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

23:44Can we use that again as markers for small vessel disease? And then vice versa, like if someone says to me, I have a patient with metabolic syndrome and a high A1C, obesity, diabetes, hyperlipidemia, etc. Is that a high -risk patient that I should be really counseling and talking to about sexual medicine? And then using that as a reason, managing those issues to preserve sexual health. And I think we need to define, first of all, what is the role of literal Doppler testing? There's no research on coronary calcium scores or coronary CTs on women and their correlates with sexual function. And can we use these both as mirrors of sexual function and predictors of other issues?

24:21other vascular issues for women, I feel like this is the most important growing field that it needs to catch up. You know, that we can't just look at like, oh, she's complaining, she's post -matter pause, I think I'll hand her a lubricant because she's not feeling things. That's very crude compared to what we have available for understanding men at this point. So that's a long discussion because it's an area of great fascination, but practically speaking, we don't have a lot to offer women in the office yet, but we need to. But it sounds like we're moving in the same direction that we kind of cleavoclear sense of what's going on with men, which is, and by the way, this is something I do see in my practice quite often, which is you have a guy that shows up with a hemoglobin A1C of 5 .9.

25:02So he doesn't have type 2 diabetes, but he clearly has too much blood glucose and dyslipidemia. A year later, when you've got all those biomarkers improved, he also notices is he doesn't need his siallus anymore. That's a very obvious, clear, repeatable, common story. So I don't think it's a huge stretch to assume that women could experience the same thing. I like to, when I talk about this with my patients and my colleagues, I like to say there's the motivator and there's the mirror. That's obvious when you're talking about a man. They're like, with these parameters and then you say, you know, so tell me about your sexual function.

25:36How is it going? Any difficulty with the retions? They report it. And you say, well, you know, that they can sometimes go hand in hand or, and that's a good motivation overall for many men, right? They want to improve everything. And that might be sometimes even the biggest motivation. That's important to them. So that's a reason to lose weight. I think we need to have the same, you know, way to think about women. And I think the other thing for all people is that we don't do enough to teach that prevention and lifestyle and disease management is important for sexual health and validate how important that is for quality of life.

26:08Like, there's all these reasons you don't want to have heart disease. You know, we should be saying you don't want to have sexual dysfunction. There's not enough education when people are before they have issues. How clear is that, Sharon? Again, empirically, it just makes sense. But what can we say about sexual health and general health? What I mean by that is overall well -being as a function of sexual health. We've already established the causality in the other direction, meaning when your metabolic health is poor and your vascular health is poor, it can impact sexual health. But what I'm saying is even independent of that if a person is otherwise healthy physically, but still having sexual dysfunction, how does that translate into the rest of their life?

26:48There's a couple ways to look at this. One thing is most of the research, I guess we're talking about women today. Yes. Yes. Most of the research is association research. So it's sometimes a little hard to tell. I think you understand the difference between really risk factor and cause and effect. We know which lifestyle and health factors seem to be associated with better sexual function, better satisfaction, better sexual activity. And most of the research is actually in desire when it comes to that. For example, I'll give you examples. And women, there's interesting research that being resilient, having a positive attitude for women, especially as they get older, having a partner, being connected socially, having to support normal BMI, the funny one is Mediterranean diet, actually.

27:29You probably have to do with overall health and well -being and the other benefits. All those things are associated with good sexual function. And whether people who do those things preserve their sexual function or those things preserve sexual function is still, it's association. I sort of think it doesn't matter. You know, you want, they're both are good. Where it matters as a motivator is that validating the importance of sexual function to quality of life is critical for people feeling that they have permission. Like, that's a good reason for me. Because sometimes it's like an afterthought, like, oh, okay, it's okay.

27:58I could prevent heart disease. but do I have to preserve my sexual function? That's a little indulgent. Why should I go to the gym just to have better sexual function? My kids need me to help them with their homework. But if 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 that for people that probably there's strong association. On the other hand, we know what the heavy hitters are in terms of overall sexual function and biological medical conditions and psychiatric disorders. I'm not sure if this is exactly what you asked me, but it's an point that I think is important to make.

28:26We can go back and clarify if you wanted to hear or anything different. So the heavy hitters, we could talk about categories. There's what we've already been talking about. There is associative data that metabolic syndrome and women, obesity, particularly interestingly hyper -trageless rademia, which probably makes sense to you. And then coronary artery disease and diabetes. But what's interesting about the last two is that the condition itself is in this clearly correlated as the psychological adaptation or relationship to the disorder is for women. So for example, if someone had a heart attack or has heart disease and they're female, it's more about how they see themselves and their interest or enthusiasm in becoming re -engaged with activity than clearly the severity of cardiac disease.

29:07And that might just be we don't have good research or it might be different in women. And same thing is two with diabetes. Like in men it's clear, like the higher A1C, the more sexual dysfunction, neurovascular disease, et cetera. But in women, it's more about the impact of diabetes so far in the research. Are they depressed because they have diabetes? They don't like wearing the monitor, so they're embarrassed to have sex or like things like that or their feet are numb and it makes them negative Rather than their blood sugar control But I think that part of the problems we don't have is good research and then there's the whole bucket of Genital urinary symptoms, menopausal symptoms and cancer.

29:41We haven't even talked about cancer yet breast cancer, gynecologic cancer, cervical and urinary cancer, or a varying cancer So those are the categories all those things I just mentioned that are associated with lower sexual function and sexual problems in women And then there's the whole bucket of depression, anxiety, and their treatments that also clearly interacts with sexual function in women and can be problematic. And I'm kind of curious about both of those in both directions. So for example, like if you take two women who are identical in all ways, but one of them is sexually active and sexually healthy and the other one is having sexual dysfunction for whatever reason.

30:16And let's assume it's not a physiologic reason. So let's assume it is a super -tintorial reason. And as a result of that, she's just not sexually active. Do we have a sense of their quality of life, their well -being as a result of that? In other words, what I'm really trying to understand is how important is sexual health for overall well -being, in particular in this case for women. There's kind of a collection of different buckets of research looking at this. Probably the strongest and most consistent research comes out of the desire literature. and looking at the impact of hyper -artosexual desire disorder, which is more like a diagnosable condition or distressing low desire on overall quality of life.

30:55And there's, I could quote you studies, but there's a number of well -done both survey studies, which are like in the community and population studies, and clinical data studies, collect and clinical settings, suggesting that there's a strong correlation with impaired desire and overall quality of life. The problem I think with this research is that dichotomy or distinction you're making, that it's purely supercentorial or psychological, relational lifestyle is sometimes so hard to tease out. I'm sure. Because no one person has zero biology impacting sexual function. But I will say something that does support that point of view.

31:32Practically speaking, you look at the, if you're a clinician, let's say, or someone comes to you, you look at the biology, you look at the psychological factors, maybe it's sometimes even past sexual function or sexual trauma or religious upbringing or how they saw themselves as a sexual being from the time they were young, even as a physician I asked those questions. Then you look at the relationship, you know, and how that is or the culture. And then you look at the things that you think are contributing and those that are amenable to intervention. And you do get to the idea sometimes that it is the psychology.

32:06You can reach that, but you want to be careful not to assume that you thought about everything in their biology until you have. But that said, you were asking me the condition of someone who was like a psychological sexual dysfunction and what is the level of distress like. When people identify it and they want it to be different, it's extremely distressing and quite impairing the quality of life. And it can be a mirror for very distressing feelings. There are studies that look at the level of distress and the qualities and they show things like for example loss of sexual desire, despairing, hopeless, feel old, feel ugly, don't feel connected, feel sad, feel hurt.

32:44You know, there's a whole collection of emotions associated with it, and typically in this research, they also look at discrepancy. And when they look at the discrepancy between, for example, a conditions perspective or perception and the patients when they're asked by like like someone else, like an independent reviewer, usually it's way underestimated how distressing or impairing it as to quality of life. We don't do a great job of understanding this. Part of it is legitimizing this. And that's what we're doing here today. It's like really legitimizing. Like this is a real thing for you. In fact, your quality of life, it's okay to tell me and it's okay to want this to be different.

33:19And when women are given that permission either because they're being interviewed in the study or somewhere in a doctor's office or they're, They embrace it because it is something that they're feeling. They're feeling impaired quality of life. I think that's what you're sort of getting at. This is worth emphasizing, giving this audience permission to understand that you can seek assistance or understanding or even treatment for these things for different sexual assumptions that we can get into defying them a little more specifically soon. And that's good. It's not something you should put as like an afterthought in your life.

33:50Because first of all, it's good for quality of life. It's good for your relationship. And there's also some, I don't know if you quite asked me this, but there is some research supporting the idea that it improves overall health. That's not a stretch, right? I mean, whether or not that turns out to be true, we would only know with more rigorous study. But there's plausibility to that based on other things that we understand about the relationship between hypercordisolemia, HPA dysfunction, stress, all sorts of things that we know do directly impact physical health. So my way of thinking about these things is they may or may not impact the length of your life, but the quality of your life is at least as important if not more important.

34:33And it's very hard to argue it doesn't impact the quality of life, especially if as you say it is being perceived that way. So I'm going to preface my next question with an assertion, which is just because evolution didn't care about something doesn't mean we shouldn't. And the example I would use is atherosclerosis. So evolution had no interest in preventing atherosclerosis. If it did, it would have got rid of APOB hundreds of thousands of years ago because we didn't need it. I mean, we would have got rid of it in the last thousand years, I think. And we wouldn't have atherosclerosis today. But given that it didn't interfere with our reproductive fitness, it's of no concern to Darwin.

35:12That said, now that we can live longer, we have every reason to care about it, and we've taken great pains to reduce our risk of dying from it. Okay, so put that aside for a moment as I ask a very naive, potentially question, but one that I've often thought about, which is, do women have it harder when it comes to sexual health? Because evolution didn't necessarily care about their sexual function post -childbearing years, Whereas in theory, evolution might care if men could reproduce through the length of their life. You know, absolutely. This is a really important topic, an area for discussion.

35:54So let me start with a point that I make often. I mean, women who are parrymenopausal, menopausal and postmenopausal aren't sick. And so sometimes people talk about it and when you have postmenopausal, vovo vaginal atrophy, like that's a horrible term. Talk about evolutionary terms that make people feel bad. It needs a whole PR firm to come in and just come up with better terminology here. As an aside, I think you've heard this terminology is that the North American Manipul Society and International Society for the Study Women's Sexual Health about, I guess it's almost a decade ago at this point.

36:23And I was involved with this process. We got together and had a whole panel on what to do about this name, Volvo vaginal atrophy for a whole variety of reasons. And concluded that it is what happens, you know, things atrophy. But it's not what we went women to think about. So we came up with the terminology genital urinary syndrome of manopause. So vulva vaginal artery can lead to genital urinary symptoms during and after manopause and the syndrome of manopause. So it took away the disease state. It's not really an illness. It's a syndrome which could be thought about in many other ways. I mean happiness is a syndrome.

36:59And so we were really trying to neutralize it. I don't know how well it stuck. It does speak to this idea. First of all, a few concepts. One is when people talk about symptoms or treatments, are we talking about a disease? I guess when we're talking about atherosclerosis and aging, we're talking about a disease. So on the one hand, you could put them as parallels, right? There's hormonal changes. The ovary stops making things. The brain does other things to the sex story at home. It's testosterone declines and both ovarian and adrenal production, et cetera. And we have physiologic changes which lead to aging, lead to decreased sexual function, and even complete loss of good sexual function.

37:33and pain, doesn't allow women to engage in quality of life and proving sexual activities, relationship building activities. So evolution has not been kind to women in a whole collection of ways. I think that's what you're asking me. And although women aren't sick, our position in the field, and certainly mine, is that we have the skills, the tools, and the sophistication to manage it and to reverse it and to have a very different outcome than evolution would command. I'll speak not too personally, but I'm a midlife woman. I'm not ready to turn in the towel. And I can tell you that most of my colleagues and friends and family members have the same attitude.

38:08And so the challenge in the area is, first of all, not medicalizing this too much, and making someone feel sick or give them things that make them sicker. And to balance that for lack of a better word, lethality, therapy, balanced to the point where you're optimizing without giving people other problems. Like you give a hormone, you don't want to give breast cancer or a neometrial cancer. or you give Astrid and you don't want to cause cardiac disease. And so that's the work that we do in this field is learning how to trick mother nature or evolution, safely, but optimize all these things, sexual function quality of life, longevity, even.

38:45We could get into the discussion about whether or not therapy improves longevity. I know that's an area of interest to viewers. Okay. This has been an excellent foundation for us to now go through some of these various things. So let's start with sexual dysfunction and I'll leave it to you which one you want to start with. So do you want to talk about a rousal and desire separately and kind of walk through that? Sometimes I find this helpful sharing with other podcast guests where we do actual case studies. So I can make some up but you can feel free to adjust them and say, okay, so a 35 -year -old mother of two married comes into your office and says, I love my partner.

39:28I just don't want to have sex. I'm just not in the mood. So tell me what's your workup? That's basically all she says on presentation. Let's just pretend that the kids are old enough now that she's not like sleep deprived, waking up every 10 minutes. So her kids are, you know, 10 and 12 or something like that. and let's make her 39 if her kids are 10 and 12. Okay, perfect. So she's 39, her kids are 10 and 12. Or 41, right, where things may be starting to change. Yeah, yeah, perfect. So she's, she's, She's, she's, She's pre -menopausal as the point I'm really just trying to get at. Right. And that's it.

40:01And she doesn't have tiny kids waking her up in the middle of it. That's right, she's out of the difficulties of childbearing. Okay, well how do you want to work her up and how do we help? Let me just give you the categories and tell you how I would think about her. Who have you seen masters of sex? So the whole concept or had organized sexual dysfunction was based on the work really first of masters in Johnson that there was a response cycle that had an order. They looked at both men and women. They were actually really quite progressive. And the idea was that people started with getting aroused.

40:29And I think in their concept it was all physiologic because they mostly just looked at physiologic parameters. They understood the psychology of things to some extent. That there was this idea that people get physically and mentally excited. They reach some sort of escalation and maybe even a peak or plateau. And that can be variable and there's some models that for women there's more variability in plateaus. And then the classic response cycle is it results in an orgasm, climax, peak, lots of different words get used, but we're just going to use the word orgasm, keep it simple. And that there's different patterns for that too, right?

41:04So, I ask a question, but I'm curious to have it. that goes before that. So what comes first? Desire or a rousal? Desire comes first, does it? Or do you have to have some a rousal to then trigger desire? I'm going to talk about desire in a moment because that's an interesting question. But in their model, they kept it simple. You engaged in sex and you got a roused. And so maybe they thought like the interest in having sex was about being turned on or being a roused, they didn't really get distinguished about it. And then you have an orgasm and for women like there's different patterns. It could be happen in different ways with literal stimulation, vaginal stimulation, etc.

41:39and sometimes multiple orgasms, which is more characteristic for the variability in women. And then there's this idea of the refractory or resolution phase. And that's kind of for like many decades since they're working the late 50s or early 60s. That's how people are organized their thinking. A few people came along notably Hellen singer Kaplan in the 70s and she happened to be a psychologist at Cornell and has like a whole discipline and following some of which are my colleagues still there a few around and added this idea of wanting or desire and felt that it was really distinct thinking about anticipating willingness to engage and that if you didn't separate it you were missing something about what could be a problem for someone like so that 35 year old or that 39 year old we're talking about I think she's 41 now but yeah no we made her food because her kids were 10 I wasn't letting her have kids at 25 but some do okay good good kids when she said they were 10 and 12 I was just trying to be realistic.

