bone loss. And probably we're also treating osteoporosis when

02:31:53.640 it becomes established and that the other options, although there are good ones, have limitations and

02:31:58.120 you don't get the added benefit of some of the things that combined hormone therapy has.

02:32:01.660 So there's a few conversations. One is what to do for her now. Like at this point, I'd probably say

02:32:05.680 it's going to help your symptoms. Let's say nothing else has helped her. She's tried the over-the-counter

02:32:09.540 stuff. Maybe she even tried black coho. Sure. She ate some soy. You have to eat a lot of soy every

02:32:13.520 day to make it work. Let's get all that. Say she tried all that. And then I'm like, look, this is

02:32:18.420 going to help you. Let's use the safest, lowest dose. You're certainly not going to get cancer from

02:32:23.040 this. You might get it. The other thing is that people don't know that like other things they do

02:32:27.200 are riskier for breast cancer than their hormone. We don't probably have time to get into the comparative 0.97

02:32:32.100 data, but drinking- Well, yeah. Having insulin resistance, drinking alcohol, exactly.

02:32:36.240 Drinking alcohol more than one drink a day. Not exercising.

02:32:39.920 Being overweight that goes along with having metabolic dyslipidemias, high blood sugar,

02:32:45.740 metabolic syndrome, being overweight. Those are probably more important for breast cancer risk

02:32:49.860 than small doses of transdermal hormones for a couple of years for symptoms. Now,

02:32:55.340 when you get into continuing, at least past a few years or even through 60, the first 10 years,

02:33:00.980 whatever, that's a different conversation. But like you're already getting at the point that

02:33:04.760 there's a lot of data and a lot of reasons to keep going. And we've all heard some famous friend,

02:33:10.320 quote, when do you stop your hormones? Some variation of like three days before you die,

02:33:15.940 or I've heard that from a few different ways from a few different experts, including those that used

02:33:21.300 to worry about the WHI. For example, Joanne Manson speak in a number of meetings. She was the original PI 0.86

02:33:26.620 on this. And Joanne's really, she seems to be the one who has reversed most of the initial

02:33:32.180 sort of fear around the WHI. And I'll be sitting down with Joanne to talk about this.

02:33:37.220 She can speak about it. And really analyzing carefully the subgroups, the follow-up data.

02:33:43.100 It's not to say she's refuting what was published. That's accurate. It's just that it-

02:33:47.240 It's the interpretation.

02:33:48.240 Right. She's not the one that said three days before you die, by the way. I don't want to

02:33:52.100 misquote her. I just put her in the same paragraph. The one thing that's very clear is that it's the

02:33:58.240 best treatment for symptoms. And the North American Menopause Society and sort of the other like

02:34:03.000 formal experts say like the shortest dose for the period of time that you need to manage their

02:34:07.200 symptoms. At a minimum, we need to like turn around anybody who doesn't understand that.

02:34:11.400 There's also other pharmaceuticals. You can use SSRIs actually for hot flashes,

02:34:14.680 but we already explained they have some issues and they don't work as well. You can use clonidine,

02:34:18.520 which has low rates of success and a lot of side effects, but, or gabapentin, same thing.

02:34:23.660 Which again, all of those seem so backwards to me because there's no ambiguity about what is

02:34:29.100 causing those vasomotor symptoms. I don't go there unless I'm stuck. And I have to for a variety of

02:34:34.580 reasons. We don't want to forget to remember that there's other things she's complaining about. And

02:34:38.740 I'm guessing we don't have too much time left, but she's also telling you that she has dryness and

02:34:44.100 discomfort. So does that estrogen you're sending in her system, let's say she agrees to take that 1.00

02:34:49.460 transdermal, does it get to the vulvovaginal tissue? You know, I have some patients who say,

02:34:54.080 yeah, that's fine. My lubrication is fine. I'm not dry. Others need more locally delivered and it is

02:34:59.780 not contraindicated to give both. And in fact, indicated. So there are two main symptoms, three I

02:35:05.200 see with GSF, vulvovaginal atrophy and general urinary syndrome or symptoms of menopause. Vaginal dryness,

02:35:10.860 pain with sexual activity, and a collection of genital urinary symptoms, even independent of

02:35:15.500 sex. So you can try lubricants with sexual activity for comfort. You can give vaginal

