259 - Women's sexual health: Why it matters, what can go wrong, and how to fix it

1. 0:00 – 1:27

   Intro

   1. PAPeter Attia0:00

      How important is sexual health for overall well-being?

   2. SPSharon Parish0:05

      Usually it's way underestimated how distressing or, um, impairing it is to quality of life. We, we, we don't do a great job of understanding this, and it's, it's, part of it is legitimizing this, right? And that's what we're doing here today is, like, really legitimizing. Like, this is a real thing for you. It affects your quality of life. It's okay to tell me, right? And it's okay to want this to be different. And when women are given that permission, either because they're in, being interviewed in a study or somewhere in a doctor's office or they're... They embrace it because it, it is something that they're feeling. They're feeling impaired quality of life.

   3. PAPeter Attia0:40

      [upbeat music] Hey, everyone. Welcome to the Drive Podcast. I'm your host, Peter Attia. Hey, Sharon. Thank you so much-

   4. SPSharon Parish0:51

      Hi, there

   5. PAPeter Attia0:51

      ... for, uh, for making time to, to meet with me today. Uh, th- this is a topic that is, you know, incredibly applicable to more than half our population because while we're gonna 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 listening population. It's also a topic, um, where, you know, there seems to be a lot of misunderstanding, um, a lot of asymmetry in attention. We're gonna talk about a bunch of those things, uh, as we get going. Uh, before we do, though, I just kinda wanna give people a sense of your background and

2. 1:27 – 7:19

   Sharon’s interest in sexual medicine and the current state of the field

   1. PAPeter Attia1:27

      how you arrived where you did. So you, you went to medical school. You did your residency in internal medicine and primary care, correct?

   2. SPSharon Parish1:34

      That is right. I was in, in a, a... In primary care, i- meaning with a focus on ambulatory medicine and being sort of a, a, a general f- m- m- medical physician in, eh, with a focus on, on primary care and, and academic general medicine.

   3. PAPeter Attia1:50

      And so at, at what point during that, uh, process did you realize that your, your interest, uh, was in sexual health?

   4. SPSharon Parish1:58

      When I was in med school, really.

   5. PAPeter Attia1:59

      Mm.

   6. SPSharon Parish1:59

      Um, I was always struggling. It, it seems like a little bit of a strange union, but always struggling between deciding whether I wanted to be a general internist, a psychiatrist, or a gynecologist.

   7. PAPeter Attia2:09

      Mm.

   8. SPSharon Parish2:10

      Um, and you know, this interface, uh, 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 w- comprehensive or, for lack of a better word, holistic care for all sort of was always tugging at me in three different directions. And, and somehow when I eventually found my way to sexual medicine, it just kind of brought it all together. Um, I, I, um, was v- did some projects on women's health, and then in residency also on various women's health issues and reproductive issues. Um, I worked, for example, in, um, a contraception clinic, an adolescent medicine program, STD program. So I, you know, I, I did a lot of work in that area. Dur- I did a fellowship afterwards, uh, at b- NYU Bellevue in psychosocial and behavioral medicine in the general medical f- field. Um, and I worked with, um, then some sexual medicine experts in some projects, and that's when I really, uh, moved more deliberately toward the field.

   9. PAPeter Attia3:12

      And so how does, how does the field stand today? Um, h- how many physicians are there in the United States, if you had to estimate, um, that have your degree of training and clinical focus?

   10. SPSharon Parish3:24

       Well, I think that, um, the, the field of men's sexual health is a little more clearly defined.

   11. PAPeter Attia3:29

       Mm-hmm.

   12. SPSharon Parish3:29

       Like, there's many, um, psychiatrists, uh, urologists, and even men's health internists who, who have, like, a clear distinction. I think women's sexual health i- is less clear, but, um, again, gynecologists, some internists, family medicine physicians, a few psychiatrists, and then there's psychological therapists. Um, it, it goes across disciplines. It's a little hard to define, but I can say that there's many fewer who clearly identify. Um, I went to the International Society for the Study of Women's Sexual Health annual meeting a couple weeks ago, and there were 600 attendees.

   13. PAPeter Attia4:04

       Mm.

   14. SPSharon Parish4:04

       Um, five to 600, and that probably represents most people who work in the field.

   15. PAPeter Attia4:09

       Okay.

   16. SPSharon Parish4:09

       Um, you know, there, there's sexual ther- 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, it's not robust, right? And if you go to the AUA, I, I think everybody there, s- s- th- 20,000 people, think they could probably handle a male ED problem, so if that gives you a point of comparison, right?

   17. PAPeter Attia4:29

       Yeah. Yeah. That, that, that, that's sort of in line with w- what, what my expectations were. Um, l- let's also just maybe f- by way of background sort of, um, perhaps start with what, what is encompassed in this field, right? So you've already kind of alluded to it a little bit. Um, there's clearly a, um, supratentorial component to this. There's also an anatomic component to this or physiologic component to this. Um, how, how does it make sense to, to maybe walk me and the, the listeners through the, the background knowledge of this physiology anatomy, uh, t- so that we can better kind of g- go into what some of the problems are and what some of the treatments are?

   18. SPSharon Parish5:15

       So w- with any, um, issue where you're looking at the mind, the body, genital, you know, a genital response, a hormonal response, y- you know, the integration, I always take people back to the concept of the biopsychosocial model, right? And you're... I g- I guess you're asking when it comes to sexual response, what are, what are the bio, what is the psycho, and what is the social-

   19. PAPeter Attia5:36

       Yeah

   20. SPSharon Parish5:36

       ... and what is the contextual?

   21. PAPeter Attia5:37

       Mm-hmm.

   22. SPSharon Parish5:38

       Um, so f- f- for m- maybe just for sexual health problems, the brain is a really active organ, uh, as I'm sure you can imagine. We have, um, thinking and feeling, and that probably on a biological or, or neurophysiological level transmit- translates into neurotransmitters and the interaction with hormones and pathways, brain, brain neural pathways, neural networks, and there's the psychological concepts of conditioning and learning and unlearning. Um, you know, and p- reward and, and disappointment, et cetera, all plays a role, and it's fascinating how that might all interact. Um, there's the general medical state, our vascular system, nervous system, and, like, systemic medical issues that might impact those. And there's hormones, the ... and they get stimulated by the master glands in the brain. Um, our, our genital making, you know, our genitals that make, uh, sex steroids, um, and our adrenal glands and thyroid. So there's a collection of hormonal locus- locuses that play a role potentially in sexual health. And then there's the local genital milieu or ... and that might include, um, the vascular system, the nervous system, small nerves, the mucosa, the surface, and then there are muscles and soft tissue, so all in the genital tract. So the ... I think ... And then there's the bladder and the rectum, um, and, uh, the breasts, um, which play a role in stimulation. So that, I think that that's the big s- big picture. How does this all come together, um, in a three-dimensional concept where you integrate, um, experience, um, relational issues, culture, and time, um, is really the fascinating part of this field.

   23. PAPeter Attia7:18

       So how do these

3. 7:19 – 10:30

   How hormones change in women over time and how that impacts sexual function

   1. PAPeter Attia7:19

      things change, um, during a woman's life? I mean, obviously puberty is a very important milestone, but I suspect also, uh, menopause is an equally important transition, um, that is much more abrupt, at least from an endocrine standpoint, than, uh, men would experience at the same age.

   2. SPSharon Parish7:39

      Yeah, so I think there are times when hormones, like, sort of play a more, more master role in sexuality and sexual response. You know, what's tricky about this is ... And, 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. But, um, menopause is kind of a longer process than people think, right? It's, there's perimenopause, there's menopause, there's postmenopause, and there's a lot of life cycle stuff going on. Um, uh, you know, that's probably, um, the most defining moment for women in that it interfaces with no longer being able to reproduce. There are, are significant changes in hormone levels like estrogen that affect vaginal, level of vaginal comfort, and at the same time androgens decline. That affects desire. Um, and when you're starting up with puberty, that's probably all roaring up and getting going. Um, and you're also developing the, the, the cognitive skills of relational issues and, and, and sexual, sexual relationships. So those are two peak times. Um, I, I have worked with adolescents. I have more experience with, with midlife women. That's the focus in my, often in my practice. And those are the people that's ... Of, of ... This is a good point, time to mention this point. Um, the data suggests, and my, uh, experience with this field suggests, that the time when women are most interested in looking into it is in those perimenopausal, late reproductive, perimenopausal, and early postmenopausal years. And I think we have to do this-

   3. PAPeter Attia9:05

      When you say looking into it, do you mean looking into-

   4. SPSharon Parish9:08

      Like for themselves.

   5. PAPeter Attia9:09

      I see. Okay. Yep.

   6. SPSharon Parish9:09

      Yeah. Or, so it might be that they have a problem.

   7. PAPeter Attia9:12

      Mm-hmm.

   8. SPSharon Parish9:12

      It might be they wanna understand it better. It might be they wanna be proactive and preserve their sexuality.

   9. PAPeter Attia9:17

      Mm-hmm.

   10. SPSharon Parish9:17

       Um, it usually is that something's changing and they weren't expecting it, and, and w- and wanna know why, or they want it to be better. Um, 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, uh, I think that's what makes the midlife, um, sexual medicine challenges the most, um, complex and challenging, but also the most interesting and the most rewarding. Um, I think there's, um, also the most, um, likelihood where women are ... Women, midlife women are youthful. They're young. They're active. They're connected. They're not like, you know, some other time in our, in our universe where they're becoming the wise woman sitting in the tent, you know, retiring from r- childbearing and, and everything else. I mean, often women are peaking in their career. Um, if they're having ... You know, these trends vary a little bit. Children later. You know, they've got college, teenage children, college children, aging parents-

   11. PAPeter Attia10:14

       Mm

   12. SPSharon Parish10:14

       ... big careers, body's changing, partners wanting, you know, and wanting partners, and there's a lot going on. Um, so they're the most likely to seek attention, actually.