42:31The other thing is I feel like it comes up in that, if it's not late reproductive post -menopausal, it's like 38 to 41. I don't know why, but I hear that a lot. There's sort of time frames that come up. We can talk about why that one is, but that's why I picked it. But she might say to me like, you know, I'm exhausted. I have these kids, I have this job, but I agree, and I'm always kind of like, it's still even to the state, surprised to hear, but I said you get turned on. Well, yeah, I mean, I feel fine. I do have an orgasm. Oh, yeah. And is that satisfying? Yeah. But I don't want sex. If you get rid of the idea that desire is separate, you miss that.

43:08You know, there's a lot of variation on that. We could talk about a different patient where they say, theoretically, I really want to be with this person. But I know that things aren't going to work. I'm not going to feel anything. I'm not going to get wet. I'm going to have pain. So that I avoid. And that I don't want because of that reason. There's variations on that. So it's really helpful to keep these concepts separate. There's some work coming out, I don't know if you want to get into this. It's come out over the last decade actually in some sort of lay press books that are smushing them together saying that they're indistinguishable for women, but I feel they shouldn't be.

43:38I feel they need to be separated. And that's based on, first of all, vast clinical experience that you need to walk people through this to understand the problem by separating them. Secondly, that the available treatments target different things And the physiologic plausibility for separation is strong in terms of risk factor and response to treatment intervention and the opportunity for future direction in improving sexual function. If we keep them together, we're going to lose that. And to get very granular about this, the psychiatric compendiums has now combined them, desire and arousal as one thing called female sexual interest in arousal disorder, whereas the sexual medicine societies have put out strong position statements as well as nomenclature papers suggesting that we have to have these categories be separate.

44:21And the upcoming ICD or the International Classification of Diseases is going to maintain separate coding for desire and arousal for both men and women. And yet you're saying the DSM combines them? The DSM -5, which came out now, almost 10 years ago, interestingly. They just put out a revision, which I worked on actually as a medical reviewer. They insisted on keeping it the same. They told me that at the onset. You can review this, but we're not separating. And they wanted me to look at sort of the medical piece of this. Again, it's based on the idea, and I think this is fair for the kinds of people that show up in psychological and psychiatric offices, that for women it often is interchangeable, like it can be.

44:58It is still separate for men. Do you want to digress for this for a moment? Because it's interesting, and I think it resonates for people, and then we'll come back to how we would evaluate your 39 -year -old or 41, whatever she is now. So Rosemary Besson is sort of the mother of this model, and there have been others that have written about this. primarily the professional literature, but there's some books out right now, some lay press books about this. And the idea is that instead of this linear response cycle, that a better model for many women or for some women is something more circular. It's called the circular incentive model.

45:29And it's the idea that what drive sexual response isn't linear. Women go, I want to have desire. I want sex. I'm going to go find my partner. I'm going to initiate or I'm going to receive. And then I'm going to be turned on and then I'm going to have an orgasm. It's say that to people, lots of people are going to say that, I must be abnormal, because I don't feel that way. And that their normal is more something like this. Like they're not particularly feeling spontaneous sexual desire, but the circle starts with the motivation and the incentive to be close to drive toward intimacy. They're mostly neutral, but because they are close to their partner, or even we should make sure we understand that sex with oneself fits in here too.

46:08They like want to feel the benefits that come from a sexual encounter with either a partner oneself, and they're receptive or seek the stimuli, but not because they're feeling like sex hunger, the classic desire, but because of that motivation. And if everything's intact, psychological and biological influences that govern a rousability or intact, they're going to have all that arousal. The brain's going to turn on, their heart rate's going to go up, your nipples become a wreck, you're going to feel the genital sensations, and that will trigger engagement or arousal. That'll make you feel more invested and then more desire and then more arousal and that will lead to satisfaction and maybe an orgasm.

46:45So that's a chain reaction there sort of? Right. It's modeled as a circle but it's the idea that that satisfaction knowing it's good, knowing you're gonna feel close. One of my favorite expressions from one of my own more understanding patients is the after glow is what motivates it. How you feel together with how she feels connected. Not just herself good but in the relationship and that if you don't normalize that thing where design ralsal kind of smushed together, when everything works, you know, make people think there's something wrong with them that they don't have spontaneous sexual desire.

47:18So there's a book out there, for example, I'm going to go through a book called Come As You Are, some of the work of Laurie Brotto, these are live press books, looks at this, that we want to make it okay that you can be motivated by other reasons, but where this model gets confusing is that it doesn't normalize low sexual desire where you can't make it work. So let's go back now, let's go back to your example. So if she says to me, everything works fine, but I still, even though I have a good experience, I still come back to this and I don't want to have sex, then that model doesn't apply to her and she's not normal.

47:52And where that model misses is they forget that we have to make sure that people who don't feel reinforcement, don't feel motivated to re -engage, don't have the desire, the willingness, or the interest, it isn't normal. Where I do find this idea, and where it's the most, where people are kind of neutral, but they engage to be closest in long -term relationships, because they know what makes the relationship work. So this person comes to you, what I'll do is I'll walk her through. I'll say, you know, do you feel sex hunger? Do you initiate? Are you receptive? No, no, I avoid it. I finally give in because I know he's grouchy or she or whatever.

48:24How does everything work? Does your brain turn on? Do you get breast sensations? Does your body get general arousal. Do you get genital sensations? Do you feel en gorge? Do you get lubricated? The degree to which I ask specific questions is variable. Sometimes I ask more general questions. Like do your genitals get turned on? And do you peak? Do you climb? I've tried to find the language. I just say do you have an orgasm? And there's sometimes, you know, that's a whole no other discussion. Women aren't sure. So I try to help them understand what it is they're experiencing. And there's a lot of variability in the female orgasmic response.

48:55But women orgasm. Can we put a pin in that and come back to that? I want to make sure we cover that, but let's continue with this patient. And then I always ask, this gets forgotten often, is, do they have pain? Now this is a pre -menopausal woman, right? Likelihood, she's no longer breastfeeding, she's probably ovulating regularly, having regular menstrual cycles. So I enter weath of the gynecologic history, like what's the menstrual history? A 39 -year -old could be having an early menopause. I make sure that I'm not missing that. Emerging dryness, pain, discomfort. You can't always assume you know someone's age, you know what's happening.

49:28So regular cycles, are they having dryness pain? Are they, these cases no longer ovulating? Are they taking some other medication? Are they on an antidepress, so then I'd look at factors. Things like medications can affect multiple different phases. But so I collect that information for a variety of reasons. Someone with low desire, I would collect medication, information, some with rousal difficulty. What are some of the worst offenders there? I know that SSRIs certainly wreak havoc in men. Do they also do so in women? So if you're talking about general sexual dysfunction that can affect a variety of phases, antidepressants, but all psychotropics, all categories of psychotropics, and these days people aren't just on antidepressants.

50:07The SSRIs and SNRIs are probably most well -known to cause multi -phase dysfunction. There's differences, though. I mean, that's one of the areas that I consult with a lot, because I work closely with psychiatry here. Is that not all drugs are the same. It is a class of fact. but there are better drugs and then there are other categories. Like for example, buproprian, which is more dopaminergic, is a different choice for a variety of reasons. That's well -butron. That's the brand name for that as well -butron. The generic is buproprian. Within that class of drugs, what are the ones that are more likely to reduce desire?

50:39So the classic SSRIs, most of them fit in that. And the bundle together, are they clustered together somewhere around 35 to 40 % of what we call treatment emergency sexual dysfunction. But I want to make a really strong caveat in a moment about this, because there's some actually some new research kind of debunking some of this a little bit. But that said, so the SSRIs, you want me to use brand names because people know that better or genetics. So, pro -Zach flu, I'll do use both. I mean, be mindful of this. Pro -Zach fluoxetine, searchling zooloth, paxil peroxetine, those are the SSRIs and probably escatolacram, like supra and citrogram.

51:17They're probably similar. That said, I have patients who say like, I develop low -designin prozoic or I have difficulty with orgasm on searchling, on paxole, but not on prozoic. So we sometimes try a few, if I think an esosterous of best choice. That's definitely been our experience clinically, is that yeah, there's a class effect, but at the end of the day, it's kind of drug -specific. And I always tell patients, we're not the ones that are prescribing those, we're not psychiatrists. But if your doctor is prescribing you an SSRI or an SNRI, I always say the probability that you're going to get it right on the first one in terms of efficacy and side effects is actually not that high.

51:56So you have to be willing to switch drugs to find that right combination of efficacy and avoidance of side effects. And you'll be able to stay within the same class usually, but there seem to be non -trivial effects. So again, we're talking about the condition that you're treating it for. Usually it's depression or anxiety or both. And then there's the side effects, which amongst them is sexual dysfunctum. So then there's another category, the SNRIs, the serenergic neuro -upendurcs, which I know you're familiar with. There's more variability in the data on that. So there's duoxetine, there's venlofaxine, which is a faxer, which is probably the most commonly used one.

52:33And then there's pristique, which is desvenlofaxine. They're probably, all of them are probably similar to the SSRIs, but then the vaccine is interesting at a low level, low -dose, it functions more like an SSRI, and that as you kick in above, like 75 is up to 75 is probably low, somewhere over 100 to 150 functions more like an SNRI. So teasing out the sexual dysfunction and the dose dependency is a little tricky on that one. But just keep that in mind. Then, deads, then the vaccine has some data suggesting it's less likely to cause sexual dysfunction. And it probably has to do with the chemical composition and how it's different than menophaxine.

53:10Then there's some new drugs. I guess they're not so new anymore. Velazodone and voreoxetine, which have very unique and different mechanisms. And they seem to be better. They're complex serenergic dopaminergic transporters. They're a little complicated in their mechanism, but the bottom line is they work both with serenergic transporters as well as dopaminergic drugs. So it's the multi receptor factors that when you're looking at the sexual dysfunction component, that's why the theory is that they're better. The best data is actually with the lousidone. Though I have some - Best data for fewest sexual side effects.

53:46Lack of sexual dysfunction. The problem with the research on the three newest that seem to be the better, that is Desvene Lafaxine, Vortiacsitine of lousidone, is that this studies weren't perfect. There was a lot of high pre -treatment sexual dysfunction. So when they separate from placebo and not having treatment emergent, it may be the effect of just treating disease state of depression and improving sexual function, which speaks to the point that I told you I wanted to make in a minute about what some of the newer research says about this in general. The other drug is metasophen, which is kind of a typical SSRI.

54:19It is very low in sexual dysfunction compared to the other SSRIs, but it has some other problems with side effects. It can be sedating, which is good for people who don't sleep, and there's some weight gain that people report with that and why that is a little unclear, but probably the dopamine energy component. Let's assume that this woman is not taking any of those psychotropic meds. Would her being on an oral contraceptive? Yes, yes. Thank you. Okay, so what's the role of oral contraceptives in this? Yeah, so I was going to tell you about that in a minute. When we talk about hormones in this age, pre -menopausal women, let me make my point though, because I don't out both in menopause for menopausal women and in general, that the best thing to do for a depressed person for sexual function is to treat their depression.

55:04I still am having trouble teasing this out. That probably the best thing to do is pick the best drug for them for their depression and that it's more important to get them underpressed in terms of sexual function and that a small percentage, even though the numbers in other studies say 30 to 40 percent will get what's called treatment emergency sexual dysfunction. But one of my colleagues who I admire greatly who does a lot of work in this area said something to me the other day we're working on a project a paper that relates to this. She said, look, the bottom line is here's the simple answer.

55:34If you treat their depression, most likely their sexual functions don't get better. If it doesn't, it's due to the drug. And I thought if they don't want to, it's not because their depression is not better because depression is associated with sexual dysfunction. And then that's when you start to say, well, if this is important to that person, you switch the drug around. And this is where we can come in, is where we can say, look, this is an important reason to switch meds. But some people say, I don't care. Like, I just am so happy I'm feeling good. And I sometimes say, great. Or sometimes I say, well, you could feel good on something else and still have good sexual dysfunction.

56:06Don't dismiss that. So it depends on the patient. So the other big categories, so we talk about psychotropic, they're less commonly prescribed in like ordinary situations, but anti -psychotics, anxiety meds, they all have some issues around sexual function. And should that be relevant, we could discuss So the other categories, like not so much for this woman, blood pressure meds, there's some discussion about how to think about those collection of pain medications or another big bucket, hormones, suppressing drugs, but I give someone's on a aromatics inhibitor for cancer, prophylaxis, et cetera.

56:37But the thing that we really want to make sure we talk about in this age group and you're bringing this up is combined hormonal contraception. I'm glad you gave this to Peter. So confusing area also. So people are very polar on this and very opinionated. But I think it's important not to recognize, not just oral contraceptives, it's combined systemic hormonal contraception. So people take birth control pills, which have estrogen and progesterone. They also use patches like the orthoeverpatch and the ring, like the newver ring, right? And those combine and there's a whole bunch of different types of these.

57:12But the idea here, what are you doing when you give contraceptive hormonal contraception? You're turning off the brain and that feedback loop that makes you ovulate, you know, make a lining, shed it, and be able to have a pregnancy and then shed it if you don't. And you're turning it all off by giving super high doses of hormones. So what happens, the short answer is with combined contraception, that's probably most noted in the research, is that a small percentage of women get that high level of estrogen, but the voval vaginomyocosis doesn't recognize it. And you can develop a vestibulidinia, of vestibularitis, the vestibules that tissue around the entrance to the vagina, not so much inside the vagina, but that surrounding tissue called the vestibule, is very sensitive to the drop in these endogenous estradiol and the synthetic estrogen sometimes don't do their trick.

58:01And they can develop a vestibular denium, meaning pain and dryness, and almost look like a postmenopausal woman when it comes to that. That's one issue with contraception. It's probably that number, you want to number the work of some of my colleagues in this area who do sexual pain and vestibular dinew work say it's somewhere around 10%. Meaning 10 % of women that are re -receiving systemic. Users. Okay, we're receiving systemic growth. And that it's probably similar with rings and patches, but it's not as well documented. And then there's some variability. Like higher dose oral contraceptives have been more likely, low, I'm sorry, the very low have been more likely implicated and people do better if they have like more robust high dose, like sort of more standard 35 microgram pills as opposed to these ultra low, like the 20 micrograms.

58:47Like is low low estrin considered low? Yes, that's an example. So the ultra low ones tend to be the biggest culprits. That said, the experts in the field feel this is very important for us to understand the ordinary gynecologic community thinks it's relatively insignificant whether they're under detecting this particular piece of it or not is something that needs more development. The other issue with birth and control pills is that it can't have an effect on neurotransmitters and sometimes women will develop mood issues with, as you probably know, with like high dose oral contraceptives. And that may have an impact on the neurotransmit on the nix that leads to sexual dysfunction and low sex drive.

