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

Episode Date: June 19, 2023

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Sharon Parish is a Professor of Medicine in Clinical Medicine and Clinical Psychiatry at Weill Cornell Medical College and a prominent sexual medicine specialist who has been practicing for 30 years. In this episode, Sharon tackles the topic of women's sexual health, including the conditions associated with decreased sexual function and desire and available treatment options. She explores the influence of sexual health on overall well-being while also examining the potential effects of childbirth, birth control, metabolic health, and more on sexual function and desire. Through case studies, Sharon teases apart the differences between desire and arousal, explains the various factors that affect them, and walks through hypothetical treatment plans for the case study patients. In addition, she delves into the subject of menopause, addressing its impact on sexual health as well as the misguided fears around hormone replacement therapy. Stay tuned for next week's launch of our complementary podcast on men's sexual health. We discuss: Sharon's interest in sexual medicine and the current state of the field [3:00]; How hormones change in women over time and how that impacts sexual function [8:15]; Changes after childbirth and its impact on sexual function [11:00]; The role of metabolic health and systemic vascular health in sexual health [20:15]; Conditions associated with decreased sexual function and the importance of sexual health for overall wellbeing [26:15]; Sexual dysfunction case study #1: A 41-year-old mother of two, the sexual response cycle, and the difference between arousal and desire [38:45]; Medications that may reduce sexual desire [49:45]; The effect of birth control pills on sexual desire [56:30]; The importance of testosterone in women for sexual function and desire, and why the FDA hasn't approved exogenous testosterone as a therapeutic [1:01:15]; Challenges faced by physicians who are open to prescribing off-label testosterone for women, and Sharon's approach in managing this aspect with her patients [1:14:30]; A hypothetical treatment plan for the patient in case study #1 [1:26:45]; The role of DHEA (a precursor to testosterone) in female sexual health [1:32:15]; Case study #2: A 30-year-old woman with anorgasmia (inability to orgasm) [1:38:30]; Resources for helping women and their partners to enhance the pleasure experienced during sex, overcome anxiety, and increase desire [1:51:30]; Two drugs for premenopausal women with low desire [1:59:30]; Why treatments are potentially underutilized for both desire and genitourinary syndrome of menopause [2:13:15]; Case study #3: A menopausal woman with symptoms [2:19:00]; Addressing the misguided fears around hormone replacement therapy and cancer [2:24:15]; Symptoms and treatment of genitourinary syndrome of menopause [2:32:45]; Age 65 and beyond, and resources for finding a provider [2:37:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Atia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you want to take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are, or if you want to learn more now,

head over to peteratia MD dot com forward slash subscribe. Now without further delay, here's today's episode. I guess this week is Dr. Sharon Parish. Sharon is a prominent sexual medicine specialist and professor of medicine in clinical psychiatry and clinical medicine at while Cornell medicine. Throughout her career, she has become a leading expert in sexual medicine, focusing her work on helping patients overcome sexual dysfunction.

She has published numerous articles and book chapters on sexual health and is a sought after speaker and educator on the topic. In this episode, we focus the entire conversation around women's sexual health. So for folks who are curious about men's sexual health, not to worry, next week we'll be launching the complimentary podcast to this that focuses exclusively on men's sexual health. In this episode, we review the female physiology and anatomy in order to better understand

some of the potential problems and treatments available to women that we cover throughout the interview. We speak about how sexual health and sexual dysfunction can affect a woman's well-being, and how childbirth and metabolic health can affect women's sexual health. From there we cover a variety of issues a woman may face throughout her life by looking at three different case studies. Using these case studies, we differentiate and tease apart the differences between desire and arousal. We talk about different classes of drugs that are available for women as

it relates to desire and arousal. We talk about the impact of birth control. We talk about treatments for women who are having difficulty achieving orgasm, including testosterone and DHA. And we of course talk about the role of hormone replacement in addition to many other things. One final point, I learn something with every podcast I do. In other words, every time I finish interviewing somebody, regardless of how well I know the subject matter beforehand, I always come away learning something. But it might be the case that this episode in particular

taught me more that I didn't know relative to any other podcast I can recall. So I think it's safe to say that whether you're a man or a woman, you will learn a lot from this episode that will improve the quality of your life. So without further delay, please enjoy my conversation with Dr. Sharon Parrish. Hey Sharon, thank you so much for making time to meet with me today. This is a topic that is incredibly applicable to more than half our population, because while we're going to be talking about sexual function in women, of course, women have partners. And so by extension,

I would argue this is a topic that is applicable to our entire listing population. It's also a topic where there seems to be a lot of misunderstanding, a lot of asymmetry in attention. We're going to talk about a bunch of those things as we get going. Before we do, though, I just kind of want to give people a sense of your background and how you arrived where you did. So you went to medical school, you did your residency in internal medicine and primary care, correct? That is right. And primary care, meaning with the focus on ambulatory medicine and being sort of a general medical physician,

with a focus on primary care and academic general medicine. But what point during that process did you realize that your interest was in sexual health? I think when I was in med school, really, I was always struggling. It seems like a little bit of a strange union, but always struggling between deciding whether I went to be a general internist, a psychiatrist or a gynecologist. You know, this interface, particularly, although I do, as an internist, I do take care of men's sexual health as well.

This interface between women's health, the mind and the body, behavioral issues, and comprehensive, or for lack of a better word, holistic care for all sort of was always tugging at me in three different directions. And somehow, when I eventually found my way to sexual medicine, it just kind of brought it all together. I did some projects on women's health and then in residency also on various women's health issues and reproductive issues. I worked, for example, in a contraception clinic and adolescent medicine program, STD program. So I did a lot of work in that area. I did a fellowship afterwards at NYU Bellevue

in psychosocial and behavioral medicine in the general medical field, and I worked with then some sexual medicine experts in some projects, and that's when I really moved more deliberately toward the field. And so how does the field stand today? How many physicians are there in the United States if you had to estimate that have your degree of training and clinical focus? These field of men's sexual health is a little more clearly defined. Like there's many psychiatrists,

urologists, and even men's health internists who have like a clear distinction. I think women's sexual health is less clear, but again, gynecologists, some internists who have like a clear distinction. I think women's sexual health is less clear, but again, gynecologist, some internists, family medicine physicians, a few psychiatrists, and then there's psychological therapists. It goes across disciplines. It's a little hard to define, but I can say

that there's many fewer who are clearly identified. I went to the international society for the study of women's sexual health annual meeting a couple of weeks ago, and there were 600 attendees, five to 600. And that probably represents most people who work in the field. There's sex therapy meetings and pelvic floor physical therapy meetings that have others. But if you're looking at the field of sexual medicine, it's not robust. Where if you go to the AUA, I think everybody there, 20,000 people, think they could probably

handle Mali D-Problem. So if that gives you a point of comparison. That's sort of in line with what my expectations were. Let's also just maybe by way of background, perhaps start with what is encompassed in this field. So you've already kind of alluded to it a little bit. There's clearly a super-tintorial component to this. There's also an anatomic component to this, or physiologic component to this. How does it make sense to maybe walk me and the listeners through the background knowledge