   13. PAPeter Attia10:23

       Yeah.

   14. SPSharon Parish10:24

       Um, and we, we can say a lot about helping them today.

   15. PAPeter Attia10:28

       I also would like to talk a little bit about

4. 10:30 – 21:45

   Changes after childbirth and its impact on sexual function

   1. PAPeter Attia10:30

      how the anatomy changes post childbirth, and does that have anything to do with, um, sexual function. Um, and I, and I guess I wanna kind of also at some point soon define some of the problems, right? So I can think of like-

   2. SPSharon Parish10:45

      Sure. Yeah. Of course

   3. PAPeter Attia10:45

      ... I can think of three off the top of my head, right? One would be, uh, low sexual desire or hypoactive sexual desire. One would be, uh, inability to have an orgasm, and a third would be discomfort or pain. Clearly a big problem for women post menopause due to vaginal atrophy. So those are three things I think we must address today. Do you think there are others that are, uh, important enough that to a non-expert audience we should also, uh, present?

   4. SPSharon Parish11:12

      Well, I think, um, uh, I never want the forgotten, um, we'll call her sister, the forgotten sister, um, to desire as arousal. And having women understand that ... Y- you know, when they come to me, they're like, "I, I no longer get turned on." And I mean, so, so is it about wanting?

   5. PAPeter Attia11:27

      Mm.

   6. SPSharon Parish11:28

      Is it about mental or subjective or cognitive excitement? Is it that bridge between desire, meaning thinking and actually being in a moment and being excited? Or is it their genitals are no longer responding, and then that sometimes is, is uniquely ti- or can be tied to orgasmic difficulties.

   7. PAPeter Attia11:45

      I see. Got it. Okay.

   8. SPSharon Parish11:46

      And I think it's really, um, i- in the field it's an area of, you know, discussion and sometimes even controversy, but, um, I think for women it's hard to separate, um, what they're asking for. Like, it, you know, sometimes women come to me and they say, like, "I no longer want sex, but everything works okay." Sometimes they say, like, "I love this person," or, "I want to have sex with myself." It's, 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 it, it, that can be often, I think it gets commonly tied to orgasmic changes. Um, and we could certainly discuss, uh, whether they're the same process or different. Um-

   9. PAPeter Attia12:25

      Okay

   10. SPSharon Parish12:25

       ... you know, childbirth, I, I, I don't know if you wanna talk about that now.

   11. PAPeter Attia12:28

       I-

   12. SPSharon Parish12:28

       It, it is a, um-

   13. PAPeter Attia12:28

       Yeah. Let's talk about it just because I think-

   14. SPSharon Parish12:30

       Yeah

   15. PAPeter Attia12:30

       ... we, we, we've already established that these, there are these two enormous hormone swings, right? There's the swing on, which is, you know, 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.

   16. SPSharon Parish12:46

       Right.

   17. PAPeter Attia12:47

       Um, uh, it's also worth mentioning, uh, that, that it's the estrogen and progesterone that are coming off really quickly. The testosterone is kind of coming off not as quickly. We can-

   18. SPSharon Parish12:57

       Correct

   19. PAPeter Attia12:57

       ... maybe come back-

   20. SPSharon Parish12:58

       Yeah

   21. PAPeter Attia12:58

       ... to that in a moment. Um, so yeah. Let's just, let's, let's talk about anatomy in a, in a minute because I, 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. Um, but anyway, yes. Let- let's, let's talk a little bit about how that might impact any of the elements of, of sexual health in a woman's life.

   22. SPSharon Parish13:30

       Yeah. So I, you know, it's not the time typically where the sexual problems that people come to me for, I'm also not a gynecologist-

   23. PAPeter Attia13:38

       Mm-hmm

   24. SPSharon Parish13:38

       ... um, i- i- kick in and stay. They t- tend to be for some women relatively transient, um, postpartum, but it also depends on, like, how many kids and what age and all of that. But, but so, so let maybe go, let's talk about the pelvic floor for a moment 'cause that's where that might impact with childbirth. So, um, the pelvic floor is kind of a mysterious concept, but it, um, if I had to give it one concept, it's the idea that it's a basket of muscles.

   25. PAPeter Attia14:06

       Mm-hmm.

   26. SPSharon Parish14:06

       And they a- attach from various parts of the inner pelvis, so like, you know, onto the pubis ramus, onto the ischial spine, onto the bones in the, you know, in the, around our pelvis. Um, i- in- internally and into the walls, and then also onto, into the organs, and they create a, a basket around the uterus, around the urethra. They, 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, um, m- motion during childbirth. They allow for the childbirth process. They're quite active during sexual activity. They contract and release. Um, they help us with urination, with defecation. Um, so, and so forth. And you know, it, it'd be easier if we had, like, the opportunity to show people a diagram, but I think the best way to understand is-

   27. PAPeter Attia14:57

       We'll, we'll, we'll include, uh, we'll include diagrams-

   28. SPSharon Parish14:59

       Yeah

   29. PAPeter Attia14:59

       ... in the show notes. So, so yeah.

   30. SPSharon Parish15:00

       That would be wonderful.
5. 21:45 – 28:48

   The role of metabolic health and systemic vascular health in sexual health

   1. PAPeter Attia21:45

      before we leave the sort of basics and the foundational stuff is the role of, uh, metabolic health/systemic vascular health. So again, in men, this is really clear. Um, right? So for example, uh, the, you know, higher incidence of ASCVD, higher incidence of ED, right? Similar concept to, you know, endothelial damage. Uh, higher incidence of type 2 diabetes, microvascular disease, higher incidence of erectile dysfunction. How clear is that relationship in women? In other words, do the things that drive glycosylation of proteins and microvascular disease, uh, in other parts of the body, do they contribute to, uh, sexual health in women as they do in men through the ED pathway?

   2. SPSharon Parish22:35

      So I'm glad you brought this up, 'cause this is really an emerging, uh, discussion in the field. Um, so y- for those that, that are not aware, in men, there's like kind of a really clear literature and guidance that if a man is having ED, it may be a mirror to small vessel cardiovascular, cerebrovascular disease. And we can use surrogate markers like looking at Doppler studies of v- v, you know, in the, in the urologist's office of penile and genital blood flow, and then send them for a coronary calcium score or 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 s- those are discussions when, if they have-

   3. PAPeter Attia23:21

      And just-

   4. SPSharon Parish23:21

      Yeah

   5. PAPeter Attia23:22

      ... 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. Uh, so but-

   6. SPSharon Parish23:35

      And so, you know, I, I, I was, I think we, before we got started, I was telling you I was just at a two-day meeting where this was the, the depth of the discussion. You know, where are we with understanding the presentation of erectile dysfunction as a marker 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, the medications that, PDE5 inhibitors that dilate-

   7. PAPeter Attia24:01

      Mm

   8. SPSharon Parish24:01

      ... the small vessels work? And, um, my participation in, in this particular conference was a, was about the discussion of do we have similar measures in women?

   9. PAPeter Attia24:10

      Mm.

   10. SPSharon Parish24:11

       Right? Um, 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, right? Um, um, I mean, there's also nerves there, but, you know, the, it, it's, it's, it's really not as clear-cut. Like a man comes in and says, you know, "I don't have an erection," right? Women's like, "I don't feel," uh, you know, I can't be sure that ... e- exactly what it is. But, um, there's been some research looking at using something called clitoral color Doppler ultrasound, or CDU, with assess- with assessment of, like, the blood flow, which is called the pulsatile index, um, looking at resistance to blood flow as an objective measure of how to assess arousal in women. So right now it's just at the level of the lab or research. It's not really being used clinically except in a very few selected practices who d- also research this. So, like, if someone comes in and says, "I don't feel," can I put a clitoral Doppler on and look and see, yes, that, that, that's the explanation?

   11. PAPeter Attia25:05

       Mm-hmm.

   12. SPSharon Parish25:05

       And, uh, 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 clitoral sensation and doing testing, both to understand her sexual function and also as a mirror for her systemic blood v- vascular risk? Again, we don't, we're, we're starting to study that, but we don't have clear information. This, there's this concept called the, the female genital vascular district. Um, and does that whole area, the larger vessels and the small vessels, does that give us a correlate or a window, and, you know, can we use that, again, as, as markers for small vessel disease? And then vice versa, like if someone says to me, you know, I have a patient with, uh, metabolic syndrome and a high A1C, um, you know, uh, uh, obesity, diabetes, um, l- hyperlipidemia, et cetera, should, sh- 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-

   13. PAPeter Attia26:08

       Yeah

   14. SPSharon Parish26:08

       ... managing those issues to preve- 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.

   15. PAPeter Attia26:21

       Hmm.

   16. SPSharon Parish26:21

       And can we use these both as mirrors of sexual function and predictors of other issues, other vascular issues for women? And I, I feel like this is the most important growing field, that it needs to catch up. Um, you know, that we can't just look at, like, oh, she's complaining. She's postmenopausal. I think I'll hand her a lubricant, uh, because she's not feeling things. That's very crude compared to what we have available for understanding men at this point. Right?

   17. PAPeter Attia26:45

       Okay.

   18. SPSharon Parish26:45

       So that's a long discussion, but as I said, area of great-

   19. PAPeter Attia26:48

       Yeah

   20. SPSharon Parish26:48

       ... fascination. But, um, we, we, p- practically speaking, you know, we, we don't have a lot to, to offer women in the office yet, but we need to.