59:23Then finally, and this is probably more important as women get a little older. It might bleed us into the discussion about testosterone, is that so three things. One is they can have an effect on the local vulvar tissue if we have this issue, particularly to be the lowest dose estrogen. The other thing is depends on the angiogenicity of the birth control pill, that's yet another issue. And there are angiogen receptors in the voval vaginal tissue. So that may change sensitivity or even lead to pain, that piece of it. The second thing is that intersection with brain neurotransmitters and mood, and that effect on sexual function could also be clinically important.

59:57And then finally, and this is like a whole other thing. What do you do when you send all that hormone when it's someone's body, you increase the production of SHBG. So you're binding up more of the hormone as well? The easiest way to think about it is you need something to carry it around with. And that SHBG goes up in other states, like pregnancy. You might ask me the same for central flesum pregnancy or when you take thyroid hormone, there are other things that make that production of that go up. The data across situations is like, you could say, okay, it's like around 100 such with this or is not so clear.

1:00:30I think it's best just to say it makes it go up. Now, that is 100 % of women. Like I get asked this question like does it matter? 100 % of women have a higher SHBG if they take for example. Let's just say high dose birth in 12 pills. Let's just stick to that for now. Everybody who takes it has that. And what does that do? So it helps carry it around, but it also, fortunately, unfortunately, whatever you want. The fellow travelers, Androgens or testosterone gets carried by SHBG. So because you're increasing SHBG, there's some thinking that you're bonding up the circulating testosterone and you may be lowering free testosterone in those women and that might be another potential contributor low desire.

1:01:10Now we get into testosterone when you talk about that but has testosterone effect desire probably at the level of brain receptors and turning on those pathways of desire and there's some general changes to in the metabolites of the amdrogens that change sensitivity and that might impact desire but that's a secondary state and we're also like abruptly changed so much like ovarian hormones with menopause that it's more of a gradual decline. So, the intersection between contraception and women in their late 30s and early 40s and testosterone is interesting. So, if you look at my arm, when you're 18 to 24, that's when we start to study reproductive, your testosterone's like up here in the 40s for women, right?

1:01:50And then it kind of goes down like, I wish I could do it better, but it declines. By the time you're in like those late 30s, early 40s is about half, like if you look at normal ranges, studies that have tried to, of what you were when you were 18. And then it levels off somewhat lower in your 40s and 50s and actually goes up a little bit past 60 and kind of levels off down there. So if you're in birth control pills, that curve is way down. A woman at 40 might be much more sensitive to that effect than she was if she was on a birth control pill at 25. And that difference in her testosterone, her free testosterone, may be significant in and that she'll come and say, I like I have no sex drive, or I have no general sensitivity.

1:02:29That's kind of an important thing that most people don't tell their patients when they put them on a birth control pill or combine contraception for 20 years. Now the other thing, and I think it was in, we get some notes in advance, it was one of the questions you asked, what happens? Believe it or not, even though people say it doesn't come back, like let's say you take a birth control pill from 20 to 40, and then you decide to switch to an IUD after your second baby or your third baby, which happens a lot. What happens to my SHBG? There's really only, believe it or not, really one good study that was done by Claudia Panzer in like 2000, something like that.

1:03:02And we need more. There's some other data, but not a good study. And she looked at current users, never users, and stopped users, who stopped six months ago. And the bottom line was at six months, the stopped users, the previous users were in the middle of the other two. They hadn't gone down to normal. Now, no one ever studied them out to three or four years. But I can tell you, and my colleagues can say that if that woman walked in and she'd been on birth control pills and I checked her SHBG, even if she had stopped it, it's always going to be higher than the person who ever used them. I just see that all the time.

1:03:31So does that mean that her free testosterone at 40 is lower than it would have been if she hadn't used birth control pills for 20 years? Well, that's the theory. Wouldn't it have to be unless her testosterone has gone up? I mean, because SHBG is doing the lion's share of the binding. I mean, albumin is a relatively small contributor to this process. So isn't it about 85 % of the antigen binding is coming through SHBG? It depends a little on how much you have, but that's roughly the idea to answer your question. It depends a little bit on how much SHBG you have, but most of the binding is through SHBG and a small percentage, just through Albioman.

1:04:07There's one more point, which before we go back to talking about binding in a second, is part of the controversies, it's not clear that free testosterone is the bioactive component to what makes desire happen, both in the cells and in the brain. So the naysayers are saying, well, okay, but that's not necessarily the active component. And like looking at SHBG and free tea might not be what we need to be doing anyway. And sorry, just let's go down that rabbit hole a little bit further because this is something that fascinates me endlessly is at least in men the way I think about this, but I would think that's parallel in women.

1:04:45The one thing that's missing from all biomarkers that we can measure. So let's just make sure people understand that lingo you and I are throwing around. Testosterone is a measurement assay. When you go and measure, when you ask what's a person's testosterone level, there's an assay that breaks apart and separates testosterone from albumin from SHBG and you actually measure in nanograms per desoleter the concentration of testosterone in that plasma. When people talk about free testosterone, that is not measured, that is calculated, it's estimated based on the measured testosterone, the measured SHWG and the measured albumin.

1:05:25But there's a whole other issue here which I don't think gets enough attention. I do plan to explore this in subsequent podcasts because I find the topic really fascinating, which is Androgen Receptor Saturation. I'll give you a very clear clinical example I see in men, but I know it applies to women, which is you take two guys that both have a total testosterone of 500. And let's just assume that their free testosterone are estimated to be roughly the same. And you give them both testosterone. So now they both have a total testosterone of a thousand. One of them feels significantly better. The other one says, I don't really notice a difference.

1:06:02There's an argument that says that the guy who doesn't feel any different already had his Androgen receptors saturated. So yes, you drove up his testosterone and yes, more of it is free, but it doesn't matter because where it matters most in the nucleus at the Androgen Receptor, you haven't increased it. Whereas the guy who says, oh my god, you've changed my life. My libido is higher. I'm recovering from workouts better. I'm putting on muscle. Everything feels better. He was probably under -saturated. So this is something, I mean, to my knowledge, Sharon, we don't have a way to measure this clinically.

1:06:35You know, I know that there are people in the lab who can do this, but... Right. So this is part of all of that emerging understanding and lack of clarity is... Now being brought to the question of female testosterone too, and even less is understood about the role of the circulating actual measurable testosterone, what we think is free or bioavailable, and how that's interacting with the antigen receptor, both in non -genomic and through genomic mechanisms. And then all of that, what cells do we even mean in a woman? Is it her brain? Is it her genitals? Is it her nipples? Like we don't even know.

1:07:10But the theory is that the most important place that testosterone acts as in the brain. So is it where is that happening at a cellular level in the brain? If you look at the most general concepts, is that testosterone is the formula of desire to testosterone its metabolites and that it interacts with brain neurotransmitters to turn on pathways of desire. And when it drops, it's sensitive. If you look at the early work of Helen Singer -Cappellan, it was a psychologist. I love reading her work because she actually talked a lot about this and said, the goal, And this is like my mantra, I have it in a couple of slides, which is to fine tune that just the right amount of giving exogenous testosterone, safely, to turn the rain back on, to where she was when she was satisfied, meaning, like, free menopausal satisfied, but not invoking lethality and keeping her safe.

1:07:59And that titration is the work of desire, you know, the desire treatment, right, when you're using pharmaceuticals. So the argument is, First of all, do we know what's actually happening? And then do we know what we want to fix? Getting back to our original discussion. This woman, let's say she was on birth and 12 ,000, it's been 20 years. And like she stopped them on and off for her kids, but she still is taking them. And her SHPD is high and her free tea measures low. And then she has low desires. Are we confident enough to say that's why? And then the answer question is, we'll stop your birth until they'll solve the problem for SHPD's to come down.

1:08:32Or am I going to give her Doomsday prognosis? Because women will say to me, well, what if it doesn't come down? will I be like this forever? And then it gets into this whole question of like, is she a candidate for exogenous testosterone? She's pre -mediposal and she's don't menstruating. So we could go on and on with where this leads us. I think we wanna talk about like what do we know? What do we know? And what are the pragmatic or practical implications of what we do understand and how we counsel patients ultimately? Well, I think this is as good a time as any to go a little further down the testosterone hole because I think we're making this up as we go along vis -a -vis this case.

1:09:02I think where we're arriving organically is actually quite a common phenomenon. on. You know, I've made this point on a previous podcast. I think when I was on Andrew Hubertman's podcast a long time ago, I made this point. It's worth making again, which is we think of testosterone as the man's hormone estrogen progesterone as the women's hormone, not entirely correct. In fact, one of the challenges is the way the labs report the units of estrogen and testosterone are different. Testosterone is typically reported in nanograms per desolida, just a leader. Whereas estrogen is reported in picograms per milliliter.

1:09:38So when you convert these to the same units so you can do an apples to apples comparison, you realize that testosterone is much higher in a woman than estrogen is. Let me repeat that. A woman has much more testosterone in her body than she has estrogen. This is a staggering thing that surprises most women and most men alike. And to me at least the implication is given that testosterone is the most abundant sex hormone in a woman's body, both pre and postmenopause. And by the way, postmenopause, the gap is even bigger because of the reasons we've already discussed. It is not a surprise that changes in testosterone, a hormone that is largely responsible for desire can be just as important in women as they are in men.

1:10:27So this brings me to this asymmetry. Such an important point is like really people just such a hard time wrapping their brain around it. They think that the only hormone they should be talking about is their astrogen. And then there's this idea that astrogen supplementation improves sexual function and that's like a whole nother discussion. But it's so poorly understood how important testosterone is to the functioning of women, particularly when it comes to sex organs and sexual desire or sexual function. So this is where I think there are lots of places we can fault the medical system and we're going to line those up and stack them here in a minute.

1:11:00But let's start with one of them which is the double standard and frankly the lack of scientific rigor around evaluating testosterone replacement for women. So there recently was, there were two trials actually looking at a, If I'm not mistaken, a gel and a transdermal testosterone product for use in women, I believe that gel didn't find a benefit. I can come up with several reasons why not. But the transdermal testosterone, it began with an eye. I don't remember the... In trinza. Yeah, in trinza. There was a Johnson and Johnson patch, 300 microbes. So even trickier, when you think of these numbers, it was a 300 microgram patch.

1:11:37People aren't struggling with the numbers. But here's the thing. It raised testosterone. It improved sexual function, and the side effect profile was not of concern. This was a drug that should have been approved. Why did the FDA not approve it? There was more than one trial. There's a wonderful paper. It was in Lancet, I think, in 2019. That's a meta -analysis of over like 50 -something studies. There are some that are sort of most well -known because they resulted in presentations of campaigns toward the FDA. But there have been a number of randomized controlled trials using patches. The entrance of brand by Johnson & Johnson was a particular campaign that was brought to the FDA based on their randomized trial.

1:12:20That study was, I think it was also, I'm using the 2000 a lot, it approximates it. It was actually Jen, Jeffrey and I knew in the journal, and the first study that she looked at was the equivalent of the 300 microgram patch in O -ferrectimized women, young women who had low desire. They had distressing low desire and the estimation from the 300 micrograms is that's the physiologic amount. This is also a little complicated, but that's the physiologic amount that approximates what you would get in a mid -reproductive or late -reproductive age to bring you back to that level somewhere around, let's say, 30 -ish, 27 to 38, something like that.

1:12:56It's based on the reference range for normals for women and that when you gave that patch, they looked at outcomes. The outcome of interest was high -published sexual desire disorder or sex driver libido, and it showed positive improvements, and it was based on both self -report, satisfying sexual events, etc. As well as other phase responses, arousal orgasm, overall satisfaction. And it showed really no adverse effects in the short run, but they looked at that and other data looking at longer -term safety studies. We can talk about some of the other trials in day -to -toe, but it looked at intermediate Carviasca outcomes, cancer outcomes, and metabolic outcomes.

1:13:35And there were no hits, but it was a 24 -week trial, six months. And the main thing in small percentage of women was what's called hercitism. So it was a little hair growth like on the face along the nipple. It was about 18 % and a little acne. But women didn't get viralized. Like hercitism sounded a scary word. They had a little extra hair. I like hair growth, a little hair growth. Easily handled by dipolation and strategies that women use anyway. And the acne was relatively mild. And women did well, and they liked it. And it was brought to the FDA at that time. And the issue wasn't efficacy.

1:14:06It was lack of long -term safety data. There was a lot of rankering. I know some of my colleagues were very, very upset about it at the time. And it did get approved in Europe for some time, for that indication. Oh, for recognized women, low -desiring. It was used off label in other postmenopausal women. It went off the market for reasons other than efficacy or safety, and it's no longer available in Europe as a 300 microgram patch. So no patch is available anywhere in the world for women. So let's just level set for people so they understand something. There's an undercurrent of bad science here, which was one of the reasons given for the fear around this use of topical testosterone was extracted from the incorrect and erroneous fear that still lingered from the Women's Health Initiative.

1:14:58So that's kind of problem one here. I think problem two is the double standard, which is how many topical, injectable, transdermal testosterone products are approved for men right now in the United States? We can say at least two dozen, like depending on how you look at the indication, whether it's for hypogonatism or seksalism, you know this, right? So let's just say two dozen. Okay. So those products get approved on biochemical efficacy. Do they or do they not raise testosterone? And also outcome, like the outcome of, you know, that they are looking for the target outcome of the study. They don't require the far -off -year safety window because we've already established over decades that exogenous testosterone at physiologic doses is safe.

1:15:47So again, you could make the point, well Peter, why do you care about this? I mean, you can prescribe it off label to women, which of course we do. Oh, no, there's a huge reason to care. So let's talk about, why does this matter? There's been a lot of feeling that the standard, just to emphasize this clearly, applied to the first drug. The libigel, you asked me about that, it never made it to the FDA. They withdrew their applications, and so forth. I'll talk about why. It didn't have efficacy, right? It was called libigel. They looked at the data for out to five years and had like seven years of women patient data research.

1:16:20And it didn't show any hits for being unceased. And it was loaded for women with cardiovascular risk factors. There was no increased rates above baseline rates of cardiovascular disease, a breast cancer, of intermediate markers for metabolic or cardiovascular risk, like A1C lipids, inflammatory markers. And they reached the therapeutic level in the blood. So they felt that they could clearly state that this represented safety data. But the efficacy hit wasn't met. And so they did not take it further to the FDA, unfortunately. And that's been the last effort since then. But just going back. So the problem is that you're saying, like, why do they approve these test assessment products?

1:16:56Because the concept has already been proven, right? That we know if the FDA makes this assumption that it's safe. But when this was taken to the division that looks at this, it's really the hormone and reproductive end. There's no precedent. But the lack of approval doesn't then permit the precedent, the history, the knowing, the expert consensus in the field that it's safe. So you never can get there if you don't approve something at 24 weeks. So this is the conundrum that we face. This is the problem. There's only one place in the world that has a government -approved product of testosterone.

1:17:26It's the continent of Australia. They have a product that is now available that you can get. It's called Androfem. And it's five milligrams. This is the dose. So you can go up to 10 milligrams of the item that testosterone that gives you this physiologic amount of testosterone. People get confused because the patch was 300 micrograms. But it is available in Australia. It's government approved. It's based on the same research, the same numbers, the same blood levels, the same outcomes. There's a way for practitioners and from other countries by sending their licensing information to actually order it for patients, but it's not done very much.