of this physiology anatomy so that we can better kind of go into what some of the problems are and what some of the treatments are? With any issue where you're looking at the mind, the body, a general response, a hormonal response, you know, the integration, I always take people back to the concept of the biosecosocial model. I guess you're asking when it comes to sexual response. What are the bio, what is the psycho

and what is the social and what's the contextual? Maybe just for sexual health problems, the brain is a really active organ, as I'm sure you can imagine. We have thinking and feeling, and that probably on a biologic or no physiologic level, translates into neurotransmitters and the interaction

with hormones and pathways, brain neural pathways, neural networks. And there's the psychological concepts of conditioning and learning and unlearning. We warden and disappointment, et cetera, all plays a role. And it's fascinating how that might all interact. There's the general medical state, our vascular system, nervous system, and like systemic medical

issues that might impact those. And there's hormones and they get stimulated by the master glands in the brain, our genitals that make sex steroids, and our adrenal glands and thyroid. So there's a collection of hormonal locuses that play a role potentially in sexual health. And then there's the local genital milieu. And that might include the vascular system, the nervous system, small nerves, the micoza, the surface, and then there are muscles in soft tissue. So all in the genital tract. And then there's a bladder and the rectum, the breasts, which play role in stimulation. So that I

think that that's the big picture. How does this all come together in a three-dimensional concept where you integrate experience, relational issues, culture, and time is really the fascinating part of this field. So how do these things change during a woman's life? Obviously, puberty is a very important milestone, but I suspect also menopause is an equally important transition that is much more abrupt, at least from an endocrine standpoint, than men would experience at the same age.

Yes, so I think there are times when hormones like play a more master role in sexuality and sexual response. What's tricky about this is, and I guess the body's kind of programmed and smart, is that there's a lot of life cycle and life stage things happening, and those are prime times as well, whether one commands the other or not, it's hard to know. Manopause is kind of a longer process than people think. There's perimenopause, there's menopause, there's postmenopause, and there's a lot of life cycle stuff going on.

You know, that's probably the most defining moment for women in that it interfaces with no longer being able to reproduce. There are significant changes in hormone levels like estrogen that affect vaginal, level of vaginal comfort and at the same time, androtens decline that affects desire. And when you're starting up with puberty, that's probably all growing up and getting going. And you're also developing the cognitive skills of relational issues and sexual relationships. So those are two peak times. I have worked without a lesson, I have more experience within mid-liath women, that's the focus in my, often in my practice, and those are the people

that, this is a good time to mention this point. The data suggests, and my experience with this field suggests that the time when we're most interested in looking into it is in those paramanopausal, late reproductive paramanopausal and early postmenopausal years. When you say looking into it, do you mean looking into it? For themselves. So it might be that they have a problem. It might be they want to understand it better. It might be they want to be proactive and preserve their sexuality. It usually is that something's changing and they weren't expecting it and want to know why or they want it to be better. People have a little trouble sorting out It usually is that something's changing and they weren't expecting it and want to know why, or they want it to be better.

People have a little trouble sorting out, like, is it the relationship at this point, is it the menopausal changes overall, is it the sexual function, or is it sort of all of it? And I think that's what makes the midlife sexual medicine challenges the most complex and challenging, but also the most interesting and the most rewarding. I think there's also the most likelihood where women are, midlife women are youthful, they're young, they're active, they're connected,

they're not like some other time in our universe where they're becoming the wise woman sitting in the tent, retiring from childbearing and breathing else. I mean, often women are peaking in their career if they're having these trans variant, a little bit children later, they've got teenage children, college children, aging parents, big careers, bodies changing, and wanting partners, and there's a lot going on.

So, the other more likely to seek attention, actually. We can say a lot about helping them today. I also would like to talk a little bit about how the anatomy changes post-child birth, and does that have anything to do with sexual function? And I guess I want to kind of also, at some point soon, define some of the problems. I can think of three off the top of my head, right? One would be low sexual desire or hyperactive sexual desire. One would be inability to have an orgasm, and a third would be discomfort or pain, clearly a big problem for women postmenopause due to vaginal

atrophy. So those are three things I think we must address today. Do you think there are others that are important enough that to a non-expert audience we should also present? I never want the forgotten, we'll call her sister, the forgotten sister, to desire as a rousal. And having women understand that when they come to me, they're like, I no longer get turned on. And I mean, is it about wanting?

Is it about mental or subjective or cognitive sightment? Is it that bridge between desire, thinking, and actually being in a moment and being excited? Or is it their genitals are no longer responding? And then that sometimes is uniquely, can be tied to orgasmic difficulty. I see. And I think it's really in the field, it's an area

of discussion and sometimes even controversy. I think for women, it's hard to separate what they're asking for. Sometimes women come to me and they say, like, I know longer one sex, but everything works okay. Sometimes they say, like, I love this person or I want to have sex with myself. That's not the problem, but nothing's turning on.

Like, I'm not feeling anything. And learning about that for one's body and being able to articulate that, and I think it gets commonly tied to orgasmic changes. We can certainly discuss whether they're the same process or different. You know, childbirth, I don't know if you want to talk about that now.

Yeah, let's talk about it just because I think we've already established there are these two enormous hormone swings, right? There's the swing on, which is reasonably quick, and then there's the swing off, which is relatively abrupt, but as you point out, it's occurring over years, not months. It's also worth mentioning, it's the estrogen and progesterone that are coming off really quickly. The testosterone is kind of coming off not as quickly.

We can maybe come back to that in a moment. Let's talk about anatomy in a minute because I'm guessing that women have very different experiences with childbirth and presumably a vaginal delivery is different from a C section in terms of the impact it has on the pelvic floor. By the way, that's something we should define for people so they understand the anatomy of the pelvic floor. But anyway, yes, let's talk a little bit about how that might impact any of the elements of sexual health in a wounds life. You know, it's not the time typically

where the sexual problems that people come to me for. I'm also not a gynecologist, kick in and stay. They tend to be for some women relatively transient, postpartum, but it also depends on like, how many kids and what age and all of that. So let's talk about the pelvic floor for a moment because that might impact with childbirth. So the pelvic floor is kind of a mysterious concept,

but if I had to give it one concept, it's the idea that it's a basket of muscles. And they attach from various parts of the inner pelvis, so like onto the pubis ramus, onto the ischial spine, onto the bones around our pelvis, internally and into the walls, and then also into the organs, and they create a basket around the uterus, around the urethra. Like, for example, there's a sling around the urethra

and the anus that holds it up, and also holds up the uterus, and they also provide motion during childbirth. They allow for the childbirth process. They're quite active during sexual activity. They contract and release. They help us with urination, with defecation, and so forth. And it would be easier if we had like the opportunity to show people a diagram.

