The Peter Attia Drive - #260 ‒ Men’s Sexual Health: why it matters, what can go wrong, and how to fix it | Mohit Khera, M.D., M.B.A., M.P.H.

Episode Date: June 26, 2023

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Mohit Khera is a world-renowned urologist with expertise in sexual medicine and testosterone therapy. In this episode, Mohit provides a comprehensive overview of male sexual health. He begins with an in-depth exploration of erectile dysfunction, shedding light on its prevalence across different age groups, diagnostic methods, and its intriguing connection to cardiovascular disease. He then ventures into Peyronie's disease, penile fractures, penile enlargement treatments, prolonged erections, premature ejaculation, and anorgasmia. Shifting gears, Mohit delves into the intricate workings of testosterone, DHT, and estrogen, emphasizing their physiological significance and interplay. He explains blood tests for diagnosing low testosterone, the correlation between symptoms and blood levels in cases of low testosterone, and the pros and cons of different methodologies for increasing testosterone. He concludes with a thought-provoking conversation about the role of testosterone in patients with prostate cancer and addresses concerns surrounding DHT, finasteride, and post-finasteride syndrome. We discuss: Mohit’s career path and interest in sexual medicine and infertility [3:00]; The anatomy of the male genitalia [5:45]; The prevalence of sexual dysfunction, its impact on quality of life, and the importance of seeking help [7:15]; Erectile dysfunction (ED): definition, diagnosis, pathophysiology, and more [11:00]; The history of medications to treat ED and the mechanisms of how they work [15:30]; Relationship between aging and erectile dysfunction and Mohit's approach to treating patients and prescribing medications [20:00]; The impact of lifestyle on sexual health and the association between ED and cardiovascular disease [29:30]; Causes and treatments for Peyronie’s Disease, penile fracture, and more [37:30]; The value of ultrasound for ED diagnosis and management strategies [47:45]; Various treatment options for ED: injections, penile prosthesis, and more [50:15]; Priapism (prolonged erection): what is happening and when to seek treatment [57:15]; Shockwave therapy as a treatment for ED [1:02:45]; Stem cell therapy for ED [1:08:15]; Platelet-rich plasma (PRP) injections as a treatment for ED [1:12:00]; Premature ejaculation (PE): prevalence, pathophysiology, and treatment [1:14:45]; Anorgasmia: causes and treatment [1:22:00]; The interplay of sex hormones, the impact of aging, symptoms of low testosterone, and considerations for testosterone replacement therapy (TRT) [1:26:45]; Methods for increasing endogenous testosterone [1:38:45]; Testosterone replacement therapy: various forms of exogenous testosterone, weighing risk vs. reward, and more [1:52:30]; The physiology and purpose of testosterone and DHT, why some men feel fine even with “low” testosterone, personalized approaches to treating low testosterone, and more [2:02:30]; Post-finasteride syndrome [2:09:00]; The role of testosterone in prostate cancer and addressing the notion that TRT could increase risk [2:16:15]; The effects of testosterone as an adjunct to therapy for estrogen-sensitive breast cancer in women [2:27:15]; Resources for those looking for healthcare providers [2:28:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

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

what those benefits are, or if you want to learn more now, head over to peteratia MD dot com forward slash subscribe. Now without further delay, here's today's episode. My guess this week is Dr. Mohit Kera. Moe is a professor of urology at Baylor College of Medicine. He is also a renowned expert in male and female sexual dysfunction, declining testosterone levels in aging men and male infertility. This episode is a follow-up to last week's episode with Dr. Sharon Parrish, which focused on sexual health and females. This episode focuses on the other side of that conversation, all things related to male

sexual health. We start by talking about erectile dysfunction. We speak about the percentage of men who deal with this issue at various ages, the way it is diagnosed, and what we know about erectile dysfunction and cardiovascular disease. We then speak about various drugs, shockwave therapy, stem cells, PRP, and lifestyle modifications that can help with erectile dysfunction. We then talk about Peronii's disease, which is a curvature of the penis, including its causes and treatments. The conversation includes discussions around penal fractures and what is known about

penal enlargement treatments. From there, we speak about what happens when a person has an erection for over four hours, and why that's problematic, premature ejaculation, the causes and treatments, and an orgasmia or delayed orgasms, both causes and treatments. We then shift the conversation to talk about testosterone, including the physiology of how testosterone, DHT, and estrogen work, and how we should think about them and why they all matter. Talk about which blood panels you should use

to measure your testosterone and the difference between the blood levels and the symptoms that we might see in the case of low testosterone. We talk about testosterone replacement therapy and the various ways to increase testosterone, including the use of pellets, topical formulations, injectable formulations, oral formulations, and intranasal formulations. We even discuss the role of testosterone in patients with prostate cancer. We end the conversation talking about DHT and finasteride and some of the

concerns around post-finasteride syndrome. As you can hear, this conversation is really a tour de force as it relates to various topics around sexual health in males, and I think anyone who listens to this will walk away learning something as I did. So without further delay, please enjoy my conversation with Dr. Mohit Karratt. Oh, thanks so much for making the trip over here from Houston. Although I know you didn't come to see me, you came for tennis, but I'll take what I can get. Anytime we can do one of these in person, it's great. There's a lot we want to talk about today. 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 going to talk about, it turns out I know as little about this as I know about the contrapositive in women's sexual health. So, you know, a lot of times I go into a podcast having more knowledge about a substance, and I can guide the discussion more thoroughly. So, I'll be kind of leaning on you heavily, but maybe we can just start by talking a little bit about your background, your training, and how that leads you to doing what you're doing. So, after medical school, what did you go and do?

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 Boston University, got my MBA, got my MPH, I was a healthcare analyst for about two years. I didn't like it very much, but I met my wife in Boston. She was at BU Medical School at the time. So I had a change of course in career path

and I went to University of Texas, San Antonio, for medical school. Then after that, I went to Baylor College of Medicine. They had won your internship in general surgery, then they had five years in urology, then they did a one year fellowship and a male reproductive medicine surgery where I really got into sexual health and infertility.

And I'm in a bailer now since 2007 on faculty. Tell me about what that means. So when I did my general surgery residency, the urologist I was working alongside with, because one of my best friends, Ted Schaefer, who you know of course, is a urologist. A big emphasis in urology, at least as I saw it from the outside, was of course on urologic cancers. So 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. 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 men. So what was that fellowship like and what were the things that you sort of focused on? It was great. So listening to urology is multiple subspecialties.

It could be stones, it could be cancer, it could be female urology. But one subspecialty is sexual medicine and the other one is infertility and usually they're combined. And so really what you're focusing on is reproductive medicine in terms of the septumular reversals, doing procedures to help men recover from

madagena cysts, varicoseal repair, sperm retrieval, but also sexual medicine, taking care of erectile dysfunction, premature ejaculation, peronease disease, and a big focus of that is also hypogonatism. So that's really what I focus my career on is really the sexual medicine side, and that's where we have my research and my basic science lab. Does it make sense to just quickly orient listeners to the anatomy of what we're talking about? Sure. 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, 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 sperm into the ejaculatory ducts. Those ejaculatory ducts mix with the seminal fluid, from the seminal vesicles, and that gives a man his acritic. Above the urethra are two, what we call them tubes, if you will. These are called the corpracavinosa. Essentially what it is is just smooth muscle inside.

So those two smooth muscle bodies, corpracavinosa, are responsible for erections below the tube, called urethra, responsible for urinary. So again, you just have three systems all coming together. And so do you in your mind, because I'd rather do us through the lens of your framework, do you think about this by problem or by age, or by some other metric? How do you go about thinking through a holistic system? You think about it because each of these can affect the others. For example, let's talk about the testicles. You know, when you talk about infert each of these can affect the others. For example, let's talk about the testicles. When you talk about infertility, that can also affect hypogonatism. Hypogonatism can also infect fertility.

Patients also, when you think about the urinary system, patients can have a retrograde ejaculation by taking medication for BPH. That may affect a fertility, that may affect their sexual function. All three are interrelated. Think about it as a whole. Does it make sense to start with a certain set of problems and then maybe talk about how they change temporally in terms of prevalence by age? And if so, where would it make sense to start?

Do you want to start with premature ejaculation? A rectal dysfunction? Start with ED, and I think about sexual health in general. I think I just want to put this in a context. Why don't you think about this? So we know that 52% of men over the age of 40 suffer from erectile dysfunction. Some degree, 52% of men.

Even if you take conservative numbers, that's 30 million men in the US suffer from this disease. And how are we defining it? Is it one time I had too much to drink and I couldn't get in a direction? Or how do we think about it? So what we use is we use a questionnaire, validated questionnaire called the IIEI-E-F.