1:18:01So no other place in the entire world has approved a testosterone for women. So you're asking me like, why does this matter? we've just prescribed it off label. The problem is there's no regulation to it. So let me say something else that I think was implied, but you're mentioning the study about the 300 microgram patch that went to the F, they come in there with the FDA. There've been a number of randomized control trials looking at similar doses, mostly in patches, looking at women on and off estrogen, pre -imposed menopausal, surgical and natural menopause that have shown the same efficacy with the outcome of HSDD, high -public sexual desire, being the primary outcome, and showing other parameters with improvement like arousal orgasm, satisfaction, etc.

1:18:42And based on that consensus papers that have come out in the last couple of years, really say that this is indicated, and probably reproductive age, there's two different guidancees, and definitely post -menopausal women based on this efficacy and safety data, and these numbers of randomized trials. And this large meta -analysis that looked at efficacy and safety of numerous studies demonstrates this. So you can prescribe it. It's off -label, but it's supported by all of this data. The problem is, it's impossibly hard to prescribe it carefully, and with the precision, unless you're in Australia, that we should command for our patients.

1:19:16So yeah, it's really in precise, and it's a problem. And let's explain this because I want to talk about it, which is because you have to basically rely on one of three methods. One is using a male topical product, but then their doses are wrong. You're stuck using like Androgel, which by the way, I think is a suboptimal product even for men. So you're now taking a product that I don't think is very good for men trying to apply it to women. You can cut patches into tiny little areas, so take an FDA -approved patch and cut it. You cannot use the FDA -approved injectable because the concentration is too high.

1:19:54Those are 200 milligrams per milliliter, and you can't get enough into a neat, like it's basically you just need what's in the needle let alone in the syringe. So you're basically left with three options. None of them are an FDA approved product. One is a compounded cream. One is a compounded injection. So they can compound it at 20 milligrams per milliliter of testosterone sipping it. which is one tenth. So just to be clear, we want to give about one tenth of the male dose. That's right. And then the third is compounded pellets, which again, you can get an FDA certificate for the raw ingredient, but it is not an FDA -approved product.

1:20:37The way, for example, your Vavelle dot is FDA -approved as top -glestrogen. So therein lies the rub. That's the crux of it, as I see it. I think it's good to explain this to people. So we said earlier that testosterone was the most, in a little more depth, was the most for about circulating hormone and women. That said, there are normal ranges for women. They are sort of broken down by decade and quartile, so like 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 studies, particularly by Andregue, and when Goldstein was involved with this work, looking at like creating normal ranges.

1:21:13So the idea is when you treat a woman, you wanna go to the physiologic range for mid to late reproductive age women. So therefore you're not like overshooting and you're not undershooting and probably that's the time that Like that's the best range. So somewhere like for example 28 to 35 or 28 to 37 with a standard direct total testosterone as we didn't talk about like what you should measure in fall We can come back to that and that was what they found was safe and a efficacious in these studies was that physiologic range For mid reproductive age women based on normal ranges in studies By the way, I want to correct myself.

1:21:51The data I just have in front of me is that it was 46 studies looking at 36 of the trials were randomized and like 8 ,500 women, close to 8 ,500 women. There's lots of data. It's not lacking. There's probably even more that didn't get into the Sman Alcics and it didn't meet the criteria. We have lots of data. It's not based on lack of data. And we do have decent outcome data, meaning it's extension trial data for up to four to five years and randomized trial data clearly up to 24 weeks, but certainly in some trials up to even two years. So, it's not any different than what we have for men. We just have long -term use with FDA approved products as they've approved them.

1:22:26You were speaking about it. So, it's a little bit of a cart -horse problem, which is we're stuck in this paradigm where, unless we get some approval, we can't get out of it to do the longer studies that you'll see post -market. That are carefully done and will satisfy future approvals, right? Effectively the phase four trial. Right, so you need to use one -tenth of the male dose because that's probably what gets you to this physiologic range that I was talking about. Now, the Australian approved government product does do that. It starts there and then you monitor levels and there's no cut point for saying, this testosterone is the one, you don't treat a testosterone, you treat a syndrome.

1:23:03That's the first thing, you treat a HSTD. And I usually check baseline levels to make sure they're not high. Because if someone comes to me and they're 52 and they're testosterone surprisingly high, They're not in that later quartile. I might say to them, I don't think this is the solution to your problem. But if it's low, as I expect it to be, they're not abnormal, they're not deficient, they're just normally what they should be, then I shoot to treat them to that reproductive physiologic level. So you want to use one tenth of the male dose. The position papers that I've been involved with state that because it's so hard to get the concentrations consistent, we recommend using transdermal, male products at female dose as opposed to compounding.

1:23:42And if you're going to compound, you're probably better off the transdermal than a pellet or an injection because of the peaks and the difficulty in not getting into the key things you don't want to get into that super physiologic level, which hasn't been demonstrated to be safe in women. And so the trick 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 joke. I prescribe a year, 30 -day supply, for example, of the tubes. So 1 % of testosterone tubes. They go to the pharmacy. The pharmacist rejects the prescription. They're not covered by insurance.

1:24:15The pharmacist calls me and says, do you know what's a woman? I'm like, I write it on the prescription. Didn't I say the patient is a woman? I vote androgenism is the diagnosis, HSDD. And yes, she's going to pay for it. I tell them to look at a cost -saving app and find the cheapest place. It's usually $200. They buy 30 days. They have to hope it works because they have to waste the $200. Then I say, take a tube and waste one, divide it into 10 little piles. And then figure out what you're going to do to get that amount into your body every day, and then we'll do a blood test in three to four weeks.

1:24:43That is not the kind of medicine I want to practice. So one strategy is to tell them that you can buy them in the pharmacy, five CC syringes, and squirt the thing in and use 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 most brilliant patient. She's a baker. So she discovered that the cooking spoon, somewhere between a pinch and a smidge, was a tenth of her packet. And then when her level's a little high, she's like, okay, I'll level the spoon a little differently. This is crazy. There's no better solution. Yeah, it's total alchemy. Tell me, what's the instruction you give women for how and when to apply?

1:25:19Do you say I want you to do this right after the shower? I want you to exfoliate your inner thigh. I want maximum absorption. Like how are you making this as consistent as possible? A relatively hairless area. a bottle can outer thigh the back of the calf just so gets absorbed. You obviously don't want to wash within a couple of hours. It doesn't matter the time of day if you want to make sense to do it the same time of day. The other thing to really hurl is it can transfer. So if you have children that you're holding or if you have a female partner and it's skin to skin contact, it actually can transfer and it's not thought to be insignificant.

1:25:54There are two important points for us to all know. It can transfer, so you want to put it somewhere, it won't transfer if that's going to be an issue, even though the amounts are much smaller, and everyone knows that about male. Like if you squeeze one of those tubes out on a male shoulder, you know this, it's like a whole big surface area. It's much smaller in women, but still. And if you're going to get a blood test, don't put it where you're going to draw it, or don't try to wait some hours, so that you still get a little bit of a peak, even though with daily use of transdermal, it's more of a steady state.

1:26:20The other caveat is if there's a potential for getting pregnant, they really have to be on good contraception. So who might that be? So there is a biological plausibility and the guidance in the clinical guidelines says that you can consider this and later reproductive age women. And so every now and then a menstrual cycle peaks in and all of us have heard of an unexpected pregnancy in those women. Probably by the time you discover your pregnant, the testosterone's not gonna do much harm to the fetus because it's usually only a few weeks. But we don't want people using testosterone and getting pregnant.

1:26:49That's one of the big reasons, I mean, and we didn't get back to this with the all contraceptive patient. And the solution isn't to leave her under birth control pill and give her testosterone. First of all, it's not indicated for premenopausal women. Second of all, that's not what you do, right? You try to correct the hormonal imbalance. If this is the woman we're talking about going back to her, right? Going back to our hypothetical case. Yeah, let's just say that that's the path we're going down. You would remove her from the OC, probably switched to an IUD. If SHBG levels were still sufficiently high and free testosterone, well, let's just say total testosterone was kind of 40th percentile.

1:27:20You'd say, look, we're going to bring that up higher. given that your SHBG is so high it's going to bring your free testosterone right up to about the 50th percentile and again you're using that as a guidepost but it's ultimately symptoms that you're treating. You're managing symptoms and - So let's say that's what I decided I look at the biological psychological and social factors in this woman and I decide like that's the thing that's amenable to intervention I'm going to change our contraception. So it's not just women who are already on these that I tell I'm a little birth control pills combined contraception I want to make this disclaimer, patches and rings are extremely effective.

1:27:54And most women don't have a problem. So if you ask me what should I take, you have to talk to your doctor. Should I use NiuD to start with? I can tell you how I counsel my own daughter, but that's my college -aged daughter, but that's different than what I would tell patients and people. They're incredibly effective worldwide. They prevent unwanted pregnancies, they protect against fertilities, etc., worldwide. They liberate women all across the world. We don't want to say nobody should take birth and children. But for this discussion, if somebody has a problem, that's something you can change.

1:28:24And if it's one of the problems we talked about, what you should tell a 20 -year -old about whether you use birth neutrophils or put it in an IUD is like a whole another conversation. To be preventive, again, this is a small percentage of people who develop these issues. Some women aren't sensitive to that. Everyone gets a change in their SHPG. Some women aren't sensitive to it. Some women aren't sensitive to the nonindodging as estradiol and their vestibules. Some aren't. So I can't tell you who that's going to happen to. Again, the decision about what to use over time is a discussion with your doctor.

1:28:51I think more than a gynecologist need to offer informed consent, so women can choose more carefully at the onset, and this is an important campaign that gets missed. There's no informed consent. They just say, people, first of all, 21, you should give women choice. But anyway, so getting back to testosterone. So I think the challenges then, 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 to then have to do that. one tenth of the male dose, but you do have to follow levels because women are all over the place. Like how well they get one tenth, how that one tenth of a product that wasn't.

1:29:24Well also how variable the absorption is, not all people have the same skin. These were not designed for women. I can tell you that the data in Australia is very positive, for example. I work very closely with one of the main researchers there, a woman named Susan Davis, who's done a lot of the work in this field, both in Australia and worldwide. And a first author on a number of really important testosterone consensus papers. She impresses me, but what she told me about the clinical outcomes and the ability to get kind of steady -state good blood levels because it's a controlled product designed for women regulated and formulated.

1:29:55We need that. That said you do have to follow levels mainly to make sure that you're achieving safe doses. So like if you said to me, well, like what say someone has a level that it's too low and they're not getting benefit, would you go up and say sure? because we haven't achieved the physiologic range, and I know it's still safe. So I am like checking it to make sure if they're not having symptoms that are improving to see that were given them enough. But the most important reason for monitoring blood levels and I monitor because of what you explained, the smartest thing is just to mentor a total T.

1:30:30We didn't go through this elaborate detail. It's not clear that that's the best marker for knowing whether that's the way to tell whether testosterone is helping a patient and their cells and in their brain. Their genital cells, their brain and some other body cells too. But that's probably the grossest best measure we have. Free tea is calculated, and we don't even know if that's the bioactive component. To testosterone, it's a very complex, what now is called intraconology. It hits the cells, it gets converted into metabolites, antigen -dHT, it enters the cell through the antigen receptor and has both genomic and non -genomic effects.

1:31:03Non -genomic means direct action, genomic means it causes gene translation, other protein development, which then has trophic effects. And so all that's happening, probably the total T is the best measure of both not being too toxic and also probably targeting. Now you ask me what's the best type of total T? So most people have direct assays in their lab if you send your patient to your hospital lab or a cluster lab corps. They're imprecise when you use them for women. They're not the best measure but they're good enough for what we're doing and what we're talking about. The mass spectrometry testing, which has fancy names, is used in research and clinical labs.

1:31:38And I believe you can specifically order that. So we do order LCMS when we send our patients. I don't know if people know that with that as well. When we order estrogen levels, testosterone levels, we actually request LCMS because we've seen how, believe it or not, supplements that you're taking can dramatically impact the readings. And we noticed this actually first in men. We were getting men who would get estrogen levels back that were, you know, normally a male estrogen level might be 25 to 40. We'd see guys with like 200. I'd be like, that's impossible, right? First of all, he has no symptoms of having an estrogen of 200 come to realize he's on some supplement for, I don't know what, and that's impacting with the assay.

1:32:15You send him to get an LCMS and it comes back normal. So all of the stuff gets very complicated very quickly. Just quickly, I want to talk about one other hormone before we leave this and go to our next topic, and that is the role of DHEA. For folks who might might be familiar, DHEA is a precursor to testosterone. DHA is actually not regulated in the United States. It's a hormone you can buy over the counter, which is odd. I don't really understand why it's unregulated, but that's another story. What is the role of oral or topical DHA in female sexual health? Testosterone and it's metabolites in its precursors are also like an area of confusion.

1:32:53The simple version, which is good right now, is the DHA is a precursor. So why not use that and then make testosterone? testosterone. So testosterone gets metabolized to things, for example, like five alpha DHT, which is probably the most potent metabolism, metabolite, and aromatase to astrobiol. So when we're throwing all these things out, we're talking about, do we want to look at a precursor or a metabolite and then what's actually working in the body or in the cell? So the short answer is there've been some trials looking at oral DHA for the outcomes of interest that we're talking about here, for example, low sexual desire, and they have not been convincingly positive.

1:33:29Safety has not been nearly well studied to the extent to which I just told you there's all these randomized trials of efficacy and safety for testosterone for women using the product, the 300 microgram or gel products, right? 300 microgram patch. And again, that's even in the blood level, which we're measuring in Pycograms for Mellies. Pycograms for Mellies, what we measure for one, we'll come back to the measurement in a second. But the oral DHA, which is administered in milligrams, some outcome studies have been done. They've been small. They've been problematically designed. All the criteria for good randomized trials haven't been met.

1:34:04And there's no good safety data really looking at this. But the biggest thing is that efficacy has not been demonstrated. So we don't recommend oral DHA for the indication of HSDD. I know people use it, whether it helps some patients and whether we're doing anything problematic to the way we're measuring different things is impossible for me to tell you because we don't have a good control data on this. That said, there is very good data supporting the use of a vaginal, intra -vaginal DHA. The chemical is called prostarone. The brand is called intrarosa. Basically, it's like a little suppository.

1:34:40It's used for Volvo vaginal atrophy, resulting in genital urinary symptoms of manopause and the indication is just from your pain, postmenopause, and it has very good efficacy and safety data with very little systemic absorption for that indication. And the rationale for it, instead of using an estrogen local product, then maybe we'll have a few minutes to get into that, is that there are mixed receptors in the genitals that need both estrogen and androgen. So it gets metabolized into both androgen and then eventually to estrogens at the intracellular level. that's the theory of it, right? Because again, remember DHA is a precursor.

1:35:19How do you decide Sharon for a woman who's presenting with a pretty common presentation? Whether to give estrogen. Whether you're going to use an estrogen suppository or whether you're going to use a DHA suppository. The data suggesting differences and efficacy isn't there. So you really could offer, we can get into like, how do I even, even among the estrogen products, there's a whole bunch of choices. There's creams, there's rings, there's inserts, and then there's tablets. They're all local, badger, and estrogen products that help with dryness and pain and the sexual activity. And then DHA, the introsa product, is an option.