But I think the best way to understand is... We'll include diagrams in the show notes. That would be wonderful. The best way to understand is it's a basket diagrams in the show notes. That would be wonderful. The best way to understand is it's a basket of muscles that hold things up and help things move. And when they're not working properly, they can result in, for example, difficulty with your nation or incontinence or sometimes pain during sexual activity or changes in orgasmic function. That's sort of the broadest concept we can get into the nitty gritty of disorders. But I guess you were asking about childhood.

So with pregnancy, those muscles stretch a lot. Things are expanding. Sometimes, women will notice improvements actually in their sexual function because if they've had type pelvic floor muscles that are causing changes in sexual response or even pain, it sometimes gets better. Sometimes with deliveries, they get stretched, they get irritated, they get torn. It's rare that any of those things I find persistent, unless there was really a birth trauma.

It often gets confused with what happens with other things during childbirth. For example, apesiatomies, lacerations, suturing, where there can be scarring, there can be inflammation around a suture line, there can be et cetera. So I think the general process of muscles stretching during childbirth is one thing during pregnancy it's different and any other related injuries are trauma during the actual birthing process of vaginal livery is another. The

only other thing about C-section versus vaginal delivery this could be a whole another topic but in general vaginal livery is a better for women. Yeah, same more about that. Again, I'm very ignorant of most of these topics. I think people have this idea that they're going to preserve the size of their vaginal canal or prevent their pelvic floor muscles from stretching, etc. And the truth is that most of that goes back. You know, it's not all that unusual for women to just have a like a transient difficulty for four to six weeks and things improve. But having surgery and abdominal surgery, you know, you're opening your abdominal wall, there are muscles, there's scarring, it sometimes leads to other kinds of later difficulties that

people don't anticipate. And it's also safer for the mother and the baby not to have surgery. What is the, for lack of a better word, incidence of C-section versus vaginal birth today in the United States, do you know? I don't know that number. We could easily find it. I don't have it off hand. I'm not an obstetrician, I don't deliver babies. But the biggest concern that I hear in sexual medicine discussions is that people have this idea that it's better for their sexual health not to deliver babies vaginally.

Maybe that's the most important message. And that the number of C-sections has been going up and is alarming, and that routine scheduled C-sections to preserve sexual health for a whole number of reasons isn't really better for women, than that might be a myth. I'm not an expert in childbirth or in delivery, because I'm not a nutrition organicologist, but if someone asks my opinion, I say, like,

have your baby vaginally, and most people preserve their sexual function, that's not a peak time. The bigger problem actually is postpartum that comes up in my practice. People are breastfeeding. They're essentially like postmenopausal women, because their hormones are dipping way down. They're still keeping ovulation off by breastfeeding.

They're experiencing vaginal dryness, irritation, sometimes changes in sex drive, and they're not aware of the effects of breastfeeding on sexual function, on a vulnerable vaginal changes and sexual response. There's easy things to do for that, sex drive and they're not aware of the effects of breastfeeding, unsexual function, unavailable vaginal changes, and sexual response. And there's easy things to do for that, especially the vulver and vaginal symptoms. Can you give me a sense of how high the FSH and LHR during breastfeeding?

You're asking are they organically comparable to a post-menopausal woman, I guess, is the question? Yeah, and is estradiol sufficiently low as well? Yeah, I'm trying to understand how low estradiol is, how high FSH is. I think there's so much variability. So it depends on, like, if you're completely breastfeeding, you can see it in the ovulatory,

women can look postmenopausal. Wow. That's defined as an FSH over 35. Most women aren't fully in ovulatory. They're having irregular cycles that are ovulating intermittently. So I think the numbers are all over the board. But you can have ester dials as low as like 20 or 30, right?

Yeah, might as well be in menopause. Yeah, and everybody's like HPA access and sensitivity to lactation is a little bit different. And sometimes women aren't breastfeeding completely. And the correlation with how much milk they're making and whether they're ovulating isn't clear cut either. What I would say is if you're breastfeeding and you're not having men's teeth for six months, the likelihood that you're hormonally similar to a postmanopausal woman is higher

and that you're completely an ovulatory and that if you're having dryness and difficulty and pain and low sexual function, then you should talk to your doctor because there's things that we would do some of the same things that we'll probably get into in a little while. We're going to talk about that because I guess you could make the case that if there's one thing we want listeners to take away from this program, it's that there's really no reason for any woman of any age to be struggling with vaginal dryness regardless of how far she is into menopause or whatever. We have the technology to solve that problem all day long, right? There's a number of approaches, and that is the most treatable or the most manageable amongst

these conditions, and the algorithm or the options for that are the most clear cut. So I'm a general internist by heart. You know, I'm a card-carrying general internist, although I've gotten quite specialized in my work. So some of the my colleagues say to me, well, you know, you're not doing procedures, you're not a gynecologist, you know, what's the big deal? You just come here and I'm a lubricant, I'm a moisturizer. So some of the my colleagues say to me, well, you know, you're not doing procedures, you're not a gynecologist, you know, what's the big deal? You just come, you hand them a lubricant, a moisturizer, maybe some vaginal hormones, what's the complexity of the concept or the consult? And what it comes down to is we're going to really, really don't understand the whole thing.

What's happening in their body, the difference between the things that we can offer them and how to put them together and use them, and that had to integrate that into their sex life. And that's what I would say, like the number one concept that I get or referral that I get is to help a woman walk through that. So one other thing I want to talk about before we leave the sort of basics and the foundational stuff is the role of metabolic health, slash systemic, vascular health. So again, in men, this is really clear. So for example, higher incidence of AACVD, higher incidence of ED, similar concept to endothelial damage, higher incidence of type 2 diabetes, microvascular disease, higher incidence of a rectal dysfunction.

How clear is that relationship in women? In other words, do the things that drive glycosylation of proteins and microvascular disease in other parts of the body do they contribute to sexual health in women as they do in men through the ED pathway? So I'm glad you brought this up because this is really an emerging discussion in the field. For those that are not aware in men, there's kind of a really clear literature and guidance that if a man is having ED, it may be a mirror to small vessel,

cardiovascular, so we have a vasco disease. And we can use surrogate markers like looking at doppelished studies in the urologist's office of P. Nile and General Bloodflow and then send them for a coronary calcium score, even a coronary CT, right? And look and see if we can see those correlations. And there's good evidence supporting that they mirror one another. And so if a man has erectile dysfunction and sexual dysfunction associated, they should have a cardiovascular assessment. That's sort of the

emerging, those are discussions. Just so folks know, a Doppler study is a study that uses waves to look at blood flow through blood vessels. And it's very helpful when you're looking through these sort of smaller blood vessels that you wouldn't otherwise be able to get a good look into. And so I think before we got started, I was telling you, I just had a two day meeting where this was the depth of the discussion. Where are we with understanding the presentation of erectile dysfunction as a market for cardiovascular

disease? And if someone has cardiovascular disease, what kind of recommendations should we make about asking men about sexual function? And then what do you do about it? Do vasodilators to medications that PD5 inhibitors that dilate the small vessels work? And my participation in this particular conference

was about the discussion of, do we have similar measures in women? So first of all, if someone comes to me and says like, I have no genital sensation, does that mean that she has vascular disease? I mean, there's also nerves there, but it's really not as clear cut, like a man comes in and says, you know,