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, modern, or severe ED. So when they gave the original study in 1994, that when it came out, 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 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, 50% at 50, 60%, 60%, 70%, 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, and we'll talk about that. But again, it's a prevalent condition. I 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 U.S. Some have some degree of premature ejaculation or ejaculate toward dysfunction. 79% of men have peronies disease. How many? 79% of men in the U.S. US have paronies. We should set aside time to talk about it. The problem is that this population I call it sufferance silence. They never talk about it. They never talk about it. In fact, 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. So we know that a third of men who have ED have suffered from depression because of their ED, 37% of men who have ED have anxiety because of their ED. We know that it causes impairment and 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 sex problems. And so when you said suffering in silence, you weren't just referring to Peronia's disease, you're talking about all sexual dysfunction. Allfunctions. So there's reasons for that. So one is, if you look at surveys, it was, actually, I got to bring this up

because it was in 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 a triad, not mental and physical. And they're all related. But the survey found that roughly 40% of men From my world, it's mental, physical, and sexual health. It's a triad, not mental and physical. And they're all related. But the survey found that roughly 40% of men in the survey had some drug use sexual dysfunction.

50% of those men said, I would love to get treatment, but I don't know where to go, 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 and silence. And the main reason was they were embarrassed. Also, clinicians don't ask about it. When you go to a doctor's office, my wife is guilty, my wife's a family practitioner. She said to me, look, I have to take care of diabetes, hypertension, OSA, and all these conditions in X amount of time and ED tends to be the bottom

of the list. I don't have the time to ask about it. So, clinicians don't ask about it. Patients are embarrassed to ask about it, and that's the suffering in silence. Well, one of the desired outcomes of this podcast, of course, is to empower people of both sexes plus their physicians to hopefully take a more active role in this. 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? Sure. I think one of the easiest ways to look at it is to use a question called the septu and the septu.

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. Are you able to maintain that erection sufficient for penetration? It's either yes or no. And are you able to maintain that erection till orgasm? It's either yes or no. If they answer no to either one of those questions, they have ED. 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. Then they had one episode of ED. So it's graded. But by definition, if someone says, and the number one cause of ED, typically is, I can't maintain it.

That's the first sign. They say, Doc, I can get it, but I can't maintain the direction. They're telling you, I have Venus leak, which is the first sign. I sometimes have a rectal dysfunction. 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 can maintain a direction, I can't ejaculate. We're going to talk to a separate problem. That's right.

That's not ED. Okay. So let's talk about the pathophysiology of this, again, at the risk of sounding and demonstrating my ignorance. How much of this is physiologic, i.e. neurovascular, how much of this is psychological? So the nomenic I teach the medical students is vent. What are the ideologies?

Vascular, endocrine, neurologic, and trauma, and peronies, these can be trauma as well. So vascular, endocrine, neurologic, trauma, don't forget medications. We'll talk about those beta blockers, for example, anti-androgen, finasteride. There's a lot of medications that can cause impaired erectile function, and then there's psychogenic ED. Now, psychogenic ED. Now, psychogenic ED typically is in younger patients. It's not common that a young patient has organic ED, but they have psychogenic ED.

And psychogenic ED is treated very differently than organic ED. 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. Do you get morning erections? Oh, yeah, I get morning erections, but I have difficulty having sex. They're telling you they have psychogenic ED. Do you get morning erections? Oh, yeah, I get morning erections, but I'm have difficulty having sex.

You're telling you you have psychogenic ED. So you want to prove for that, because psychogenic ED is treated with sex therapy. I use daily seals and these patients, it's very effective, I think. There's a way to treat that. That's very different than organic ED. Tell me a little bit more about what that means.

So do you refer out to sex therapy? What are sex therapists doing in these situations? How are they helping people? Sure. So sex therapy, I do use sex therapists, and I think they're very effective. The problem is that many men don't want to see a sex therapist. They say, I want the pill. That's typically. And if they do want to see a sex therapist, now it's getting a little bit easier because telehealth, so they can do tele visits. And before they have to go into the sex therapist's office, and they're a little bit more likely to use the telehealth.

But what has been very effective for young patients is we will give them daily to the elephant. So when they take daily sealas, what they'll notice is that their erections are starting to get better. And you'll do this at 5 milligrams. Now, what's interesting is that when a young person or anyone has erectile dysfunction in one time, we call it the vicious cycle. What happens is the next

time they engage sex activity, they say to themselves, as are having sex, I hope I don't lose my erection. I hope, and they will lose their erection. Guaranteed because they're so fixated. Sort of like in driving, we say, you know, if you're trying to not drive off the track as you're exiting a corner, looking where you don't want to go is exactly where you're going to go. Right. That's the same philosophy. The car follows the eyes. as you're exiting a corner, looking where you don't want to go is exactly where you're going to go. That's the same philosophy. The car follows the ice. The same philosophy.

So what happens is, and then when they engage at the next time, the next time, they say, I can't believe it's happened two or three times. And then it's just a total vicious cycle. So they get anxious, and they also undergo subconscious aversion. They start avoiding sex because they're scared it's going to happen. The partner thinks they have a low libido. Is it really a low libido, or are they really anxious about getting at ED? So typically daily sales, when they engage

this extra activity, they start noticing, hey, things are working, things are fine, it's okay. And then you can many times we lean it off. But you just want to show them that everything's working great again. Reaves a lot of peanut ultrasound in my office. And it helps me look at the peaks of stolic velocity and diastolic velocity.

Many times getting an ultrasound and showing them that everything is perfect is therapeutic. Interesting. So I'm gonna come back to the pino ultrasound and to the, like some of the, what's the gains? Yeah, so that's different. So that's the ultrasound for diagnostic purposes. What I do in the office, we put an injection

in the penis in duosin erection. The other ultrasound you're referring to is shockwave therapy to treat erectile, this functions. There's three areas here, there's stem cells, PRP and shock weapon. That's a treatment option. We'll come back to that in a second, but let's go back to this. Maybe just for folks explain briefly how sealas, viagra work. What's the mechanism? The erections are caused are induced by the parasympathetic nerves, and you can get stimulation oral, I mean, excuse me, ocular vision, hearing, sensory, and 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. Once the nitric oxide goes up, we get to increase in something called cyclic GMP. Cyclic GMP causes intracellular calcium to go down. It causes the dilation of the sinusoid and increases the blood vessel diamer and the blood comes in. Now there's a bad thing there.

There's something called phosphodiestrace. And phosphodiestrace eats up the cyclic GMP and therefore you will lose the erection. So how does viagra, siallus, levietro work? It's a phosphodiastase inhibitor. So it blocks phosphodiastase. So you have more cyclic GMP so you can keep the erection around. Now, there's 11 different phosphodiastases in the body. So for example, type 5 is in the penis.

Six is in the eye. 11 is in the back. So some of these medications have cross reactivity with the other phosphodiastases. So you get side effects. For example, siallus has more side effects with phosphodiesterase type 11, so you may get more back pain. Viagra has more cross reactivity with type 6, so you may get changes' ocular vision. So ideally, you want one that only affects five and nothing else. And is there one to date that does that?

In my opinion, the newest one of Anaphy has the least cross-reactivity with the other phosphodascerys. So I think it has less side effects. The only difference is that it is not generic yet. So it's expensive. Much more expensive. Yeah. So the generic, now you go to cost plus or you know, more Cubans or you go to good or

X. It is so cheap to get Seattleist today. But Vanneville is still not generic. You want to tell people the story of how Viagra was developed? So Viagra was developed to be a blood pressure medication to control the blood pressure, and they sort of noticed that everyone was getting, or cardiovascular medication,

everyone was getting erections in the trial. Everyone who got the Viagra as opposed to the placebo. Very interesting. Other drugs were the same wayra as opposed to the placebo. Very interesting. Other drugs were the same way you may have heard of the drug Adi. We used this to treat female sexual dysfunction or flu-bansion. That was used as a medication for depression. It was by Boranlingheim in Germany. And so they give it to women for depression and they noted these women wanted f-sex.

And that's how we got the development of Adi. And my recollection is Viagra was not successful as a systemic reducer or blood pressure. In other words, that trial failed. And what I read, I don't know if it's true, but what I read was the trial failed, it was Pfizer, I believe, to develop the drug. So as they were kind of tailers between their legs

and they're saying, well, that sucks. We just lost how this money on a drug that doesn't treat blood pressure. But what they noticed was a difference in the samples being returned. So the patients who were on the placebo were very happy to send their samples back and somehow the majority of patients

on the treatment drug, Viagra, which wasn't called Viagra at the time, of course, were disproportionately keeping it, which then prompted them to ask follow-up questions and say, why are you keeping it? And that's how they sort of backed into this unintended consequence, which is amazing in that it went from a whole, hum blood pressure drug that would have had a market size of

this to a market size of this. And it was a game changer in my field. So in our field, sexual medicine, I'm part of this sexual medicine with America, game changer in the way we treat men free. We'll come back to this, I suppose, but we'll put a pin in it. There isn't probably a single drug that has had that effect on women's sexual health, is there? You know, the first drug that ever came out

was in 2015 called Adi. The second drug was called Vilece, but not even close to the impact that Viagra had in men. Both are excellent drugs. And they're more about desire. They're more about desire, and we are learning that they may have some other functions as well, off label like orgasmic function.

