Peter Attia MD260 ‒ Men’s Sexual Health: why it matters, what can go wrong, and how to fix it
EVERY SPOKEN WORD
150 min read · 30,006 words- 0:00 – 1:18
Intro
- MKMohit Khera
The survey found that roughly 40% of men that, in the survey had some degree of sexual dysfunction, right? 50% of those men said, "I would love to get treatment, but I don't know where to go."
- PAPeter Attia
Hmm.
- MKMohit Khera
But what was very interesting, the clincher was, only 51% of those men told their doctor about it. Only 44% of those men told their partner or their wife about it. That's suffering in silence, and the main reason was they were embarrassed. Also, clinicians don't ask about it.
- PAPeter Attia
[upbeat music] Hey, everyone. Welcome to "The Drive" podcast. I'm your host, Peter Attia. Mo, thanks so much for making the trip over here from Houston. Uh, although I know you didn't come to see me.
- MKMohit Khera
[laughs]
- PAPeter Attia
You came for tennis, but I'll, I'll take what I can get.
- MKMohit Khera
It's okay.
- PAPeter Attia
Anytime we can do one of these in person, it's great. Um, there's a lot we wanna talk about today. Um, I will admit my insane capacity for ignorance in this domain. So when one of our analysts was working on, you know, sort of the topics we were gonna talk about, it turns out I know as little about this as I know about the contrapositive in women's sexual health. So, uh, you know, a lot of times I go into a podcast having more knowledge about a substance and, and, and I can guide the discussion more thoroughly. So I'll be kinda leaning on you heavily. But, um,
- 1:18 – 3:25
Mohit’s career path and interest in sexual medicine
- PAPeter Attia
maybe we can just start by talking a little bit about your background, your training, uh, and, and how that leads you to doing what you're doing. So, so after medical school-
- MKMohit Khera
Sure
- PAPeter Attia
... what did you go and do?
- MKMohit Khera
Sure. So first of all, thank you for having me on the show. So after... I went to college at Vanderbilt, and I first went to, uh, Boston University, got my MBA, got my MPH. I was a healthcare analyst for about two years. Uh, I didn't like it very much.
- PAPeter Attia
Hmm.
- MKMohit Khera
But I met my wife in Boston. She was at BU Medical School at the time, so I had a change of course and career path. Then I went to University of Texas, San Antonio, uh, for medical school. Then after that, I went to Baylor College of Medicine, did a one-year internship in general surgery, then did five years in urology, and then I did a one-year fellowship in male reproductive medicine surgery, where I really got into sexual health and infertility, and I've been at Baylor now since 2007 on faculty.
- PAPeter Attia
So tell me about what that means. So, you know, when I did my general surgery residency, the urologist I was working alongside with, 'cause one of my best friends, Ted Schaeffer, was, who you know, of course, is a urologist, uh, a big emphasis in urology, at least as I saw it from the outside, was of course on urologic cancers.
- MKMohit Khera
Right.
- PAPeter Attia
So, um, the big things that we saw the urologist doing was removing prostate cancer, removing bladder cancers, removing kidney cancers. Those were big parts of it. Um, because I was only limited in how much urology I did, I didn't really see much of any of the other stuff, so I don't really know what constituted reproductive health or sexual health for a man. So w- what was that fellowship like, and what were the things that you sort of focused on?
- MKMohit Khera
It was great. So listen, you know, urology is multiple subspecialties. It could be stones. It could be cancer. It could be female urology. But one subspecialty is sexual medicine, and another one is infertility, and usually they're combined.
- PAPeter Attia
Hmm.
- MKMohit Khera
And so really what you're focusing on is reproductive medicine in terms of vasectomy reversals, d- doing procedures to help men recover spermatogenesis, varicocele repair, sperm retrieval, but also sexual medicine, taking care of erectile dysfunction, premature ejaculation, Peyronie's disease, and a big focus of that is also hypogonadism. So that's really what I've focused my career on, is really the sexual medicine side. Um, and that's where we have my research and my basic science
- 3:25 – 5:06
The anatomy of the male genitalia
- MKMohit Khera
lab.
- PAPeter Attia
Does it make sense to just quickly orient listeners to the anatomy of what we're talking about?
- MKMohit Khera
Sure.
- PAPeter Attia
Okay.
- MKMohit Khera
Sure. So when people think about the penis, they think just about one simple organ, but there's actually a confluence of three different organs. It's really the urinary system, it's the reproductive system, and it's the sexual system together. So the urinary system, meaning the bladder. Next to the bladder comes the prostate. From the prostate comes the urethra. Now, in the prostate, there are two ducts called the ejaculatory ducts, and from those ejaculatory ducts, the testicles, through the vas deferens, will put some sperm into the ejaculatory ducts. Those ejaculatory ducts mis- mix with the seminal fluid from the seminal vesicles, and that gives a man his ejaculate. Above the urethra are two, what we call, call them tubes, if you will. These are called the corpora cavernosa, and essentially what it is, is just smooth muscle-
- PAPeter Attia
Mm-hmm
- MKMohit Khera
... inside. So those two smooth muscle bodies, corpora cavernosa, are responsible for erections. Below the tube, called the urethra, are responsible for urinary. So again, you just have three systems all coming together.
- PAPeter Attia
And so do you, in your mind, uh, 'cause I'd rather do this through the lens of h- your framework, do you think about this by problem, or by age, or by some other metric? How, how do you go about thinking through, uh, these issues?
- MKMohit Khera
It's, it's a holistic system.
- PAPeter Attia
Okay.
- MKMohit Khera
You think about it because ev- each of these can affect the others. For example, let's talk about the testicles. You know, when you talk about infertility, that can also affect hypogonadism. Hypogonadism could also affect fertility, right? So patients also, when you think about the urinary system, patients can t- have retrograde ejaculation-
- PAPeter Attia
Mm-hmm
- MKMohit Khera
... by taking medication for BPH. Well, that may affect a fil- fertility, and that may affect their sexual function, right? So all three are interrelated. So you think about it as
- 5:06 – 8:58
The prevalence of sexual dysfunction & impact on quality of life
- MKMohit Khera
a whole.
- PAPeter Attia
Yeah. Well, does it make sense to start with a certain set of problems, uh, and then maybe talk about how they change temporally-
- MKMohit Khera
Sure
- PAPeter Attia
... over, you know, in terms of prevalence by age? And, and if so, wh- where would it make sense to start? Do you want to start with premature ejaculation, erectile dysfunction?
- MKMohit Khera
Let's, let's start with ED.
- PAPeter Attia
Okay.
- MKMohit Khera
And I think about sexual m- he- health in general. I think, you know, I just want to put this into context. You've-- Why don't you think about this? So we know that 52% of men over the age of 40 suffer from erectile dysfunction of some degree. 52% of men. Even if you take conservative numbers, that's 30 million men in the US suffer from this disease. And-
- PAPeter Attia
And how are we defining it? Is it one time I had too much to drink and I couldn't get an erection? Or h- how do we think about it?
- MKMohit Khera
Great. So what we use is we use a, a questionnaire, a validated questionnaire called the IIEF, and this questionnaire, there's several forms, but there's a shorter version with six questions. And essentially based on those numbers, you can tell if someone has mild, moderate, or severe ED. So when they gave the original study in 1994, the, when it came out The, there's 52% of men over the age of 40 had some degree of erectile dysfunction. And you talked about aging, but it's very interesting. On that graph, 40% of men at 40 had some degree of ED.
- PAPeter Attia
Mm.
- MKMohit Khera
50% at 50, 60% at 60, 70% at 70. So it's an easy way to remember what percentage of men suffer from ED. Now, it's not necessarily aging, I think, that causes the ED. I think it's the acquisition of comorbid conditions as we get older.
- PAPeter Attia
Yeah.
- MKMohit Khera
And we'll talk about that. But again, it's a prevalent condition. Think about women. I treat a lot of women for sexual dysfunction. 43% of women in the United States suffer from some degree of sexual dysfunction. 30% of men in the US, some have some degree of premature ejaculation or ejaculatory dysfunction. 7 to 9% of men have Peyronie's disease. So this is-
- PAPeter Attia
How many?
- MKMohit Khera
7 to 9% of men-
- PAPeter Attia
Wow
- MKMohit Khera
... in the US have Peyronie's disease.
- PAPeter Attia
Which we'll, we, we should set aside time to talk about that.
- MKMohit Khera
And, and they don't... But the problem is that this population, I call it suffer in silence.
- PAPeter Attia
Yeah. That's what I was going to ask you.
- MKMohit Khera
They never talk about it.
- PAPeter Attia
Yeah.