I don't have an erection. Women like, I don't feel, you know, I can't be sure that exactly what it is. There's been some research looking at using something called literal, codler, doppler, ultrasound, or CDU with assessment of like the blood flow, which is called the puls codler, doppler, ultrasound, or CDU with assessment of the blood flow, which is called the pulsatile index, looking at resistance to blood flow

as an objective measure of how to assess a rousal in women. So right now it's just that the level of the lab or research, it's not really being used clinically except in a very few selected practices who also research this. If someone comes in and says, I don't feel, can I put a literal doppler on and look and see, yes, that's the explanation. That's one thing. The second thing is how well does this correlate with the risk factors that we have seen in men,

things like metabolic syndrome, hyperlipidemia, diabetes. And if someone has those things, should I then be asking her about chlial sensation and doing testing, both to understand her sexual function and also as a mirror for her systemic blood vascular risk. Again, we're starting to study that, but we don't have clear information. There's this concept called the female genital vascular district, and does that whole area, the larger vessels and the small vessels, does that give us a correlate or a window? You know, can we use that again as markers for small vessel disease? And then vice versa, like if someone says to me, you know, 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 clitoral doppler testing? There's no research on coronary calcium scores or coronary CTs on women and their correlate with sexual function.

And can we use these both as mirrors of sexual function and as predictors of other issues, other 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 puzzle, 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, but 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 cleavaclear 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.

So we doesn't have type two 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 he doesn't need his sealis 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. How's 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. Like 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? There's a couple ways to look at this. One thing is, most of the research, I guess we're talking about women today, 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 in 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. It probably has 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, 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

if they have permission. That's a good reason for me. Because sometimes it's like an afterthought, okay, it's okay, I 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 and they help them with their homework. But if it's like, okay, I can't have heartgent. 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. We could go back and clarify if you wanted to hear

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 hypertrageless 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

isn't as 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, then clearly the severity of cardiac disease. And 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 things like that, or their feternum, and it just makes them negative, rather than their blood sugar control. But I think that part of the problem is we don't have as good research. And then there's the whole bucket of genital urinary symptoms, menopausal symptoms, and cancer. We haven't even talked about cancer yet.

Breast cancer, gynecologic cancer, cervical and urinary cancer, or barian 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. And 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-artisanal desire disorder, which is more like a diagnosable condition or distressing low desire on overall quality of life. And 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 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. Practically 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 ask 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. You 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. You 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 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. And when women are given that permission either because they're being interviewed in the study or somewhere in a doctor's office or 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 an afterthought in your life, because, 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. And 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 that 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-child-bearing 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 and area for discussion. So let me start with a point that I make often.

I mean, women who are a 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 it. And when you have postmanopausal, vovovaginal 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 Manipause Society and International Society for the Study Women's Sexual Health about, I guess it's almost a decade ago at this point. And 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 a terminology, genital urinary syndrome of manopause.

So Volvo vaginal atrophy 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. And 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 hormones, 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. 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.

And so the challenge in the area is, first of all, not medicalizing this too much and making someone feel sick or you give them things that make them sicker. And to balance that for lack of a better word, lethality, therapy, balance 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 numitrile cancer, or you give astrotid 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.

We could get into the discussion about whether or not there would be improved solongevity. 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 arousal 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, I just don't wanna 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. So her kids are 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 point is, she's- I have reasons for that. She's pre-menopausal as the point I'm really just trying to get at. Right. And that's it.

And she doesn't have tiny kids waking her up. 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 her? 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 how to organize 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 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. And 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?

Like, so- Can I ask a question different patterns for that too, right? So, I've got a question that I've been waiting for. That's a different way to have it. Sure. What comes first? Desire or arousal? Desire comes first, does it? Or do you have to have some arousal 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 aroused. And so maybe they thought like the interest in having sex was about being turned on or being aroused, they didn't really get to distinguish 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. And 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 have 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 in 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 it 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 because her kids were 10. I wasn't letting her have kids at 25, but some do. Okay, good point. Her kids, when she said they were 10 and 12, I was just trying to be realistic. The other thing is I feel like it comes up in that, if it's not late reproductive postmanopausal, 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 argument. 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. You know, there's a lot of variation on that.

We could talk about a different patient where they say like theoretically, I really want to be with this person, but I know that like 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. Like 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, but 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, I 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 and 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 in a Rousal, as one thing,

called female sexual interest in a rousal 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. And the upcoming ICD or the International Classification of Diseases is gonna maintain separate coding 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, it's 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 jump in psychological and psychiatric offices, that for women, it often is interchangeable, like it can be. It is still separate for men. Do you want to dig rest for this for a moment? Because it's interesting. I think it resonates for people. And then we'll come back to what we would, 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. And 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 going to be great.

And that when you 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 feelings 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. They 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, your heart rate's going to go up, your nipples become a rack, 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. So 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 going to feel close, one of my favorite expressions from one of my own long-standing patients, is the afterglow 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 desire and ralza 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. So there's a book out there, for example, I mean, the ghost who wrote a book called, Come As You Are, some of the work of Lori Brado, 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. And 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 we're 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. How 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 engorged? 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 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, but women orgasm. Can we put a pin in that and come back to that? I wanna 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.

So it's 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 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 arousal 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, anti-depressants, but all psychotropics, all categories of psychotropics, and these days, people aren't just not antidepressants. The 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. It's not all drugs are the same. It is a class effect, 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? So the classic SSRIs, most of them, fit in that.

And the bundle together, or they cluster together, somewhere around 35 to 40% of what we call treatment emergence, actual 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 to use brand names

because people know that better, or genetics. So pro-Zach flu, I'll do use both. Being mindful of this. Prozac fluoxetine, searchling zooloth, paxyl peroxetine, those are the SSRIs and probably escatologram,

lexapro and citologram. They're probably similar. That said, I have patients who say like I develop low-dysarm prozac or I have difficulty with orgasm on searchling, on Paxil, but not on ProZac. So we sometimes try a few,

if I think an SSRI is the 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. So 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, you know, 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 dysfunction. So then there's another category, the SNRIs, the serenergic neuro-upendepin drugs, which you know you're familiar with.

There's more variability in the data on that, so there's deloxetine, there's venlofaxine, which is a faxer, which is probably the most commonly used one, and then there's pristique, which is desvenlofaxine. They're probably, all of them are probably similar to the SSRIs, but venlofaxine 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. And so teasing out the sexual dysfunction and the dose dependency

is a little tricky on that one. But just keep that in mind. And then, Des Vennel-Faxing has some data suggesting it's less likely to cause sexual dysfunction. And probably has to do with the chemical composition and how it's different than ventilifaxine. Then 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 drug. 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 lousy zone. Though I have some- Best data for fewest sexual side effects. Lack of sexual dysfunction. The problem with the research on the three newest that seem to be the better, that is Desvenlo-Faxing, Voriacetin of Velazodone, is that the 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. It 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

of people report with that and why that is a little unclear, but probably the dopaminergic 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 want to forget. So there's some research that's come 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. I 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 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.