Both are good drugs, but they just really never took off like biagra. It might be that the single most potent agent for women's sexual health, at least as a woman is aging, is actually HRT. Yes. It's probably that estrogen has the greatest single. But there is a synergistic effect because if you use HRT and you use these medications, because of different mechanisms of action,

that's right. They're accretive. Yes. Okay, so this phosphodisorant is inhibitor, which now we're into our third generation of them, basically, solve a physiologic problem. Right. So what is it the root of that problem? I mean, I understand that by inhibiting phosphatoresterase, you

keep around more cyclic GMP. You maintain the flow of blood in the smooth muscle. But what is it about the aging process and or its comorbidities that is leading to that venous leak in the first place? You nailed it. So the main issue is venous leak, or we call a venocluse of dysfunction. You have to think of 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, inside those two tubes are muscle and sinusoid. Down the center of the tube is an artery.

And think of the wall of the tube as a thick casing called the tunica albogenia. Right under the tunica albogenia are veins. We call it sub tunic veins. So, as the blood comes in, it presses against the wall and prevents the blood from coming out. So, very clever system. The more blood comes in, the muscle can get pressed against the wall and prevent the blood from coming out of the peanut tissue. The problem is, as we age, we get atrophy of the muscle and we get fibrosis of the muscle.

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. Because we can't maintain enough pressure on the venous wall. That's right. How do you overcome that? There's several ways. One is that you can actually, so it's a simple outflow inflow game. If the inflow is 10 and the outflow is 15,

you're not gonna get an erection. But if you give someone by Agra and you make the inflow 25, you can overcome the Venus leak by increase the inflow. That's one way, the second way is actually some people use something called a Pinau band. Like a tourniquet. Like a tourniquet, because if you use a tourniquet,

you can actually compress the veins and still allow the inflow. So if I may... So you haven't fixed the inflow problem, but you've increased the back pressure on the outflow. That's exactly right. So if a man took his hand while he's having an erection and placed his hand and grabbed the penis at the five and seven o'clock position, put pressure, you'll notice that you'll get

better and better erection because you're blocking the outflow, which can't keep your hand. And tell people why you said five and seven o'clock. Well, it's circumventual. Oh, it is. It's circumventual. I thought the veins were disproportionate. Yeah, it's circumventual, but if you put your hand there,

it gives you almost a 180 protection. I see. So it's circumventual, but. So it's not like the fingers were at about five and seven. No, it's all the way around. It's all the way around. It's all the way around.

Okay, got it. That's why if you apply an alternative, you actually prevent being asleep. Or, but most people say, I don't want to use a turn to get, I said, it's fine, just increase the inflow. That's why we use intra-cavernoso injections, we'll use Viagra, I mean, there's ways

we can significantly increase the inflow to overcome the outflow. But aging, aging does cause of being asleep. We know that lower testosterone levels have been implicated for causing a being asleep, because it's atrophy of the P-NL muscle. I do a lot of procedure called a P-NL prosthesis, and I have a lab. So what I do is we have a protocol where we can take the tissue, the PNL tissue at that time. We send it to the lab and then

we'll look at it, high high density of angers receptors within the PNL tissue. As the antigens go down, you start getting atrophy of the PNL muscle. That is very interesting and I do want to come back to the intracellular and nuclear distribution of Androgen receptors, testosterone and DHT. So again, I'm trying to keep track of my mind of all the things I want to come back to. If you said to me, Peter, how can an aging person prevent atrophy of their muscle? The most obvious thing that comes to my mind is use it. It's a use it or lose it, sister. Is the same true of the penis? It's very true.

So if you look at patients who are not using the peanut muscle, for example, let's look at patients who have a radical prostatectomy, very unfortunate. Young man say he's 52 years old and right after that surgery, he's not using the peanut tissue. You will start getting atrophy of the muscle just if I put your arm in a cast today. So regular erections, so nocturnal erections are very important also. So that's how we get our oxygen into the peanut tissue

through the nocturnal erections, through sexual activity. There are studies suggesting that daily PD5 inhibitors, Cialis via agra, can help with hypertrophy of the cavernosal smooth muscle. So that's why I particularly like to give patients daily Cialis because- Even if they don't have ED. So let's think about this for a second. I just mentioned earlier that 40% of men have ED at 40, 50% if it's an aging process,

right? To some degree. So when you take Viagra, you are not curing your ED, you're just covering it that night while the disease continues to progress. But daily CLS has been shown to cause hypertrophy of the cavernosal smooth muscle, keep the tissue healthy. So in many ways, I look at daily seals as a preventative measure to keep the tissue healthy. Now, I tell patients, when is the best time to start? When you start noticing if there's a mild degree of ED,

something starting to show up for ED, that's when I want you to start taking the daily seal. Not only to help you with what your issue is, but I look it to me as a preventative measure. Talked about daily CLS. My recollection is that there were basically two dosing strategies, right? There was 20 milligrams. The idea, I think it was, you know, hey, take 20 milligrams on Friday and it'll hold you through till Sunday, and you can basically have sex on demand. Alternatively, it's having five in your system every single day produces the same tissue level.

Is that directionally right? Close. So the conversion is 1.6 as the multiplier. So if you take five milligrams every day, it's like having almost like eight milligrams all the time in your system. Eight. That's the conversion is 1.6. So eight is obviously less than 20, but some men really don't need 20.

So that five daily, remember, there's other benefits. Five daily has been FDA approved for BPH, and let's, we'll talk about BPH and even FDA approved. So you can give someone flomax, or you can give them daily sales. Well, the problem with flomax is retrograde ejaculation. You got it. So I think the young man, if they had a choice, they'll say, I'll take the Seattle's, and the side effect will be better erections. So FDA approved for BPH.

Why, what's the mechanism? So mechanism unknown. That's what's a little bit interesting. We do know, it even says in the packet, mechanism unknown, but we do know that IPSS scores, these are urinary symptom scores, do improve in men who take daily PD5 inhibitors. That's true.

So you just have to be careful not to, if you do take Cialis and a flow max medication, not to take them too close together, there's a warning because you can get a high potensive. So we have to separate them. But daily PD5 inhibitors are also FDA-approved for pulmonary hypertension. That I knew. And there were wonderful studies looking at daily Cialis versus on-demand Cialis, showing that the patients who took it for four weeks daily significant improvement in endothelial dysfunction and we'll talk about that later

but endothelial dysfunction outside of the penis outside of the penis. Meaning systemic and they were looking at blood markers IL-6 see reactive protein not so specific they were looking at flow media and vasodilation break your artery and they were shown that even if the patients stopped, this was a study by aversa, even if the patients stopped the daily siallus versus the on demand, those patients who took the daily still had persistent improvement. So maybe, maybe something going on in the endothelium as well. So I think about endothelium, I think about pulmonary hypertension, I think about BPH, other than ED, it's 5 million daily, very affordable. Okay, maybe we can...

What would you say is the biggest downside of siallus? I used to say cost, and it was unbelievably... How much did C. Alice cost? It was almost $15 to $20 uphill. $15 or $20 for a $5 million? Well, it was $20 million uphill, but it was still absorbing. It was almost $400 for a 30-day supply of $5 million, which was unbelievable.

So then we started going to the compounding pharmacies. We said, okay, the compounding pharmacies said, we can make it for a dollar a pill. That's great. But it's hard to trust the quality, right?. We said, okay, the compounding pharmacies said we can make it for a dollar pill. That's great. But hard to trust the quality, right? Some are better than others, and some compounding pharmacies are FDA-proofed, so that makes it a little bit better. But then the generics came out, and it was shocking.

If I give a patient who goes to HEB, they can get 90 pills of Cialis for $17 with no insurance. 90 pills, five million. Are you concerned, I've become very concerned with the quality of generics and realizing that not all companies are the same. Like Sandos is a good company, but some companies are, do you have preferred brands of generics that you fancy? I don't have a preferred brand, although I haven't seen the generics significantly less

effective than the brand when it comes to PD5 inhibitors. That's one thing that I think I have not seen it less effective. That's great to hear. This is sort of indirectly related to ED, but what about refractory period? So any guy listening to this can think back to being in his 20s where you seem to be able to, you know, have an erection, ejaculate, and seven minutes later have another erection. Sure. You could have intercourse 27 times in a day.

Sure. And then something happens when you get older, those days are done. Like, you might get to a day. Sure. Is that considered a lagging or leading indicator of ED is the fact, like, what's different about that 20-year-old versus the 50-year-old? Yeah, so there's no question that the refractory period goes up as we age. One of the implications for refractory time is prolactin.