   21. PAPeter Attia26:57

       Right.

   22. SPSharon Parish26:58

       Right?

   23. PAPeter Attia26:58

       But it sounds like we're moving in the same direction that we kind of have a clear sense of what's going on with men, which is... A- and by the way, I, this is something I do see in my practice quite, quite often, which is you have a guy that shows up with a hemoglobin A1C of, you know, 5.9, so he doesn't have type 2 diabetes, but he clearly has too much blood glucose and dyslipidemia. A year later, when you've got all those biomarkers improved, he also notices he doesn't need his Cialis anymore. I mean, that's-

   24. SPSharon Parish27:27

       Yeah

   25. PAPeter Attia27:27

       ... that's a very obvious, clear, r- repeatable common story. So it, it's, it... I don't think it's a huge stretch to assume that women could experience the same thing.

   26. SPSharon Parish27:41

       So I, I, 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, right?

   27. PAPeter Attia27:47

       Mm-hmm.

   28. SPSharon Parish27:48

       So, and, and I think this makes sense when you're talking about... That's obvious when you're talking about a man, right? Like, you know, they're, like, with these parameters, and then you say, "How..." You know, "So tell me about your sexual function, you know, how, how's it going? Any difficulty with erections?" They report it, and you say, "Well, you know, that they can sometimes go hand in hand," or, you know, and that's a good motivation overall for many men, right? They want to improve everything.

   29. PAPeter Attia28:11

       Yeah.

   30. SPSharon Parish28:11

       And that might be sometimes even the biggest motivation.
6. 28:48 – 43:29

   Conditions associated with decreased sexual function and the importance of sexual health for overall wellbeing

   1. PAPeter Attia28:48

      I, I'm sure, a- again, empirically it just makes sense, but what can we say about sexual health and general health?

   2. SPSharon Parish28:56

      Um, well, I think-

   3. PAPeter Attia28:57

      And, and by the way, I sort of, let me phrase my question a little bit better. Um, what I mean by that is overall well-being as a function of sexual health. I, I, 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, um, w- 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?

   4. SPSharon Parish29:26

      Well, so I think w- there's a couple ways to look at this. One thing is, um, the, most of the research, I, I guess we're talking about women today?

   5. PAPeter Attia29:33

      Yes, yes.

   6. SPSharon Parish29:33

      Um, most of the research is association research, right?

   7. PAPeter Attia29:37

      Yeah.

   8. SPSharon Parish29:37

      So it's a, sometimes a little hard to tell. I, I think you understand the difference-

   9. PAPeter Attia29:41

      Of course

   10. SPSharon Parish29:41

       ... between really risk factor and cause and effect. You know, so we know which lifestyle and health factors seem to be associated with better, better sexual function, better satisfaction, better sexual activity, right? Um, and most of the research is actually in desire when it comes to that.

   11. PAPeter Attia29:57

       Mm-hmm.

   12. SPSharon Parish29:57

       Like, we know that, like for example, I'll give you a few examples. In women, there's interesting research that, um, being resilient, having a positive attitude, um, for, for women especially as they get older, having a partner, right? Um, being connected socially, having support, normal BMI. The funny one is Mediterranean diet, actually. It probably has to do with overall health and well-being and the-

   13. PAPeter Attia30:19

       Yeah

   14. SPSharon Parish30:19

       ... other benefits. All those things are associated with good sexual function, right? And whether people who do those things preserve their sexual function or those things preserve sexual function is still, it's association.

   15. PAPeter Attia30:31

       Yeah.

   16. SPSharon Parish30:31

       Right? I sort of- Think it doesn't matter. You know, you want to-- They're both are good, right? Um, where it matters as a motivator is that, um, validating the q- the importance of sexual function to quality of life, you know, i-is, is critical for people feeling that they have permission. Like, that's, that's a good reason for me, right?

   17. PAPeter Attia30:49

       Mm-hmm.

   18. SPSharon Parish30:49

       'Cause sometimes it's like an afterthought. Like, oh, okay. Like, okay, it's okay. I could prevent heart disease, but do I have to preserve my sexual function? That's a little indulgent, right? Why should I go to the gym just to have better sexual function? My-- and my kids need me to help them with their homework, you know? And but if it's like, "Okay, I can't have heart disease, I have to go to the gym," you know. So, so I think part of it is validating that for people that probably there's strong association. And then vice-- on the other hand, we know what the heavy hitters are in terms of overall sexual function and biological medical conditions and psychiatric disorders, right? Um, I'm not sure if this is exactly what you asked me, but it's at a point that I think is important to make, and you-- we could go back and clarify if you wanted to hear anything different.

   19. PAPeter Attia31:29

       Yeah, yeah.

   20. SPSharon Parish31:29

       Um, so the heavy hitters, we, we could talk about categories, right? There's what we've already been talking about. There is associative data that metabolic syndrome in women, obesity, particularly interestingly, hypertriglyceridemia, which probably makes sense to you, right?

   21. PAPeter Attia31:42

       Mm-hmm.

   22. SPSharon Parish31:44

       Um, and then coronary artery disease and diabetes. But what's interesting about the last two is that the, the condition itself isn't as clearly correlated as the psychological, um, ada- adaptation or relationship to the disorder is for women. So for example, if someone had a heart attack or-

   23. PAPeter Attia32:01

       Mm

   24. SPSharon Parish32:01

       ... has heart disease and they're female, it's more about how they see themselves and their i-interest or enthusiasm in becoming re-engaged with activity than clearly the severity of card- cardiac disease. And that might just be-

   25. PAPeter Attia32:13

       Uh-huh

   26. SPSharon Parish32:13

       ... we don't have good research.

   27. PAPeter Attia32:14

       Mm-hmm.

   28. SPSharon Parish32:15

       Or it might be different in women. And same thing is true with diabetes. Like in men, it's clear, like the higher A1C, the more sexual dysfunction, neur- neurovascular disease, et cetera. But in women, it's more about the impact of diabetes that it's so far in the research. Do they-- are they depressed because they have diabetes?

   29. PAPeter Attia32:32

       Yep.

   30. SPSharon Parish32:32

       Is it impacting, like they don't like wearing the monitor, so they're embarrassed to have sex or like, y- you know, things like that, or their, their feet are numb, and it turn-- just makes them negative rather than their, their blood sugar control. But I think that part of the problem is we don't have as good research. Um, but so 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 ur- urinary cancer, ovarian 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, right, that also and clearly interacts with sexual function in women and can be problematic.
7. 43:29 – 56:20

   -Sexual dysfunction case study #1: A 41-year-old mother of two, the sexual response cycle, and the difference between arousal and desire

   1. PAPeter Attia43:29

      has been an excellent foundation for us to now go through some of these various things. So, so let's start with sexual dysfunction. Um, and I'll leave it to you which one you wanna start with. So again, I was... D- do you wanna talk about arousal, uh, and desire separately and, and kind of walk through that? I, sometimes I find this helpful, Sharon, with other podcast guests where we do actual case studies. So, um, I, I can make some up, but you can feel free to adjust them and say, okay, so, um, a 35-year-old mother of two, married, comes into your office and says, "I love my partner. Um, I just don't wanna have sex. Like, I'm just not in the mood." And, um, like, so, so tell me what's your workup? How do you... That, that's, 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, um-

   2. SPSharon Parish44:37

      Let's make her 39 if her kids are 10 and 12 [laughs]

   3. PAPeter Attia44:40

      Okay. Okay. Perfect. So she's 39. Her kids are 10 and 12.

   4. SPSharon Parish44:43

      Or 41, right?

   5. PAPeter Attia44:44

      Okay. Fair enough. Fair enough.

   6. SPSharon Parish44:45

      When things may be starting to change.

   7. PAPeter Attia44:46

      Yeah, yeah. Perfect. So sh- the point is she's-

   8. SPSharon Parish44:47

      So I have reasons for that. Yeah

   9. PAPeter Attia44:49

      Yeah, yeah. She's premenopausal is the point I'm really just trying to get at.

   10. SPSharon Parish44:52

       Yeah. Right.

   11. PAPeter Attia44:52

       Um, okay. And that's, and that's it. So, so this is all-

   12. SPSharon Parish44:55

       And she doesn't have tiny kids waking her up-

   13. PAPeter Attia44:56

       That's right. Yeah, yeah

   14. SPSharon Parish44:57

       ... you know, in the middle of the night

   15. PAPeter Attia44:57

       So she, she's out of the, the, the, the, the difficulties of child rearing. Okay. So, so, okay, so what do we want-- well, how do you wanna work her up and how do we-

   16. SPSharon Parish45:05

       So let me, let me just give you the categories and tell you how we would think about her.

   17. PAPeter Attia45:08

       Okay.

   18. SPSharon Parish45:09

       Right? Um, so y- y-- I don't know who, who of you have seen Masters of Sex, right? So the, the whole concept or, or how to organize, um, sexual dysfunction was based on the work really first of Masters and Johnson, right? That there was a response cycle that had an order, right? And their, their work primarily fo- they looked at both men and women. They were actually really quite progressive. Um, and the idea was that people started with getting aroused, right? And I think in their concept, it was all physiologic 'cause they mostly just looked at physiologic parameters, although they understood the, 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 a plateau, and that can be variable. You know, and there's some models that for women there's more variability in plateaus. And, and then it-- the classic response cycle is it results in an orgasm, climax, peak. Lots of different words get used, but we're just gonna use the word orgasm, keep it simple, and that there's different patterns for that too, right? Like, so and different ways to have-

   19. PAPeter Attia46:11

       Wait, can I, can I ask a question before that-

   20. SPSharon Parish46:13

       Sure

   21. PAPeter Attia46:13

       ... that, that goes before that? So, um, what comes first, desire or arousal? Is desi- desire comes first, does it? Or do you have to have some arousal to then trigger desire?