If 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 they're depression, it's not better because depression is associated with sex and 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.

Don'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 that.

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. But 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 raised this, Peter. So confusing area also. There's like 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 orthoever patch and the ring, like the newver ring, right? And those combine and there's a whole bunch of different types of these. But the idea here, what are you doing when you give contraception, 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, it'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 vestibulidier, a vestibular itus, that 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. And they can develop a vestibular denier, meaning pain and dryness and almost look like a postman of a woman when it comes to that. That's one issue with contraception. It's probably that number, you want a number, the work of some of my colleagues in this area who do sexual pain and vestibular deni work say it's somewhere around 10%.

Meaning 10% of women that are receiving systemic... Oh, users. Okay, who are receiving systemic growth? And that it's probably similar with rings and patches, but it's not as well documented. percent of women that are 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 dose 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 microgram pills as opposed to these ultra low, like the 20 micrograms. Like is low, low, eastern 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 earth and troll pills is that it can 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 neurotransmitter and the mix that leads to sexual dysfunction and low sex drive. Then, finally, and this is probably more important

as we'll 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 the lowest dose estrogen. The other thing is it depends on the angiogenicity of the birth and toll pill, that's yet another issue.

And there are angiogen receptors in the vulvar vaginal tissue. So that may change sensitivity or even lead to pain, that's yet another issue. And there are androgen 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.

And then finally, and this is like a whole other thing. What do you do when you send all that hormone to 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 like the same with first and then false infregnancy 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. I 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 Hydro-Sperth and 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 to low desire.

Now, 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 Androgens, that change sensitivity, and that might impact desire, but that's a secondary state. And we're also gonna, when we talk about testosterone, we were talking about how it doesn't like a broccoli change 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 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 up here in the 40s for women, right? And then it kind of goes down, like, I wish I could do it better, but it declines.

By the time you're in 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, free testosterone may be significant in that she'll come and say, I like, I have no sex drive or I have no general sensitivity. That's kind of an important thing that most people don't tell their patients when they put them on a birth and 12 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 have, you know, 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 Panser in like 2000, something like that. And 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 that six months, the stopped users, the previous users, we're 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. So 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 energy 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 Albumin. There'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. the 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 SHBG, and the measured albumin. But 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 and 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 pre-testosterones 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. There'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. You 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. But the theory is that the most important place that testosterone acts as in 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 the formula of desire, testosterone is metabolized, and that it interacts with brain neurotransmitters to turn on pathways of desire. And when it drops, it's sensitive. Like if you look at the early work of Helen Singer-Capplin,

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 metapausal satisfied, but not invoking lethality and keeping her safe and 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 in 2000, 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 hiring her free team 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. Or am I gonna 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-menopausal and she's demonstrating. So we could go on and on with where this leads us. I think we want to 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. I think where we're arriving organically is actually quite a common phenomenon. You know, I've made this point on a previous podcast.

I think when I was on Andrew Heuberman'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 woman'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 desolid.

Where as estrogen is reported in picograms per milliliter. So 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. So 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 estrogen. And then there's this idea that estrogen supplementation improves sexual function. And that's like a whole another 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 gonna line those up and stack them here in a minute. But 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 the 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 the gel didn't find a benefit. I can come up with several reasons why not. But the trans dermal testosterone, it began with an eye. I don't remember the... In trinza.

Yeah, in trinza. There was a Johnson and Johnson patch, 300 micrograms. So even trickier, when you think of these numbers, it was a 300 microgram patch. People 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. That study was, I think it was also, I'm using the 2000 a lot, it approximates it. It was actually Jen, Chair for the Newling 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, 27-38, something like that. It'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-pubed sexual desire to solar or sex driver libido. And it showed positive improvements. And it was based on both self-report,

satisfying sexual events, et cetera, as well as other phase responses, arousal orgasm, overall satisfaction. And it showed really no adverse effects in the short run, but they looked that and other data looking at, like longer term safety studies. And we can talk about some of the other trials in data too, but it looked at intermediate cardiovascular outcomes,

cancer outcomes, and metabolic outcomes. And 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 percent 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.

It was brought to the FDA at that time. And the issue wasn't efficacy. It 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 with low desire.

And 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.

So 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, you know, hypergonatism versus sexual dysfunction, 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-out of your safety window because we've already established over decades that exogenous testosterone at physiologic doses is safe. So 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 libige, you asked me about to emphasize this clearly, applied to the first drug. The libido gel, you asked me about that, it never made it to the FDA. They withdrew their applications and so forth.

I'll talk about why. You didn't have efficacy, right? Right. It was called libido gel. They looked at the data for out to five years and had like seven years of women patient data research. And it didn't show any hits for being unsafe. 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? Because the concept has already been proven, right? That we know it's, 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 prove something at 24 weeks. So this is

the conundrum that we face. Like, this is the problem. There's only one place in the world that has a government-approved product of testosterone. It'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. 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. So 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 have 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-product sexual desire, being the primary outcome, and showing other parameters with improvement, like arousal orgasm, satisfaction, etc. And 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 in lesser in Australia that we should command for our patients. So yeah, it's really

and 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 man, sort of 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. Those are 200 milligrams per milliliter and you can't get enough into a need, like it's basically you just need what's in the 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 wanna 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. The way, for example, your Vavelle dot is FDA-approved as top-glestrutin. 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 in 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 Andruge, and when Goldstein was involved with this work, looking at like creating normal ranges. So 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's the best range. So somewhere like, for example, 28 to 35 or 28 to 37, with a standard direct total testosterone assay. We didn't talk about what you should measure in fall. We can come back to that. And that was what they found was safe. And an 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. The data I just have in front of me is that it was 46 studies looking at 36 of this 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 this men out, so it didn't meet the criteria. We have lots of data. It's not lacking. There's probably even more that didn't get into this men's house, so 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 that you were speaking about. 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 try. Right. So you need to use one-t 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 it testosterone.

You treat a syndrome. That's the first thing. You treat 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, is I expected 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 and female doses as opposed to compounding. 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, 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 prescribed a year, 30-day supply, for example, of the tubes, the 1% testosterone tubes. They go to the

pharmacy, the pharmacist rejects the prescription. They're not covered by insurance. The 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 onto your body every day, and then we'll do a blood test in three to four weeks. That 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 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? Do 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 badaq and outer thigh, the back of the calf, just so it 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 herl 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-casing contact, it actually can transfer. And it's not thought to be insignificant.