So when you have an ejaculate, your orgasm, your prolactin levels go up, and that's been implicated as the reason for the refractory time. But as men get older, you're right. ED is more prevalent. So it's harder to get the next direction direction and the refractory times go out. And I'm sorry, is there anything different about the prolactin secretion? I've never seen a study showing that, although I would intuitively think the prolactin may be a longer period of time, but I have not seen any study showing that.

So that might be the indication, basically, that even if you don't have ED, things are changing. Your physiology is changing. Absolutely. And I think the majority of it is, it is more difficult to get in a reaction as we get older and therefore that contributes to the refractory time. It's so interesting how evolution simply, you would argue that, you know, not that we want to spend too much time speculating on evolution given that as Andrew Heberman would say, neither of us were there for the design phase. But it's interesting in that 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, 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. I don't know about that. We have patients who are older that have great semen parameters. I think it's based on your quality of your health, healthier men. Which, by the way, would make sense.

Yeah, it makes sense because you're more likely to reproduce. So we look at men who are in their 80s, who are in great shape, they're having sex, no issues, no even unassisted. Meaning they don't even require, they use a bit of I grew up. Yeah, but some do some don't. I mean, I have patients at 70, 80 years old, great shape, no issues having 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 burns, badgenesis, even at older ages. It's based on your quality of your health.

You know, I have younger patients who are 30 that are in terrible shape, pull quality erections, terrible, even parameters. I don't know if age is like the main driver. No, I think that makes sense. And I think I talked about this with Sharon on the podcast, but I almost wonder if the greatest motivation for a patient, especially a male patient with respect to insulin resistance, is actually a rectile 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. Again, I'm not talking about a one point change, but if someone goes from having a hemoglobin A1C will often notice an improvement in erections. Yeah. 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 represents probably about a 25 milligram per desoleter reduction in average blood glucose,

that's a person who says, I used to need Cialis for every erection to, I'm totally fine. So you bring up a really important point. It's lifestyle modification. Lifestyle modification has a huge impact on the quality of the 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 your erections and your quality of life. 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, 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. If I made a column of the risk factors for ED and cardiovascular disease, they're almost identical 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 card attack or a stroke. 15%. It's the first sign of cardiovascular disease. Numerous studies have shown that. And just to be clear, this is not Psychogenic ED. Organic has to be. So say that again, what percent? 15% percent. So in 2004, Ian Thompson had the Project Cancer Prevention trial, roughly 4,000 men did not have ED healthy men. He followed them prospectively.

From the day they developed ED, 15% of them in seven years had a cardiovascular event. That's significant. And he wasn't the first numerous studies have shown a correlation between ED and cardiovascular disease. Montorci, that same year showed that if you had a cardiovascular event, 50% of the men had ED 39 months prior to having the cardiovascular event.

It is the sentinel sign of cardiovascular disease. So it's a real canary in the coal mine when it comes to microvascular health. Particularly if it's arterial and sufficiency. So the question is what's the relation? So one theory was arterial diameter theory. And it doesn't make a lot of sense, but this is the theory. If you look at the peanut arteries, they're one to two millimeters. The coronaries are three to four millimeters. The peripheral arteries are six to seven millimeters. And if you get 50% occlusion of an artery, you know you get an organ damage. So you're more likely to include the

peanut artery before you include the coronary coronary before the peripheral. So that was the theory. Now, it doesn't work very well because most of ED is an occlusive disease. And really, it's the pedendol artery, not a cavernosal artery, but that was one theory. The most prevailing theory is endothelial dysfunction. That is the common link between ED and cardiovascular disease. Well, the cardiologists were very clever before the urologist

to show that if you improve endothelial dysfunction, you can actually reverse cardiovascular disease. So if that's the common link as urologist, we just copy them. Well, two of the three biggest risk factors for cardiovascular disease are taking aim at the endothelium. So the three big ones, APOB, that's not an endothelial issue, but smoking and blood pressure are one being a chemical, one being a mechanical disruption of the endothelium.

And I suspect both blood pressure and smoking are high risk factors. Elimination would mediate ED. For sure, OBC, diabetes is one of them also. This is called reversal. The best study I ever saw was Esposito 2004 in JAMA. She just simply said, I'm going to give you a diet and exercise program. 110 obese men, 55 went on a diet and exercise program, 55 went on nothing. And she followed them for two years prospectively. If you simply had

diet and exercise, you lost weight. It was a Mediterranean diet, by the way, I really believe in a Mediterranean diet. If you lost weight and took the Mediterranean diet, you saw three point, which was significant, increase on the IIEF score. This is on that six point scale. On the six questions, after 25s, you know, but a three point and on the IIEF, with no Viagra, no intervention, except diet and exercise on. Does that three point increase translate to a clinical meaningful improvement? Close. Usually it's four, so it's pretty close.

And the meaningful improvement is broken down into, think of this as two, five, and seven. If you have mild ED, you want to see at least two, moderate ED five, and severe ED seven. So depends where they started. See the way they started, right? But typically you want to see about a four, but even just a three, just on diet and exercise on, they saw improvements in endothelial function function in terms of IL-6, they lost weight. I mean, just diet and exercise alone reversed or had an improvement in ED.

So lifestyle modification is very important when we talk about a resexual dysfunction. So let's go back to what you were saying in the office, some of the diagnostic tests. So a guy comes in, you quickly, or maybe not quickly, but you rule out psychogenic ED and now you're realizing this is something physiologic. So you mentioned a diagnostic ultrasound.

So you're doing an ultrasound of the penis. You inject something into the penis to induce an erection. Yes. So we typically inject trimics, which is a medication that's compounded. You can actually also inject alpracidil, which is commercially available like edex. And you're injecting this into the corpus.

Into the corpus. And it will cause a vasodilation. And just because every guy listening to this is freaking out, saying, you're sticking a needle in my penis. Right. But you'd be surprised not in the arena. Not in the arena. Through at the base of the penis, we injected at the two or 10 o'clock position. And within five to 10 minutes, it induces a very good

erection. But what we're able to do with that is we're able to look at something called the peaks, a stolic velocity. If the peaks, a stolic velocity is less than 30, particularly if it's less than 25 milliliters per second, he has arterial insufficiency. Now, that's important. The name is not enough blood flow is coming into the penile tissue. If the end diastolic velocity is greater than 5 millimetres per second, then he has venous leak.

So, that's important. So, I can now see if there's a hemodynamic problem going on in the penile tissue. And just so folks understand this, right? Diastole or both start with systolecystole is what's happening when the heart is contracting. So you think about that as the flow out diastole is when the heart is relaxing in itself, it's filling. And so you're measuring kind of backflow through the venous system.

Right. And that venous leak is important because remember, that's the number one cause. That's the problem. The majority of the patients who have ED will start out with venous leak. So, but then there's other. Just to be clear, the venous leak is usually happening before you see arterial insufficiency. In most cases. And what's important is you can also look at the corporate cavernosa. I can look at plaque.

I can look at plaques. That plaque's important because that's what causes an abnormal curvature. You actually see plaque in the muscle? Not in the muscle, so in the wall, the tunic abagenia. So think about the two tunic abagenia coming together. As I come together, in that V is where you see the plaque predominantly.

Most of the plaque happens in the V. So most curvature in the penis is dorsal. So it actually goes upward, 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, because that's prohibitive for intercourse, and it is 60 degrees. So patients can have 90 degrees, they can have almost 180 degrees, it can be very significant. Wow.

That is a very significant disease. Patients who have paronies disease really suffer from depression. They feel like there's a disfigurement. There's a treatment now. In 2015, the first FDA approved treatment in the world came out for peronies, which is called Zaeflex or Collagenase, where I can inject collagenase into the plaque and break it down so that I can improve the curvature. So that's very important because historically, until 2015, we had no medical treatment. Everything was off label

And what would that include? So people used to give vitamin E and they used to give culture scene. So in 2015 I was involved in the American Neurologic Association Peronies Guidelines, first guidelines and we said do not give vitamin E. It's not indicated. Coltracy doesn't work, but the only medication that's indicated are anti-inflammatories. The way Peronys works is- This is administered locally or systemically. Systemically, so that's what we give. Think about this.

The way Proneys is these 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. Sorry, does this mean that Peronis disease is always born of trauma? It's the prevailing theory and sexist trauma, by the way. And so when a patient engages in

sexual activity, if he has a 100% rigid penis, less likely to injure, if he's 70, 80 or 90% rigid, he's going to penetrate and he's going to injure. So ED many times precedes PD, Peroni's disease. Interesting. But we do think it's due 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 going to happen? Everything's going to expand except the duct tape and you're going to curve in the direction of the duct tape. 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. And you can't in size, you can't put a slit in the duct tape. You can. So that's the surgical therapy. But in terms of medical therapy, you can actually put the injection called collagenase, it breaks it up and it can help straighten the penis.

The second thing you can do is actually surgical. You can put stitches on the opposite side and plicate it to make it straight, or I can cut out the plaque and put a patch, a graft, a tutoplast, or human pair of cartons. So we put a patch. Or if they have some erectile dysfunction with it, then I put in a penile prosthesis. Because what's the point of making the penis straight if you can't get an erection? In that case, I put a Pinau prosthesis.