- MKMohit Khera
They never talk about it. In fact, there are many studies showing they're completely silent. They don't seek care. And the issue is it has a significant impact on their quality of life, right? So we know that a third of men who have ED have suffered from depression because of their ED. Th- so 37% of men who have ED have anxiety because of their ED. We know that it causes impairment in quality of a relationship between a couple. And if you look at quality of life scores, they're significantly impaired in men who suffer from sexual dysfunction.
- PAPeter Attia
And so when you said suffering in silence, you weren't just referring to Peyronie's disease. You're talking about all sexual dysfunction.
- MKMohit Khera
All sexual dysfunction.
- PAPeter Attia
Wow.
- MKMohit Khera
So, so there's, there's reasons for that. So one is, if you look at, uh, surveys. There was... Actually, I got to bring this up because there was a, a great survey that came out last year. 1,500 men surveyed between the ages of 18 and 80, and they asked about their mental, physical, and sexual health. So in my world, it's mental, physical, and sexual health. It's, it's a triad, not s- mental and physical.
- PAPeter Attia
Yep.
- MKMohit Khera
And they're all related. But the survey found that roughly 40% of men that, in the survey had some degree of sexual dysfunction, right? 50% of those men said, "I would love to get treatment, but I don't know where to go."
- PAPeter Attia
Mm.
- 8:58 – 13:41
Erectile dysfunction (ED): definition, diagnosis, pathophysiology
- PAPeter Attia
Um, not to put you on the spot and ask you what those six questions are, but just directionally, what are the criteria for ED in terms of severity, frequency, and such?
- MKMohit Khera
Sure. So I think one of the easiest ways to look at it is to use a question called the SEP 2 and the SEP 3. So there's just two simple questions you have to ask the patient. Are you able to get an erection sufficient for penetration? It's either yes or no. And are you able to maintain that erection till orgasm?
- PAPeter Attia
Okay.
- MKMohit Khera
It's either yes or no. If they answer no to either one of those questions, they have ED.
- PAPeter Attia
Under any condition, even if it happens just once? Or if it says, "Well, you know, eight times out of nine, I'm okay, but one time out of nine, I can't"?
- MKMohit Khera
So they had, then they had one episode of ED.
- PAPeter Attia
I see.
- MKMohit Khera
So it's graded, right?
- PAPeter Attia
Yep.
- MKMohit Khera
But by definition, if someone says, "I can't..." And, and the number one cause of ED typically is, "I can't maintain it." So they're going to... That's the first sign. They say, "Doc, I can get it, but I can't maintain the erection." They're telling you, "I have venous leak," which is the first sign-
- PAPeter Attia
I see
- MKMohit Khera
... of some kind of erectile dysfunction.
- PAPeter Attia
To be clear, this is not confused with something I do hear quite a bit of from patients, which is, "I can get an erection. I can maintain an erection. I can't ejaculate."
- MKMohit Khera
We're going to talk about that.
- PAPeter Attia
That's a separate problem.
- MKMohit Khera
Uh, yeah. Yes, that's right. [laughs]
- PAPeter Attia
Okay.
- MKMohit Khera
Yeah.
- PAPeter Attia
So that's not ED.
- MKMohit Khera
Yeah.
- PAPeter Attia
Okay. So let's talk about the pathophysiology of this. Um, again, at the risk of sounding and d- demonstrating my ignorance, how much of this is physiologic, i.e. neurovascular? How much of this is psychological?
- MKMohit Khera
So the mnemonic I teach the m- teach the medical students is VENT. What are the re- etiologies? Vascular, endocrine, neurologic, and trauma. And Peyronie's disease can be trauma as well. So vascular, endocrine, neurologic, trauma. Don't forget medications. We'll talk about those.
- PAPeter Attia
Mm-hmm.
- MKMohit Khera
Beta blockers, for example, antiandrogens, finasteride. There's a lot of medications that can cause impaired erectile function. And then there's psychogenic ED. Now, psychogenic ED typically is in younger patients, right? It's not common that a young patient has organic ED.
- PAPeter Attia
Mm.
- MKMohit Khera
But they have psychogenic ED. And psychogenic ED is treated very differently than organic ED. And you, you want to ask them some questions. Are you able to get an erection with masturbation? If they say, "Yeah, no problem," that's psychogenic. They're telling you they have psychogenic ED.
- PAPeter Attia
Mm.
- MKMohit Khera
Uh, can you get an ere- do you get morning erections? "Oh, yeah, I get morning erections, but I'm have difficulty having sex." You're telling you have psychogenic ED. So you want to probe for that because psychogenic ED is treated with sex therapy. I use daily Cialis in these patients. It's very effective, I think. There's ways to treat that that's very different than organic ED.
- PAPeter Attia
Okay. So tell me a little bit more about what that means. Like, what... So do you refer out to sex therapy? What are sex therapists doing in these situations?
- MKMohit Khera
Sure.
- 13:41 – 18:21
The history of medications to treat ED and the mechanisms of how they work
- PAPeter Attia
this. Um, maybe just for folks, explain briefly how Cialis, Vi- Viagra work. You know-
- MKMohit Khera
Yeah, so-
- PAPeter Attia
... what, what's the mechanism?
- MKMohit Khera
The mechanism. So the erections are caused or induced by the parasympeth- parasympathetic nerves, and you can get stimulation oral... I mean, excuse me, ocular vision, hearing, sensory, any kind of sensory stimuli or tactile can induce the nerves to secrete nitric oxide, which will then go to the endothelium. This is the key. The endothelium will secrete nitric oxide, which is really the on-off switch.
- PAPeter Attia
Mm-hmm.
- MKMohit Khera
Once the nitric oxide goes up, we get an increase in something called cyclic GMP. Cyclic GMP causes intracellular calcium to go down. It causes the dilation of the sinusoids and increases the blood vessel diameter, and the blood comes in. Now, there's a bad thing there. There's something called phosphodiesterase, and phosphodiesterase eats up the cyclic GMP, and therefore you will lose the erection. So how does Viagra, Cialis, Levitra work? It's a phosphodiesterase inhibitor, so it blocks phosphodiesterase, so you have more cyclic GMP, so you can keep the erection around. Now, there's 11 different phosphodiesterases in the body. So for example, f- type five is in the penis.
- PAPeter Attia
Hmm.
- MKMohit Khera
Six is in the eye. 11 is in the back. So some of these medications have cross-reactivity with the other phosphodiesterases, so you get side effects. For example, Cialis has more side effects with phosphodiesterase type el- 11, so you may get more back pain. Viagra has more cross-reactivity with type six, so you may get changes ocular vision. So ideally, you want one that only affects five and nothing else.
- PAPeter Attia
And is there one to date that does that?
- MKMohit Khera
Uh, yes. Uh, in my opinion, the newest one, Avanafil, has the least correct creas- uh, ra- cross-reactivity with the other phosphodiesterases, so I think it has less side effects. The only difference is that it is not generic yet, so it's expensive.
- PAPeter Attia
Much more expensive.
- MKMohit Khera
Yeah. So the generics now, you can... If you go to Cost Plus or, you know, Mark Cuban's, or you go to GoodRx, it is so cheap to get Cialis today, but Avanafil is still not generic.
- PAPeter Attia
I see. Um, you wanna tell people the story of how Viagra was developed?
- MKMohit Khera
So Viagra was, uh, developed to be a... It was in 199- before 1998, but it was developed to be a blood pressure medication to control the blood pressure, and, uh, they started noticing that everyone was getting... or a cardiovascular medication, and everyone was getting erections in the trial, right? And that's how they found-
- PAPeter Attia
Everyone who got the-
- MKMohit Khera
[laughs] Got the placebo
- PAPeter Attia
... everyone who got the Viagra as opposed to the placebo.
- MKMohit Khera
Yeah, the placebo.
- PAPeter Attia
Yeah. Yeah.
- MKMohit Khera
Yeah. Very interesting. Uh, other drugs were the same way. I- You may have heard of the drug Addyi. Why- We use this to treat female sexual dysfunction or Flibanserin.
- PAPeter Attia
Yep. Yep.
- MKMohit Khera
Uh, that was used as a medication for, um, uh, depression. Uh, it was by-
- PAPeter Attia
Yep
- MKMohit Khera
... Boehringer Ingelheim in Germany.
- PAPeter Attia
Yep.
- MKMohit Khera
And so they gave it to women for depression, and they noted these women wanted to have sex, and that's how we got the development of Addyi.
- PAPeter Attia
Yeah. And, and my recollection is Viagra was not successful as a systemic reducer of blood pressure.
- MKMohit Khera
Yes.
- PAPeter Attia
Other words, that trial failed.
- MKMohit Khera
Right.
- 18:21 – 29:14
Relationship between aging & erectile dysfunction and Mohit's approach to treating patients
- PAPeter Attia
Um, okay, so this phosphodiester- ase inhibitor, which now we're into our third generation of them, um, basically solve a physiologic problem.