There are two important points for us to all know. It can transfer. So you want to put it somewhere on 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. The 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 that you can consider this 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 you're pregnant, the testosterone is not going to 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. That's one of the big reasons, I mean, and we didn't get back to this

with the all contraceptive patient. 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. You'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.

So, let's say that's what I decided. I look at the biological, psychological, and social factors in this woman and 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.

And most women don't have a problem. So if you ask me what should I take, you have to talk to your doctor. What should I use and how you need 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 birth fatalities, et cetera, worldwide. They liberate women all across the world. We don't want to, like, say, nobody should take birth and child pills. But for this discussion, if somebody has a problem,

that's something you can change. And 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 non-indodging 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. I 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 hand, I'm 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 gonna 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- Well, also have 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 worked 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 tells 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. We 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 that if they're not having symptoms that are improving to see that we're giving 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 matter a total T. We didn't go through this in 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. They're 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 that's the bioactive component. To us, it's a very complex, what now is called intra-conology.

It hits the cells, it gets converted into metabolites, antishidion DHT. It enters the cell through the antiterm receptor and has both genomic and non-genomic effects. Non-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 and is... And I believe you can specifically order that. So we do order LCMS when we send our patients... I don't know if people know what that is. 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. That'd be like, that's impossible, right? Normally a male estrogen level might be 25 to 40. We'd see guys with like 200. That'd be like, that's impossible, right? Firstly, there's 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. You send him to get an LCMS and it comes back normal. So all of this 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 DHA. For folks who might be familiar, DHA 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. The simple version, which is good right now, is the DHA is a precursor. So why not use that and then make testosterone? So testosterone gets metabolized to things, for example, like five alpha DHA, which is probably the most potent metabolism, metabolite, and a rheumatase test or dial. 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. Safety has not been really 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 mattering in pica grams for amelis. Pica grams for amelis, 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, and 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 good control data on this. That said, there is very good data supporting the use of a vaginal intravaginal DHEA. The chemical is called prostarone, the brand is called intrarosa. Basically, it's

like a little suppository, it's used for Volvo vaginal atrophy, resulting in genital urinary symptoms of manopause, and the indication is just for renear pain, post-menopause. 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 androgens and then eventually to estrogens at the intracellular level. That's the theory of it, right? Because again, remember, DHA is a precursor. How do you decide, Sharon, for a woman who's presenting with a pretty common presentation? Whether to give estrogens. Whether you're going to use an estrogen suppository 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 DHEA 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, vaginal, estrogen products that help with dryness and pain, sexual activity. And then DHA, the intrarosa product, is an option. And so the standard practitioner will start with an estrogen product,

and if it doesn't work switch to intrarosa, 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 will 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 endometriol around breast cancer or clots. So it has to do with both endometrial and breast cancer and vascular thrombolembolysm and there are a few other things thrown in there. The idea is that they're applying the risk factor data, primarily from the WHOI 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, you know, 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 Astridid, but they'll use this and there's no real rationale, there's no proof that it's any more or less likely to cause any cancer at all. The other issue is that in cancer survivors, it doesn't have a 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 forectomy and doesn't want to go on systemic hormone therapy, and I know that her testosterone levels and her androgen levels have plummeted overall because over the overy, 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.

We didn't talk about this. So in every woman, half of your, about half of your antigens are made in your adrenal gland, and half of your ovary. 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 ovars out of the 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 angrogen removal, abruptly. So that's someone I might say,

and they're not using systemical ones, I might say, let 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 inorgasmia. 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 inorgm is. I'm really teeing this up so that you can explain what an orgasm is because in a male it tends to be somewhat more binary.

I'm curious as to how you would counsel this woman. 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 or there are 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. We'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 female deposit 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, Peter, because a young-ish woman, but old enough to start realizing, like, hey, I'm 30 by now, like this should have happened. You know, or is there something wrong with me? Sometimes they don't care, but they think there might be something wrong with them. Sometimes they're like, you know what, it's

enough. I want one of these, you know? 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 had anorgasm 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. And 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 on 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. It'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. There's sensory input. 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 muscle 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. Like, 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, vasoactamin, testinopolypeptide, there's some involved in nitric oxide and CNP-likein men contributing to both vasodilotation, 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, measure, pelvic floor contraction, they may get secretions, and then they feel the teviden orgasm. So 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 it'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 within 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. I 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 nother 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 arousal and then 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. Where 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 or... No, I find this to be a totally fascinating topic 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... 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. It's that they don't feel like they're getting that overall like sensation and peeking 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 sum R and some R, 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, but 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. This is from Mary. The thing about secondary orgasm to know 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 a neurologic condition or something. And it could be things like,

one of my colleagues is really into the nerve damage from spinning classes. Now, that says me, don't go out and get rid of your peloton, but in men, nerve damage can blunt sensation and may interfere with it. So 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. This is why I just fake it in these bugging me, and I'm coming here to see if I can have a real one. And I've heard that. And, you know, sometimes I explore it further,

I never accept the answer at face value. I'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, okay, 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. Don't worry, it's normal. Go away. Someone's come to me, so we look to see are there strategies they could do to have it. So there are multiple kinds of orgasms. 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 total stimulation, about 33 vaginal and 30 have flexibility. Now what techniques for reaching orgasm vary widely across women. Some women can have orgasms 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. Other women through the thrusting of the

intercourse and like there's again the question, where's 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. 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 start with. Whether it's clear-to-roll vaginal, or intercourse or not, it's more about what the stimulation patterns are and how much they've explored learning about that. That'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, as 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.

What 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 we've been talking about. Primary and regasmia tends 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. But 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. It people in the field of hurtful, called the preside study. It was sort of the largest population-based study. It was a 31,000 women, a 50,000 survey,

31,000 women reported. We still report 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 side? 18 to like 100 to like 99. So all women effectively.

But midlife, all orgasmic disorders midlife when women are most likely to report it, but primary orgasmic tends to be the most likely reported in the younger room. So 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, intervenes.

So let's go back to this woman. How are you going to do the workup? So, I'd say it's 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 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? Does she have a partner? What does she do with her partner? You know, 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? You know, like I'll get into what her knowledge about and what techniques for stimulation

of she used herself, what is her partner's time and what she able to do in terms of communicating with her partner. So the real question is does she know what stimulates her and can she teach or train or ask her partner to do that for her if it's in partner sex? The 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 don't have any pathology.

So if you don't have diabetes or vascularism, many women need more stimulation with age, even if you don't have any pathology. So if you don't have diabetes or vascularism, many women need more stimulation with age because this sensitivity goes down. And 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, 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, the side, for example, around the vestibule, the sides of the clitoral hood, just inside where some people call the G-spot. These are where the neurovascular bundles are concentrated. That top of the clitoral hood is actually very easily irritated and not doesn't like these puffed very much. And like some partners are sitting there rubbing, 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 for stimulation. So I send people to books. There's a number of books and we could talk about those. So that's where bibliiblio 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 in still a great book. What 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 Leibhlem has a couple of different books. She's a sex therapist who's no longer with us yet, an unfortunate accident, but she's written several different books. She's a sex therapist who's no longer with us yet, unfortunate accident, but she's written several different books. More 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. I'm like, oh my god, yes, I guess. So sorry, the website is just www.omgyys.com.