   22. SPSharon Parish46:23

       So I, I'm gonna talk about desire in a moment-

   23. PAPeter Attia46:25

       Okay, okay

   24. SPSharon Parish46:25

       ... 'cause that's i- an interesting question. So but in their model, they kept it simple.

   25. PAPeter Attia46:29

       Okay.

   26. SPSharon Parish46:29

       You, you engaged in sex, and you got aroused. And, and so maybe they thought, like, the interest in having sex was about being turned on or being aroused. They didn't really get distinguished about it, right? And then you have an orgasm, and for women, like, there's different patterns. It could be happen in different ways with clitoral stimulation, vaginal stimulation, et cetera. Um, and sometimes multiple orgasms, which was, is more characteristic for the variability in women. And then there's this idea of the, like, refractory or resolution phase. And that's kinda for, like, many decades since their work in the late '50s or early '60s. That's how people have organized their thinking. Um, a few people came along, n- notably Helen Singer Kaplan in the '70s, and she happened to be a, a psychologist at Cornell and has, like, a whole discipline and following, some of which are my colleagues still. There are a few around. And added this idea of wanting or desire and felt that it was really distinct, like 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.

   27. PAPeter Attia47:29

       Mm. Yep.

   28. SPSharon Parish47:30

       Like, so that 35-year-old or that 39-year-old we're talking about-

   29. PAPeter Attia47:34

       I think she's 41 now, but yeah.

   30. SPSharon Parish47:35

       No, we made her... [laughs]
8. 56:20 – 1:04:35

   Medications that may reduce sexual desire

   1. PAPeter Attia56:20

      SSRIs certainly wreak havoc in men. Do they also do so in women?

   2. SPSharon Parish56:25

      So if you're talking about general sexual dysfunction that can affect a variety of phases, antidepressants, but all psychotropics have some. They're all-

   3. PAPeter Attia56:34

      Mm-hmm

   4. SPSharon Parish56:34

      ... categories of psychotropics. And these days people aren't just on antidepressants. The SSRIs and SNRIs are probably most n- m- well known-

   5. PAPeter Attia56:41

      Yep

   6. SPSharon Parish56:41

      ... to cause multiphase dysfunction. Um, there's differences, though. I mean, that's one of the areas that I consult with a lot 'cause I work closely with psychiatry here, is that they're-- not all drugs are the same. It is a class effect, but there are better drugs and, and some-- and then there are other categories like, for example, bupropion, which is more dopaminergic. It, it is a different choice for a variety of reasons. Um-

   7. PAPeter Attia57:00

      That's Wellbutrin?

   8. SPSharon Parish57:02

      That's the brand name for that-

   9. PAPeter Attia57:03

      Yeah

   10. SPSharon Parish57:03

       ... is Wellbutrin. So generic is bupropion.

   11. PAPeter Attia57:04

       So what are, what are, what, w- within that class of drugs, what, what are the ones that are more likely to reduce desire?

   12. SPSharon Parish57:13

       The-- So the classic SSRIs, most of them fit in that. And the, the-- they bundle together or they cluster together somewhere around 35 to 40% of-

   13. PAPeter Attia57:22

       Wow

   14. SPSharon Parish57:22

       ... what we call treatment-emergent sexual dysfunction. But I wanna make a really strong caveat in a moment about this, um, 'cause there's some, actually some new research kind of debunking some of this a little bit. Um, but that said, so the SSRIs, um, I'm, uh, uh-- Do you want me to use brand names or because people know that better-

   15. PAPeter Attia57:39

       Sure

   16. SPSharon Parish57:39

       ... or generics? So-

   17. PAPeter Attia57:41

       Yeah, both

   18. SPSharon Parish57:41

       ... Prozac, Fluox-

   19. PAPeter Attia57:41

       Yeah

   20. SPSharon Parish57:42

       ... I'll do both. [chuckles]

   21. PAPeter Attia57:43

       Yeah.

   22. SPSharon Parish57:43

       Um, 'cause being, being mindful of this. Prozac, fluoxetine, um, Sertraline, Zoloft, um, pr- uh, Paxil, paroxetine, um, those are the SSRIs, and probably escitalopram, right? Lexapro and citalopram, Celexa, those-

   23. PAPeter Attia58:01

       Celexa, yep

   24. SPSharon Parish58:01

       ... they're pro- Yeah, they're all probably similar. That said, I have patients who say, like, "I develop low desire on Prozac," or, "I have difficulty with orgasm on Sertraline, but, uh, on Paxil, but not on-"

   25. PAPeter Attia58:12

       Yeah

   26. SPSharon Parish58:12

       ... "So-- I'm not on Prozac." So we sometimes try a few if I think an SSRI is the best choice.

   27. PAPeter Attia58:18

       That's definitely been our experience clinically, is that-

   28. SPSharon Parish58:21

       Right

   29. PAPeter Attia58:22

       ... yeah, there's a class effect, but at the end of the day, it's kinda drug specific. And I always tell patients, "Look, if you're, if you're..." 'Cause we're, we're not the ones that are prescribing those. We're not psychiatrists. But, but if your doctor's prescribing you an SSRI or an SNRI, um, I always say the probability that you're gonna 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, you'll be able-

   30. SPSharon Parish58:55

       Right
9. 1:04:35 – 1:09:48

   The effect of birth control pills on sexual desire

   1. SPSharon Parish1:04:35

      really wanna make sure we talk about in this age group, and you're bringing this up, is combined hormonal contraception. I'm, I'm glad you raised this, Peter. So confusing area also, right? And, um, this is like people are very polar on this and very opinionated.

   2. PAPeter Attia1:04:48

      Mm.

   3. SPSharon Parish1:04:48

      But, um, I think it's important now to recognize it's not just oral contraceptives, it's combined systemic hormonal contraception, right? So people take birth control pills, which have estrogen and progesterone. They also use patches, like the OrthoEvra patch, and the ring, like the A- like the NuvaRing, right?

   4. PAPeter Attia1:05:07

      Yep.

   5. SPSharon Parish1:05:07

      And those combine, and there's a whole bunch of different types of these. But, um, the th- the idea here, what, what are you doing when you give contracep- hormonal contraception? You're turning off the brain and that, um, feedback loop that makes you ovulate, sh- you know, make a lining, shed it, and be able to, be, 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, high doses of hormones, right? 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 vulva vaginal mucosa doesn't recognize it, right?

   6. PAPeter Attia1:05:45

      Mm.

   7. SPSharon Parish1:05:45

      And you can develop a vestibulodynia, a vestibulitis, that particularly the, the, the v- the vestibule is 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, the endogenous estradiol and the synthetic estrogen sometimes don't do their trick. And they can develop a vestibulodynia, meaning pain and dryness, and almost look like a postmenopausal woman when it comes to that.

   8. PAPeter Attia1:06:15

      Mm.

   9. SPSharon Parish1:06:15

      Um, it's-- that's one issue, right? With oral con- contraception. It's, it's probably that number, you want a number, um, the, the work of some of my colleagues in this area who do like sexual pain and vestibulodynia work say it's somewhere around 10%, um, that it's harder to recognize.

   10. PAPeter Attia1:06:29

       Meaning 10, 10% of women that are re-receiving systemic-

   11. SPSharon Parish1:06:33

       Of users

   12. PAPeter Attia1:06:33

       ... yeah, okay, who are receiving systemic birth con-

   13. SPSharon Parish1:06:35

       And that is probably similar with rings and patches, but it's not as well-

   14. PAPeter Attia1:06:39

       I see

   15. SPSharon Parish1:06:39

       ... documented. And, and, and then there's some variability, like higher dose or- oral, uh, contraceptives have been, um, more likely, um, 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. Those-

   16. PAPeter Attia1:06:59

       Like is low low estrogen considered low?

   17. SPSharon Parish1:07:02

       Yes. Yes, that's an example. So the ultra low ones tend to be the biggest culprits. That said-

   18. PAPeter Attia1:07:07

       Interesting

   19. SPSharon Parish1:07:07

       ... um, the experts in the field feel this is very important for us to understand. The ordinary gynecologic community thinks it's, it's relatively insignificant. Whether they're under-detecting this particular piece of it or not is, is, is something that needs more development. The other issue with, um, birth control 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. Um, and that may have an impact on the neurotransmitter milieu and the mix that leads to sexual dysfunction and low, low sex drive. So, um, then finally, uh, and this is probably more important as when we get a little older, and it might lead us into the discussion about testosterone, is that birth-- So, so, so three things. One is they can have an effect on the local vulvar tissue, right? If we have this issue with particularly the lowest dose estrogen. The other thing is it depends on the androgenicity of the birth control pill. Um-

   20. PAPeter Attia1:08:00

       Hmm

   21. SPSharon Parish1:08:00

       ... that's not the-- that's, that's, that's yet another issue. Um, and there are androgen receptors in the vulvovaginal tissue, so that may change sensitivity or even lead to pain, that piece of it. The second thing is that that intersa- intersection with brain neurotransmitters and mood, and that effect on sexual function could also be clinically important. And then finally, and this is, like, oh, like a whole 'nother thing, um, what do you do when you make all-- send all that hormone into someone's body? You increase the production of SHBG, right?

   22. PAPeter Attia1:08:30

       Yep.

   23. SPSharon Parish1:08:31

       So it goes-

   24. PAPeter Attia1:08:32

       So you're binding up more of the hormone as well.

   25. SPSharon Parish1:08:34

       Right. So, right. You need something-- Well, y-the easiest way to think about it is you need something to carry it around with.