- MKMohit Khera
Right.
- PAPeter Attia
So what is at the root of that problem? I mean, I understand that by inhibiting phosphodiesterase, you keep around more cyclic GMP, you maintain the flow of blood in the smooth muscle. But what is it about the aging process-
- MKMohit Khera
Right
- PAPeter Attia
... and/or its comorbidities that is leading to that venous leak in the first place?
- MKMohit Khera
Right. So the... You nailed it. So the main issue is venous leak, or we call it v- venocclusive dysfunction. So, uh, you have to think of the ama- anatomy. So it's actually very clever how the system was designed. So if you think of the two tubes I was talking about earlier-
- PAPeter Attia
Yep
- MKMohit Khera
... inside those two tubes are muscle and sinusoids. Down the center of the tube is an artery, okay? And think of the wall of the tube as a thick casing called the tunica albuginea, okay? Right under the tunica albuginea are veins we call, uh, subtunical veins. So as the blood comes in-
- PAPeter Attia
Hmm
- MKMohit Khera
... it presses against the wall-
- PAPeter Attia
Yeah
- MKMohit Khera
... and prevents the blood from coming out. So very clever system. The more blood comes in, the muscle can then press against the wall and prevent the blood from coming out of the penile tissue. The problem is, as we age, we get atrophy of the muscle, right? And we get fibrosis of the muscle.
- PAPeter Attia
Hmm.
- MKMohit Khera
So as we get atrophy and fibrosis of the muscle, we are able to get the blood in, but we can't keep the blood in.
- PAPeter Attia
Because we can't maintain enough pressure-
- MKMohit Khera
Right
- PAPeter Attia
... on the venous wall.
- MKMohit Khera
That's right. And so how do you overcome that? There's several ways. One is that you can act- so if... So it's a simple outflow/inflow game. So if the inflow is 10 and the outflow is 15, you're not going to get an erection, right? But if you give someone Viagra and you make the inflow 25, you can overcome the venous leak-
- PAPeter Attia
Yeah
- MKMohit Khera
... by increasing the inflow. That's one way.
- PAPeter Attia
Hmm.
- MKMohit Khera
The second way is actually some people use something called a penile band.
- PAPeter Attia
Like a tourniquet.
- MKMohit Khera
Like a tourniquet. Because if you use a tourniquet, you can actually compress the veins and still allow the inflow. So if a man-
- PAPeter Attia
So you haven't fixed the inflow problem, but you've increased the b- back pressure on the outflow.
- MKMohit Khera
That's exactly right. So... And so if a man took his hand dur- while he's having an erection and placed his hand and grabbed the penis at the 5 and 7 o'clock position, and pin- s- uh, press- put pressure, you'll notice that you'll get better and better erection, 'cause you're blocking the outflow.
- PAPeter Attia
Hmm.
- MKMohit Khera
But you can't keep your hand-
- PAPeter Attia
And, and tell people why you said 5 and 7 o'clock.
- MKMohit Khera
Well, it's r- that's typically... Well, uh, well, it's circumferential.
- 29:14 – 37:52
The impact of lifestyle on sexual health & the association between ED and cardiovascular disease
- PAPeter Attia
It's so interesting how evolution simply, you know... Y- you would argue that, you know, not that we want to spend too much time speculating on evolution, given that, as Andrew Huberman would say, neither of us were there for the design phase.
- MKMohit Khera
[laughs]
- PAPeter Attia
But, um, it's interesting in that you can, you can certainly understand, I think, in the case of women, why, based on the change in reproductive state, evolution didn't care as much about their sexual health as they got older. Is the same true for us, where evolution sort of thought, "Eh, the older you get, the more genetic mutations in your sperm. I actually don't want you reproducing as much when you're 50 as you are when you're 20"?
- MKMohit Khera
Yeah, I don't know about that. You know, I, we have patients who are older that have great semen parameters. I think it's based on your quality of your health.
- PAPeter Attia
Mm.
- MKMohit Khera
Right? So healthier men-
- PAPeter Attia
Which, by the way, would make sense
- MKMohit Khera
... you know, h- it makes sense 'cause you're more likely to reproduce.
- PAPeter Attia
Yeah.
- MKMohit Khera
So we look at men who are in their 80s, 80s, who are in great shape. They're having sex, no issues, no, even unassisted, you know?
- PAPeter Attia
Meaning they don't even require-
- MKMohit Khera
Viagra. Vi-
- PAPeter Attia
They use a bit of Viagra.
- MKMohit Khera
Y- yeah, but some do, some don't. I mean, I have patients at 70, 80 years old, great shape, no issues having s- uh, uh, uh, erections. The patients that come to me who are older, 60, 70, who are also trying to conceive, they marry someone younger, and you'll be surprised. Typically, sometimes you will see patients with sperm or spermatogenesis even at older ages.
- PAPeter Attia
Mm.
- MKMohit Khera
It's based on your quality of your health. You know, I have younger patients who are 30 that are in terrible shape, poor quality erections. terrible semen parameters. So I don't know if age is like-
- PAPeter Attia
Yeah. Yeah
- MKMohit Khera
... the main driver.
- PAPeter Attia
No, I think that makes sense. Um, and I, and I think I talked about this with Sharon on the podcast, but, um, the... I almost wonder if the greatest motivation for a patient, especially a male patient, with respect to insulin resistance, is actually erectile function. Because definitely one of the things I've seen in my practice is that patients who go from having a higher hemoglobin A1C to a lower hemoglobin A1C will often notice an improvement in erections.
- MKMohit Khera
Yes.
- PAPeter Attia
And, and a- again, I'm not talking about a one-point change, but if someone goes from having a hemoglobin A1C from, you know, 5.9 to 5, which, you know, represents probably about a 25 milligram per deciliter reduction in average blood glucose, that's a person who says, "I used to need Cialis for every erection," to, "I'm totally fine."
- MKMohit Khera
So you bring up a really important point. It's lifestyle modification. Lifestyle modification has a huge impact on the quality of a man's erections. And the four pillars that I stress all the time for most sexual dysfunctions, diet, exercise, sleep, and stress reduction. If you chose to do one of them, it would have an impact on your quality of erections and your quality of life, right? And there's other manifestations that would improve as well. But you're talking about insulin resistance, and when you improve insulin resistance, when you improve obesity, um, uh, stop smoking, all of these things improve. Now, I think there's a reason for this. There's a strong correlation between cardiovascular disease and ED.
- PAPeter Attia
Yep.
- MKMohit Khera
If I made a column of the risk factors for ED and cardiovascular disease, they're almost identical-
- PAPeter Attia
Yep
- MKMohit Khera
... on both sides. So I say, what is the common link? Why is ED... So many studies say that if you get ED today, within seven years, 15% of those men will have a heart attack or a stroke. 15%. It's the first sign of cardiovascular disease. Numerous studies have shown that.
- PAPeter Attia
And just to be clear, this is not psychogenic ED. This is-
- MKMohit Khera
It has to-- Organic.
- PAPeter Attia
Yeah.
- MKMohit Khera
Has to be.
- 37:52 – 48:32
Causes and treatments for Peyronie’s Disease & penile fracture
- MKMohit Khera
most cases.
- PAPeter Attia
Yep.
- MKMohit Khera
In most cases. And what's important is you can also look at the corpora cavernosa. I can look at plaque. I can look at plaque, 'cause that plaque's important because that is what causes an abnormal curvature.
- PAPeter Attia
You actually see plaque in the muscle?
- MKMohit Khera
Not in the muscle. So in the wall, the tunica albuginea.
- PAPeter Attia
Ah.
- MKMohit Khera
So think about the two tunica albuginea coming together. As they come together, in that V-
- PAPeter Attia
Yep
- MKMohit Khera
... is where you see the plaque predominantly. Most of the plaque happens in the V.
- PAPeter Attia
Huh.
- MKMohit Khera
So most curvature in the penis is dorsal, right? So it actually goes upwards, so 80%. And so these patients will have a curvature of the penis when it's erect. It's important when it gets greater than 60 degrees, 'cause that's prohibitive for intercourse, right? And it is-
- PAPeter Attia
60 degrees.
- MKMohit Khera
So patients can have 90 degrees. They can have almost 180 degrees. It can be very significant.
- PAPeter Attia
Wow. Huh.
- MKMohit Khera
So, so when... So but that is a very, that is a very significant dis- the patients who have Peyronie's disease really suffer from depression. They f- they're disfigured. They feel like there's a disfigurement. Um, there's a treatment now. Uh, 2015, the first FDA-approved treatment in the world came out for Peyronie's, which is called XIAFLEX or collagenase, where I can s- inject collagenase into the plaque and break it down so that I can improve the curvature. So that's very important, 'cause historically, we... until 2015, we had no medical treatment. Everything was off-label, you know?