I just Google it and it pops up. OMG, YES, oh my god, yes, I mean, we'll just say it, that's what 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. I 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... Right, it's designed for female stimulation. But it could be for the partner and... It could be for the partner just as much for the...

And sometimes it's easier for someone to sit and watch a video with their partner than to have to show them themselves. So it's not uncommon. They'll say, well, you could start by yourself and figure out which videos you might want to watch with your partner. You know, so that's another example. There's 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. For an orgasm, the sex therapist use much more explicit techniques. So they use things like directed masturbation. 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 service. And so the techniques for learning about orgasm with a sex service, for example, directed masturbation, it's kind of some of what we're talking about, but they might instruct them more. These sex service these days, it's not like

if you saw again, masters and childs, and 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 may 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 will develop a lot of anxiety. So and that makes the problem worse. They'd be developed like what's called spectator 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. And 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 they enter a sexual encounter, they'll have an intrusive thought. And maybe there's mixed in PTSD.

Or there was very strong religious prohibition or cultural prohibition. And 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.

So I was thinking we were gonna go there with that 39 year old orald, we 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, well, 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 do this too in your work is help people look at how their life's startless. So 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 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, and you look at modifiable medications, other things you can change. And then if you reach the point where you're like, I wanna use something explicitly for sexual desire, in postmenopausal 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 olfrec music a young age, early menopausal, post-menopausal women who are just stressing low desire. And then, you have to, of course, do inform consent when you do that. Now, for pre-menopausal women,

who we reach the same conclusion, like, there's nothing I can modify or nothing obvious, we do have two FDA- FDA approved products for this. And strangely, they're around and they're available and very few people, when 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'd me just explain what they are. like many people have. I have not. No. 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 FlowBanserin. The brand name is Adi, ADDYI. And it was like a lot of these drugs. It's a centrally acting drug. It acts on serotonergic 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 Serenetic receptors to B and to C. And that region's specific effect seems to be

Prosexual. We studied for depression, but discovered to be helpful for low desire. Kind of like Viagra was studied for blood pressure. Yeah. 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 centrally acting drug could be helpful. It's FDA-proved. You're supposed to kind of rule out this other stuff and manage all the biopsychosocial

factors before you consider it. That said, like you use the same criteria 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? So 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 proof since 2019, it's been around. There was a long road at 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. And for some time, it had a REMS,

we're 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 pharmacist 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 in 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. It's similar in class to SSRI's. 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 it out four weeks, but usually they say give it 8 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 were a little complicated, 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. And 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 and whether we stop and I can answer questions about that. Again, the side effects are similar to SSRI's, about 10 to 12 percent of people get dizzy

or tired, but that's fine if you take it at night. Dry mouth, unhandful, it's as 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, it is being looked at and it sometimes uses 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. That's a whole

another discussion about what to do with treatment, emergency sexual dysfunction. We talked a little bit about just changing drugs or switching or adding repropanon. I don't do this first. So that's one drug. I don't know if you want to 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 Bremelanetide is the chemical. The brand is called Vylesi. These are both the only drugs available. There's no generics out there. Their websites have good information for patients. This one is the complicated one that I'll tell you about. It's a cyclic, seven amino acid melanocortin receptor agonist with a high affinity for what's called the type form of melanocortin receptors. It's an analog

of MSH, which is melanocyte stimulating hormone. And what it does in the end is it acts in brain pathways that stimulate dopamine or allergic pathways. So it's a direct hit for desire, right? The other one is a little more complicated in like cooking, you know, you're like sprinkling a little this receptor and that receptor. This one hits the dopamine or allergic pathways. It's given on demand as a self-injected treatment. Injected.

Yeah, so it looks like an FEPA on a little bit. You have to look at a picture on the website. I wish 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 have 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 until like your abdomen or your thigh, like a thick muscle, and it takes about five seconds to go in. So you say 1, 2, 3, 4, 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. This is where this bridge between desire and arousal comes.

They start to feel like, hey, you know, I'm feeling kind of interested and turned on and then 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.

How much does this drug cost? Full of cancer and 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 full Banserin, 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 you 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, there'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, 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%. It's up to 40. And then it's down to about 8%. 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 morning, seeing people notice it does sort of last for at least 12 to 15 hours, maybe even 24. Or just lay down some people prescribed like a dose of anti-nausea pill with it for the first dose or for a couple of doses. I don't find the nausea is 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. If 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. You know, do they want an on-demand? So the other thing about this, I want to mention, is there is a rare occurrence of focal hyperpigmentation, about 1% in the clinical trial, when they used it more than 8 times a month. But we tell people probably to stick to four a month to limit that risk. And sorry, hyperpigmentation at the injection site

or just in general? No. Face, ginger, of a breast, 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. Or if 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 was small increases in blood pressure about 8 to 10 millimeters of systolic and thysolic.

It's probably not. It's probably overkill. We've just really studied as an intranasal and it did raise blood pressure, intranasal squirt, and it did raise blood pressure more, so they switched 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 ray of male sexual dysfunction. So the other point I want to make is there are a couple of at least one good large RCT and postmenopausal women. You should have asked me why is this not approved for postmenopausal women. So the other point I want to 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 postmenopausal 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 required either that they put in an application for either a pre or 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.

Is it typically given or prescribed by a 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 lancers, and I'm sorry, there's no RCT both in outcomes and risk and safety. And no RCTs and that's for for a lancor. And I'm sorry, there's no RCTs for Vilecee for Adi. There's post-menopausal data for Adi, none for Vilecee. So you're in no man's land if you're prescribing this off label for post-menopausal women, but there's no physiologic plausibility for the risk.

But you could give Adi and testosterone to post-menopausal women without contraindication. Well, 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, really. I was a 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 it's off label, that there's research supporting

it. I don't have not used, if I we see in post-metaposal 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. Are these scheduled for? Are they controlled or uncontrolled? They're not controlled. Testosterone is.

Yes, testosterone is, yeah. Yeah, if you have a DA number, it's controlled. You can only give them a month at a time, which is easy 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 were, again, they were

proof of pre-medipolzal 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. So the SIP-3A4 inhibitor issue is a problem for full bandsthrin.

Someone's on other psychotropic drugs, and I'm worried about over sedation. 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 diphlucan. You have to wait. There's guidance about how long to wait

in between all the SIP-3A4s. 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 philanthropy, 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 a version to get nauseous for the first time, I mean, it's a discussion. Some 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 and tell 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 on my institution, I'm at Wal-Cornell, that I know that routinely

would offer this to people. I'm a referral source. I work both in medicine and psychiatry. And 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. You could 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. I don't know if they're underutilized. Well, there's one other point I'm gonna 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 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. That's where this whole idea of blending the Zeynraels is, 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 stop the birth control pills. It's six months later, and still no desire. Why not try adding? They need to be validated. It's okay to want to want.