   26. PAPeter Attia1:08:39

       Yep.

   27. SPSharon Parish1:08:39

       Right? And that SHBG goes up in other states, like pregnancy. Um, and you're-- you might ask me, like, "Is it the same with birth control pills in pregnancy or when you take thyroid hormone?" Any-- There are other things that make that production of that go up.

   28. PAPeter Attia1:08:53

       Yeah.

   29. SPSharon Parish1:08:53

       Um, the data across situations is-- can-- 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. Um, now, um, the-- 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 exa- Let's just say high-dose birth control pills, right? Let's just stick to that for now. Everybody who takes it has that. And what does that do? So it, it, it helps carry it around, but it also unfo- you know, fortunately or unfortunately, whatever you wanna-- it's a f- the fellow traveler is androgens or testosterone gets carried by SHBG. So because you're increasing SHBG, there's some, um, thinking that you're binding up the circulating testosterone, and you may be lowering free testosterone in those women, and that might be another potential contributor to low desire. And

10. 1:09:48 – 1:25:17

    The importance of testosterone in women for sexual function and desire, and why the FDA hasn’t approved exogenous testosterone as a therapeutic

    1. SPSharon Parish1:09:48

       how does desi-- But now we, when we get into testosterone, we can talk about that.

    2. PAPeter Attia1:09:51

       Yeah.

    3. SPSharon Parish1:09:51

       But how does testosterone affect desire? Probably at the level of brain receptors and turning on those pathways of desire, and there's some genital changes too, right? In the, in the metabolites of androgens, um, that change sensitivity and that might impact desire, but that's a secondary state. So, um, if someone-- And w-we're also gonna-- When we talk about testosterone, we were talking about how it doesn't, like, abruptly change so much like ovarian hormones with menopause, that it's more of a gradual decline. So the intersection between b- contraception and women in their late 30s and early 40s and testosterone is interesting. So if you look at my arm, d-- When you're 20, 18 to 24, that's when we start to study reproductive, your testosterone's like up here in the 40s for women, right? And then it kinda goes down, like... I wish I could do, do it better. But it declines. By the time you're in, like, those late 30s, early 40s, it's about half of what-- like, if you look at normal ranges, studies that have tried to nor- of what you were when you were 18. And then it levels off at somewhat lower in your 40s and 50s, and actually goes up a little bit past 60, and kinda levels off, like, down there. So if you're on birth control pills, that curve is way down. And so women-- a woman at 40 might be much more sensitive to that effect than she was if she was on a birth control pill at 25. And that difference in her testosterone, her free testosterone, may be significant in that she'll come and say, like, "I have no sex drive," right? Or, "I have no genital sensitivity." And so, um, that's a kind of an important thing that, like, most people don't tell their patients when they put them on a birth control pill or a combined contraception for 20 years. Now, the other thing, and I think it was in, you know, we, we get some notes in advance. It was one of the questions you asked. What happens? So 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, right? What happens to my SHBG? So there's really only, believe it or not, really one good study that was done by Claudia Panzer in, like, 2000, something like that, and we need more. Um, there's some other data, but not a good study. And she looked at, she looked at, um, con- current users, never users, and stopped users who stopped six months ago. And the bottom line was at six months, the stopped users, the pri- previous users, were in the middle of the other two. They hadn't gone down to normal. Now, no one ever studied them out to three or four years.

    4. PAPeter Attia1:12:13

       Hmm.

    5. SPSharon Parish1:12:13

       But I can tell you, and my colleagues can say that if, like, if, 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 gonna be higher than the person who never used them. I just see that all the time, right? 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, right?

    6. PAPeter Attia1:12:33

       Well, I mean, it would-- wouldn't, wouldn't it have to be unless her testosterone has gone up? I mean, because SHBG-

    7. SPSharon Parish1:12:38

       It-- Yeah

    8. PAPeter Attia1:12:39

       ... is doing the lion's share of the binding. I mean, albumin is a relatively small contributor to this process. So-

    9. SPSharon Parish1:12:45

       Correct

    10. PAPeter Attia1:12:45

        ... isn't it about 85%-

    11. SPSharon Parish1:12:46

        Right

    12. PAPeter Attia1:12:47

        ... of the androgen binding is coming through SHBG?

    13. SPSharon Parish1:12:51

        Yeah. So, well, it, it-- It, it depends a little on, uh, how, how much y- you have-

    14. PAPeter Attia1:12:57

        Mm-hmm

    15. SPSharon Parish1:12:57

        ... but that's roughly the idea, right? So i- i- if that is to answer your question.

    16. PAPeter Attia1:13:02

        Yeah.

    17. SPSharon Parish1:13:03

        Depends a little bit on how much SHBG you have, but most of the binding is through SHBG, and a small, small percentage is for a- through albumin. Um, and so w- with le- there's one more point, which before we go back to talking about binding in a second, is that it's still... W- Part of the controversy is it's not clear that free testosterone is the bioactive component-

    18. PAPeter Attia1:13:24

        Mm

    19. SPSharon Parish1:13:24

        ... to what makes desire happen, both in the cells and in the brain, right?

    20. PAPeter Attia1:13:29

        Yep.

    21. SPSharon Parish1:13:30

        So the naysayers are saying, "Well, okay, but that's not necessarily the active component. And like looking at SHBG and free T might not be like what we need to be doing anyway," right? But I, I, I, I think-

    22. PAPeter Attia1:13:46

        A- and sorry, just let, let's go down that rabbit hole a little bit further-

    23. SPSharon Parish1:13:49

        Yeah. Mm-hmm

    24. PAPeter Attia1:13:49

        ... because this is something that fascinates me endlessly-

    25. SPSharon Parish1:13:52

        Yeah

    26. PAPeter Attia1:13:52

        ... is, um, at least in men, the way I think about this, but I, I, I would think that it'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 the lingo you and I are throwing around. Testosterone is an, is a measurement assay. When you go and measure, uh, 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 deciliter 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, um, 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. So we... You know, so let's just... I'll give you a very clear clinical example I see that I see in men, but I know it applies to women, which is you take two guys that both have a total testosterone of 500, and let's just assume that their free testosterones are estimated to be roughly the same. And you give them both testosterone, and one of th-... So now they both have a total testosterone of 1,000. 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-

    27. SPSharon Parish1:15:36

        Mm-hmm

    28. PAPeter Attia1:15:36

        ... 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, uh, I mean, this is something I... I mean, to my knowledge, Sharon, we don't have a way to measure this clinically. This is... You know, I know that there are people in the lab who can do this, but you know.

    29. SPSharon Parish1:16:08

        Right. Right. So this is, um, part of what that, 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, um, actual measurable testosterone, what we think is free or bioavailable, and how that's interacting with the androgen receptor, both in non-genomic and gen- through genomic mechanisms. And then all of that, what cells do we even mean in a woman?

    30. PAPeter Attia1:16:40

        Yeah.
11. 1:25:17 – 1:39:13

    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. PAPeter Attia1:25:17

       something. There's a, there's an undercurrent of bad science here, which was one of the reasons given, uh, for the fear around this, uh, 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?

    2. SPSharon Parish1:25:56

       So we can say at least two dozen. You know, um, the numbers, like depending on how you look at the indication, whether it's for, you know, hypogonadism-

    3. PAPeter Attia1:26:04

       Yeah

    4. SPSharon Parish1:26:04

       ... versus sexual dysfunction. You know this, right?

    5. PAPeter Attia1:26:05

       Call it, call it 25.

    6. SPSharon Parish1:26:06

       So let's just say two dozen.

    7. PAPeter Attia1:26:07

       Yeah. Okay.

    8. SPSharon Parish1:26:07

       Right. Let's just say-

    9. PAPeter Attia1:26:08

       So-

    10. SPSharon Parish1:26:08

        Yeah

    11. PAPeter Attia1:26:09

        ... those products get approved on biochemical efficacy. Do they or do they not raise testosterone? They're, they're not-

    12. SPSharon Parish1:26:18

        And it-

    13. PAPeter Attia1:26:18

        Yeah.

    14. SPSharon Parish1:26:19

        And also outco- like the outcome of desi... You know, that you're looking for, the target outcome of the study.

    15. PAPeter Attia1:26:24

        Right. But the, the point is-

    16. SPSharon Parish1:26:25

        Like the main outcome

    17. PAPeter Attia1:26:25

        ... they, they don't require the five-year safety window-

    18. SPSharon Parish1:26:27

        No

    19. PAPeter Attia1:26:27

        ... because we've already established over decades that exogenous testosterone at physiologic doses is safe.

    20. SPSharon Parish1:26:35

        Is safe.

    21. PAPeter Attia1:26:36

        Yeah. So a- again, you could make the point, "Well, Peter, why do, why do you care about this? I mean, it's just pr- you can prescribe it off-label to women," which of course we do.

    22. SPSharon Parish1:26:46

        Oh, no.

    23. PAPeter Attia1:26:47

        But it's-

    24. SPSharon Parish1:26:47

        There's a huge reason to care.

    25. PAPeter Attia1:26:48

        But yeah, so, so let's talk about why does this matter?

    26. SPSharon Parish1:26:51

        Right. So, um, the, there's been a lot of feeling that the standard, just to emphasize this clearly, applied to the first drug. Uh, the, the Libigel, you, you asked me about that. It never made it to the FDA.

    27. PAPeter Attia1:27:05

        Right.

    28. SPSharon Parish1:27:05

        They, they withdrew it. They withdrew their applications in, in 2011.