- PAPeter Attia
And what would that include?
- MKMohit Khera
So people used to give vitamin E, and they used to give, um, colchicine. So in 2015, I was involved in the, uh, American Urological Association Peyronie's guidelines, first guidelines. And we said, "Do not give vitamin E. It's not indicated. Colchicine doesn't work." But the only medication that's indicated are anti-inflammatories. The way Peyronie's works-
- PAPeter Attia
This is a- administered locally or systemically?
- MKMohit Khera
No. Oral or systemically.
- PAPeter Attia
Okay.
- MKMohit Khera
So that's what we give. Think about this. The way Peyronie's disease works, there's an active phase and there's a quiescent phase. So the day you have an injury, for about 12 months, it's constantly changing. We have the rule called the 15, 40, 45 rule. 15% of patients will get better within the first year. That's awesome.
- PAPeter Attia
Sorry. Does this mean that Peyronie's disease is always born of trauma?
- MKMohit Khera
It's the prevailing theory. So we think that we... And, and sex is trauma, by the way. So and so when a patient engages in sexual activity, if he has 100% rigid penis, less likely to injure. If he's 70, 80, or 90% rigid, he's gonna penetrate, and he's gonna injure. So ED many times precedes PD, Peyronie's disease.
- PAPeter Attia
Interesting.
- MKMohit Khera
And so... And but we do think it's due to trauma during intercourse. That buckling trauma will then cause a plaque. So I tell patients, "Think about this. You have a balloon. I put a piece of duct tape on the balloon. I blow up the balloon. What's gonna happen? Everything's gonna expand except the duct tape, and you're gonna curve in the direction of the duct tape."
- PAPeter Attia
Yep.
- MKMohit Khera
Right? And the greater the duct tape, the greater the curve. So how can I treat this? I can use medications to remove the duct tape or the plaque.
- PAPeter Attia
And you can't incise, put a... You can't put a slit in the duct tape?
- MKMohit Khera
You can. So that's the surgical therapy.
- PAPeter Attia
Okay.
- 48:32 – 51:55
The value of ultrasound for ED diagnosis and management strategies
- PAPeter Attia
okay. So going back again to the diagnostics. So you induce the erection chemically. You look for arterial inflow and outflow, venous outflow, um, you diagnose... Let's just say the problem is purely on the arterial side. So venous problem, no issue. You mentioned you can still use the phosphodiesterase inhibitor to compensate.
- MKMohit Khera
You can.
- PAPeter Attia
So how does the ultrasound result change your management?
- MKMohit Khera
It lets me know where the problem is. So if it's a venous leak, you can offer a band. You wouldn't really wanna offer a band if you didn't have venous leak 'cause it's arterial insufficiency.
- PAPeter Attia
Yep.
- MKMohit Khera
Right? And it tells you how bad it is also. So if I see that the venous leak is end-diastolic of 10, 15, it just tells you the severity d- of ED, which is very important.
- PAPeter Attia
Tell me what normal is again.
- MKMohit Khera
So you want less than five on the end-diastolic. You want at least greater than 25 or 30 preferably on the peak systolic.
- PAPeter Attia
And so w- what would the typical numbers... Not that you're doing this on guys that have no issues, but if you did this on, like, a 20-year-old, you know, who had no issues whatsoever, what would you literally see as the numbers?
- MKMohit Khera
A peak systolic of 40.
- PAPeter Attia
Yeah.
- MKMohit Khera
Uh, end-diastolic of less than one.
- PAPeter Attia
Of two.
- MKMohit Khera
Yeah, yeah.
- PAPeter Attia
Yeah. Nothing. Okay.
- MKMohit Khera
So nothing. And, and, and, uh, what's important is that remember that each corpora cavernosa will have a different number sometimes.
- PAPeter Attia
So you're doing both sides.
- MKMohit Khera
You have to do both sides.
- PAPeter Attia
And what... How often do you see significant asymmetry?
- MKMohit Khera
Uh, usually it's not that significant, but at-- sometimes you can, so I just wanna be very clear. This is-
- PAPeter Attia
I see.
- MKMohit Khera
And so you could say, "You know, look, you're having some peak systolic, a low peak systolic on the right, but not on the left." You know, so it just gives you another diagnostic. Remember, what's interesting about the penis is it's fenestrated, right? So that whatever you have on one side compensates on the other.
- PAPeter Attia
Yeah.
- MKMohit Khera
So if you inject a medication on the right, it also gets to the left.
- PAPeter Attia
It's gonna go to the left.
- MKMohit Khera
Right. So it's fenestrated, so it does make it very easy. But the... You mentioned something important. You know, this peak systolic velocity, if it's low in a young man, I am worried, right? Because it, I think it's a marker for cardiovascular risk. You know, when, you know, you... W- There was this machine I ha- I was using in my fellowship. I was a fellow, and we got this machine called the EndoPAT 2000, and it would check endothelial function.
- PAPeter Attia
What was it called?
- MKMohit Khera
Endo- EndoPAT 2000. Was it... By Israeli company Itamar.
- PAPeter Attia
I lo- I love that she p- that it has the 2000 at the end of it.
- MKMohit Khera
[laughs]
- 51:55 – 59:38
Various treatment options for ED: injections, penile prosthesis
- PAPeter Attia
Okay. Now let's talk about some of those therapeutic options you mentioned. So, um, when is a man a candidate for an injection, and how long does that last?
- MKMohit Khera
So let's think about it. We used to have... In 2018, the guidelines came out in terms of therapies.
- PAPeter Attia
Yep.
- MKMohit Khera
And we used to think of therapies as first level, second level, third level. We don't think of that anymore. But the old level, first level, was we start out with the pill. See how the pill works. The pill could be Viagra, Levitra, Cialis, or Stendra is the newest. A PDE5 inhibitor. Uh, in that level, you should think about sex therapy. You should talk about lifestyle modification, which is very important.
- PAPeter Attia
Yep.
- MKMohit Khera
And then the second level was injections. So if the, uh, the in- medication's no longer worked, we would go into penile injections, and these injections are extremely effective. Um, it's just that-
- PAPeter Attia
What are you injecting?
- MKMohit Khera
So either Trimix, which is papaverine, phentolamine, and prostaglandin, it's three medications, into the penile tissue, and it dilates the arteries, and it's very effective. And-
- PAPeter Attia
Lasts for how long?
- MKMohit Khera
It's dose-dependent, so you gotta be very careful because if you inject too much, you have a priapism. They have to go to the ER, and I may have to surgically bring it down.
- PAPeter Attia
Yep.
- MKMohit Khera
So the first injection should always be in the office and taught how to inject, and usually I ask the- bring the partner 'cause 50% of the partners inject for their, uh, husband, pa- you know, partners.
- PAPeter Attia
Oh, I see. So this is something where you inject, use it, and it should go away, and you're done. So you inject every time you need the treatment.
- MKMohit Khera
You inject every time you wanna have sex.
- PAPeter Attia
I got it.
- MKMohit Khera
You inject every time you want sex, and within 5 to-
- PAPeter Attia
At the base of the penis.
- MKMohit Khera
At the base of the penis, 2 and 10 o'clock position. And, uh, but we teach you how to do it, and we have you slowly titrate up to finally get to 80% rigidity 'cause you'll get the other 20% rigidity with foreplay. And y- once you find your number, whether it be .2 mLs, .25 mLs, you use that number. The problem, again, remember, is ED is a progressive disease, so many men will start having to use higher and higher-
- PAPeter Attia
Higher
- MKMohit Khera
... doses. Then they'll have to go to a higher strength solution to a higher strength solution. And finally, the third level is a penile implant. Now, in today's, uh, new paradigm, we don't have the first, second, and third. We offer the patients all the options. We use something called shared decision-making. If a patient says, "I don't wanna start with a pill, I wanna start with injection," that's fine. We don't use the urethral suppositories anymore. They... We used to use them quite a bit in the past. It's a prostaglandin suppository that you place into the urethra, and it causes a vasodilation in the penis. I thought, in my opinion, they didn't work very well. Um, they were good for combination therapy with-
- PAPeter Attia
I mean, doesn't... Isn't that uncomfortable?
- MKMohit Khera
It can cause significant urethral burning. That is true. Some bleeding as well, and they can cause a little bit of hypotension in some patients as well.
- PAPeter Attia
Hmm.
- MKMohit Khera
So, so it... We stopped using those. But the penile prosthesis has been around now for 50 years. This year is 50 years. Invented at Baylor in 1973, and it is a phenomenal treatment option for ED.
- PAPeter Attia
And, and what does it look like in its current form?