So 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. If I have pain, we didn't have a lot of discussion about treating vulgar nitri-causing GSM. There's the options for lots of things. There's 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 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. At least it's normalized, like 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?

This 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 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, this is all hilarious. 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.

My most common age group is midlife women. And for the reasons we've been talking about. And I also do work in Man practice as well. My most common age group is midlife women and for the reasons we've been talking about and I also do work in Manopause too so that's probably why they come to me for the mixture of things like my most common patient would be like menopausal symptoms, soft-flesh, 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. And 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 vulvodyne of a stabula dinea. And that tends to be more of a referral issue. Herpes, sort of how to deal with that. And not so much like quality of sex, quality of life, connecting and relating.

I'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 worlds that I know aren't having partners. 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? Does 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. Biochemically, it's also unambiguous. Her 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, there 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.

You have a hot flash, they sweat, they wake up, they worry, they can't get 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 shouldn't 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 it's also going on. So I watch carefully for mislabeling mental health issues in this time frame, which is it's 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. So there may be root changes, and they may be incominent mental disorders, 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.

But you also mentioned there were some homonally 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 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 andandrogens that sort of parallel this timeframe. So I kind of like help people break it down and say, if it lets figure out which things

we want to start with, we 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 like people that have a your 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, 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 their partner being upset that there's decreased frequency because they're more tired or maybe they can't communicate with their partner and can't teach them to use a lubricant because they're afraid to ask. So 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, 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. For 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 fudge 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 bear to 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. You know, 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. I can't promise that you won't get breast cancer because one in eight or nine women get it anyway, and you might be jamming them or likely, but 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 gonna go into now because I'll have a dedicated podcast 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 WHO. Yes, 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 progesterone, which you couldn't use them, but nobody does. There are oral therapies available. They're bioadenical. And 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 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 than people who started hormones. The WHO wasn't for symptoms. It was for disease prevention.

It was osteoporosis and cardiovascular. 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.

Not only that, they almost achieve statistical significance by 0.2 of a p-value for a reduction in the incidence of breast cancer, in effect that also has persisted for over 20 years. This is looked at in every subanalysis. So I think you're making the strong point that the reanalysis of subgroup by age, and they were 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. None 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 endometriol hypoplasm.

I think you need to use it, even maybe very short term you don't, but for this indication, you do. So the venospromble 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. So these are like patches of gels that are available for these products, for both estrogen. There's an estrogen-progesting patch,

and then you can use an estrogen-gel with an 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 coded 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 progester in IUD for endometrial protection. Clinically, 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 a new mutual protection. Usually it's the higher dose, the morena. And it's good for five to seven years although some feel that you could leave it in longer and still get the protection because the levels stay present for some time. And that's a strategy used by many, whether you put it in before they don't tell the Earth of a Justin or you just decide that, and the theory is that also

that it's an alternative, but also might provide overall less progestin exposure, although the oral progestin is biovedenical, the levonestinal gestural isn't. So there's back in front of that, but that's a strategy. Now remember, this is for hot for all these symptoms. 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, if you're 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. So it's bone protective. It's not considered a treatment for osteoporosis, it's a very good drug. So 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. 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. But 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, it'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 on therapy has. So there's a few conversations. One is what to do for her now.

Like at this point, I'd probably say it's gonna help your symptoms. Let's say nothing else has helped her. She's tried the over-the-counter stuff. Maybe she even tried black ho-ho, 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 gonna help you. Let's use the safest, lowest dose. You're certainly not gonna 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. We 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.

And 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 Mansonon 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 WHO and I'll be sitting down with Joanne to talk about this. She can speak about it and really analyze and carefully the subgroups, the follow-up data. It's not to say she's refuted in 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 manopause of sighting, similarly, formal experts say, like the shortest dose for the period of time that you need to manage their symptoms.

At a minimum, we need to like turn around anybody who doesn't understand that. There's also other pharmaceuticals. You 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. So does that estrogen you're sending in her system? Let's say she agrees to take that trans-droid, time left, but she's also telling you that she has dryness and discomfort.

So does that estrogen you're sending in her system? Let's say she agrees to take that transfer, does it get to the vulvo 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, vulva agenotrophy and general urinary syndrome

or symptoms of vanopause. Vaginal durinus, 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, supositories, lotions.

There'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, 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, for sexual function, as an aside, I remind them that they might need more stimulation. So lubricants can be help with comfortable stimulation, silicone particularly, although it's slippery, adding vibrators. So that's all for like, and there is some with sexual function, the use that are losing phenomenon, so promoting regular sexual 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, there'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 vulva vaginal atrophy. Somebody wants to take an oral pill, which is a whole nother category. It's called Asfina, the chemical's Asfemapin, and it has some of the serum issues, but it is indicated. One of the main benefits is 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 ester dial. It's not an ester dial, it's a serum. It's a serotonin esters and receptor modulator. It's a little unusual. A lot of people don't know that it's FDA proof. It's not very commonly prescribed and not that when we choose it. It's indicated, it's an oral serum

indicated for yes, vulva vaginal atrophy causing dysperunia. It's called esfena at 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 certain kind of, sometimes a rock's fiend is used for breast-proposal axis, but it's not indicated for that. It might have positive effects on bone, but again, not indicated for that. I 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

who won 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 sex activity, and proof that. But 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 the 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 stevechromone, 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 five to 10, 15 years out. And 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,

you know, like warming liquids, scented things, you know, use things that are like a little less filled with stuff. But then someone will come to me at 65 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.

It's not 100%. Atrophies are 100% of people but the degree and the severity varies. There's some endogenous hormone factors, whether they've had an o-frectomy. The use of stemical amounts probably figures them to 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. And 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. Feels like a lot. I didn't have to do anything for my vulva in vagina

when I was 25 or 30. And now I'm 60, 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. I 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, et cetera. 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 be a little bit more proactive potentially during that aging cycle. Again, 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, it 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. So it worries me that as we pull back on 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 you're still menstruating, but your sexual desire might be dwindling. You know, like how to integrate my brain and my body if I'm under a lot of stress and anxious and depressed, like should I take a medication? What are the implications for my 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 the implications for my 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 going to be enthusiastic. But you're also noticing changes in your vagina, your vulva, your genitals. 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. I 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's showing up with a question would be. So that's the last thing I'll say. It's like, it's a long lifespan. There's a lot of different issues and 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 course, Peter. I mean, there's this huge area.

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. But if there are 600 people of your qualification at a recent conference, my hope is that people will know where to do it. 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 like 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, and you might hear that from some of your speakers on mail. They'll have find a provider websites.

You know, you might wanna 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. 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 ASC, ASS, ECT has a website with finder provider, a sex therapist, there are websites, for example, ASS, ECT, has a website with Find the Provider, the 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 found 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. Like 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. Thank you. Very much. Great questions. 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.

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