02:35:20.080 re-moisturizing agents, which are given multiple times a week. They're available in gels, suppositories,

02:35:26.620 lotions. There's a number of good products out there. Some have hyaluronic acid, for example,

02:35:30.920 some have other chemicals. You're recommended to use those. They help these polymers and other

02:35:35.900 products help draw out some of the moisture and resurface a little bit, but they don't change the

02:35:39.920 mucosa. And then sometimes I throw in some dilators. People have been sexually inactive for a while and the

02:35:44.940 tissue is tight and guide them on that. And then sometimes for sexual function as an aside, I remind

02:35:50.120 them that they might need more stimulation. So lubricants can be helped with comfortable

02:35:54.720 stimulation, silicone particularly, although it's slippery, adding vibrators. So that's all for like...

02:36:01.240 And there is some with sexual function, the use it or lose it phenomenon. So promoting regular

02:36:05.780 sexual activity, even sex with oneself, to help with keeping regular lubrication occurring in

02:36:12.660 combination potentially with lubricants with activity, even with oneself. Use of vibratory

02:36:16.880 stimulation to enhance the response. And then vaginal moisturizers for any symptoms independent of

02:36:22.740 sexual activity regularly. That's like the formula. And a lot of women don't even know that. And if the 1.00

02:36:26.980 algorithms say, do all that, and if they're still having pain, add a low-dose vaginal hormone. 0.98

02:36:31.420 And we talked about that there are estrogen products. There's rings, there's tablets, there's

02:36:36.960 cream, there's inserts, and then there's intrarosa. There's also an oral CIRM that's indicated just for

02:36:43.460 vulva vaginal atrophy. Somebody wants to take an oral pill, which is a whole nother category. It's called

02:36:48.380 osfina. The chemical is osfemipine. And it has some of the CIRM issues, but it is indicated. One of the main

02:36:56.040 benefits is some argue it may be good for breast protection in people at risk.

02:36:59.280 But I'm sorry, it does or does not provide systemic levels of estradiol?

02:37:03.000 It's not an estradiol. It's a CIRM. It's a serotonin esterism receptor modulator.

02:37:08.140 It's a little unusual. A lot of people don't know that it's FDA approved. It's not very commonly

02:37:12.400 prescribed and not that many may choose it. It's indicated, it's an oral CIRM indicated for

02:37:17.700 vulva vaginal atrophy causing dyspareunia. It's called osfina, 60 milligrams a day. And it may be

02:37:23.500 theoretically, it's not indicated for this, but it may be theoretically useful for people who need

02:37:27.220 breast protection, you know, if they've like a family history, because it's a CIRM. Sometimes

02:37:31.360 roxafine is used for breast prophylaxis, but it's not indicated for that. It might have positive

02:37:35.760 effects on bone, but again, not indicated for that. I don't use it very often.

02:37:40.280 Do you find that the time that a woman was, you know, deficient of hormones, the longer that period

02:37:46.640 of time, the greater the likelihood she will need additional treatments beyond the systemic estrogen?

02:37:51.780 Thank you for asking. Well, so the tissue changes are progressive. So the truth is that it depends

02:37:58.640 when you catch someone. So the answer is a little nuanced. So if you catch someone three to five

02:38:02.660 years out, they're going to have more tissue changes than someone one to two years out.

02:38:06.500 So if you decide that that woman doesn't need it yet, I could just educate her a lot on lubricants, 1.00

02:38:11.140 moisturizers, using vibrators for stimulation, regular sexual activity, improve that. But by the time

02:38:16.600 she's three to five years out, she might be the same as someone that you saw. You're not going to

02:38:20.040 prevent the tissue changes five years later. So that's kind of a nuanced answer. It tends to be

02:38:24.860 more likely to be clean. Sometimes early on, they're just dry. And some of the other things

02:38:31.360 that I mentioned, the non-pharmacologics work fine. But as time progresses, either the systemic hormone,

02:38:37.320 if they're on it, is going to be enough because it's just enough to leak into that tissue and not

02:38:41.260 have the tissue changes be, or they're going to start to need it because five to 10, 15 years out.