- MKMohit Khera
There's been many iterations. Uh, there are two main, uh, suppliers. There's Boston Scientific and Coloplast, and this, uh, device essentially is a, a, a procedure where we place two cylinders or balloons into, inside those casings, the corpora cavernosa. There's a small pump in the scrotum, and there's a small reservoir behind the pubic bone typically or underneath the rectus muscle that holds normal saline. And all you're doing is when you wanna engage in sexual activity, you reach down, you press the pump, and it brings normal saline into those cylinders and induces an erection. And when you finish engaging in sexual activity, you release it, and all the fluid goes back.
- PAPeter Attia
And so just to be clear, a man would still ejaculate normally.
- MKMohit Khera
Still has pleasure.
- PAPeter Attia
But he would still have an erection after ejaculation 'cause he's not getting the signal to turn it off?
- MKMohit Khera
He, he turns it off when he wants to turn it off.
- 59:38 – 1:05:40
Priapism (prolonged erection)
- MKMohit Khera
a penile implant in, and I strongly suggest-
- PAPeter Attia
Let's tell folks what priapism is.
- MKMohit Khera
Yeah, so priapism is a prolonged erection that lasts greater than six hours. So we tell patients if it's longer than four hours, you should start seeking medical attention. The best example I can give you is this. If I take a rubber band and put it around your finger numerous times, I'm cutting off the blood supply. Well, how long does it take for that finger to start having necrosis and damage? In the penis, uh, at 36 hours, we say the chance of recovery is extremely low. So if someone says, "I've had an erection now, and it happened on Friday," and he shows up on Monday, I'm very worried. I'm say, "The chances of you recovering-"
- PAPeter Attia
But, but let me understand what that guy is going through. What is it... I mean, wouldn't he be in pain having had an erection from Friday till Monday?
- MKMohit Khera
Exactly, so-
- PAPeter Attia
But is he just not seeking care because he's ashamed?
- MKMohit Khera
He's ashamed, or he thinks it's gonna go down, which is the worst thing that could happen.
- PAPeter Attia
Hmm.
- MKMohit Khera
And so majority of the patients are astute. They've been taught, "Hey, if you get erection greater than four hours, you need to come in." But very rarely, s- they sometimes will not, and then we're in trouble. Because that patient now is... In my opinion, you have three months if you want to help him, three months to get a penile prosthesis in. Because if you try to get that in later on down the road, I cannot tell you how much fibrosis and scarring is in that tissue.
- PAPeter Attia
I see.
- MKMohit Khera
And for me to get the penile implant in-
- PAPeter Attia
Can you do it on the day of admission? So for example, if that guy comes in having been 72 hours-
- MKMohit Khera
Yes
- PAPeter Attia
... with an erection, and you're basically willing to make the call at 72 hours, "We're not gonna even wait to see if you recover. Let me put the implant in right now before there's fibrosis," you have a better outcome?
- MKMohit Khera
You can't, but, uh, but you'll have almost a similar outcome if you do it within at least the first three months.
- PAPeter Attia
Okay.
- MKMohit Khera
It doesn't have to be 72 hours. So sometimes we think it's better, especially... So the problem is a lot of times what... The first thing that'll happen is they'll get a shunt. A shunt means someone will stick a needle or a knife down the glans or in the corpora and try to detumesce them.
- PAPeter Attia
And then you get arterial to venous connection.
- MKMohit Khera
Right. So if that happens, I don't wanna put an implant in right away-
- PAPeter Attia
Yeah
- MKMohit Khera
... 'cause you have a risk of erosion slightly.
- PAPeter Attia
Mm.
- MKMohit Khera
And you have a slight m- risk for i- infection possibly because someone's manipulating the tissue. So I say, "Let it calm down. Let's c- come back in three weeks," and this gives us more time to get the implant in.
- PAPeter Attia
Do you do an ultrasound to make sure there's no shunt?
- MKMohit Khera
Uh, w- so I, I do. So, uh, what's interesting is if you do a, a shunt, most of the time the patient the next day will have an erection, and the pa- resident will call me and say, "Doc, it failed." It didn't fail. Now they have a reactive hyperemia. They have a high flow.
- PAPeter Attia
Yeah.
- MKMohit Khera
And if you ultrasound them, you'll find that they have a high flow. So I say, "Wait a minute."
- PAPeter Attia
Yeah, it's the exact opposite. He presented with a low flow-
- MKMohit Khera
Right
- PAPeter Attia
... venous outflow obstruction.
- 1:05:40 – 1:11:46
Shockwave therapy as a treatment for ED
- PAPeter Attia
okay. Last thing on ED I wanted to talk to you about is this, uh, device that a couple of my patients have talked about. I think it's called GAINSWave.
- MKMohit Khera
Sure.
- PAPeter Attia
What is it?
- MKMohit Khera
So GAINSWave is just a company, uh, but that uses devices for shockwave therapy.
- PAPeter Attia
Okay.
- MKMohit Khera
So I just have to give you a little bit of history about shockwave therapy. In 2010, Dr. Vardi, a European study, was the first to start using shockwaves to treat ED. And you... Shockwaves are not new to urologists. We use high-intensity shockwave for kidney stones.
- PAPeter Attia
Yeah.
- MKMohit Khera
Right? This is-
- PAPeter Attia
That's what lithotripsy is, right?
- MKMohit Khera
Lithotripsy is.
- PAPeter Attia
Yeah.
- MKMohit Khera
It's called high-intensity shockwave. This is called low-intensity shockwave therapy, or LiST, right? And when I first saw that, I'll be honest with you, I thought it didn't make a lot of sense. I said, "This is ridiculous. He's shocking the penis two to three times a week, three weeks, 2,500 shocks. What is he doing?" But the science is actually quite clever. The science is you're inducing trauma. When you induce trauma, you bring in neoangiogenesis. Right?
- PAPeter Attia
Mm.
- MKMohit Khera
You actually recruit stem cells, right? You help with nitric oxide synthase. So it actually is helping improve the condition. We weren't the first. Cardiologists have been doing it for years. If you look at cardiologists, they were shocking the heart, and they re- look at the reperfusion, and it was reperfusing the heart. Uh, orthopedics do it for, uh, joints, and they use it for plantar fasciitis. Um, it's used for a lot of conditions. But this was shocking the penis in 2010. [lip smack] So since then-
- PAPeter Attia
And, uh, again, s- pardon my ignorance, how is the device applied?
- MKMohit Khera
So it is... Think of it like a probe.
- PAPeter Attia
Okay.
- MKMohit Khera
And what happens, you have to have someone doing, uh, performing the procedure.
- PAPeter Attia
Yep.
- MKMohit Khera
We divide the penis in six zones. So it's shaft, hilum, and crus, and in, in two sides. So six zones, and we will typically, uh-
- PAPeter Attia
And, and so just explain where each of those is.
- MKMohit Khera
So the hilum is ba- uh, the, the shaft is obviously the shaft of the penis.
- PAPeter Attia
Yeah.
- MKMohit Khera
The hilum is where the, at the base of the penis.
- PAPeter Attia
Yep.
- MKMohit Khera
And the crus is underneath the scrotum.
- PAPeter Attia
Okay.
- MKMohit Khera
Because the, the penile tissues go underneath the scrotum. So we will deliver 2,500 shocks, uh, in these six areas, and it takes about 25, 30 minutes. And the patients will come in, and they'll come in at least one or two times a week for three or six weeks. So six, and they may have to have a booster. So when Vardi did it, he showed that-
- PAPeter Attia
And the probe is just right on the-
- MKMohit Khera
Right on the skin.
- 1:11:46 – 1:15:48
Stem cell therapy for ED
- MKMohit Khera
finishes the circle.
- PAPeter Attia
Yep, finish that up.
- MKMohit Khera
And so stem cells, um, the problem with stem cells, and we published a paper. We did use stem cells. We had a, we had an IDE.
- PAPeter Attia
There's no FDA approval for this. Is that-
- MKMohit Khera
Yeah. There's no FDA approval for stem cells for ED, so many patients will have to go to Costa Rica, Panama, outside the country to get the stem cells for ED.
- PAPeter Attia
Are there people doing it in the United States off-label?
- MKMohit Khera
They used to, but you are not supposed to because the FDA has said you cannot use stem cells-
- PAPeter Attia
Oh, I see. Got it
- MKMohit Khera
... so just in general for any therapy. We, I had a, I use a, a machine that had an IDE, uh, by the FDA, so an investigational, uh, dr- uh, device exemption, and this was, the exemption was for specifically ED for stem cells.
- PAPeter Attia
I see.