And does a patient know if trauma is the predisposing factor? Is it apparent to him that he has induced trauma? Sometimes, majority know. So sometimes you can't even say, if you act quickly, you have a better chance of salvaging this. The only way is when someone has something called a peanut fracture.

A peanut fracture is when they're engaging in sexual activity and there's a sudden pop, a sudden injury that occurs, significant swelling that occurs in the peanut shaft, and you should seek immediate medical therapy and usually it's surgical. So you'll go to the ER, they'll call me on the phone and say, Dr, can we think we have to see the peanut fracture?

We'll go in and we'll take in the surgery and we'll show up the fracture. And the fracture is what? Break in the tunic of albogenia, in the casing, I was talking about her. And the swelling is now because fluid is leaking out. It's all blood. It's a hematoma.

It's a hematoma. So you want to act quickly, but majority of men, because we always ask them on the intake, do you remember any trauma? 90% say no. I have no idea why this is happening. I'm completely freaked out why this is happening. How did this happen to me?

And then you have to say, did you know that seven to nine percent of men have this? You're not alone. This is very prevalent and it's very, very concerning for these men. Age. Age does affect this more prevalent as men get older, but I do think so.

In 2009, I wrote a paper looking at testosterone as a possible implicator. We found that 74% of men had low testosterone. That's interesting because when you have low testosterone, you have decreased rigidity to penis, so I think you're more likely to injure, but testosterone has been implicated for wound healing, really in the dermatologic literature as well. It's almost like a double hit. You're more likely to be less rigid and injure, you're less likely to heal because many people have trauma, but they don't have a plaque. And so there has to be something going on with the healing process.

So these patients will have an injury, but then the way they heal is it's a plaque that forms. 15% of men have this or sorry, 7 to 9% of men have this. Is it painful or is it just disfiguring? Yeah, so at the beginning, there's an active phase for 12 months. And in that 12 months, it's the 15, 40, 45 rule. 15% of patients get better. We just get better. 40% of patients stay the same. 45% of patients get worse.

In the active phase, it's typically associated with pain. Every time I get an erection, I'm having pain. The patient, you say, look, I'm not going to operate on you because if I operate on you and you happen to be the 45% that get worse, I'm going to have to operate on you again. Has it stabilized? Does it remodeled for me? It's not finished. So when I get to the quiescent phase, which is a year, about a year, sometimes a little less, sometimes a little bit more, better, about a year. I say, have you noticed any changes that have occurred? No, Doc, it's pretty stable. Is there any more pain with an ere No, there's no more pain. Okay, now do you want to consider a surgical

option, which would be an option? The other treatment that's off label for this that's gotten a lot of favor is traction devices. So that's been very commonly used. And these devices are devices that are at- You just want on my neck, but I'm guessing it's different. The same concept. Any part of the body is pliable. People wear braces because it changes. So constant traction can make the penis longer, wider, but straighter. How do you actually apply a traction device to the penis? There is a portion of the device that goes around the glands and it makes like clamps the glands. And then you have skills to extend the tracings. The glands is the head. The head's

right. And the base goes are at the base of the penis the head. The head's rope's listening. Yep. And the base goes at the base of the penis as well. And you can extend it as far as you is comfortable. The one that I really like. But this is on a flaccid penis. Flaccid penis. The one that has gotten the most interest is the one out of the Mayo Clinic called the Restorex.

Because the Restorex, you actually bend it in the opposite direction where you're curving in the flaccid state. It actually bends. So if you're curving up, you can bend it down. If you're curving a left, you actually bend it in the opposite direction where you're curving in the flash to say it actually bends. So if you're curving up, you can bend it down, if you're going to left, you've bent it right. And you hold it there for 30 minutes, at least twice a day, for three months, has been shown to have about 30 to 40% improvement in curvature. So penis larger, wider, and straighter, but you've got to do the work.

They're about $500, a little pricey, but they are effective. And I know somebody listening is going to think, well, wait a minute, if you don't have peronies, can you still use this device to increase length or girth? So these devices actually came from the porn sites. So before we started using them medically in 2010, porn sites were using them to increase length and girth. And they do. And actually, many patients will come to me by what percent usually about any from one to one and a half inch. You can get. So what? Yeah, one inch. I mean, it's not like that sounds like a lot to me. By what percent? Usually about any from one to one and a half inch. You can get. So what? Yeah, one inch. I mean, it's not like. That sounds like a lot to me. Two centimeters

at the maximum. And is that a permanent change or is that only a change that lasts as long as you continue to use the device? We know that patients have to, it has to be some continued therapy. So some patients, when they finish using it, will have some periodic use, say every month or every, excuse me, once a week or twice a week just for periodic use. But some studies will show up to two centimeters, you can gain in length. So it's not negligible. So we get patients to come all the time and say, can you do penis enlargement surgery? I don't do that surgery, but I think that the stretcher is a safe way without doing surgery to gain some length. And the guy will use this for how long? It's every day, twice a day, at least 30 minutes,

up to three months. The old stretching devices were two to six hours a day, but they were not bent in the opposite direction. They were just straight. And so it was two to six hours a day every day for at least three months. But the rest directs, because of the ability, I think,

to bend in the opposite direction, you could shorten the time that you have to wear it 30 minutes to waste a day. Wow. Is there a critical window in which that works, going back to Peronia's disease, where you have to do it during that 12 month period, and thereafter it becomes very difficult

for it to be successful? Yeah, so the people have looked at active versus quiets in phase, and I think you get benefit in both phases. In my opinion, I think it's better difficult for it to be successful? Yeah, so the people have looked at active versus quiet and phase, and I think you get benefit in both phases. In my opinion, I think it's better to catch it in the active phase while it's trying to prevent further progression of disease. So let's think about this. A guy comes in the active phase, and he has 30 degree curvature. How do I define success? If I get that 30 down to zero, that is awesome. I'm very happy. But what if I'm able to prevent that 30 from going to 70? That's also success in the active phase. So because if he's greater

than 60, it's prohibited for intercourse. So typically, I like to at least the stretching device. At the AUA guidelines, I want to be clear, we'll say we should probably wait until the patient is in the quietest phase, the treatment is to give them anti-inflammatories, have them come back when they're quietiescent phase, and then start therapy. And then the AUA guidelines, we did not put in any stretching devices as well. It wasn't mentioned. So the entire use of the stretching device is off label. It's off label.

Got it. And it's expensive. It's 500 bucks, but potentially worth it, depending on the extent of the damage. So going back again to the diagnostics, so you induce the erection, chemically, you look for arterial inflow and outflow, venous outflow, you diagnose, let's just say the problem is purely on the arterial side. So venous problem, no issue. You mention you can still use the phosphodiesterase inhibitor to compensate.

You can. So how does the ultrasound result change your management? It lets me know where the problem is. So if it's venous leak, you can offer a band. You wouldn't really want to offer a band if you didn't have venous leak because it's RTL and sufficiency. And it tells you how bad it is also. So if I see that the venous leak is endisolic of 10, 15, it just tells you the severity of

ED, which is very important. Tell me what normal is again. So you want less than five on the end I saw it, and you want at least greater than 25 or 30 preferably on the peaks of Stolik. And so 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,

who had no issues whatsoever, what would you literally see as a... He's a Stolik of 40 and I saw it of less than one. Yeah, so nothing. And what's important is that, remember, each corporecavinoza will have a different number sometimes. You're doing both sides.

You have to do both. How often do you see significant asymmetry? Usually it's not that significant, but sometimes you can. So I just want to be very clear. You know, look, you're having some low peaks of stolic 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 fennestrated, so that whatever you have on one side compensates on the other. So if you inject a medication on the right, it also gets it left. So it's fenestrated. So it does make it very easy. But you mentioned something important. You know, this peaks a stomach velocity. If it's low in a young man, I am worried because I think it's a marker for cardiovascular risk. There was this machine 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. What was it called? Endopat 2000. I love that it has the 2000 at the end of it. Reduces any credibility of the machine. It was just the endopat. I'd be like, oh yeah, the endopat, that's pretty cool. But endopat 2000 just sounds like nonsense.

It was endopat 2000. That's when we came out. It was by an Israeli company, but we used to put a blood pressure cuff in one arm and then it would have a probe on the finger and then a probe on the control of the finger. And we put superficial logic pressures. We release it and you would measure the dilation in the finger as a marker for endothelial function as a ratio between the two fingers. So in the Mayo Clinic in 2004, they were using this device and then they would take the patient directly into the cardiac cath and then they would look at cardiovascular

blockage. And so they found that if you had poor endothelial function in the finger, it was a marker for potentially a cold blockage. So as a fellow, I did the same thing. I would do the machine, take these results, then I'd take them into the ultrasound room and do a penal ultrasound. And if they had poor endothelial function on the endopath, you would see a poor inflow of blood on the peaks of stolic artery. So there is a correlation, but this endothelial function and cardiovascular disease. But it's not common. We see much more end-diastolic dysfunction than stolic dysfunction.