02:38:46.800 And when you get someone who comes to me, it's not unusual, 65 or 70, they've reached a threshold

02:38:51.460 then, like lubricants were working. The other thing is to avoid things that have a lot of chemicals in

02:38:56.080 them because that tissue is sensitive, you know, like warming liquids, scented things, you know,

02:39:00.640 use things that are like a little less filled with stuff. But then someone will come to me at 65

02:39:05.340 or 70 and they may be at that threshold. Somebody might be 60. I have patients who are like 80 who just

02:39:11.800 need a lubricant. Even though everyone gets the changes, the severity of tissue changes, mucosal,

02:39:18.700 loss of cushioning, decreased lubrication, tightness and shortening, that varies. It's not 100%.

02:39:24.560 Atrophy is 100% of people, but the degree and the severity varies. There's some endogenous hormone

02:39:29.260 factors where they've had an ophrectomy. The use of systemic hormones probably figures into that

02:39:33.520 because some probably leaks down there. Management of this is yet a whole nother area that I love to

02:39:38.560 talk about too, but very, very low hanging fruit in a sense, because you can do a lot.

02:39:44.280 And it's easier for people to like accept and understand once you teach.

02:39:48.100 There are some barriers, like people are kind of like disconnected. So it's not unusual. Like

02:39:53.200 somebody's 30, they have sex, they get a satisfaction, they have an orgasm, not paying 1.00

02:39:58.380 much attention to their vulva, their vagina, their vestibule, their urethra. And now you're asking 0.99

02:40:03.300 them to like, put this there, put that there, use this dilator. People don't want to mess with

02:40:07.440 this. Like you'd be surprised. It feels like a lot. Like I didn't have to do anything for my vulva

02:40:12.060 and vagina when I was 25 or 30. Now I'm 60 and I got to do all these things for my vulva and vagina. 0.98

02:40:17.600 So I'm kind of like, well, you put Botox in your forehead, you put cream on your face, 0.94

02:40:22.240 you know, that you didn't do then either. It's just the way it is.

02:40:26.160 That's a fair point. Well, listen, Sharon, this has been a really interesting discussion.

02:40:30.900 As I said at the outset, I think it's a discussion that's beneficial to both sexes. I guess there are

02:40:37.180 several takeaways here. So one is there are probably a lot of women who are unnecessarily 1.00

02:40:42.760 experiencing some form of sexual dysfunction because they don't maybe realize what's available

02:40:48.860 to them in terms of systemic tools, local tools, therapeutic tools, medications, therapy, et cetera.

02:40:55.600 And I think the other thing that you just alluded to at the end is that this is kind of a journey

02:40:59.720 over time. And in the case of women, I think the changes are more dramatic from ages, you know,

02:41:06.500 whatever, 15 to 95 than even in a man. And they probably require a little bit more willingness

02:41:14.320 to be attentive to oneself and be a little bit more proactive potentially during that aging cycle.

02:41:21.300 Again, the obvious ones that we talked about are hormones, but some of these anatomic changes

02:41:25.420 are obviously just as important, not to mention the health-related changes that may be feeding into

02:41:31.180 this, the metabolic stuff. Interesting to know that that's as important as it is in men where it's a

02:41:37.360 little bit more obvious structurally.

02:41:39.640 Yeah, no, I think those are all really important takeaways. And you hit on some of the, I think,

02:41:43.380 the most critical key points. You know, in healthcare, it doesn't always happen, but I've been hearing

02:41:49.680 about like pulling out all this education about menstruation in schools in certain states. It really

02:41:54.260 worries me because that's even like the most basic, but like in the community and healthcare, education

02:42:00.480 about sexual health and sexual function across the life cycle is really a need. So like, it worries me

02:42:08.140 that as we pull back on like the more even basic education about menstruation or STD prevention, we

02:42:13.900 have to be very proactive to make sure this doesn't go in the wrong direction. Like learning about how to

02:42:19.240 choose contraception and sexual function in your late teens and early twenties and know what your choices

02:42:23.820 might be and why. Learning about the impact of childbirth, learning in your later reproductive

02:42:29.540 years, why you're still menstruating, but your sexual desire might be dwindling. You know, like how to 0.63

02:42:34.300 integrate my brain and my body. If I'm like under a lot of stress and anxious and depressed, like

02:42:38.240 should I take a medication? What are the implications for my overall quality of life as I enter menopause?