1:35:54And so the standard practitioner will start with an estrogen product, and if it doesn't work, which to introsa, I think it works really well, so I offer it as an option. And there's some, I have some educated patients who that's what they want. The other thing is that it doesn't have a block. Any distinct pros and cons? Yeah, so it doesn't have a block box warning, which we'll also have to get into. And so some people like just like not seeing that warning. And the black box warning with the estrogen is around breast cancer or clots. So it has to do with both endometrial and breast cancer and vascular thrombolembolism and there are a few other things thrown in there.

1:36:31The idea is that they're applying the risk factor data, primarily from the WHO, which I actually, for systemic estrogen therapy, it's a class labeling requirement that has to go on these low dose products which haven't demonstrated any of the same negative outcomes. Even the systemic hormone therapy, that could be dissected. So some practitioners prefer not having a black box. Some patients prefer not having a black box. Sometimes it's someone like my mother had breast cancer. I don't want any hormones. I won't use estrogen, but they'll use this and there's no real rationale. Now, there's no proof that it's any more or less likely to cause any cancer at all.

1:37:08The other issue is that in cancer survivors, it doesn't have the black box, so sometimes on colleges, and again, that's a whole discussion we could have whether they're worried unnecessarily. And I think there's some people where I feel they're quite androgen deficient and it might be a better choice to start with. So for example, like I have a 40 -year -old had no freck to be and doesn't want to go into systemic hormone therapy. And I know that her testosterone levels and her androgen levels have plummeted overall because over the over about half of the circulating testosterone, even though she lost some of it since she was 25, you've now taken out half of what she has.

1:37:42We didn't talk about this. So in every woman, half of your about half of your androgens are made in your adrenal gland and half of your over. And the part that goes down, like in later reproductive years and through the manopausal transition, is the ovarian component. The antigen component stays about the same. There is some decline in that. So when you take someone's overs at it at a young age, you're lopping off, especially the younger the worse. Those are the people that are the most likely to have what I think is physiological, organic sexual desire, difficulties for low testosterone, from testosterone removal or antigen removal abruptly.

1:38:13So that's someone I might say, and they're not using systemic hormones. I might say, let's think this might be a better direction. That's not based on any really systematic research. It's just experience. Okay, let's come back to something you mentioned earlier in the discussion of our first patient as we now talk about our second patient. So our second patient, let's say she is younger. Let's say she's 30. She has no kids been sexually active for 12 years and she comes to you complaining of in orgasmia. So she says, I have desire, but, and I do get aroused somewhat, but I have never been able to either alone or with a partner achieve what I think I'm told an orgasm is.

1:39:05I'm really teeing this up so that you can explain what an orgasm is because in a mail it tends to be somewhat more binary. I'm curious as to how you would counsel this woman. And if you think that this is a reasonable example to use to explain that. Sure. What I thought you were going to tell me is that nothing else is going on. She has no sex driving. Are there FDA -approved drugs for low desire, which we didn't talk about for women? But that's not the question you're asking me. Let's come back. Let's turn her into someone who has a different problem after that. Because I think we don't want to forget to mention there are two drugs.

1:39:37We're talking about all this testosterone that's not approved. We should make sure before we include that we let people know there are two drugs FDA -approved for low sexual desire and chemotherapy. metapausal women. But let's go to orgasms. So one of the biggest things when someone comes to me, this is not an uncommon clinical scenario. You picked a good one because a young -ish woman, but old enough to start realizing, hey, I'm 30, by now, this should have happened. Or is there something wrong with me? Sometimes they don't care, but they think it might be something wrong with them. Sometimes they're like, you know what, it's enough.

1:40:07I want one of these. Or there's a lot of reasons why people seek it. But first thing I do is try to figure out if it's primary anorgasmia, meaning they've never ahead of orgasm or secondary, meaning they had one and now suddenly it's gone. The scenario I think you're telling me is someone who has really never really felt like an orgasm. And now, so one of the first things I asked him is like, why are you now coming here to talk to me about this? What is different? Well, let's just say I'm really with a amazing sexual partner and everything is perfect and he or she is wondering if there's something wrong with them.

1:40:45And this inability to have an orgasm is actually interfering with our relationship because it's now creating a stress where my partner feels inadequate by making this up. But I would assume that this is a classic presentation. Yeah, no, it's a common reason. So the most common reason that women suddenly decide to come to me for an orgasm is that they are now in a relationship. and it may be that they themselves want to have a more satisfying experience of the partner, wants to, sometimes they lose relationships because they, it's not so much a partner isn't willing to work it through, but they feel uncomfortable about having this problem and letting a partner see that they can't solve it.

1:41:25It's usually contextual, but not always. Sometimes women just sort of come to this realization that this is something they want to explore. So you ask me what an orgasm is. I mean, I think the idea that it's a peaking, you become interested, You feel a sense of, we've talked a little something about arousal. You feel mentally excited, your body feels turned on, there are physical changes that you notice. And then there's sort of a sensation that feels it's throughout you that you're peaking and maximal pleasure and it's an overall sense of like an escalation to something. In the genitals, what's actually happening is first there's what we can talk about what happens when you get stimulated.

1:42:02There's sensory input. But you get a stimulation to the sensation. It causes a response that heads to the spinal cord. It can trigger the autonomic nervous system. First, the parasympathetic nervous system to cause vasodilitation. Here's where the pelvic muscles sometimes can relax during sexual activity. You get muscle relaxation, vasodilitation. And then it triggers eventually, as you become more and more roused. Interestingly, the sympathetic nervous system gets triggered. And that's what triggers an orgasm. And in women, it can be a sensation of pleasure. in the brain and it's really interesting to talk about what's going on.

1:42:36Like FMRI studies have actually looked at this. But generally it's pelvic floor, the pelvic floor muscles contract, blood vessels become maximally dilated, and nerve stimulation results in the local release of some neurotransmitters which cause secretions and lubrication. So it's, for example, vasoactive and intestinal polypeptide. There's some involved in nitric oxide and CMP like in men contributing to both vasolotation, secretion and so forth. So you get like, again, you get this stimulation, parasympathetic service system, then sympathetic nervous system, then muscle contraction, local hormones, brain chemistry, local hormones, secretions, and people get this sense both of well -being, pleasure, pelvic floor contraction, they may get secretions, and then they feel the Kevin and orgasm.

1:43:22So there's a lot of variability, that's the full Monty. There's a lot of variability. Some people just feel like a intense central or a mental pleasure. Others feel a warm, intense sensation in their genitals, but don't notice lubrication. Sometimes people will come to me and that's like a part of it isn't there. Like how come I don't squirt that term comes up sometimes and that's a whole other discussion. Like is that supposed to happen? So first of all what proportion of women have that sort of ejaculatory response with an orgasm? It's hard to say some of my colleagues believe that it's part of every sexual response and that it's just not being perceived.

1:43:54I would say about 20 % of people are aware of it and that's sort of what's written. But again, so there's this whole other theme going on in the sexual medicine literature about whether women have the prostate function in the local general milieu that results in the squirting of fluid. What I can say is it's controversial and probably more commonly what I hear when people are having sort of a more normal orgasmic or a rousal in the orgasmic responses, that the lubrication from the new causal surface becomes robust. And that's probably an interaction between vasodilitation, the nervous system, and the local hormones, such as VIP and nitric oxide.

1:44:32Where the squirting of fluid and where the female prostate actually resides structurally is an area of controversy. I think that's the simplest answer. And I don't think that's the biggest piece of orgasm getting back to that. I don't know if you have other thoughts. No, I find this to be a totally fascinating topic. like as any male would who's seen all extremes of this, it's not consistent either. So you wonder, is that a super orgasm? Some women have that every single time. I mean, it's a... So I think a more interesting question. I mean, I think it's a good one, because that's not really what people are bothered by.

1:45:06It's that they don't feel like they're getting that overall like sensation and peaking sensation, both in their brain and in their generals. It's that sensory experience and the intensity and the muscle contraction that they're probably not experiencing. It's not so much they're worried about the lubrication or so to speak to squirting. That's not like the big some are and some aren't, but the biggest issue is your scenario. It's like that thing doesn't seem to be happening to me. This woman that we're presenting with, this is clearly not the issue that's germane to her. I'm trying to think where to go with this.

1:45:37But the first thing I would do is make sure I understand whether this was something she used to have or she never did. Let's assume the answer is no. This is primary. So the thing about secondary and orgasm is that if a woman has the capacity for orgasm and she loses it, one of two things have happened. Like some kind of significant psychological impact that you need to find out about. Could it be trauma, relationship struggle, something happened and you want to understand that. Or there's a physiologic factor like a medication or or neurologic condition or something. And it could be things like one of my colleagues is really into the nerve damage from spinning classes.

1:46:15Now that's just me, don't go out and get rid of your peloton, but like in men, nerve damage can blunt sensation and may interfere with. So like I look for those things, but we're not talking about that right now. So the first thing I do is find out like why and look at the context and make sure like somebody's not pressuring her, like you know, there are people who are like, I don't really care about my partner once me to have an orgasm. So I just fake it and these bugging me I'm coming here to see if I can have a real one. And I've heard that. And sometimes I explore it further. I never accept the answer at face value.

1:46:44I'm big on finding out more. Is they just given up or they really don't worry about it? And there are some people in the field who feel like saying, well, not having a New Yorkism can be normal for some women. So I avoid that. Is it not having a New Yorkism normal? I sort of say, OK, well, is this important for you to have this and find out about it? And let's learn techniques or strategies for seeing if you can reach this experience. I don't know what to say, like, don't worry, it's normal, go away. Like, you know, someone's come to me, so we look to see, are there strategies they could do to have it?

1:47:16So there are multiple kinds of orgasms, and the big buckets are literal vaginal or both. This is where there's maybe some numbers, about 30 % of women, maybe if you want to go with rough numbers, reach orgasm through pedal stimulation, about 33 vaginal and 30 have flexibility. Now, what techniques for reaching orgasm very widely across women, some women can have organisms just thinking about it. Some nipple stimulation, some women reported with even breastfeeding or like the shower water hitting their nipples. Some women need direct clinical stimulation, manual oral, some women like vibrators.

1:47:50Other women through the thrusting of the intercourse and like there's again the question where is the G -spot fit in, right? This spot that's a spongy spot just inside the vaginal canal on the roof. That's a area of sensitivity. The bottom line is there's lots of nerve bundles in lots of places and a lot of them can be stimulating enough to trigger this whole mechanism. That's what I tell women. And the big thing for you is to figure out whether you've learned where you can be most stimulated to have a more intensified response. That's where I kind of start with. So like whether it's clear or vaginal, through intercourse or not, it's more about what the stimulation patterns are and how much they've explored learning about that.

1:48:26That's sort of the short answer. Do we have a sense of the correlation between the number of women who would present as this patient as a woman who is young in her reproductive years who is an orgasmic who also does not masturbate? Is that a high correlation? In other words, it's part of the problem in the situation. She is unaware of what her sensations are or what her mechanisms are. and therefore, A, can't reach that threshold on her own, and then secondly, isn't able to communicate that with her partner, or is there no association between that? I mean, I think the data is a little hard to tease out.

1:49:04What I will tell you, first of all, is primary and regasmia versus secondary. It does somewhat correlate with age. So younger women are more likely to have primary and regasmia, whereas other sexualist functions get more market with age, you know, desire and arousal problems due to some of the factors because we've been talking about primary or any gas may attempt to get better with age when women can learn more about their orgasmic response. So that's how I'll answer that differently. In large population -based studies, it's the least common reported sexual dysfunction, either primary or secondary.

1:49:35But it may be that we just don't know how to ask about it. Like for example, there was this large population -based study that many people in the field of hurtable called the preside study. It was like sort of the largest population -based study of some 31 ,000 women at 50 ,000 survey, 31 ,000 women reported, we sell for port of distressing sexual problems. So overall sexual dysfunction desire was somewhere around 10 % to 15%. And orgasm problems were like 3 % to 6 % of the women reporting those problems. What was the age range on that 18 to like 100 to like 99? So all women effectively midlife, all orgasmic disorders midlife and women the most likely reported, but primary orgasm tends to be the most likely reported in the younger room.

1:50:16So I think once a woman learns another point is that once a woman learns about her orgasmic response, she doesn't usually lose it unless an organic or psychological factor like I mentioned in her veins. So let's go back to this woman. How are you going to do the workup? So I'd pretty quick workup wise. Mostly it's the story. Tell me about your sexual function. It's a history. I check the other phases, right? I want to make sure she's not a birth control vessel and having pain and like that is a negative. And so I'll ask her to tell me like her story. Does she have sex with herself? Has she tried masturbating?

1:50:45Does she have a partner? What does she do with her partner? And what does she know about being able to stimulate herself? Does she know the structure? Does she know I might show her a picture? Does she know where her labia are? Does she know where her clitoris is? Has she tried nipple stimulation? What have they used as a couple? Has she tried using vibrator? Like I'll get into what her knowledge about and what techniques for stimulation if she used herself? What is her partner's job? And what is she able to do in terms of communicating with her partner? So the real question is does she know what stimulates her?

1:51:16and can she teach or train or ask her partner to do that for her if it's in partner sex? There are two problems is one women don't really know yet and so the prescription might be learning more about that and there are a number of ways to do that. The other issue is communication between partners like they aren't sure how to teach their partner to do what they know works. This is not this patient but it's one thing that happens is women get older that we haven't really talked about this that you do need more stimulation with age even if you We don't have any pathology. So if you don't have diabetes or vascular disease, many women need more stimulation with age because this sensitivity goes down.

1:51:50And so I really normalize the use of a vibratory stimulation because it helps a lot. But sometimes it also helps for younger women. This is less the case sometimes for younger women because they don't need quite as much stimulation. But I ask them like, have they tried techniques for improving or enhancing stimulation? The biggest factor is that women kind of don't know their structures. The actual clitoris isn't the most sensitive. It's the sides of the clitoral, the flanks of it, for example, around the vestibule, the sides of the clitoral hood, just inside where some people call the G -spot.

1:52:20These are where the neurovascular bundles are concentrated. That top of the clitoral hood is actually very easily irritated and not doesn't like these bugs very much. Some partners are sitting there rubbing, you know, like there's an example. I mean, not to be too graphic. And so some education about vaginal vulvar and clitoral stimulation, techniques, fist emulation. So I send people to books. There's a number of books and we could talk about those. So that's where Biblio therapy, looking at some really responsible lay -press literature on like book called Becoming Our Gasmic. The Joy of Sex has been republished and published and published and published in still a great book.

1:52:55What year was the first version of that book? I think it was in the... That's a good question. I should have checked that for you, but it could be the 70s. It might even be soon. You know, it was some decades ago. Good question to find out. Call it 50 years ago. Okay, so the joy of sex. So, rattle off the names of the books that you would use as reference here. So, these are some books that I like for yourself, becoming orgasmic. The joy of sex. Sandra Leibhlerm has a couple of different books. She's a sex therapist who's no longer with us yet, unfortunate accident, but she's written several different books.

1:53:26More of her work is on desire. Laurie Brotto, on mindfulness, and it talks a lot about learning how to stimulate yourself. So there's books available. There's also a website. I have no commercial investment in any of this. I just want to make sure people know that. That I sometimes send people to. It's called OMG OMG YES. Like, oh my god, yes, I guess. Sorry, the website is just www .OMGYES .com. I just Google it and pops up OMG YES. Oh my god, yes. I mean, we'll just say it. That's what I I think it is. And it's a very responsibly produced website that has a lot of education for women. So there's a small amount of money for subscription.