- MKMohit Khera
So we conducted 30 patients. Uh, we used, uh, adipose-derived stem cells. We take the fat. We wanted to use it fresh, so we put them in a machine. We would get 37 to 50 mil-
- PAPeter Attia
So you would literally... This was autologous. You would take a man's-
- MKMohit Khera
Fat
- PAPeter Attia
... adipose tissue Get the stem cells and then re-infuse
- MKMohit Khera
You got it. But the, the-- So what I-- My-- Because I wanted a large amount of fat, I actually had a plastic surgeon do the liposuction-
- PAPeter Attia
Mm-hmm
- MKMohit Khera
... under some mild sedation. So it was a little labor-intensive. Then I would take the fat, it was a hundred and twenty cc's of fat, and put it into a machine that had the IDE for, uh, making stem cells. So the machine, after two hours, would give me anywhere from thirty-seven to fifty million stem cells, and then I would inject those stem cells into the penile tissue.
- PAPeter Attia
At the base of the penis again.
- MKMohit Khera
At the base of the penis with a tourniquet for two minutes, and you have to inject slow or you'll, uh, damage the stem cells.
- PAPeter Attia
Yep.
- MKMohit Khera
So we let them sit there for 30 minutes, and we take the tourniquet off.
- PAPeter Attia
And did you have a 30 placebo men?
- MKMohit Khera
This was non-placebo controlled, and this is important.
- PAPeter Attia
Yeah.
- MKMohit Khera
Because up to today, there's not a single placebo-controlled trial with stem cells for ED. Not one, right?
- PAPeter Attia
So given the placebo effect being so high, what was the effect you saw in these m- 30 men?
- MKMohit Khera
We saw that they had a, a increase maybe of four on the IIEF, no placebo control, but it was only, uh, durable for six, maybe nine months, and started tapering off. So it wasn't a lasting effect, but it was some effect that was going on. But we need a placebo control. So we're gonna start a placebo-controlled trial because, you know, people swear by stem cells, and some companies will say, "Fifteen thousand, we'll give you stem cells for ED." Where's the placebo-controlled trial, right? It doesn't exist, right?
- PAPeter Attia
Yeah.
- MKMohit Khera
So you have to be careful.
- PAPeter Attia
Well, the other thing I guess is at $15,000 in Costa Rica, why... We, we'd have to believe it's significantly better than daily Cialis at, uh, what, $70 a year.
- 1:15:48 – 1:18:36
Platelet-rich plasma (PRP) injections as a treatment for ED
- MKMohit Khera
with the stem cells. PRP, now that's interesting. Until, uh, last year, we f- we got our first randomized placebo-controlled trial, first one, until 2020, '21. Before then, there was one case report. One case report with five patients out of Wake Forest showing that there may be some b-benefit. And this was sold like it was the best thing since sliced bread. They call it the P-Shot, uh, which is the priapus shot, where basically take stem cells. It costs about fifty, $1,500 to $3,000. Now, honestly, to really make it, it costs $50. You take blood, you spin it, you get the supernatant, you spin it again, add some calcium chloride, you have PRP, you know?
- PAPeter Attia
[laughs]
- MKMohit Khera
And they inject it, um, into the p... Now, there may be some benefit as well, but this is the one that lacks the most science as well. So there's an excellent study at the University of Miami right now looking at PRP and shockwave combination. Dr. Raman Sawmya-
- PAPeter Attia
With placebo arms?
- MKMohit Khera
Uh, with placebo arms. So that's gonna be very interesting.
- PAPeter Attia
When is that expected to be published?
- MKMohit Khera
I think there's gonna be some preliminary results at the AUA this year in April, next month. So that's gonna be interesting.
- PAPeter Attia
Okay.
- MKMohit Khera
Uh, I think it came out as a late-breaking, so hopefully next month we'll know more.
- PAPeter Attia
Yeah. Well, by the time this podcast comes out, it'll be in the past tense.
- MKMohit Khera
It'll be past.
- PAPeter Attia
So we'll link to that.
- MKMohit Khera
Sure.
- PAPeter Attia
Yeah.
- MKMohit Khera
Yeah.
- PAPeter Attia
Um, okay. So w- my takeaway from everything on ED, just to summarize, is, uh, easy way to remember the prevalence is it's matched by age.
- MKMohit Khera
Yeah.
- PAPeter Attia
So amazing to think that at 40, which is pretty young, 40% of men are impacted. At my age, 50% of men. At 60, 60%, et cetera. Um, second thing to consider is, you know, if, if men listening to this or their partners are listening, go and get help.
- MKMohit Khera
Yeah.
- PAPeter Attia
Don't, don't suffer in silence. Uh, third thing to consider is that daily phosphodiesterase inhibitor I took away from you is a very viable solution, that there shouldn't be a stigma attached to that, and there shouldn't be a fear that I'm becoming dependent on it or something like that, in the sense that these are valuable drugs. They can also sometimes break the vicious cycle if there's a psychogenic component.
- MKMohit Khera
Exactly.
- PAPeter Attia
You wanna rule out psychogenic before you proceed to pharmacologic, um, as the only therapy. You have the diagnostic side on the arterial-venous. Um, and then I think this idea about PRP, stem cells, exosomes, and shockwave, it's still a little bit too soon to know.
- MKMohit Khera
A little bit too soon. Promising-
- PAPeter Attia
Yeah
- MKMohit Khera
... but too soon.
- PAPeter Attia
And of the four, would you say the most promising is stem cells?
- MKMohit Khera
I like shockwave.
- PAPeter Attia
Okay.
- MKMohit Khera
I like shockwave. You know why? Because when I do shockwave therapy, it recruits the stem cells, 'cause stem cells go to area of damage.
- PAPeter Attia
Yeah.
- 1:18:36 – 1:26:34
Premature ejaculation (PE): prevalence, pathophysiology, and treatment
- PAPeter Attia
Okay. So let's, let's pivot now and talk a little bit about, uh, the, the sort of states of ejaculation. Uh, so, so anorgasmia, delayed orgasm, et cetera. Um, uh- How does the prevalence of this differ by age?
- MKMohit Khera
Yeah. So ejaculatory dysfunctions are important. We know that 30% of men, 30% of men are likely to have some type, degree of ejaculatory dysfunction. More prominent is premature ejaculation, right? So premature ejaculation, uh, 30% of men, up to 30% will have it. Only 9% of that 30% will seek therapy. It's really small, and that's really because many men are embarrassed to seek therapy about this.
- PAPeter Attia
So basically, 30% of men have this. Only 3% of men in total are doing anything about it. 9% of the-
- MKMohit Khera
9%.
- PAPeter Attia
Of the-
- MKMohit Khera
That's exactly right.
- PAPeter Attia
Yeah. Yeah, no.
- MKMohit Khera
It, which is very small. But in, you know, two years ago, the guidelines came out, the new guidelines came out. So what is a premature ejaculation?
- PAPeter Attia
Yeah.
- MKMohit Khera
Two ways to think about it, and this is really important how you break it up at the beginning. It's either lifelong or acquired. That's your first step. Has this patient had it ever since they remember having sex, and they can always have premature ejaculation, or was this acquired? In either case, you have to have three variables. You must have these three. One, you have to have a decreased ejaculatory time. Now, when it's lifelong, it's typically now less than two minutes, right? So it's less than two minutes. It used to be less than one, now it's less than two. They have to have a sense of loss of control. "I couldn't control it." And number three, they have to be bothered by it. If a guy comes in and says, "I ejaculate in 30 seconds, and I'm happy," great. He doesn't have the problem.
- PAPeter Attia
[laughs]
- MKMohit Khera
He has to be bothered by it, right? So it's important.
- PAPeter Attia
What if he's not bothered by it, but his partner is?
- MKMohit Khera
Well, it's, he has to be bothered by it, right?
- PAPeter Attia
Okay.
- MKMohit Khera
So if he's bothered that she's bothered, fine, but he has to be bothered by the condition, right?
- PAPeter Attia
Okay.
- MKMohit Khera
Now, acquired's a little bit different. So look, things were great till I hit 40, and all of a sudden I develop premature ejaculation. Same principles. You have to be bothered by the condition, you have to have a sense of loss of control, and you have to have a decrease in time. Now, how do you define time? That's a little bit tricky on this one because it's anywhere from two to three minutes, or it's 50% of your typical time.
- PAPeter Attia
Hmm.
- MKMohit Khera
So let's say I used to ejaculate in 10 minutes, and now it's five. Okay, that qualifies. It's 50%-
- PAPeter Attia
Yeah
- MKMohit Khera
... of what mine. So these are the two definitions of, uh, so you want to break it down. Now, why is that important? Because how I treat somebody is very different, right? If someone's acquired, we start looking at hormones. That's important. We look at prolactin. We look at thyroid. We look at testosterone.
- PAPeter Attia
Hmm.