Now let's talk to some of those therapeutic options you mentioned. When is a man a candidate for an injection and how long did it last? So let's think about it. We used to have in 2018, the guidelines came out in terms of therapies. 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 Vagra, Levitra, Sialis, or Standra is the newest, a PD5 inhibitor. In that level, you should think about sex therapy.

You should talk about lifestyle modification, which is very important. And then the second level was injections. So if the medications no longer worked, we would go into penile injections. And these injections are extremely effective. It's just that what are you injecting? So either So if the medications no longer worked, we would go into penile injections. And these injections are extremely effective. It's just that... What are you injecting? So either trimics, which is papadrine, phentolamine, and prostaglandin, it's three medications into the penile tissue and it dilates the arteries.

And it's very effective. And lasts for how long? It's dose dependent, so you got to be very careful. Because as you inject too much, you have a prio-pism, they have to go to the ER, and I may have to surgically bring it down. So the first injection should always be in the office and taught how to inject,

and usually I ask the bring the partner, because 50% of the partners inject for their partners. 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 three. You inject every time you want to have sex. I got it. You inject every time you want to have sex. I got to. You inject every time you want to have sex within five days. At the base of the penis. At the base of the penis, two and 10 o'clock

position. And what we teach you how to do it, and we have you slowly tight trade up to finally get to 80% rigidity, because we get the other 20% rigidity with four play. Once you find your number, whether it be point two MLs, point two five MLs, you use that number. The problem again, remember is E.DDS, a progressive disease. So many men will start having to use higher and higher 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 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. And the patient says, I don't want to start with the pill. I want to start with injection. That's fine. We don't use the urethral suppositories anymore. 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. In my opinion, they didn't work very well. They were good for combination therapy with...

Isn't that uncomfortable? It can cause significant urethra burning. That is true. Some bleeding as well. And it can cause a little bit of hypotension in some patients as well. So, we stopped using those. But the Peno prosthesis has been around now for 50 years. This year was 50 years. I meant to do baler in 1973. And it is a phenomenal treatment option for ED. And what does it look like in its current form? There's been many iterations. There are two main suppliers,

it's Boston Scientific and Colo Plast, and this device essentially is a procedure where we place two cylinders or balloons inside those casings, the Copacaburnosa. 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 want engaged engage in sexuality, you reach down, you press the pump and it brings normal saline into those cylinders and do some erection. And when you finish engaging sexuality, you release it and all the fluid goes back. And so just to be clear, a man would still ejaculate normally. Still has pleasure, but he would still have an erection after ejaculation because he's not getting the signal to turn it off. He turns it off when he wants to turn it off. Meaning Physiologically the erection's not gonna go away until he

Deflits exactly. So some men find that very favorable. So essentially you have the erection whenever you want as long as you want. So in other words, even if he ejaculates prematurely, you can still finish. And the same goes with the injections. So a man who uses an injection, the injection just goes away when the drug wears on the drug wears up. So some men do use that recreationally. So what happens is even if you ejaculate with an injection, you're not going to detumess. How risky is that surgery? I would say it's not very risky at all.

It says how long does it take you to do this? About five minutes. Under general anesthesia. General anesthesia. I've used surgery has risks, so let's be clear. There are some risks associated with it. There's a small percent of risk of infection. There's malfunction.

But again, relatively very safe procedure in my opinion. But it has to be with someone who has done a lot of these procedures. Yeah, so if someone's listening to this and they think that, hey, I might be a candidate for that. How many procedures do they want that surgeon doing? Like, you know, you don't want to see somebody who does want a year. How many of these are you doing? I'm doing about 60 a year. I think at least 50 or greater. I mean,

their partner patients at least 50 to 60 a year, I think, is very reasonable just to make sure that there are no issues. When you do this for a first-time patient, what's the re-operation rate or what's the malfunction rate or the rate of complication where you have to do something else. Typically, the infection rate's less than 2%, but now typically, we'll say closer to 1%, so it's not very common.

Use a prophylactic antibody. I do, so typically I use several things. I use bank, gent, and I'll use a antifungal as well because we know that 10% of these infections can be fungal. And then we use a new arrogant called ericin. Bank and gent, why such big, big guns? Because we're so worried about getting up, of these infections can be fungal. And then we use a new arrogant called ericin. Bank and gent. Why such big, big guns? Because we're so worried about getting a,

you get a prosthetic infection. Yeah, no, it's a disaster. It's over. In other words, we're not gonna just use first and second generation sloughless borons and cover the skin. We're going all in. So the vein has to be in an hour before.

If the vein cannot get in an hour before, I'm okay with sometimes using ANSF and gent by using an antifungal. But you're using GENT? Yep, and GENT for sure. And then what we'll do intraoperative is I now use ERISEPT. ERISEPT is what the orthopedic surgeons use. And ERISEPT is chloroxidine essentially, but it's very good for fungal,

anaerobic, and it's very effective Medicaid and it's cheap. So we use ERISEPT intraoperatively. The benefit of some of these prosthetics is that they're antibiotic coated. So the Boston Scientific was antibiotic coated with minocycle and refamp in. The coal plast device is hydrophilic and you can dip it into the antibiotic and it takes it in.

The key is a short operative time. There's many things in the operating room that we do to mitigate the risk of infection. Can you wear the space suit, like the orthopods do for joints? We don't, but we limit the movement in the room. We tape the gloves. We make sure that there's no movement and that the light handles above. We don't, but we limit the movement in the room, we tape the gloves, we make sure that

there's no movement in the light handles above. I don't have more than one person at the table across from me. It's very important because if they get an infection, it has to come out. It has to come out. You can do a salvage, which means if I catch it early, I can take it out, put a new one, but it's about 86% success rate, so you just have, if you catch it early, if they're septic, they have any kind of pureness, no salvage, you're not going to do it. I mean, God forbid, just think in worst case scenario. So if a guy is septic doing this,

you're pulling the whole thing out. Do you get another chance to put one in when he's recovered? It's a really good question. You wait three months to make sure everything, but it is much more challenging to get another one in and it's going to be shorter, typically, maybe even thinner also. Sometimes you call this a peanut cripple, so you just have to be very careful. You want to really mitigate the risk of infection. The same thing goes with someone who has pricism. After 36 hours, the new guidelines will suggest that you can put a peanut implant in and I strongly suggest.

Let's tell folks what pricism is. Yes, so pricism is a prolonged direction 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 around your finger numerous times, I'm cutting off the blood supply.

Well, how long does it take for that finger to start having the crowsis in damage? In the penis, 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 shows up on Monday, I'm very worried. I'm saying the chances of you recovering. Let me understand what that guy is going through.

Wouldn't he be in pain having had an erection from Friday to Monday? Exactly. But is he just not seeking care because he's ashamed? He's ashamed or thinks it's going to go down, which is the worst thing that could happen. 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, 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 phenyl 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. And for me to get the phenyl implant in. You do it on the day of admission. So for example, if that guy comes in having been 72 hours with an erection, and you're basically willing to make the call at 72 hours. We're not going to even wait to see if you recover. Let me put the implant in right now before there's fibrosis. You have a better outcome.

You can't, but you'll have almost a similar outcome if you do it within at least the first three months. 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 will happen is they'll get a shunt. A shunt means someone will stick a needle or a knife down the glands or in the corpera and try to de-tumest them. And then you get arterial tevenous connection.

Right, so if that happens, I don't wanna put an implant in right away because you have a risk of erosion slightly and you have a slight price for affection possibly because someone's manipulating the tissue. So I said, let it calm down, come back in three weeks, and this gives us more time to get the implant. Do you do an ultrasound to make sure there's no shunt. I do. So what's interesting is

if you do a shunt, most of the time the patient, the next day, will have an erection and the resident will call me and say, Doc, it failed. It didn't fail. Now they have a reactive hyperemia. They have a high flow. And if you ultrasound them, you'll find that they have a high flow. So I said, wait a minute. It's exact opposite. He presented with a low flow, Venus outflow obstruction. Right. And you converted them, but the resident will call me and say, he's got a high flow. I said, no, he doesn't. Get the ultrasound.

Let's look. You get the ultrasound. It's a high flow. You leave them alone. So high flow is a little bit different. High flows typically someone had trauma. What is the etiology of prioepism? I know it's a side effect.

So there's many causes of phosphodastorycinhibitors, right? But it's extremely rare. It's extremely rare. The most common cause typically is when someone is injecting a trimax or an agent and inject it too much. But you can get medications like trasidone, cocaine. I mean, there's a lot of medications that can induce an erection that won't go down.

Interesting trasidone. Trasidone. Which is ubiquitous now as a sleep agent. Right. And it can cause pricism. And so... Is it dose-dependent? I don't know if it's dose-dependent.