1:54:10I think the standard programs, like around $40, and then there's a larger fee for more involved program, it's not free, but they have some demos on it. And it has a lot of educational videos, including very explicit videos on showing techniques for splitter and other kinds of stimulation. And really teaching people to learn how to stimulate themselves and become orgasmic. Is this a site that is also just as helpful for men? To learn about their partner. Female partners of other women. Right, it's designed for female stimulation, but it could be for the partner. It could be for the partner just as much for the other person.

1:54:41Sometimes it's easier for someone to sit and watch a video with their partner than to have to show them themselves. It's not uncommon that they'll say, well, you could start by yourself and figure out which videos you might want to watch with your partner. That's another example. There are some other resources, but those are some common things that I would do with that patient. You can send the person to a sex therapist, too. And I'm not a sex therapist. I counsel. We haven't talked a lot about psychological therapies. There is some data for using mindfulness -based therapy and cognitive therapy for an array of sexual disorders.

1:55:13For an orgasm, the sex therapist uses much more explicit techniques. So they use things like directed master... So you could send them to a sex therapist. I make the distinction, I counsel, and I give advice. I'm a medical physician who does kind of a multifaceted analysis and intervention, but if I think they need more work I might suggest that patient go to a sex therapist and so the techniques for learning about orgasm with a sex therapist who might be for example directed masturbation It's kind of some of what we're talking about but they might Instruct them more these sex therapists these days.

1:55:44It's not like if you saw again masters and Johnson They don't go behind a room with a glass window and like have sex in front of the sex therapist There are surrogates, that's not what I'm talking about. But they'll discuss very, you know, in more detail about technique and they'll give homework assignments. There may be advisor guidance about positioning. So they might bring the partner in and discuss positioning. They might use something called sense aid focus. So a lot of times people, in addition to that, we didn't kind of get into this yet, but people develop a lot of anxiety. So and that makes the problem worse.

1:56:16They've been developed like what's called spectary during and performance anxiety. So, there's a technique that works for any sexual dysfunction but can be used here, where you gradually introduce levels of sexual and partner communication. And you start with very non -threatening things like you sit, you hold hands, you hug, and a couple is given gradual, especially when people become very anxious that like, am I going to have an orgasm? What's going to happen? So the sense aid focus prescription can be done by sex therapists. And then sometimes more so with distraction and low desire, mindfulness and cognitive therapy can be introduced by certain people who specialize in this.

1:56:53And then the other thing we didn't mention is sometimes I discovered like a really deep -seated important psychological issue that's linked to this. Like an unfortunate scenario would be someone who was sexually traumatized. And like every time they get into a, or they develop even a general aversion, right? There used to be something called sexual aversion disorder that's been kind of removed from the DSM for a variety of reasons. But every time the intersectional encounter they'll have an intrusive thought, or maybe there's mixed -in PTSD, or there was very strong religious prohibition or cultural prohibition.

1:57:22And then if I pick that up, I really send them right to a psychological person to work with that, because it's something that's now they understand or come to realize maybe interfering with their sexual quality of life and their happiness. So we didn't say that, but at the onset, that's much more primary. Let's go back to the two drugs that we didn't talk about besides testosterone, just to make sure we close the loop on that. Yeah, I think I'm glad you raised the whole point about office counseling. So a lot of what we're talking about before we move to the drugs is that there's office counseling like I would do looking and we didn't get into this so explicitly, but I look at like what's the relationship, what's the timing, what's the lifestyle factor.

1:58:02So I was thinking we were gonna go there with that 39. Your older her, the older you decided she was. I call it the rant. So she'll come in and she'll say, I'll say, well, tell me what's going on. They'll be like, well, I have two kids. There's homework, there's dinner. I work all day, there's the house, there's a laundry. Then I have to answer my email at 12 o 'clock and then it's one in the morning and the partner wants to have, whatever partner it is wants to have sex, like I'm too tired. You know? Sometimes they're not helping me get thrown in there. And so, while a lot of what I do is dissect this fact, I'm sure you'd do this too in your work, is help people look at how their lifestyle is.

1:58:36So, that's that. So, when someone comes to me with low desire, and I look at these lifestyle factors, we look at some of the other medication factors, we look at whether there's another sexual dysfunction like contributing to low desire, and they have hypoactive meaning, distressing low desire that's clinically diagnosed, and I don't see another modifiable factor. That's where in post -menopausal women, I might think, okay, do we need to add androgens? We should say, like, first you do a biopsychosocial assessment before you use a pharmaceutical. And you look at these factors, you look for a relationship counseling factors, you look at referrals for psychotherapy or sex therapy.

1:59:12And you look at modifiable medications, other things you can change. And then if you reach the point where you're like, I want to use something explicitly for sexual desire. In post -menopausal women, you can use testosterone. like that's an option. We didn't talk about who the candidates are and when you would use that. The biggest hitters are people who've had to offer at least a young age, early menopause, post -menopausal women who are stressing low desire. And then you have to, of course, do inform consent when you do that. Now, for premenopausal women, who we reach the same conclusion, like there's nothing I can modify or nothing obvious, we do have two FDA approved products for this.

1:59:48And strangely, they're around and they're available and very few people when I either they know about it and they come to me for a prescription because I've already been through everything else when I tell them they're shocked to hear that that's available. Have you heard of these? Like many people have. I have not. Yeah. Interesting, right? So the first one, I'll briefly tell you about them and feel free to ask me questions, which I need to just explain what they are at this point. Sure. Yes, please. So there's Flow Bansaran. The brand name is Adi, ADDYI. And it was like a lot of these drugs.

2:00:20It's a centrally acting drug. It acts on serenergic and dopamine ergic receptors, and it has a complicated mechanism which is actually not fully understood. It's mixed serenergic agonist and antagonist. It's actually 5H2TA and 5H2, 1A and 2A, 1's agonist, 1's antagonist, it's mixed agonist and antagonist, and it has activity at D4, which is dopamine receptors with moderate affinity for some other serenergic receptors to B and 2C. And that region's specific effect seems to be prosectual. We studied for depression, but discovered to be helpful for low desire. Kind of like Viagra was studied for blood pressure.

2:00:59Yeah. And found to. Right, but this is essentially acting drug. So that's not to say that like women who respond to this are getting it because they're depressed, but unwonders. There may be a spectrum of like why people have no libido specifically as a presenting complain and why a sensual acting drug could be helpful. It's FDA -approved. You're supposed to kind of rule out this other stuff and manage all the biopsychosocial factors before you consider it. That said, like, do you use the same criteria you use for any decision to use a drug? Like it's not so fancy. Is it a drug that a woman takes every single day or is it one that she takes?

2:01:31So it's daily on demand, centrally acting. It's a single dose. There's only one dose. There's no titration. 100 milligrams. It's taken at bedtime. It's been FDA -approved since 2019. It's been around. There was a long road to the FDA. I was part of that more so than the testosterone I was there. I happened to be the president of, during the few years it was approved. So I spent a lot of time at the FDA trying to advocate for its approval. I can tell you more, what that struggle was like more personally. It is administered at bedtime. Initially, they did a lot of research looking at hypotension and syncopy and it's interaction with alcohol.

2:02:07And for some time it had a REMS. were meaning there was a risk mitigation strategy where doctors had to actually take a test before they could prescribe it. There's other drugs like that around. And patients had a sign of form that they wouldn't drink alcohol at the pharmacy and pharmacists had a sign that they counseled patients. It was re -looked at that it was really no different than any drug in class. Like SSRI's give hypotension if you take them and drink alcohol or make you feel woozy or sedated. And so it's drug in class advice. Now there's still black box because the FDA wouldn't go all the way.

2:02:39It's similar in class to SSRIs. The side effects are similar. Anyway, you take it at night, and most people you take it and you go to sleep. It can cause a little sedation. It's sort of like metasapine. I tell people, take it and go to sleep. Most people tell me they sleep better, and they're not drowsy. You take it, probably you see the maximum effect of that off four weeks, but usually they say give it eight to 12 weeks. If it works, you continue it. If it doesn't, you stop it. It generally is about as effective as an SSRI is for depression. The measurements in the studies that are a little complicated, and we can come back to questions about that, but it looked at both desire ratings on a validated scale called the FFFI and satisfying sexual events.

2:03:16And it was found to be moderately effective, but in responders, it was quite effective. Again, what we don't know, like when you're depressed, you see take it for six to twelve months and then we stop and we see if how they do. There's been some neuroplasticity and brain rewiring and you probably know some about this. We don't have that research. It's young about how long we treat for, whether we stop and I can answer questions about that. Again, the side effects are similar to SSRIs, about 10 to 12 percent of people get dizzy or tired, but that's fine if you take it at night, dry mouth, and a handful.

2:03:46It's safe as any central acting drug that people prescribe routinely. There are some contraindications. It can interact with CIP -3A4 inhibitors and can worsen the side effects of SSRIs, although it's not contraindicated to prescribe them to that. Are they contraindicated with? No, interestingly, is being looked at and sometimes used as a remedy for SSR and new side effects. But as I said, I induced treatment emergency sexual dysfunction, but the issue is that you may have augmented side effects in the patient's access to watch for that. I've used it in a handful of patients. It's not my first strategy, actually.

2:04:17That's a whole nother discussion about what to do with treatment emergency sexual dysfunction. We talked a little bit about just changing drugs or switching or adding preproperion. I don't do this first. So that's one drug. I don't know if you wanna just make sure we have time to talk about the other. or I can answer more questions. Yeah, let's spend a second on the other one. So the other drugs completely different. It's Bremelanetitis, the chemical. The brand is called VyVC, VYLE, EESI. There's only, these are both the only drugs available. There's no generics out there. Their websites have good information for patients.

2:04:49This one is the complicated one, but I'll tell you about it. It's a cyclic seven amino acid melanocortin receptor agonist with a high affinity for what's called the typeformal and cortin receptors, it's an analog MSH, which is melanocyte stimulating hormone. And what it does in the end is it acts in brain pathways that stimulate dopamine and urgent pathways. So it's a direct hit for desire, right? The other one is a little more complicated in like cooking, you know, like spring going a little this receptor and that receptor. This one hits the dopamine and urgent pathways. It's given on demand as a self -injected treatment.

2:05:24Injected. Yeah, so it looks like an FEPan a little bit. You have to look at a picture on the website, which I could hold one up. I actually should hold the trainer up. And you stab your thigh. It has a fine little needle. When you stab it releases it. It's very painless. I can tell you I've tried dummies and patients tell me it feels less than like a finger stick and less than a PPD. And how long does it take to? So you inject 1 .57 milligrams, which is 0 .3 ml of a solution subcutaneously with this auto injector into like your abdomen or your thigh, like a thick muscle. and it takes about five seconds to go in.

2:05:57So you say one, two, three, four, you know, and then you pull it out. You could also see that the liquid's gone down, you can look down and see it. It's a little scary for women, but you don't feel anything at first. I'm sorry, you only take this drug when you want to have sex. So it's done on demand. So what's the theory? So you should take it about 45 minutes before and it's considered on demand, one time use, self -injected, and it lasts in your body presumably about 24 hours. That's the theory. What happens is that women will say, like after a little while, they just feel more like the idea seems more interesting.

2:06:32This is where this bridge between the czar and arousal comes. They start to feel like, hey, you know, I'm feeling kind of interested and turned on and when they engage in the activity, the arousal ability is more intensified. So it's supposed to be intra -events improvements and overall sense of satisfaction. And that fits into that idea that it fuels the future. Like they know, like, hey, I might be neutral or not even interested, but if I do this, I'm going to feel more turned on and the experience is going to be more pleasurable because I'm going to feel more into it, both mentally, desirous and probably arousal.

2:07:03How much does this drug cost? Full Banserin is available everywhere. Bremen Lannetide has a specialty pharmacy that you can see on their website. Put it this way. If your insurance doesn't cover, both of them have guaranteed maxes between $40 and $90 per month. For the Lancer, you get a 30 -day supply. For this, you get a four -week supply from the specialty pharmacy. And it depends like many insurance companies don't cover this, but they guarantee a maximum. You have to... Does it need to be refrigerated? No. You keep it on the shelf. I think just in a cool, dry place. The outcomes on this...

2:07:35There's one thing to know about this. The outcomes on this have been pretty much... There's no head -to -head studies between the two. but pretty good. And they've looked at both improvements in this desire rating scale, the FSFI, as well as clinical events, like satisfying sexual events. And clinical meaningfulness has been good, good, moderate to deep solid outcomes. I can give you numbers if you want for all of this. But the main thing with this is that the first couple of dose or two people get nauseous. It's about 45 % of people, the nausea lasts about two hours, about 40 % of people. And that tolerates out by the second time It's down the data suggests it's down by about somewhere on 20 to 40 percent.

2:08:15It's up to 40 and then it goes down to about 8 percent and then most people don't mention that they feel nauseous. So do you advise that women maybe use it a couple of times without trying to have sex so that they get over the nausea? Or you can go to sleep because most people they're sleeping and then like in the mornings, do people notice it does sort of last for at least 12 to 15 hours, maybe even 24. Or just lay down, some people prescribe a dose of anti -nausea pill with it for the first dose or for a couple of doses. I don't find the nausea that clinically problematic, but if people have it, they're like it's over in a couple of hours and it didn't happen the second time.

2:08:50If you put aside sort of cost, insurance, or hesitancy with an injectable versus a pill, if you put all those things aside as non -issues, how do you decide which of these two drugs might be more appropriate? So one thing is patient preference. There's no head to head trials, but they're probably equally effective. Okay. You know, do they want an on demand? So the other thing about this, I want to mention, is there's a rare occurrence of focal hyperpigmentation, about 1 % in the clinical trial, when they used it more than eight times a month. But we tell people probably to stick to four a month to limit that risk.

2:09:22And sorry, hyperpigmentation at the injection site, or just in general. No, face, gingiva breasts, like melanocortin, melanoreceptor, sensitive tissue. And it was in the clinical trial and it was seen in 1 % of people. It's not clear if it goes away if you stop it, but if you don't use it beyond, it's not thought to occur, if you don't use it beyond the recommended guidance. They said that backwards. Use it less than eight times a month and it probably isn't going to happen, but we have to tell people that. So the two contraindications for this are uncontrolled hypertension or known cardiovascular disease because there were small increases in blood pressure about 8 to 10 millimeters of systolic and thysolic.

2:10:01It's probably not. It's probably overkill. We usually study it as an intranasal and it did raise blood pressure, intranasal squirt, and it did raise blood pressure more. So they switched to the injectable. And there were some trials on this in men, and some of my male colleagues like think about how this might be used off label for a array of male sexual dysfunctions. So the other point I wanna make is there are a couple of least one good large RCT and postmenopausal women. You should have asked me why is this not approved for postmanopausal women? So this has to do with the FDA again. The FDA required that the companies go for Indication of a category because this goes to the reproductive group of the FDA and they're required either that they put in an Application for either a prior post So they started with pre so they don't have to deal with all the hormonal complications of like hormonal status hormonal placement and never went back for post.