    29. PAPeter Attia1:27:08

        Yeah, it di- didn't have efficacy, correct? It wasn't-

    30. SPSharon Parish1:27:10

        Right.
12. 1:39:13 – 1:45:38

    A hypothetical treatment plan for the patient in case study #1

    1. SPSharon Parish1:39:13

       we... And- and we didn't get back to this with the oral contraceptive patient. The solution isn't to leave her on a birth control pill and give her testosterone, right? First of all, it's not indicated for premenopausal women. Second of all, why? That's not what you do, right? You try to correct the, the hormonal imbalance.

    2. PAPeter Attia1:39:24

       So you would, you would ta- if this is the woman we're talking about, just going back-

    3. SPSharon Parish1:39:28

       Going back to her

    4. PAPeter Attia1:39:28

       ... to our hypothetical case. Yeah.

    5. SPSharon Parish1:39:29

       Right.

    6. PAPeter Attia1:39:29

       Y- let's just say that that's the path we're going down. You would remove her from the OC, probably switch to an IUD. If test- if SHBG levels were still sufficiently high, y- and, and free testosterone... Well, let's just say total testosterone was kind of 40th percentile, you'd say, "Look, we're gonna bring that up higher," and ag- given that your SHBG is so high, it's gonna 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-

    7. SPSharon Parish1:40:00

       Right. So-

    8. PAPeter Attia1:40:00

       ... symptoms and... Yeah.

    9. SPSharon Parish1:40:02

       So let's say that's what I decided. I look at the biological, psychological, and social factors in this woman, and I decide like that's the thing that's amenable to intervention. I'm gonna change her contraception, right? And, um, so it's not just women who are already on these that I tell. I- I'm a little... You know, birth control pills, combined contraception, I wanna make this disclaimer, patches and rings are extremely effective, and most women don't have a problem, right? So if you ask me, "What should I take?" You know, it's... You have to talk to your doctor, right? "Should I use an IUD to start with?" I can tell you how I counsel my own daughter, but that's my college-aged daughter. But that's, that's different than what I would tell patients and people. Um, they, they, they're incredibly effective worldwide. They prevent un- un- unwanted pregnancies. They prova- protect against birth con- you know, b- uh, birth fatalities, et cetera, worldwide. They liberate women all across the world. We don't wanna like say nobody should take birth control pills.

    10. PAPeter Attia1:40:58

        Of course.

    11. SPSharon Parish1:40:59

        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, right? Whether you should... What you should tell a 20-year-old about whether to use birth control pills or put in an IUD is like a whole 'nother conversation, right?

    12. PAPeter Attia1:41:13

        Yep.

    13. SPSharon Parish1:41:14

        To be preventive, again, this is a small percentage of people who develop these issues. Most... Some women are insensitive to the... Everyone gets a change in their SHBG. Some women are insensitive to it. Some women are insensitive to the un- the non-endogenous estradiol in their vestibules. Some aren't. So I can't tell you who that's gonna happen to. Um, so again, the decision about what to use over time is a discussion with your doctor. Um, I think more gynecologists need to offer informed consent so women can choose more carefully at the onset, and this is an important campaign that gets missed, right? Like there's no informed consent. They're just hand people a prescription at 21, right?

    14. PAPeter Attia1:41:50

        Yeah.

    15. SPSharon Parish1:41:50

        You should give women choice. Um, but anyway. So getting back to testosterone, um, so I think the challenge is then, like w- w- we weren't gonna use it on this patient, 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-

    16. PAPeter Attia1:42:07

        Yeah

    17. SPSharon Parish1:42:07

        ... 'cause women are all over the place. Like how well they get one tenth, how that one tenth of the product wasn't-

    18. PAPeter Attia1:42:12

        Well, also how var- how variable the absorption is.

    19. SPSharon Parish1:42:15

        Correct. Right.

    20. PAPeter Attia1:42:15

        Not all people have the same skin.

    21. SPSharon Parish1:42:17

        These were not designed for women. I can tell you that the data in Australia is very positive, for example. I, I worked very closely with the, one of the main researchers there, a woman named Susan Davis, who's done a lot of the work, um, in this field, both in Australia and worldwide and, and is a first author on a number of really important c- testosterone consensus papers. She, um, impresses me by 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-

    22. PAPeter Attia1:42:45

        Yep

    23. SPSharon Parish1:42:45

        ... regulated and formulated. We need that. That said, you do have to follow levels mainly to make sure that you're achieving safe doses, right?

    24. PAPeter Attia1:42:56

        Yep.

    25. SPSharon Parish1:42:56

        So like if you said to me, well, like let's say someone has a level, but it's too low, and they're not getting benefit- Um, would you go up?" And I'd 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 they're, 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 for, because of what you explained, the smartest thing is just to measure a total T, right? It's not a g- So we, we, 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 in their cells and in their brain, right? Their genital cells, their brain, and some other body cells, too, right? But that's probably the grossest best measure we have. 'Cause T, free T is calculated, and we don't even know if that's the bioactive component.

    26. PAPeter Attia1:43:46

        Right. Yeah.

    27. SPSharon Parish1:43:47

        Testosterone d- d- it's a very complex, what now is called endocrinology. It hits the cells. It gets converted into metabolites, um, androstenedione, DHT. It enters the cell through the androgen 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, right?

    28. PAPeter Attia1:44:10

        Yep.

    29. SPSharon Parish1:44:10

        And so all that's happening, probably the te- the total T is the best measure of both not being too toxic and also probably targeting, right? And 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 Quest or LabCorp, and they're, they're not... They're imprecise when you use them for women. They're not the best measure, but they're good enough-

    30. PAPeter Attia1:44:32

        Yeah
13. 1:45:38 – 1:52:44

    The role of DHEA (a precursor to testosterone) in female sexual health

    1. PAPeter Attia1:45:38

       talk about one other hormone before we leave this and go to our next topic, and that is the role of DHEA. Um, so, you know, just for, for folks who might not be familiar, DHEA is a precursor to testosterone. Um, DHEA is actually not regulated in the United States. It's a hormone you can buy over the counter, um, which is odd. I, I don't really understand why it's unregulated, but that's another story. W- what is the role of, of oral or topical-

    2. SPSharon Parish1:46:05

       Oh, great question

    3. PAPeter Attia1:46:07

       ... DHEA in-

    4. SPSharon Parish1:46:07

       Great question.

    5. PAPeter Attia1:46:07

       Yeah, i- in, in, in female sexual health?

    6. SPSharon Parish1:46:11

       Yeah. So, so the testosterone and its metabolites and its precursors are also, like, an area of confusion. So D... Like, the simple version, which is good right now, is the DHEA is a precursor.

    7. PAPeter Attia1:46:20

       Mm-hmm.

    8. SPSharon Parish1:46:21

       Right? So why not use that and then make testosterone, right? That's-

    9. PAPeter Attia1:46:24

       Yeah.

    10. SPSharon Parish1:46:24

        And then DH... So testosterone gets metabolized to m- to things, for example, like 5 alpha DHT, which is probably the most potent metabolism, metabolite, and aromatase to estradiol. So when we're talking about throwing all these things out, we're talking about do we wanna look at a precursor or a metabolite, and then the, what's actually working in the body or in the cell? So the short answer is there've been some trials looking at oral DHEA for the outcomes of interest that we're talking about here, for example, low sexual desire, and they have not been convincingly positive. Um, 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-

    11. PAPeter Attia1:47:05

        Mm

    12. SPSharon Parish1:47:05

        ... using the product, the 300 microgram or gel p- products, right? Um, 300 microgram patch.

    13. PAPeter Attia1:47:11

        Right.

    14. SPSharon Parish1:47:12

        And, and again, that's different than the blood level, which we're measuring in picograms per ML. Everyone understand. I, uh, I mean, uh, da- da, uh, da, in... Pa- picograms per ML is what we m- measure for one. Anyway, we'll, we'll come back to the measurement in a second. Um, but the d- oral DHEA, which is administered in milligrams, right, um, ha- has been... Some outcome studies have been done. They've been small. They've been p- problematically designed and not... Like, the, 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, right? Um, so we don't recommend oral DHEA for the indication of HSDD. Um, you know, whether... I know people use it. Whether it helps some patients and whether th- we're doing anything problematic to the way we're measuring different things is, is, is impossible for me to tell you because we don't have good control data on this. Um, that said, there is very good data supporting the use of a vaginal, intravaginal DHEA. The chemical is called prosterone. The brand is called IntraRosa. It's, um, basically it's a, it's like a little suppository. It's used for vulvovaginal atrophy re- resulting in genital urinary symptoms of menopause, and the indication is dyspareunia 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, and hope- we'll, maybe we'll have a few minutes to get into that, is that there are mixed receptors in the genitals that-

    15. PAPeter Attia1:48:53

        Mm

    16. SPSharon Parish1:48:53

        ... need both estrogen and androgen. So it gets metabolized into both androgens and then eventually to estrogens in the, at the intracellular level. That's the theory of it Right. 'Cause again, remember DHEA is a precursor

    17. PAPeter Attia1:49:06

        So how, how do you decide, Sharon, for a woman who's presenting with a pretty common presentation, um, if you should go down the-

    18. SPSharon Parish1:49:15

        Whether they have estrogen

    19. PAPeter Attia1:49:15

        ... whether you're gonna use an estrogen suppository or whether you're gonna use a DHEA suppository?

    20. SPSharon Parish1:49:21

        So, um, the data suggesting differences in efficacy isn't there, right? So you really could offer, like I really-- We can get into like-

    21. PAPeter Attia1:49:30

        Hmm

    22. SPSharon Parish1:49:30

        ... 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, um, and then there's tablets, right? And there are-- they're all local vaginal estrogen products that help with dryness and pain with sexual activity. And then DHEA, uh, the Intrarosa product, is an option. And so, you know, the, 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. Um, and there are some-- I have some educated patients who that's what they want. Um, the other thing is that it doesn't have a black-

    23. PAPeter Attia1:50:06

        A- any, any distinct pros and cons that you would point to?