Typically, most patients like 50 milligrams when they go to bed, but I would assume that it could be. Interesting. So the moral of the story here is, if you have a reaction for four hours, go to the ER. Absolutely. And when that patient comes to you in the ER, you make an incision. Good point. So the two things, the first thing I do is I put in phenolephrine. So if it's less than

four hours, I'll inject the antidote. So the end of phenolephrine, and it'll usually work if it's less than four hours. If the hours are greater and greater out, what I'll do is some aspiration irrigation to try to get the old blood out and phenolephrine. If that doesn't, sorry, aspiration irrigation off the base of the penis. Of the base of the penis. So we're using an 18 gauge butterfly needle, put it in and I'm injecting normal saline and I'm aspirating. Many times we'll use cool saline.

We're just trying to get the sluggish blood out of the addition. Wow, do they ever develop like clot, venous clot? It is venous, that's what it is. Oh, it is already clot. It's already clot. It's already clot. I didn't realize that, okay. So you're basically trying to get all that clot, it sluggish blood out.

And so you'll ask for it. Do you ever run heparin in it or anything like that? We don't run heparin in it. Although if I do a shunt, sometimes people have advocated, we start him and happen or plavix to keep the shunt open. I use it typically, you use a low dose aspirin, but that's one thing you can do. So we aspirate, irrigate, then we put the phenyl effernate. If it doesn't work, then my favorite is a T-shunt. And a T-shunt is where I take an 11 blade through the

glands into the corpora. And then we have to sometimes use a hagar dilator and put it down. And doing this under local? Well, this time I'll take into the OR. It has a minus-chribender local, but I think it's just better to take them to the OR. That's traumatic. That's traumatic. And you have to counsel them, you know, if I do this hagar and disrupt the muscle, there's a high chance you're going to have erectile dysfunction and we'll have to deal with it. How often do you induce peronies in treating prioepism? After treating the prioepism, there's now going to be a scar that results in the sacymetry?

I think the question is, when we use trimics, if you use trimics regularly, that is a risk factor for peronies. Because any repetitive trauma to the corporate governance is going to actually injure the tissue. When a man is injecting for ED, do you tell him to vary the site as much as possible to avoid that trauma? Yes, we tell him to inject opposite sides every other day. So you can't do it every day.

Anject opposite sides to mitigate the trauma that you can't do it every day. Anject opposite size to mitigate the trauma that you're causing to the corporate governor. Okay, last thing on ED I wanted to talk you about is this device that a couple of my patients have talked about. I think it's called Gaines Wave. What is it? So Gaines Wave is just a company that uses devices for shockwave therapy.

So I just have to give you a little bit of history about shockwave therapy. In 2010, have to give you a little bit of history about shockwave therapy. In 2010, Dr. Vardee, European study, was the first to start using shockwaves to treat ED. Shockwaves are not new to urologists. We use high-intensity shockwave for kidney stones. That's what lithotrypsia is, right? It's called high-intensity shockwave.

This is called low-int intensity shockwave therapy or list. 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, 2500 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 neo-anogenesis.

You actually recruit stem cells. You help with nitric oxide synthase, so it actually is helping improve the condition. We were at the first cardiologists in the year, if you look at cardiologists, they were shocking the heart, and they look at the reprefusion, and it was reprefusing the heart, or the pedics do it for joints, and they use it for plantar fasciitis, and it's used for a lot of conditions. But this was shocking the penis in 2010. for plantar fasciitis, and it's used for a lot of conditions. But this was shocking the penis in 2010. So since then, again, pardon my ignorance, how is the device applied? Think of it like a probe.

And what happens, you have to have someone performing the procedure. We divide the penis in six zones. So it's shaft, high-lum, and cruse, into sites of six zones. And we will typically... And so just explain where each of those is. The shaft is obviously the shaft of the penis. The highlight is where the, at the base of the penis, and the cruces underneath the scrotum,

because the peanut tissues go underneath the scrotum. So we will deliver 2,500 shocks 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 and they may have to give a booster. So when Vardy did it, he showed that the probe is just right on the right on the skin. Is it painful? It's not painful, it's well-tolerated, no anesthetic, not necessary. When Vardy did it, he showed that there was improvement in

peanut blood flow and men were having better erections. So the issue is that there are two types of machines. There are machines that have a focal shock and those that have a radial shock. And the radial shock is a hundred times less in terms of pressure. It's over a thousand times over in terms of time, so it's a longer shock and it's less penetration. And quite frankly, this is like a pneumatic machine.

The pneumatic machine, they do nothing. But they're not dangerous. So the FDA is called this a type one medical device, low risk. Anybody can buy it. So you could be any profession, anyone on the street. They're going great for these is 500 to a thousand dollars a shock cash. Sorry, 500 to a thousand dollars for the machine. One treatment for one machine. One treatment. For one treatment. One treatment. One treatment machine cost. But you said a guy needs two of these a week for three months. Three weeks. Oh, okay.

So six treatments, let's say. So anywhere from three thousand to six thousand dollars, for a machine that's a pneumatic, that does nothing, in my opinion. But the patient doesn't. That can be bought by somebody at Costco. You got it. You could go to the gas station and the guy could fill your tank and give you a little scrotals app. You nailed it.

And he can make $500 to $6,000. And the problem is that the ED population is very vulnerable. Because they don't want to go and ask somebody for help to think about this problem. Right, and they're almost desperate. They want treatment. And the other problem is that the ED population has a very

high placebo response rate. If I gave a hundred men a sugar pill, and I told them that this sugar pill would give you the best directions of your life, 30% of men will get the best directions of their life off the sugar pill. And then of course they're going to tell their buddies, that's right. This is the best sugar pill you've ever had. So what you've seen now is an explosion of shockwave clinics throughout the country, explosion. Everywhere you go, shockwave, shockwave. Now look, there are certain shockwaves that are very effective. The machines, these are called electro-hydraulic machines, electro-magnetic machines.

These are called class type three machines. They do work. Now I have to be very careful. They don't work in all patients and we're still learning. And the class three machines, like Gaines Wave is a class three, where you use the name company. So the device, I don't know exactly what device they're using. Well, I just remember this because again, I've got two patients who are receiving or have received this treatment who both swear by it.

But I know that at least one of the patients mentioned to me, only a doctor's office can have this thing. So I assumed it was a class three, or whatever the device they were using. But those machines are more expensive. The electrolytic is exactly what the shock wave is for the kidney stone, but it's a low intensity. Electromagnetic is by stores.

But again, I just want to be fair. This is where the device took off greater than the science. The science is coming up, and I would say that it may be beneficial for patients who have mild to moderate ED, but be careful on the ads that are given on. If you look at these ads, they say, you'll get a greater erections today.

You'll have greater erections by tomorrow. The ads are unbelievable. So, part of the sexual mesocyte North America, we put out a position statement in 2018. Should we use investigationally at this time? At the AUA, the Guidelines for ED, investigational. Both will put out in 2018. It's been five years, it's been five years,

it's been new data, but I just want to say use it with caution. Don't tell everyone it's the best things to slice bread, it has potential, and more studies need to be done. So we talked about ED, does it make sense to now talk about premature ejaculation? Sure, I just want to mention two more things. On ED, it's stem cells and PRP, because that finishes the circle. And so stem cells, the problem with stem cells, and we published a paper, we did use stem cells. We had an IDE. There's no FDA approval for this, is there?

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. Are there people doing it in the United States off label? They used to, but you are not supposed to, because the FDA has said you cannot use stem cells for ED. Are there people doing it in the United States off label? They used to, but you are not supposed to, because the FDA has said you cannot use stem cells. Oh, I see. So just in general, for any therapy,

I use a machine that had an IDE by the FDA, so an investigational device exemption. And this was the exemption was specifically ED for stem cells. So we conducted 30 patients. We used adipose drive stem cells. We take the fat. We wanted to use it fresh, so we put them in a machine, we would get 37 to 55.

So you would literally, this was a tolligus, you would take a man's fat, adipose tissue, get the stem cells, and then re-infuse. You got it, but because I wanted a large amount of fat, I actually had a plastic surgeon, do the liposuction, under some mild sedation, so it was a little labor intensive. Then I would take the fat, it was 120ccs of fat, and put it into a machine that had the IDE for making stem cells. So the machine after two hours would give me anywhere from the 37 to 50 million stem cells, and then I would inject those stem cells

into the penal tissue. At the base of the penis. At the base of the penis with a tourniquet for two minutes, and you have to inject slow or you'll damage the stem cells. So we let them sit there for 30 minutes and we take the turn to get off. And did you have a 30 placebo men? This was non placebo controlled, and this is important because up to today, there's not a single placebo control trial with stem cells, 3D, not one.

So given the placebo effect being so high, what was the effect you saw in these 30 men? We saw that they had an increase, maybe a four on the IEF, no placebo control, but it was only durable for six, maybe nine months and start 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 going to start a placebo control trial because people swear by stem cells and some companies will say, 15,000 will give you stem cells for ED.