2:10:51Is it typically given or prescribed off label for post? So here's what I say, there's good RCT data for postmenopausal women that's very strong, that's just there's no difference, both in outcomes and risk and safety, and no RCTs and that's for for the answer and I'm sorry, there's no RCTs for Vilece, for Adi, there's postmenopausal data for Adi, none for Vilece. So you're in no man's land if you're prescribing this off label for postmenopausal women, but there's no physiologic plausibility for the risk. But you could give Adi and Tista Osterone to post menopausal women without contraindication.

2:11:25Well, if you're doing off -label for both, right? Off -label, yes. And I don't usually start with two. I'm a purist. I start with one thing, and either layer or switch. That's clinical scale, or it's clinical art. I have multiple. They tend to be younger postmenopausal women who are on Adi and understand that. I have them clear and form consent and understand it's off -label that there's research supporting it. I don't have not used, if I we see in post -menopausal women, some of my colleagues have, because I just, you know, nervous that there's no data. There's no biological possibility that should be harmful.

2:11:57Are these scheduled for? Are they controlled or uncontrolled? They're not controlled. Testosterone is. Yes, testosterone is, yeah. Yeah, you have a DA number. It's controlled. You can only give a month at a time, which is easy for women because you give them a box of 30. That's no man's land. They get 10 months. So these work, again, they were approved for pre -menopausal women purely because the FDA in their reproductive group required that they go for one indication the companies didn't go back. The other thing, how do I pick? So one thing is patient preference. The other one is any contraindications.

2:12:24So the SIP -3A4 inhibitor issue is a problem for full -mancerin. Someone's on other cyclotropic drugs and I'm worried about oversadation. I might not choose that. If they have to be on like, they're on HIV drugs, for example, like SIP -3A4 inhibitors, they're taking a lot of antibiotics or like flu can. You have to wait. There's guidance about how long to wait in between all the C3A4s and that's a nitty -gritty we probably don't want to get into at the moment. Liver disease is another relative or strong contraindication for for cancer because that's a metabolism. So if I BC would be a good choice in those cases, if someone has high blood pressure or they have like a version to get nauseous, you know, for the first time, I mean, it's a discussion.

2:13:03Some people are terrified of injecting themselves and it's really one like people do it. They're like, It's nobody deal. You don't have to know that until people that. It's not hard to do it. You know, what's interesting to me is I'm known to prescribe these. I don't get a lot of requests. I'm the only person in my institution I'm at Wal -Kornell that I know that routinely would offer this to people. I'm a referral source. I work both in medicine and psychiatry. When I talk about it, meetings like people are not writing a lot of prescriptions for these drugs. I don't know whether why. I was going to ask you that because I'd never heard of these drugs.

2:13:35you can argue, well, I don't take care of women with respect to sexual health. But what you're just saying seems to suggest that these are potentially underutilized. Possibly. So I'm a little bit, I think it depends a little on setting, right? I'm based at Wal -Cornell. I have a faculty practice that people refer to me from the institution from outside, but I see people from the community. I have colleagues who have sexual medicine practices that are purely private and community -based, who write lots of prescriptions every month for this. So it might be how and what people are seeking in certain settings.

2:14:07I don't know if they're underutilized. Well, there's one other point I want to make in a second, but there's certainly under not known about or under recognized. I guess the biggest question I take away from all of this or the biggest sort of observation I would take away from all of this is I think that there are probably a lot of women out there who don't know what tools are available to them or their doctors with respect to the entire spectrum of sexual dysfunction. Right, so I think there's a lot of misunderstand, just back to these drugs. There's a lot of confusion, like I was telling you earlier, about what is normal.

2:14:43That's where this whole idea of blending design rules. Like, if I don't ever want to have sex, but I can get an orgasm, why should I take a drug for desire? That's what a doctor might say. But a person might then not feel like legitimized and saying, well, you know what? I want to want. It's not good enough that I'm 39. I can get stimulated, get an orgasm. but that I still don't want to want. Maybe that person, maybe they're not on birth control pills, or they stopped the birth control pills six months later and still notice our why not try adding? They need to be validated like it's okay to want to want.

2:15:13So that's part of the problem is that there's still a taboo we could have a whole discussion about a woman wanting to want. That's part of the issue. Like it's okay, if I have pain, we didn't have a lot of discussion about treating vulgar and atrophy causing GSM. There's the options for like lots of things, list the lubricants for comfort, moisturizers for moisture, topical hormones for resurfacing. There's a whole range of options, they're safe, they're not systemically absorbed, they're erroneously worried about in terms of like the black box and other. It's easy to treat and we started, I think talking about this a little bit, there's low recognition and lack of uptake.

2:15:50At least it's normalizing, a woman should not have to be in pain, like that's more normalized. That said, I can't tell you how many women soldier on either avoiding sex or in pain because they don't either know or feel validated to seek treatment for GSM. But take desire, that's like even lower than where people feel like legitimate and validated. Like I should go to the doctor or to my clinician and get a treatment for my low desire and take a medicine every day. That's an indulgence. I have so many other priorities that people think I should have. And do you think that that's generational, Sharon, or do you see just as much of that in younger women as you do older women.

2:16:26This drug is available. People could come get a prescription from me and they're pre -menopausal and they're not banging down the door. So I think there's a whole other phenomenon going on in the younger people. To me, it feels like the connection to sexuality and quality of life is sort of delayed. I don't know what's going on. Yeah, it's funny. I hear Bill Marr talk a lot about this. He's one of my favorite commentators on all things. Right. He often talks about the literature and the statistics around sexuality in young people and he kind of seems to make the same comment. Obviously this is something you're observing in your practice as well.

2:17:01My most common age group is midlife women and for the reasons we've been talking about and I also do work in Manopause 2 so that's probably why they come to me for the mixture of things like my most common patient would be like, Manopausal symptoms, South -East night sweats, sexual function changes, relationship issues, mood, like that's my busy day. So it may be my referral source, but I do get young patients. And what I'm seeing, I guess I've been around a while, I've been in practice for a while. At this point, 30 years, I guess at this point. And it seems like people like having boyfriends and girlfriends and partners in their 20s.

2:17:39And like wondering about the quality of the relationship and thinking about the sexual relationship has gone down some, and even a lot. And it seems to be where people are seeking help at older ages, and that the concerns of people in their 20s, for example, has more to do with STD prevention. Or the other thing you'll see in this age, we haven't talked about, it's not exactly a sexual dysfunction. Sometimes they have pain in sexual dysfunction as vulva deni of Estabula deni, and that tends to be more of a referral issue. Herpes, sort of how to deal with that. Not so much like quality of sex, quality of life, connecting and relating.

2:18:18I'm not seeing that in the 20s. I don't know, it's sort of a little bit ill -defined and hard to explain. And certainly the college and young, funny year olds that I know aren't having partners. You know, they're just floating around. And they're not engaging in meaningful discovery about sexuality in a way that I think sets them up as well as maybe at other times for future relationships. That's what I wonder about. Yeah, the observations you've heard. No, I've heard these observations in multiple channels. It begs the question Why and of course the other question, which is is there anything pathological about that?

2:18:53Does that produce a state later in life or down the line that in some way diminishes happiness sense of purpose quality of interaction? So I guess it's all TBD at this point. Before we wrap everything up I just want to make sure we address effectively the third patient in this sort of hypothetical visit to Sharon's office, which is the woman who is two years since her last period. There's no ambiguity about the fact that she's in menopause. She hasn't appeared in two years. Or post -menopausal. Like being in menopause, that's such a big concept. Yeah, post -menopausal, right? Biocamically, it's also unambiguous.

2:19:29Her estradiol level is, you know, 10, her FSH is 75. She is, let's just say for the sake of argument, having some vasomotor symptoms, so she still gets hot flashes and night sweats. She's also starting to experience vaginal dryness and discomfort. And as a result of that, her sexual desire, she has some hesitancy. Let's just put it that way. She's saying, yeah, this is uncomfortable. I don't really want to do this. But she says, you know, my mom had breast cancer and hormones are obviously the worst thing in the world. So I hate waking up with my sheets soaked at night. Oh, by the way, I also turns out I've got osteophenia So anyway take it away The first thing I sort of try to do is break it down a little bit You talked about I guess they were several buckets one is what will attribute to the Menopausal transitional symptoms so typically those symptoms are collection of things you rinse in some of them Hot flushes are hot flashes resulting in sometimes sweating and sometimes at night The reason people call it night sweats is because it wakes people up and it can be bothersome and intrusive both day and night It can lead to fatigue because people are waking up.

2:20:39You have a hot flash, they sweat, they wake up, they worry and they can't come back to sleep and so you can get some difficulty with sleeping. You can get some independent insomnia people report cognitive fogginess and sometimes a little bit of mood instability I'm careful to say that like a significant mood disorder should be attributed to menopause. It's a vulnerable time because of everything else that's also going on. So I watch carefully for mislabelling mental health issues in this time frame, which is also a vulnerable time. And it may have to do with the hormonal changes, too, actually, the brain is the neurotransmitters are sensitive to fluctuations in hormones.

2:21:15So there may be root changes, and there may be a common mental disorders that sometimes emerge. That's a caveat. But the stuff we're talking about, it has to do with these. And then as you proceed through menopause, the menopausal transition and become post -menopausal. Some of that can still continue for a while on average, the stuff lasts three to five years, up to five to seven, worse one to two, typically worse like right before and right after the years that you cessate in your men's seas. It wouldn't be unusual for her to be going on like for a year or two. The sum of the teaching is she'll probably on the other side of it, and this sum of this might get better, the flashing and the symptoms.

2:21:51But you also mentioned there were some and homomonally related potential disease progression things, like bone density, which is systemic levels, and then the effect on the level of vaginal tissue, and possibly discomfort with sexual activity, and then on top of it, you mentioned changes in sexual enthusiasm or interest, which could be due to the discomfort, or it could be due to this whole other phenomenon we were talking about, about declines and androgens that sort of parallel this timeframe. So I kind of like help people break it down and say, Let's figure out which things we want to start with.

2:22:24We want to do it all at once. And what can we address with a single intervention of addressing multiple things? Like I think that's what you're kind of getting at. So it depends 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 me repeatedly say this, I'm really looking at this as like a prime lifestyle time. So the reporting of distress around this is probably to some extent influenced by any of this, particularly like the menopausal symptoms in the context of everything else going on for these people. So let's take people that are heavier body weight, exercise less, have already have sleep difficulties, have other medical problems, maybe more likely to have symptoms, lower body weight exercising, people that have relationship stress may be more likely to be sensitive to the changes in like their partner being upset that there's decreased frequency because they're more tired or and maybe they can't communicate with their partner and can't teach them to use a lubricant because they're afraid to ask.

2:23:18So you have to get some of this too, like tell me about your relationship, tell me what's going on. Are you working? Do you have kids? Do you have older parents? And then that frames how that I see or what is their health status in terms of metabolic disease and other factors, how I look at what to do and how much do it once and where to start. So there is lifestyle stuff and there's counseling and relationship stuff. Let's take that out for now. I think you want to go to the question of hormones. So, the single best treatment for disruptive vasomotor and collection of symptoms is combined estrogen progesterone therapy and no progesterone if someone doesn't have a uterus to treat those symptoms.

2:23:57For example, you can decrease hot flashes by 80%, 75 % to 80%, even more, at least 50%. And so if someone tells me like, I'm having a hot flash every two hour or two, I'm waking up, I can't get any sleep. And they're opening the window and using a fan and taking a bag of frozen peas in the back of their neck and wearing the most expensive like menopausal pajamas they could find on the internet. And nothing is helping. I'm like, you need to go on hormones. I can't. My mother had breast cancer. Okay. Let's look at whether that's really true. So using hormones for a period of time, lowest dose that treats the symptoms the most effectively is not going to give you breast cancer most likely.

2:24:37I can't promise that you won't get breast cancer because one in eight or nine women get it anyway And you might be jammed like me, but not from a short term use of the lowest dose possible to suppress your symptoms That's the important distinction there, right? Of course you have no idea if a woman's gonna get breast cancer given that it's so prevalent But what we can say with an absurdly high degree of certainty is even under the worst conditions possible Which was the conditions of the women's health initiative where, for all reasons, I'm not going to go into now because I'll have a dedicated podcast that will focus exactly on all the issues around the WHOI.

2:25:12Yes, we should. You should. Even saw in that situation only an absolute increase in risk of 0 .1%. And that was only in the incidence of breast cancer in the women receiving conjugated equine estrogen and MPA. Both products that we are not using today. Secondly, there was no increase in breast cancer mortality. Which by the way, that effect lasted till today. We still follow those women and we can see that no more of them have died of breast cancer than their counterparts. So glad to hear that you're going to dedicate a full podcast to this because there's a lot of layers to this. But the short version is the WHO's oral synthetic astrogens and oral progesterones, which you couldn't use them.

2:25:58But nobody does. There are oral therapies available. They're bioadenical. Usually people are using oral estradiol and oral progesterone that are bioadenical. The doses are different and lower. There's also now transdermal products available. The problem is that there's never been as large in RCT for the length of time. So the shortage from data is showing that there's other ways to have even better outcomes and maybe even no outcomes. And there's also been extensive reanalyses of both the actual data and subgroups. So first of all, women 50 to 59 are very different and people who started hormones.

2:26:31The WCHI wasn't for symptoms. It was for disease prevention. It was osteoporosis and cardiovascular disease. The women were actually asymptomatic. Right. They were older when they started and it doesn't apply to this patient at all. And the data also, I think, are unambiguously clear that if there's any negative effect of the combined hormone therapy in the WHOI, it had to be due to the MPA because the conjugated equine estrogen group alone got better. They had no more breast cancer or heart disease. They almost achieve statistical significance by 0 .2 of a p -value for a reduction in the incidence of breast cancer, and a fact that also has persisted for over 20 years.

2:27:11This is looked at in every subanalysis. So I think you're making the strong point that the reanalysis of subgroup by age, and then we never looked at by symptom indication, and then teasing out the effects of each of the components have even debunked the things that people think are scarier, risky. And that said, we also have similarly research, but not as large groups and not as long, other types of products that are both oral, bio -identical, and transdernal. So what I would say to this patient then is like, I mentioned like in a sort of a slew some of the lifestyle things and there are also some over the counter stuff, like black ho -ho -sh and there's using soy.

2:27:47None of that works as well as systemic estrogen and potentially with progestin therapy. And the reason for the progestin is it protects the universe against endometrior hypoplasia. And I think you need to use it, even maybe very short term you don't, but for this indication, you do. So the venous problem, embolism risk is probably, no matter what you do, it's probably a little higher, probably better with trinsturmmel. And I tend to almost never put people on oral, although there's oral products available, and there's actually a combined oral product. You can probably obviate that to some extent, but it's a low risk issue, and I haven't seen it happen with trinsturmmel clinically, although it's not proven that it doesn't.

2:28:23So these are like patches or gels that are available for these products for both estrogen and there's an estrogen -progesting patch and then you can use an estrogen -liven oral progesterone and it comes in different types of gels and this is a ring that you can use called a femurine. In women who struggle with systemic progesterone, do you find yourself sometimes using systemic estrogen with a progesterone code at IUD to provide? Sorry, I didn't mean to interrupt you. I was just so enthusiastic that you reminded me of that. So it's not a labeled indication, but you can use a progestin IUD for endometrial protection.