    24. SPSharon Parish1:50:08

        Yeah. So it doesn't have a black box warning, right-

    25. PAPeter Attia1:50:10

        Yeah

    26. SPSharon Parish1:50:10

        ... which we will also have to get into. And so some people like, just like not seeing that warning, right?

    27. PAPeter Attia1:50:16

        And the black box warning with, with the estrogen is around breast cancer or clots?

    28. SPSharon Parish1:50:22

        It ha- So it has to do with i- it-- both endometrial and breast cancer and vascular thromboembolism, and there are a few other things thrown in there. But it's-- The idea is that, um, they're applying the risk factor data, primarily from the WHI actually, for systemic estrogen therapy, that it's a, 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. And even the, even the systemic hormone therapy-

    29. PAPeter Attia1:50:54

        Yeah, yeah

    30. SPSharon Parish1:50:54

        ... you know, that could be dissected.
14. 1:52:44 – 2:08:40

    Case study #2: A 30-year-old woman with anorgasmia (inability to orgasm)

    1. PAPeter Attia1:52:44

       the discussion of our first patient, um, as we now talk about our second patient. Um-

    2. SPSharon Parish1:52:49

       Sure

    3. PAPeter Attia1:52:49

       ... so [clears throat] our second patient, um, let's say she is younger. Um, I don't know, let's say she's thirty. She has no kids, been sexually active for twelve years, and she comes to you complaining of anorgasmia. So she says, "I have desire, but I-- and I do get aroused somewhat, but I'm-- I have never been able to, either alone or with a partner, achieve what I think I'm told an orgasm is." So I'm, 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. Um, but I, I, I'm curious as to how, how you would counsel this, this woman, and i- if you think that this is a reasonable example to use to explain that.

    4. SPSharon Parish1:53:50

       So, um, sure. Um, what I thought you were gonna tell me is that sh- she's-- nothing else is going on. She has no sex drive and are there FDA-approved drugs for low desire, which we didn't talk about [laughs] for women.

    5. PAPeter Attia1:54:02

       Okay. Well, l- let's, let's come, let's come back to that then. Yeah.

    6. SPSharon Parish1:54:04

       But that's not the question you're asking me.

    7. PAPeter Attia1:54:05

       Yeah.

    8. SPSharon Parish1:54:05

       Let's come back. Let's turn her into someone who has a different problem after that.

    9. PAPeter Attia1:54:08

       Okay.

    10. SPSharon Parish1:54:08

        'Cause I think we don't want to forget to mention there are two drugs that are-- We're talking about all this testosterone that's not approved.

    11. PAPeter Attia1:54:14

        Yeah. Mm-hmm.

    12. SPSharon Parish1:54:14

        But we should make sure before we, we conclude that we let people know there are two drugs FDA approved-

    13. PAPeter Attia1:54:19

        Yep. Okay

    14. SPSharon Parish1:54:20

        ... for low sexual desire in premenopausal women. But let's go to orgasm. So, um, the, the-- One of the biggest things when someone comes to me, this is not an uncommon, uh, uh, um, r- someone-- not an uncommon clinical scenario. You picked a good one, Peter, because is, is saying, I, you know, I-- a youngish woman, but old enough to start realizing like, "Hey, I'm thirty. By now, like this should've happened," right? You know, or, "Is there something wrong with me?" Or, you know, um, 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? [laughs] Or, you know, there's a lot of reasons why people seek it, but I, I-- first thing I do is try to figure out if it's primary anorgasmia, meaning they've never had an orgasm, or secondary Um, meaning they had one and now suddenly it's gone, right? The scenario I think you're telling me is someone who has, like, really never-

    15. PAPeter Attia1:55:14

        Primary

    16. SPSharon Parish1:55:14

        ... really felt like they had an orgasm and now... So one of the first things I ask them is, like, "Why are you now bringing, coming here to talk to me about this? What is different?" Right? So sometimes, and-

    17. PAPeter Attia1:55:23

        Well, let's just say it's, uh, it's, it's... I'm, I've, I'm really with a, an 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 because they c- I'm, I'm making this up, but I would assume that this is a-

    18. SPSharon Parish1:55:51

        It's... Yeah, no

    19. PAPeter Attia1:55:52

        ... it's a classic presentation

    20. SPSharon Parish1:55:53

        It's a common reason.

    21. PAPeter Attia1:55:53

        Yeah.

    22. SPSharon Parish1:55:54

        Right. Right.

    23. PAPeter Attia1:55:54

        Yeah.

    24. SPSharon Parish1:55:55

        So, so the most common reason that women suddenly decide to come to me for anorgasmia is that they are now in a relationship. And it, it may be that they themselves want to have a more satisfying experience or the partner wants to. Um, sometimes they lose relationships because they-

    25. PAPeter Attia1:56:10

        Mm.

    26. SPSharon Parish1:56:10

        It's not so much the partner isn't willing to work it through, but they, um, feel uncomfortable about having this problem and letting a partner see that they can't solve it, right? Um, but some- that's u- it's usually contextual, right? But not always. Sometimes women just sort of come to this realization that this is something they want to explore. Um, so you asked me what an orgasm is. I mean, I think, you know, the idea that it's a peaking after, you know, you become interested, you feel a sense of... We've talked a- some about arousal. You feel, like, mentally excited. Your body feels turned on. There are physical changes that you notice. Um, and then there's sort of a, a, a sensation, um, 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, the, the... what's actually happening is first there's... Well, we can talk about what happens when you get stimulated. There's sensory input which causes... You know, you, you get a, a, a stimulation to the sensation. It causes a response that heads to the spinal cord. It can trigger the autonomic nervous system, the both the... f- first the parasympathetic nervous system to cause vasodilatation, um, a sense of, like, the p- some- here's where the pelvic muscles sometimes can then relax during sexual activity. You get muscle relaxation, vasodilatation, and then it triggers eventually, as you become more and more aroused, the s- the... 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. Your blood vessels become maximally dilated. And nerve stimulation, um, cau- results in the res- local release of some neurotransmitters which cause secretions and lubrication. So it's, um, for example, vasoactive intestinal polypeptide. There's some involve with nitric acid, nitric, nitric oxide and CMP like in men contributing to both vasodilatation secretion and, and so forth. So you get, like, again, you get this stimulation, parasympathetic nervous system, then sympathetic nervous system, then muscle contraction, local hormones, brain, brain chemistry, local hormones, secretions, and people get this sense both of well-being, pleasure, um, pelvic floor contraction. They may get secretions, and then they feel they've had an orgasm. So there's a lot of variability. That's the full, the full monty. There's a lot of variability. Some people just feel, like, a intense sensual or m- or mental pleasure. Others feel a, like 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," right? Or that term comes up sometimes. Um, and that's a whole nother discussion.

    27. PAPeter Attia1:58:58

        Yeah, what, what-

    28. SPSharon Parish1:58:59

        Like, is that supposed to happen?

    29. PAPeter Attia1:58:59

        Yeah, what, what... So first of all, what proportion of women have that sort of ejaculatory response with an orgasm?

    30. SPSharon Parish1:59:06

        It, it's hard to say. You know, I, I, I think m- my, some of my colleagues believe that it's part of every sexual response and that it's just not being perceived. Um, I would say about 20% of people are aware of it, and that's sort of what's written. But again, um... So there's this, a whole nother theme going on in the sexual medicine literature about whether women have the prostate function in the local genital milieu that results in the squirting of fluid. Um, what I can say is it's controversial, and probably, um, more commonly what I hear in, when people are having sort of a more normal orgasmic or arousal and then orgasmic response is that the lubrication from the mucosal surface becomes robust, right? And that's probably the interaction between vasodilatation, the nervous system, and the local hormones such as VIP and nitric oxide. Um, 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-
15. 2:08:40 – 2:17:32

    Resources for helping women and their partners to enhance the pleasure experienced during sex, overcome anxiety, and increase desire

    1. SPSharon Parish2:08:40

       age 'cause the sensitivity goes down. And so I, I really normalize the use of, of vibratory stimulation 'cause it helps a lot, right? But sometimes it also helps for younger women. So, like, do-- this is less the case sometimes for younger women 'cause they don't need quite as much stimulation and, um... But I ask them, like, have they tried techniques for improving or enhancing stimulation. Um, the biggest factor is that women kinda don't know their structures. The, the actual clitoris isn't the most sensitive. It's the sides of the clitoral-- the, the, the flanks of it, right? The side. For example-

    2. PAPeter Attia2:09:12

       Yeah

    3. SPSharon Parish2:09:12

       ... 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, are concentrated. That top of the clitoral hood is actually very easily irritated and not-- doesn't like being rubbed very much. [chuckles]

    4. PAPeter Attia2:09:26

       Hmm.

    5. SPSharon Parish2:09:26

       And like, so some partners are sitting there rubbing, rubbing, you know, like, as 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. I, I personally still send people-- there's a number of books, and we could talk about those. So that's where bibliotherapy, looking at some really responsible lay press literature on, like, becoming-- book called Becoming Orgasmic. The Joy of Sex has been republished and published and published and it's still a great book.

    6. PAPeter Attia2:09:54

       What, what year was the first version of that book?

    7. SPSharon Parish2:09:57

       I think it was in the-- I-- that's a good question. I should have checked that for you, but I think it was in the se- could it be the '70s? It, it might be even be s- you know, it was, is some decades ago.

    8. PAPeter Attia2:10:06

       Yeah, yeah. Oh, like fifty years ago.