02:42:43.460 What do I do about my system? One thing like with hot flashes, if you're not sleeping and you're

02:42:48.200 exhausted and you're feeling poorly, you're not going to be enthusiastic, but you're also noticing 0.99

02:42:53.400 changes in your vagina, your vulva, your genitals. How do I address those? Like, don't just lump it 1.00

02:42:58.120 all together. Like, oh, it's menopause. That's supposed to happen to me because that's what the

02:43:01.980 clock says. And then we didn't get a lot into like much older women, but there is a whole sexual 1.00

02:43:07.160 understanding for like the sexuality of older yet women, you know, seventies, eighties, nineties. 0.98

02:43:12.780 I get women coming to me with some of the same, but also different questions. People in some of

02:43:18.920 these studies were up to a hundred. People can be sexual well into their long years. And

02:43:23.300 there's a lot of ageism. I want to end with that. Talk about menopausal sexual health ageism and

02:43:29.340 menopause ageism. As you get into even older women past like 70, 75, there's a lot of ageism.

02:43:35.860 And in a man coming to a doctor at 80 for a drug for erectile dysfunction, wouldn't be surprising,

02:43:39.720 right? But a woman showing up with a question would be. So like, that's the last thing I'll say. 0.98

02:43:45.100 It's like, there's a long lifespan. There's a lot of different issues and we need to work on clinical

02:43:50.300 skills, resources, treatments, as well as like education in every forum for teaching women how 0.91

02:43:57.200 to think about this. We could do a course, Peter. You know, I mean, it's this huge area.

02:44:02.480 Look, I hope that this podcast, which covers a lot more content than you're typically given in a

02:44:07.200 conference to speak about, you know, gets some circulation and provides the public health

02:44:11.680 message that we want to get out there. And if nothing else, at least gets people

02:44:14.980 speaking to their doctors a bit more and finding their way to people like you. Again,

02:44:18.980 there aren't nearly as many of you as maybe there should be. But if there were 600 people of your

02:44:24.180 qualification at a recent conference, my hope is that people will know where to do it. So I guess

02:44:28.220 let's close on that. If a person wants to find a doctor like you, what are they searching for?

02:44:34.220 What's the qualification? How do they ask their primary care physician for a referral to someone of

02:44:38.920 your skill? We're sort of talking about like sexual medicine. There are sexual medicine physicians.

02:44:44.100 Some of the sexual medicine societies, I was talking a little bit about the International

02:44:48.820 Society for the Study of Women's Sexual Health. There's the Sexual Medicine Society of North America.

02:44:53.820 And you might hear that from some of your speakers on mail. They all have find the provider websites.

02:44:58.580 You know, you might want to say to your clinician, like, can I have a referral to someone who does

02:45:02.580 sexual medicine or deals with sexual health? They may not know. So you can go to these society

02:45:07.920 websites. When you're talking about menopausal medicine, I should say like the North American

02:45:11.720 Menopause Society has a bigger meeting. There's several thousand. But they also have a find your

02:45:16.840 provider website. If you think you want to kind of a subgroup, like for example, a sex therapist,

02:45:22.100 there are websites, for example, ASECT, A-S-S-E-C-T has a website with find the provider.

02:45:28.080 The physical therapy, there's a national physical therapy website. I could send you these websites.

02:45:34.000 Let's do that. And we'll link to them all in the show notes so that there's a very clear

02:45:38.220 reference trail. I think that's faster, right? But the point is that each of these kinds of

02:45:43.200 subgroups that I mentioned have find the provider websites. But remember like sexual medicine

02:45:48.240 specialist, menopause specialist, pelvic floor physical therapist, sex therapist.

02:45:52.860 Those are the buckets. Those are the kinds of keywords. Yeah.

02:45:55.820 Well, Sharon, thank you very much for the generosity with your time and your insight. Like I said,

02:46:00.280 a lot I've learned and I suspect a lot that everyone have learned. So thank you very much.

02:46:03.880 Great question. Thank you for listening to this week's episode of The Drive. If you're interested

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The Peter Attia Drive - June 19, 2023

#259 - Women's sexual health： Why it matters, what can go wrong, and how to fix it ｜ Sharon Parish, M.D.

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