2:28:58Clinically, there's some prevalence studies, or risk studies looking at this, I should say, their perspective is the best word I could use for them. And they're really looking at like the outcomes of the number of people who have the adverse outcomes when they use the IUD and they don't point to a signal, although it hasn't been randomized. So there are many clinicians feeling like there's good data to justify using an IUD for endometrial protection. Usually it's the Ohio dose, the Marena. And it's good for five to seven years, although some feel that you could leave it on longer and still get the protection because the levels stay present for some time.

2:29:28And that's a strategy used by many, whether you put it in before they don't tell earth about the protestant or you just decide that. And the theory is that also that it's an alternative, but also might provide overall less progesterone exposure, although the oral progesterone is by a identical, the legal nest, no gestal isn't. So there's back in point about it, but that's a strategy. Now remember, this is for hot for all these symptoms. Now, Now the decision to continue or treat, it's also a very good treatment for osteoporosis, but that's a different conversation. So beyond this view, just going to do symptoms you tried for a year or two, then tap or see how they did, if you want to continue for bone protection, it's a very good drug.

2:30:04So it's bone protective. It's not considered a treatment for osteoporosis as a preventative measure, but it probably also prevents further fracture. We can get into that data too, but... I've done the back of the envelope math just to get on my soapbox here. And first of all, prevention is everything when it comes to bone loss. We don't really want to wait until someone has osteoporosis to whip out the best phosphonates, which frankly don't necessarily have an enormous impact on fracture risk, because while they're increasing bone mineral density, it doesn't necessarily come with some of the torsional qualities of bone that we might want to see in a healthy bone that hasn't gone through that period of degradation.

2:30:43But let's put that aside for a moment and just acknowledge that if you do the math far more women will die as a result of fractures of femur, hip, pelvic bones later in life that could be ameliorated by the use of judicious hormone replacement therapy to prevent them from getting there, then will ever die from breast cancer as a result of hormones. And by the way, it's not even close. We're talking orders of magnitude difference. And this is what I find most frustrating in the HRT discussion, frankly, is even if you discount symptoms, and I don't know how you can, I mean, symptoms is everything in medicine, but even if you didn't care about symptoms, simply on the basis of bone health.

2:31:29It's a real tragedy to me that there is an entire generation of women for the past 20 years that have been largely deprived this therapy, on the basis of very bad science and far worse reporting an interpretation of said science. I couldn't agree with you more that there's a lot of misconceptions about the importance of preventing bone loss and probably we're also treating osteoporosis when it becomes established and that the other options, although there are good ones, have limitations and you don't get the added benefit of some of the things that combine home and therapy has. So there's a few conversations.

2:32:03One is what to do for her now. Like at this point, I probably say it's going to help your symptoms. Let's say nothing else has helped her. She's tried the over -the -counter stuff. maybe she even tried black hoho, she ate some soy. You have to eat a lot of soy every day to make it work. Let's get all that, say she tried all that. And then I'm like, look, this is going to help you. Let's use the safest, lowest dose. You're certainly not going to get cancer from this. You might get it. The other thing is that people don't know that like other things they do are riskier for breast cancer than their hormone.

2:32:30We don't probably have time to get into the comparative data. But drinking... Well, yeah, having insulin resistance, drinking alcohol, exactly. Drinking alcohol more than one drink a day. Not exercising. Being overweight that goes along with having metabolic dyslipidemia, high blood sugar, metabolic syndrome, being overweight, those are probably more important for breast cancer risk than small doses of trans -dermal hormones for a couple of years for symptoms. Now, when you get into continuing, at least past a few years or even through 60, the first 10 years, whatever, that's a different conversation, but like you're already getting at the point that there's a lot of data and a lot of reasons to keep going.

2:33:07And we've all heard some famous friend quote, when do you stop your hormones? You know, some variation of like three days before you die, or I've heard that for a few different ways from a few different experts, including those that used to worry about the WHO. For example, Joanna Manson speak in a number of meetings. She was the original PI on this. Joanne's really, she seems to be the one who has reversed most of the initial sort of fear around the WHOI and I'll be sitting down with Joanne to talk about this. She can speak about it and really analyzing carefully the subgroups, the follow -up data.

2:33:43It's not to say she's refuting what was published. That's accurate. It's just that it... It's the interpretation. Right. She's not the one that said three days before you die by the way. I don't want to misquote her. I just put her in the same paragraph. The one thing that's very clear is that it's the best treatment for symptoms and the North American menopause deciding similarly, like formal experts say, like, the shortest dose for the period of time that you need to matter to symptoms. At a minimum, we need to, like, turn around anybody who doesn't understand that. There's also other pharmaceuticals.

2:34:12You can use SSRIs, actually, for hot flashes, but we already explained they have some issues, and they don't work as well. You can use Clonidine, which has low rates of success and a lot of side effects, but or GABA pentin same thing. Which again, all of those seem so backwards to me because there's no ambiguity about what is causing those vasoma -hooder symptoms. I don't go there unless I'm stuck, and I have to, for a variety of reasons. We don't want to forget to remember that there's other things she's complaining about, and I'm guessing we don't have too much time left, but she's also telling you that she has dryness and discomfort.

2:34:45So does that estrogen you're sending in her system? Let's say she agrees to take that transfer. Does it get to the vulval vaginal tissue? You know, I have some patients who say, yeah, that's fine. I'm a lubricationist fine. I'm not dry. others need more locally delivered and it is not contraindicated to give both and in fact indicated. So there are two main symptoms three I see with GSM, VOLVO Agile Atrophy and General Euromers Syndrome or Symptoms of Vanipause. Vaginal Dyrinus, pain with sexual activity and a collection of genital urinary symptoms, even independent of sex. So you can try lubricants with sexual activity for comfort, you can give vaginal remorcerizing agents which are given multiple times a week, they're available in gels, suppositories, lotions.

2:35:27There's a number of good products out there. Some have hyaluronic acid, for example, some of other chemicals. You recommend it to use those. They help these polymers and other products help draw out some of the moisture and resurface a little bit, but they don't change the mucosa. And then sometimes I throw in some dilators. People have been sexually enacted for a while and the tissue is tight and guide them on that. And then sometimes, first sexual function as an aside, I remind them that they might need more stimulation. So lubricants can be help with comfortable simulation, silicone particularly, although it's slippery, adding vibrators.

2:35:59So that's all for like, and there is some with sexual function, the use that are losing phenomenon. So promoting regular sex activity, even sex with oneself, to help with keeping regular lubrication occurring in combination potentially with lubricants with activity, even with oneself, use of vibratory stimulation to enhance the response. and then vaginal moisturizers for any symptoms independent of sexual activity regularly. That's like the formula. And a lot of women don't even know that. And the algorithms say, do all that and if they're still having pain at a low dose vaginal hormone. And we talked about that there are estrogen products.

2:36:34There's rings, there's tablets, there's cream, there's inserts, and then there's intrarosa. There's also an oral serum that's indicated just for a bubble of vaginal atrophy. Somebody wants to take an oral pill, which is a whole another category. It's called asphena, the chemical's asphemapine, and it has some of the serum issues, but it is indicated. One of the main benefits of some argue it may be good for breast protection in people at risk. But I'm sorry, it does or does not provide systemic levels of estradiol. It's not an estradiol, it's a serum. It's a serotonin esters and receptor modulator.

2:37:08It's a little unusual. A lot of people don't know, but it's FDA -approved. It's not very commonly prescribed, and not that when we choose it. It's indicated, it's an oral serum indicated for yes, the olivateral atrophy causing dysperunia. It's called esphenate 60 milligrams a day. And it may be theoretically, it's not indicated for this, but it may be theoretically useful for people who need breast protection. You know, if they have like a family history, because it's a serum, sometimes a rock's phenose used for breast -pophiloxis. But it's not indicated for that. It might have positive effects on bone, but again, not indicated for that.

2:37:38I don't use it very often. Do you find that the time that a woman was, you know, deficient of hormones, the longer that period of time, the greater the likelihood she will need additional treatments beyond the systemic estrogen? Thank you for asking. Well, so the tissue changes are progressive. So the truth is that it depends when you catch someone. So the answer is the little nuance. So if you catch someone three to five years out, they're going to have more tissue changes than someone one to two years out. So, if you decide that that woman doesn't need it yet, I could just educate her a lot on lubricants, moisturizers, using vibrators for stimulation, regular sexual activity, improve that.

2:38:15But by the time she's three to five years out, she might be the same as someone that you saw. You're not going to prevent the tissue changes five years later. So that's kind of a nuanced answer. It tends to be more likely to be cleats. Sometimes early on, they're just dry. And some of the other things that I mentioned, the non -pharmacologics, work fine. But as time progresses, either the stevechormone, if they're on it, is going to be enough, because it's just enough to leak into that tissue and not have the tissue changes be, or they're going to start to need it, because 5 to 10, 15 years out.

2:38:47And when you get someone who comes to me, it's not unusual, 65 or 70, they've reached the threshold that, like lubricants were working. The other thing is to avoid things that have a lot of chemicals in them, because that tissue is sensitive, like warming liquids, scented things, use things that are a little less filled with stuff. But then someone will come to me at 60 or 70 and they may be at that threshold. Somebody might be 60. I have patients who are like 80 who just need a lubricant. Even though everyone gets the changes, the severity of tissue changes, mucosal, loss of cushioning, decreased lubrication, tightness and shortening, that varies.

2:39:23It's not 100%. Atrophies are 100 % of people but the degree in the severity varies. There's some endogenous hormone factors, whether they've had an o -frectoromy. The uses of stemical amounts probably figures into that because some probably leaks down there. Management of this is yet a whole nother area that I love to talk about too, but very very low hanging fruit in a sense because you can do a lot And it's easier for people to like accept and understand once you teach. There were some barriers like people are kind of like Disconnected so at the Sun unusual like somebody's 30 they have sex they get a satisfaction They have an orgasm not paying much attention to their vulva, the vagina, their vestibule, their urethra.

2:40:02And now you're asking them to like put this there, put that there, use the style later. People don't want to mess with this. Like you'd be surprised. It feels like a lot. I didn't have to do anything for my vulva in vagina when I was 25 or 30. Now I'm 60 and I gotta do all these things for my vulva in vagina. So I'm kinda like, well, you put Botox in your forehead, you put Cream on your face, you know, that you didn't do that neither. It's just the way it is. That's a fair point. Well, listen, Sharon, this has been a really interesting discussion. As I said at the outset, I think it's a discussion that's beneficial to both sexes.

2:40:36I guess there are several takeaways here. So one is there are probably a lot of women who are unnecessarily experiencing some form of sexual dysfunction because they don't maybe realize what's available to them in terms of systemic tools, local tools, therapeutic tools, medications, therapy, etc. And I think the other thing that you've just alluded to at the end is that this is kind of a journey over time. And in the case of women, I think the changes are more dramatic from ages, you know, whatever 15 to 95 than even in a man. And they probably require a little bit more willingness to be attentive to oneself and and be a little bit more proactive potentially during that aging cycle.

2:41:21Again, the obvious ones that we talk about are hormones, but some of these anatomic changes are obviously just as important, not to mention the health -related changes that may be feeding into this, the metabolic stuff. Interesting to know that that's as important as it is in men where it's a little bit more obvious structurally. Yeah, no, I think those are all really important takeaways, and you hit on some of them. I think the most critical key points in healthcare, it doesn't always happen, but I've been hearing about like, pulling out all this education about menstruation in schools in certain states that really worries me, because that's even like the most basic, but like in the community and healthcare education about sexual health and sexual function across the life cycle is really a need.

2:42:06So like it worries me that as we pull back on like the more even basic education about menstruation or STD prevention, we have to be very proactive to make sure this doesn't go in the wrong direction. Like learning about how to choose contraception and sexual function in your late teens and early 20s and know what your choices might be and why. Learning about the impact of childbirth, learning in your later reproductive years, why are you still menstruating but your sexual desire might be dwindling? You know, like how to integrate my brain and my body if I'm like under a lot of stress and anxious and depressed, like should I take a medication?

2:42:39What are the implications for my the overall quality of life as I enter Manopause, what do I do about my system? One thing like with hot flashes, if you're not sleeping and you're exhausted and you're feeling poorly, you're not gonna be enthusiastic, but you're also noticing changes in your vagina, your vulva, your generals, how do I address those? Like don't just lump it all together, like oh, it's Manopause. That's supposed to happen to me because that's what the clock says. And then we didn't get a lot into like much older women, but there is a whole sexual understanding for like the sexuality of older yet women, you know, 70s, 80s, 90s.

2:43:13I get women coming to me with some of the same, but also different questions. People in some of these studies were up to 100. People can be sexual well into their long years. And there's a lot of ageism. I want to end with that. Talk about menopausal sexual health ageism and menopausal ageism. As you get into even older women, past like 70, 75, there's a lot of ageism. And a man coming to a doctorate 80 for a drug for a rectal dysfunction wouldn't be surprising, right? But a woman showing up with a question would be. So that's the last thing I'll say. It's like, here's a long lifespan. There's a lot of different issues.

2:43:48And we need to work on clinical skills, resources, treatments, as well as education in every forum for teaching women how to think about this. We could do a coursepeader. I mean, there's this huge area. Yeah. Look, I hope that this podcast, which covers a lot more content than you're typically given in a conference to speak about, you know, get some circulation and provides the public health message that we want to get out there. And if nothing else, at least gets people speaking to their doctors a bit more and finding their way to people like you, again, there aren't nearly as many of you as maybe there should be.

2:44:21But if there are 600 people of your qualification at a recent conference, my hope is that people will know where to do So I guess let's close on that. If a person wants to find a doctor like you, what are they searching for? What's the qualification? How do they ask their primary care physician for a referral to someone of your skill? We're sort of talking about sexual medicine. There are sexual medicine physicians. Some of those sexual medicine societies was talking a little bit about the international society for the study of women's sexual health. There's the sexual medicine society of North America.

2:44:53And you might hear that from some of your speakers on mail. They'll have find the provider websites. You know, you might want to say to your clinician, like, can I have a referral to someone who does sexual medicine or deals with sexual health? They may not know, so you can go to these society websites. When you're talking about menopausal medicine, I should say like the North American menopausal society has a bigger meeting, there's several thousand, but they also have a finder provider website. If you think you want kind of a subgroup, like for example, a sex therapist, There are websites, for example ASS, ESST has a website with Find the Provider.

2:45:28The physical therapy, there's a national physical therapy website, I could send you these websites. Let's do that and we'll link to them all in the show notes so that there's a very clear reference trail. I think that's faster, right? But the point is that each of these kinds of some groups that I mentioned have Find the Provider websites. But remember, like, sexual medicine specialists, menopause specialists, pelvic floor physical therapists, sex therapists. Those are the buckets. Those are the kinds of keywords, yeah. Well, Sharon, thank you very much for the generosity with your time and your insight.

2:45:59Like I said, a lot I've learned and I suspect a lot that everyone have learned. So thank you very much. Well, thank you very much. Great question. Thank you for listening to this week's episode of The Drive. If you're interested in diving deeper into any topics we discuss, We've created a membership program that allows us to bring you more in -depth exclusive content without relying on paid ads. It's our goal to ensure members get back much more than the price of the subscription. Now, that end, membership benefits include a bunch of things. One, totally kick -ass comprehensive podcast show notes that detail every topic paper person thing we discuss on each episode.

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