- MKMohit Khera
We look at some d- more diagnostic. If it's lifelong, we don't do a lot of diagnostic workup. You're not supposed to. It's the acquired where you start figuring out. You know, the four reasons for this, uh, premature ejaculation, one is the biological, the theory that there's increased sensitivity of the glands.
- PAPeter Attia
Hmm.
- MKMohit Khera
Right? So if they're born with increased sensitivity, that's why one of the therapies is using lidocaine or some of these numbing agents on the glands. They're over the counter. There's sprays that actually lidocaine on the penis 10 minutes prior to engaging in sexual activity.
- PAPeter Attia
But doesn't that then put lidocaine onto the partner?
- MKMohit Khera
You wipe it off before you engage in sexual activity.
- PAPeter Attia
I see. Okay.
- MKMohit Khera
And so, and, and, and, but be careful, 'cause if you spray too much, it causes ED.
- 1:26:34 – 1:31:52
Anorgasmia: causes and treatment
- PAPeter Attia
Um, okay. At the other end of that spectrum is anorgasmia.
- MKMohit Khera
Sure.
- PAPeter Attia
And, uh, how... What's your workup for that?
- MKMohit Khera
Right. So anorgasmia, and we put this in the same as a delayed ejaculation. So sometimes patients have delayed ejaculation, taking a long time, and the same principles are the same. Is it acquired or lifelong?
- PAPeter Attia
Mm.
- MKMohit Khera
And the same principles. Are you bothered by it? Uh, is there a, uh, no ability, lo- loss of control or no inability to control? And more importantly, the timing. So what is the average amount of time that a man takes to ejaculate in the United States? Typically about six to seven minutes on average. Six to seven minutes is the norm. So-
- PAPeter Attia
That's self-reported?
- MKMohit Khera
Uh, in numerous studies. And it's interesting how we do that.
- PAPeter Attia
How do you do that?
- MKMohit Khera
Great question. So we look at something called the intravaginal ejaculatory latency time, IELT, and it's typically self-reported. But when it's self-reported, it's inaccurate.
- PAPeter Attia
Yeah, it's gotta be.
- MKMohit Khera
It's inaccurate because when men-
- PAPeter Attia
Who's keeping track of time?
- MKMohit Khera
Right. So what happens is when you ask a man who has premature ejaculation, he underestimates the time. If he ejaculated in two minutes, he says, "I... It was 90... 30 seconds." And if you act- ask a guy who doesn't have premature ejaculation, he overestimates the time. He says if he ejaculated in eight minutes, he says, "Yeah, it was 15 minutes," right? So it's a big discrepancy. So how we do it is we give the partner a stopwatch, and when they engage in sexual... When he orgasms, she's supposed to click the clock, right? And that's the best way to get intravaginal ejaculatory length. So IELT is best by stopwatch.
- PAPeter Attia
And based on [laughs] that gold standard, it's six to seven minutes.
- MKMohit Khera
Six to seven minutes. Now, look, certain countries have different numbers. So Asian countries, lower numbers. European countries, higher numbers, longer ejaculatory latency.
- PAPeter Attia
What, what, what, what do you attribute that to?
- MKMohit Khera
Cultural, right? There could be cultural differences as well.
- PAPeter Attia
Huh.
- MKMohit Khera
But the- there's, there's some differences. But when you look at, uh, for example, these medications like SSRIs, they are very effective in prolonging the IELT. Very effective. And there was a study in 2004 by Waldinger. He was looking at the different, different, uh, SSRIs. Paxil was number one by far. So Paxil is typically used the most. Zoloft was number two. And you can see, uh, based on the dose, 'cause it's dose-dependent. So the higher the dose, the greater the ejaculatory time. But at the end of the spectrum, it was 25X, right, with Paxil. So typically, it's about 10X you'll see in eject- a delay.
- PAPeter Attia
But without getting to the point of ED.
- MKMohit Khera
Without, without getting to... So you... So remember, you can dose... If, if, if I'm using too much Paxil, I bring it down, right?
- PAPeter Attia
Yeah.
- MKMohit Khera
So one of the problems, we'll talk about this, delayed orgasmia. A lot of these patients are, have it because they're on an SSRI.
- PAPeter Attia
Yeah.
- MKMohit Khera
That's why they have it, right? So if they're on 40 milligrams of Paxil, maybe we just go to 30. We still get the benefits of depression, but we improve the ejaculatory latency time-
- PAPeter Attia
Yeah
- MKMohit Khera
... 'cause it's very sensitive on those doses, right? So when w- there's no set number on delayed orgasmia, but typically someone will say f- greater than 15 to 20 minutes. If it's greater than 15 to 20 minutes, that could be considered delayed orgasmia. We have no FDA-approved treatments for this condition. There are no FDA approvals for it. So everything I'm gonna tell you today is off-label use-
- PAPeter Attia
Mm-hmm
- MKMohit Khera
... for how we treat this condition.
- 1:31:52 – 1:44:49
Sex hormones, impact of aging, symptoms of low T, & considerations for testosterone replacement therapy (TRT)
- PAPeter Attia
Okay. I kinda wanna talk, shift gears a little bit and talk about testosterone replacement therapy.
- MKMohit Khera
Sure.
- PAPeter Attia
So let's, um, maybe give folks a little bit of an explanation of how the hypothalamus, pituitary, testes, and adrenals all play a role in the generation of the hormones that we're about to talk about, which means let's talk about everything-
- MKMohit Khera
Yeah
- PAPeter Attia
... from LH and FSH to testosterone, SHBG, DHT, et cetera, and then let's talk about what deficiencies mean and p-
- MKMohit Khera
Sure
- PAPeter Attia
... what the, what the consequences are and how m- we wanna go about addressing it.
- MKMohit Khera
Sure. So let's talk about the physiology-
- PAPeter Attia
Yeah
- MKMohit Khera
... 'cause it's important. So GnRH, secreted from the hypothalamus. GnRH then it goes to the pituitary, secretes two hormones, LH and FSH.
- PAPeter Attia
And what's the signal for GnRH? Is it estrogen?
- MKMohit Khera
Uh, well, the, it, and that's a negative feedback.
- PAPeter Attia
Yep.
- MKMohit Khera
So estrogen can't have a negative feedback on it. It's a pulsatile pulse, GnRH.
- PAPeter Attia
Okay.
- MKMohit Khera
We know that pulse goes down as we age. So that's an important part of aging we'll talk about as well. The LH and FSH will then go to the testicles. I tell the residents, "Remember that LH has an L, goes to the-
- PAPeter Attia
Goes to Leydig cell
- MKMohit Khera
... Leydig cells. FSH has S, goes to Sertoli cells," right?
- PAPeter Attia
Yeah.
- MKMohit Khera
So LH goes to the Leydig cells and produces testosterone. FSH goes to the Sertoli cells and produces sperm, right? The two functions of the testicle are basically sperm and testosterone. So essentially what, if a patient comes in and they have, um, remember that the majority of a patient's, a man's testicles are comprised of Sertoli cells. That's important because that is rule m- the exam is more of a indicator of his fertility status than his hormonal status, right? So that's important.
- PAPeter Attia
When you say exam, you mean size?
- MKMohit Khera
Size.
- PAPeter Attia
Yeah.
- MKMohit Khera
So they should be four centimeter in diameter, 20 cc's. And so when I'm looking at an infertility workup, if the patient has small testicles, elevated FSH and LH, I say there's a production problem. He's not making it.
- PAPeter Attia
Mm.
- MKMohit Khera
If he has normal FSH and LH and normal testicles and no sperm, it's an obstruction problem. So that's very important. The exam's very important. So we talked about the fact that the testicle's making, uh, making testosterone, but there's a negative feedback. That negative feedback, testosterone goes back and feeds back negatively on the pituitary and also on the hypothalamus, but also estrogen goes back and feeds back negatively. Testosterone can be broken down m- majority's gonna-
- PAPeter Attia
And by the way, is, is, which, is one of those stronger than the other as a signal?
- MKMohit Khera
I don't know if one's stronger than the other. I know that both are. I mean, we'll talk about SERMs and just how SERMs work is they block that negative feedback-
- PAPeter Attia
Yeah, yeah
- MKMohit Khera
... on the estrogen. Um, but remember that testosterone then is converted into estrogen.
- 1:44:49 – 2:00:03
Methods for increasing endogenous testosterone
- PAPeter Attia
Yeah. So let's talk about this. I'll, um... Maybe we'll talk about all the different ways that we can replace testosterone.
- MKMohit Khera
Sure.
- PAPeter Attia
So the three ways that we have historically done it in our practice, I guess technically four, um, one is, and we don't do this anymore, um, we used to use clomiphene.
- MKMohit Khera
Mm-hmm.