    9. SPSharon Parish2:10:06

       Good question to find out. Yeah, I mean, I think-

    10. PAPeter Attia2:10:09

        Okay. So, so The Joy of Sex. So what-- rattle off the names of the books that you would use as reference here.

    11. SPSharon Parish2:10:13

        So, um, For Yourself. Here's some-- these are some s- books that I like. For Yourself.

    12. PAPeter Attia2:10:18

        Okay.

    13. SPSharon Parish2:10:19

        Becoming Orgasmic. I-- The Joy of Sex. Um, there-- Sandra Leiblum has a couple of different books. Um, she's a sex therapist who's no longer with us. She had an unfortunate accident. But she's written several different books. Some of them n- and more of her work is on desire. Lori Br- Lori Brotto on mindfulness, and it talks a lot about learning how to stimulate yourself-

    14. PAPeter Attia2:10:42

        Hmm

    15. SPSharon Parish2:10:42

        ... and create, um... So, so there's books, you know, available. There's also a website. Um, 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, OMGYES. Like, oh my God, yes, [chuckles] I guess. Um-

    16. PAPeter Attia2:11:00

        So sorry. The, the website is just www.omgyes

    17. SPSharon Parish2:11:05

        OMGYES

    18. PAPeter Attia2:11:06

        .com.

    19. SPSharon Parish2:11:06

        Yeah.

    20. PAPeter Attia2:11:07

        Okay.

    21. SPSharon Parish2:11:08

        I guess it's dot-

    22. PAPeter Attia2:11:08

        All right.

    23. SPSharon Parish2:11:08

        I just Google it and it pops up.

    24. PAPeter Attia2:11:10

        Yeah, yeah.

    25. SPSharon Parish2:11:10

        OMGYES. Oh my God yes. I mean, God is just... We'll just say it. That's what I think it is.

    26. PAPeter Attia2:11:14

        Yep.

    27. SPSharon Parish2:11:15

        And it's a very responsibly produced website that has a lot of education for women, including-- So you have to s- have a sm- there's a small amount of money for a subscription. I think a, the standard program's, like, around forty dollars, and then there's a larger fee for a more involved program. You can-- 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 s- for clitoral and other kinds of stimulation, and really teaching people to learn how to stimulate themselves and become orgasmic. So I tell-

    28. PAPeter Attia2:11:45

        And is it, is this a site that is also just as helpful for men, uh, or female partners-

    29. SPSharon Parish2:11:51

        To learn about their partners

    30. PAPeter Attia2:11:51

        ... of other women?
16. 2:17:32 – 2:32:36

    Two drugs for premenopausal women with low desire

    1. SPSharon Parish2:17:32

       strangely, they're around, and they're available, and very few people when I-- Either they know about it, and they come to me for a prescription 'cause they've already been through everything else, or they, uh, when I tell them, they're shocked to hear that that's available, right? I don't know. Have you, have you heard of these? Like, many people haven't.

    2. PAPeter Attia2:17:46

       I have not.

    3. SPSharon Parish2:17:46

       So-

    4. PAPeter Attia2:17:46

       No.

    5. SPSharon Parish2:17:47

       Yeah. Interesting, right? So the first one I'll talk to you about, and I'll, I'll briefly tell you about them and feel free to ask me questions. Um, would you like me just to explain what they are at this point?

    6. PAPeter Attia2:17:55

       Sure. Yes, please.

    7. SPSharon Parish2:17:56

       Yeah. So there's flibanserin. The brand name is Addyi, A-D-D-Y-I. And it was like a lot of these drugs. It was discov- It's a centrally acting drug. It acts on serotonergic and dopaminergic receptors, and it has a complicated mechanism which is actually not fully understood. It's mixed serotonergic agonist and antagonist. It's actually 5-H2TA. And 5-H2, um, i- 1A and 2A are both agonists. One's agonist, one's antagonist. It's mixed agonist/antagonist and has activity at D4, which is dopamine receptors with mode- moderate affinity for some other serotonergic receptors, 2B and 2C. And that region-specific effect seems to be pro-sexual. It was studied for depression but discovered to be helpful for low desire. Um, it's je-

    8. PAPeter Attia2:18:49

       So, so kind of, kind of, kind of like Viagra was studied for blood pressure-

    9. SPSharon Parish2:18:52

       Yeah

    10. PAPeter Attia2:18:52

        ... and found to... Yeah.

    11. SPSharon Parish2:18:54

        Right. But it, it-- this is a centrally acting drug.

    12. PAPeter Attia2:18:57

        Yeah.

    13. SPSharon Parish2:18:57

        So that's not to say that, like, women who respond to this are getting it 'cause they're depressed, but, you know, one wonders, right? I'm not gonna let the-- like there may be a, a spectrum-

    14. PAPeter Attia2:19:05

        Mm-hmm

    15. SPSharon Parish2:19:05

        ... of like why people have low libido specifically as a presenting complaint and why a centrally acting drug could be helpful. Um, it's FDA approved. It-- 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 do use the same criteria you use for any decision to use a drug, right? It's not fancy.

    16. PAPeter Attia2:19:24

        Is it a, is it a drug that a woman takes every single day, or is it one that she takes-

    17. SPSharon Parish2:19:28

        So it's daily.

    18. PAPeter Attia2:19:28

        Okay.

    19. SPSharon Parish2:19:29

        On demand, centrally acting. It's a single dose. There's only one dose. There's no titration. A hundred milligrams. It's taken at bedtime When it first-- It's been FDA approved since twenty nineteen. 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. Um, I happened to be the president of ISSWSH at the t- during the few years it was approved, so I spent a lot of time at the FDA trying to advocate for its approval. So I, I can tell you more what, what that struggle was like more personally. [laughs] It, um, it is administered at bedtime. Initially, they did a lot of research looking at hypotension and syncope and its interaction with alcohol. And for a few y- for some time, it had a REMS, where 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 s- patients had to sign a form that they wouldn't drink alcohol at the pharmacy, and pharmacists had to sign that they wouldn't count-- that they wouldn't, um... that they counseled patients. It was re-looked at that it was really no different than any drug in class. Like SSRIs give hypotension if you take them and drink alcohol or make you feel woozy or sedated. And so it's drug in class advice now. It, it's-- they're still black box because the FDA wouldn't go all the way, but it's, um, it's not anymore-- it's similar in class to SSRIs. The side effects are similar. Um, anyway, you take it at night, and most people, you take it and you go to sleep 'cause it does, like-- and it can cause a little sedation. It's sort of like mirtazapine.

    20. PAPeter Attia2:20:55

        Mm.

    21. SPSharon Parish2:20:55

        I tell people, "Take it and go to sleep," right? Um, most people tell me they sleep better and they're not, not drowsy. You take it, um, for... Uh, probably you see the maximum effect about, uh, four weeks, but it usually they say give it eight to twelve weeks. Um, if it works, you continue it. If it doesn't, you stop it. Um, it generally is about as effective as an SSRI is for depression. It-- The, the measurements in the studies are a little complicated, and we can come back to questions about that, but it looked at both desire ratings on a validated scale called the FSFI, FSFI, and satisfying sexual events. And it was found to be moderately effective. But in responders, it was quite effective. Um, again-

    22. PAPeter Attia2:21:33

        Mm

    23. SPSharon Parish2:21:34

        ... um, you use it. And what we don't know, like when you're depressed, you say, "Take it for six to twelve months," and then we stop and we see if-- how they do. If there's been some neuroplasticity and re- brain rewiring, and you probably know some about this. We don't have that research. So I-- it's kind of needs-- 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 SSRIs. About ten to twelve percent of people get a little-- get dizzy or tired, but that's c- fine if you take it at night. Um, dry mouth on a f- handful. It's, it's, uh, relatively safe. It's no-- It's as safe as any central acting drug that people prescribe routinely. Um, there are some contraindications. It can interact with CYP3A4 inhibitors and, um, can worsen the side effects of SSRIs, although it's not contraindicated to prescribe them together.

    24. PAPeter Attia2:22:21

        Are they contraindicated with... Okay. Yeah. I was gonna ask you that.

    25. SPSharon Parish2:22:24

        No. Interestingly, it is being looked at and it is sometimes used as a remedy for SSRI-induced side effects, but-- S- SSRI-induced treatment-emergent sexual dysfunction. But the, the issue is that you may have in, you know, augmented side effects, and the patient just has to watch for that. Um, I've used it in a handful of patients. It's not my first strategy, actually. That's a whole nother discussion about, like, what to do with treatment-emergent sexual dysfunction. We talked a little bit about just changing drugs or switching or adding bupropion. I don't do this first. Um, so that's one drug. I don't know if you wanna just make sure we have time to talk about the other-

    26. PAPeter Attia2:22:54

        Yeah. Let, let's spend a second on the other one

    27. SPSharon Parish2:22:56

        ... or answer more questions.

    28. PAPeter Attia2:22:56

        Let's spend a second on the other drug.

    29. SPSharon Parish2:22:57

        Yeah. So the other drug's completely different. It's bremelanotide is the chemical. The brand is called Vyleesi, V-Y-L-E-E-S-I. There's only-- These are both the only drugs available. There's no generics out there. Um, their websites have, like, good information for patients. This one is, um, a, it's a complicated one, but I'll tell you about it. It's a cyclic seven amino acid melanocortin receptor agonist with a high affinity for what's called the type IV melanocortin receptors, and it, it's an analog of MS- MSH, which is melanocyte-stimulating hormone. And what it does in, in the end is it acts in brain pathways that stimulate dopaminergic pathways. Um, and it's-- so it's a direct hit for desire, right?

    30. PAPeter Attia2:23:39

        Yeah.

Episode duration: 3:10:53