- PAPeter Attia
So we would give Clomid. It had the advantage of several things. One, it's, uh, it's a pill, very convenient.
- MKMohit Khera
Yep.
- PAPeter Attia
You take it three times a week. Uh, two, it preserved, uh, function.
- MKMohit Khera
Sure.
- PAPeter Attia
Meaning you, you preserved both testicular volume and spermatic function.
- MKMohit Khera
Mm-hmm.
- PAPeter Attia
Uh, so you preserved fertility. Um, and actually it was quite efficacious.
- MKMohit Khera
Yeah.
- PAPeter Attia
I found it to be dep- because you could titrate the dose and get to almost whatever you need. The drawback is if the man didn't have testicular reserve-
- MKMohit Khera
Mm-hmm
- PAPeter Attia
... uh, he wasn't going to get much of a bump.
- MKMohit Khera
Sure.
- PAPeter Attia
So, so, you know, there were some guys who had kind of peripheral hypogonadism-
- MKMohit Khera
Mm-hmm
- PAPeter Attia
... as opposed to central. This was a great treatment for central, but you were at the limit of what the testes could do. Th- there were reasons we ended up stopping it that I won't necessarily get into, but we basically haven't used that in a very long time. We then would use as the alternative to that HCG.
- MKMohit Khera
Mm-hmm.
- PAPeter Attia
HCG is just a mimetic for LH, luteinizing hormone, which you talked about, of course, is the direct stimulant of the Leydig cell, which makes testosterone. Uh, lots of disadvantages. It's pretty expensive.
- MKMohit Khera
Mm-hmm.
- PAPeter Attia
It's an injectable. It's a very delicate injectable, so it has to be refrigerated. If you drop the bottle, the protein misfolds-
- MKMohit Khera
Uh
- PAPeter Attia
... and it's, it's crap.
- MKMohit Khera
Mm-hmm.
- PAPeter Attia
So lots of problems associated with it. But again, seems to preserve testicular volume, which young men care about. Uh, maybe older men do it as well. Um, not clear if it's as good as Clomid at preserving fertility.
- MKMohit Khera
Mm-hmm.
- PAPeter Attia
I would love to hear your opinion on that.
- MKMohit Khera
Sure.
- 2:00:03 – 2:11:03
Testosterone replacement therapy: various forms of exogenous testosterone & weighing risk vs. reward
- PAPeter Attia
That's so interesting. So, um, when a... if a guy comes to you and you go down the path and decide you're going to go down the exogenous route, not the-
- MKMohit Khera
Yes
- PAPeter Attia
... endogenous route, how are you deciding between pellets-
- MKMohit Khera
Yeah
- PAPeter Attia
... which we should explain what they are, topical, like AndroGel or compounded, injectable, such as, you know, Cipionate or Zyus-ted, or intranasal-
- MKMohit Khera
Yeah
- PAPeter Attia
... or oral now.
- MKMohit Khera
Yeah, oral. So there's... So I, I go through all the options, first of all.
- PAPeter Attia
Yep.
- MKMohit Khera
Say, because a lot of times it can be cost prohibitive and we find out which is the most affordable. Although I would tell you that injectables, uh, cash price from a compounding pharmacy is $25 a month.
- PAPeter Attia
Yep.
- MKMohit Khera
We have them inject sub-Q, either enanthate or cypionate, and it's based on age. I use cypionate for younger patients and enanthate for older patients.
- PAPeter Attia
How come?
- MKMohit Khera
I think cypionate's more anabolic. It has more s- more sodium retention.
- PAPeter Attia
Mm-hmm.
- MKMohit Khera
And so I teach the residents that cypionate has a C for child and enanthate has E for elderly, and I typically use like 50 or 60. But I l- look at the patient, but I think that, you know, it has a little more sodium retention, so I try to, I try to way... stay away from the swelling and the edema in older patients. So that's how I make my decision.
- PAPeter Attia
And where do you make that cutoff age-wise?
- MKMohit Khera
It's typically around 50 to 60, around there. I just... You know, if, if they're using injectables.
- PAPeter Attia
Yeah.
- MKMohit Khera
So I'll say, "Okay." Now, what I like about the injectables is, okay, we use sub-Q, always sub-Q.
- PAPeter Attia
Yep.
- MKMohit Khera
And we have-
- PAPeter Attia
So 25-gauge needle, short needle.
- MKMohit Khera
Yeah, 5/8 inch.
- PAPeter Attia
Yeah.
- MKMohit Khera
One cc syringe, 25 gauge.
- PAPeter Attia
Yep.
- MKMohit Khera
It's big enough to draw it up. It's small enough to inject.
- PAPeter Attia
In the butt. Outer part of the butt or belly?
- MKMohit Khera
Belly.
- 2:11:03 – 2:18:25
The physiology and purpose of testosterone and DHT, why some men feel fine even with “low” testosterone, personalized approaches to treating low T
- PAPeter Attia
Okay. Let's now talk about physiology. So how does testosterone work? How does DHT work? How should we think about testosterone, DHT, and estrogen, and why do they all matter?
- MKMohit Khera
Right. So we talked about the breakdown, testosterone going into estradiol, as testosterone going into DHT. Testosterone has numerous effects on different body parts at different levels, right? So we know that erectile function typically is around 200 nanogram per deciliters. When you start falling below 200 nanogram, you start losing nocturnal erections, right? Muscle tends to be higher. Bone tends to be higher. So different body parts, I guess, call it turn on at different levels, right? So the issue is that-
- PAPeter Attia
So in other words, what's the highest? What has the greatest sensitivity to falling testosterone?
- MKMohit Khera
Right. So the way to cover yourself is just be in the upper quartile.
- PAPeter Attia
Yeah.
- MKMohit Khera
That's why I... If I'm in the upper quartile, I know I'm covering-
- PAPeter Attia
Hitting everything. Yeah
- MKMohit Khera
... 'cause everyone's different, so-
- PAPeter Attia
But again, you're saying, when you said 200 nanograms per deciliter, that's total. How do we determine the free?
- MKMohit Khera
Right, and that's-
- PAPeter Attia
The, the cutoffs
- MKMohit Khera
... yeah, that's important. Everyone's different.
- PAPeter Attia
Yeah.
- MKMohit Khera
So, you know, I, I have to say this. I never understood why we use this number 300. What are you telling me? 300 nanogram is a, is the definition for hypogonadism. So are you telling me that 290 we must all feel bad, and at 310 we must all feel good? That is not true.
- PAPeter Attia
Not even close.
- MKMohit Khera
Right?
- PAPeter Attia
Yeah.
- MKMohit Khera
But that's what the, that's what it's, it, it's, it's, it's-
- PAPeter Attia
Yeah
- MKMohit Khera
... it's come to. So the reality is that there are many patients at lower levels that feel good. It's based on the sensitivity of the androgen receptor. So when I was a fellow in, in my lab, very beginning, we would take the blood, we'd go back and count the CAG repeats. Patients who had longer CAG repeats would have more sensitive receptors. And the more-
- PAPeter Attia
And why is that?
- MKMohit Khera
... insensitive receptors, excuse me. Because everyone's different. Your receptors and my receptors have different sensitivities. Genetically how we're made, v- so everyone has a different sensitivity of the receptor. So many have shown that people will respond differently to different doses based on sensitivity. Dr. Zitzmann in Germany showed that depression can be associated with d- sensitivity to the interceptor, sexual function. So, so sometimes people need more to feel better.
- PAPeter Attia
Yep.
- MKMohit Khera
And I think that's a, a misconception because a lot of times people say, "Well, you're in the normal range. You're at 400." Something else may be going on. And invariably, if you can raise them to the upper quartile of normal, cover them, you may see symptomatic improvement.
- PAPeter Attia
Do, do you think we're ever going to get to the point where, um, TRT can be tr- customizable based on a more broad view, where a patient comes to see you and you do an androgen receptor assay on them, and you couple that with what their free T is and make decisions based on that as opposed to just sort of flying a little bit blind and having to guess?
- MKMohit Khera
Yeah. That would be amazing. And that's what we started... And so we did that in our lab. And so I had some of my colleagues say, "Hey, could you... I have this patient I don't understand. Can you look at the sensitivity to androgen receptors?" My lab is not CLIA certified, so I couldn't give you diag-
- PAPeter Attia
You can't give advice. I got it
- MKMohit Khera
... I can't give advice, you know. So but I can look at different assays. Um, but I think that would be amazing. So there's got to be other factors that can predict, 'cause right now it seems very Are a pain
- PAPeter Attia
How complicated is the assay?
- MKMohit Khera
It's so easy to run, but the only thing is it does take a little bit of manual labor. My technician would have to sit there and he literally would have to-
Episode duration: 2:42:02
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