Where's the placebo control trial? It doesn't exist. So you have to be careful. Well, the other thing I guess is, at $15,000 in Costa Rica, we would have to believe it's significantly better than daily siallis at what, $70 a year. So I would say, look, there may be some benefit.

I do think there's some benefit in stem cells for ED. The number of 15,000, I don't know, some people have different numbers, but Costa Rica, there are certain places I think that are doing it better than others, and they have more science behind it, but we still need more science. So do I think that stem cells have potential for ED?

Yes, I do. Do we need more studies? Absolutely, to show the efficacy. And the question is, if I'm spending a lot of time doing a liposuction in it last for six months, I can't do this for a lifetime. That's not a practical way to do it. Although one might argue, oh my God, that's fantastic. I'm getting free liposuction every six months.

At some point, you're going to take all the subcutaneous fat on my body, but no, it's not a viable solution. But exosomes, maybe the next way. What are exosomes? It's basically the secret home. What's coming out of the stem cells? So people are looking at exosomes, and I think that may be another alternative

to looking at the future. How are they harvested? You can look at the placental. Also, you're looking from the patient's own tissue, typically fat, but mostly from bone marrow. So they get it from the bone marrow. But again, you have to believe that the durability of this is much longer to justify this.

I mean, can you imagine saying, we're gonna take a bone marrow biopsy on you every six to nine months to get your stem cells, to give us your exosomes, to do this procedure? Some people will take the stem cells and they'll multiply them and they'll get billions and then they'll give you pieces of that. Now remember, every time you multiply them,

every time you get past four, the FXC starts going down. So that'd be a little careful, you know? So I do think there's some potential promise, but we still are lacking in the science with the stem cells. PRP, now that's interesting. Until the last year, we got our first randomized placebo controlled trial, first one, until 2020, 2021.

Before then, there was one case report, one case report with five patients out of Wake Forest so that there may be some benefit. And this was sold like it was the best thing since sliced bread. They call it the pea shot, which is the prior pea shot. It basically takes stem cells, it costs about $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 pure pee. And they inject it. You spend it, you get to supernat and you spend it again, add some calcium chloride, you have PRP. Are they injected? 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. Robins. With Lisi Bohrms.

With Lisi Bohrms. So, that's going to be very interesting. When is that expected to be published? I think there's going to be some preliminary results at the AUA this year and April next month. So, that's going to be interesting. I think there's going to be some preliminary results at the AUA this year in April next month. So that's going to be interesting. I think it came out as a late breaking. So hopefully next month we'll know more. Yeah, well, by the time this podcast comes out, it'll be in the past tense.

So we'll link to that. Sure. So we might take away from everything on ED, just to summarize is easy way to remember the prevalence is it's matched by age. 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% etc. Second thing to consider is if men listening to this or their partners are listening, go and get help. Don't suffer in silence. Third thing to consider is that daily phosphodiesterase

inhibitor, I took away from you as a very viable solution. There shouldn't be a stigma attached to that, and there shouldn't be a fear that I'm becoming dependent on, or something like that, in the sense that these are valuable drugs. They can also sometimes break their vicious cycle if there's a psychogenic component. You want to rule out psychogenic before you proceed to pharmacologic as the only therapy. You have the diagnostic side on the arterial venous. And then I think this idea about PRP stem cells, exosomes and shockwave, it's still a little bit too soon to know. A little bit too soon, promising, but too soon.

And of the four, would you say the most promising is stem cells? I like shockwave. You know why? Because when I do shockwave therapy, it recruits the stem cells. Because stem cells go to area of damage. So essentially, I'm getting the stem cells, I'm getting the knee out in genesis. It's not invasive, it's quick, it's not.

So we're probably most optimistic on shockwave least on PRP. So far, maybe there's a combination. Shockwave and PRP are shockwave. Let's see that with the results this area is soon. Okay, let's pivot now and talk a little bit about the sort of states of ejaculation. So, in orgasm, you had delayed orgasm, et cetera. How does the prevalence of the say-way suit. Okay, let's pivot now and talk a little bit about the sort of states of ejaculation. So, in orgasm, you had delayed orgasm, et cetera.

How does the prevalence of this differ by age? So, ejacatory dysfunctions are important. We know that 30% of men, 30% of men are likely to have some degree of ejacatory dysfunction. More prominent is premature ejaculation. Pre-mature ejaculation, 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. So basically 30% of men have this, only 3% of men in total are doing anything about it. That's exactly right. Which is very small. But two years ago, the guidelines came out. The new guidelines came out. So what is a premature ejaculation? 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 decrease a jackulatory time. Now, when it's lifelong, it's typically now less than two minutes. 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 jack late in 30 seconds and I'm happy, great, he doesn't have the problem. He has to be bothered by it, right? So it's important. What if he's not bothered by it, but his partner is?

Well, he has to be bothered by it, right? So if he's bothered that she's bothered, fine, but he has to be bothered by the condition. Now, acquired is a little bit different. So look, things were great till I hit 40 and all of a sudden I developed 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. So let's say I used to jacolate in 10 minutes and now it's five. Okay, that qualifies. It's 50% of what it means. So these are the two definitions of, you wanna break it down. Now why is that important? Because how I treat somebody is very different. If someone's acquired, we start looking at hormones, that's important. We look at prolactin, we look at thyroid,

we look at testosterone, we look at some, more diagnostic. If it's lifelong, we don't do a lot of diagnostic workup. You're not supposed to. It's the acquired way you start figuring out. You four reasons for this premature ejaculation one is the biological. The theory that there's increased sensitivity of the glands. So if they're one 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 part to engaging sexual activity. But doesn't that then put lidocaine onto the partner? You wipe it off before you engage in sexual activity. I see. But be careful because if you spray too much, it causes the ED. So that's one. So it's the biological. There's a neurobiological essentially meaning the neurotransmitters. So essentially that there's too little serotonin. The neurotransmitters are causing an impairment for the ejaculation. There's some belief on genetic.

We don't have an assay right now, but there are four genes that have been implicated. The sum gene. But these genes are only implicated in lifelong or in acquired? In acquired. Sort of in lifelong. I'm sorry. And there's polymorphism of the neuro-steroid receptor genes, and there are four of them, but we don't use this clinically.

We don't look for the assay. We just know that more studies need to be done. The last one's important. It's psychological. If you have a new relationship, stress, any kind of, they cause us some psychological impairment, that can actually cause premature. Give a sense of why stress can have opposite effects. Why is it that in one man,

stress might result in ED, and in another man, it might result in no difficulty and in another man it might result in no difficulty with an interaction, but premature ejaculation. I can't answer that. I don't know the answer. I do know that stress, though, significantly in effect, you in all sexual function. I call it sad. It's stress, anxiety, and depression.

Patient suffer from those, so stress can have a significant impact on all forms of sexual dysfunction. But stress has a huge impact when it comes to sexual dysfunction. A lot of men, when the stress have difficulty getting an erection, but it does affect premature ejaculation as well. So these are the reasons why men have it. So how do you treat it? There's some treatment options.

And the first line therapy, typically, is the spray I was talking about, lidocaine spray, that you can use, we use pro-messon, it's over the counter, it's easy to get. The second one you can use typically is SSRIs, so antidepressants. But some men say, I don't want to take an antidepressant. I say, okay, you don't have to take it every day, all that works best if you take it every

day, but you can take it on demand. The problem with on demand is you got to take it six to eight hours ahead of time. Which is counterintuitive, right? Because one of the side effects of an NSSRI is reduction in libido, right? And ED, both, and reduction in libido. So you're right. So you just have to realize that those are,

and in first-line therapy, you should always be sex therapy. This is one area where sex therapy is very effective. And sex therapists are what is the formality of training to be a sex therapist? They are certified, yet to have a certification to be- To be psychologists or psychiatrists. Typically, psychologists, not psychiatrists, but psychiatrists can be certified in sex therapist. They are certified, yet they have a certification to be a psychologist or psychiatrist.

Typically, psychologists, not psychiatrists, but psychiatrists can be certified in sex therapy. They're very helpful because there's two techniques, the stardustop technique, the squeeze technique that teach patients how to prolong the ejaculate. But again, a lot of times patients say, just give me the pill. I say fine. But if they did the work, that's a cure. That's a cure for PE. So those are the first line therapies. There are second line therapies. The two second line therapies are Tramidol,

a narcotic, and actually has been shown, if you look at the Jacotort time less than one minute, a lot of studies to seven minutes. The problem is a narcotic. Yes. And it's been used quite often as a treatment. And it's in the guidelines as a guidelines. What's the risk of addiction or exacerbation of? Very high. I had a patient once that started using, you know, five a month. Then he started asking for 10 a month. And then once he called for 30 a month and I said, this is ridiculous. He goes, well, I'm having sex every day.

I wanted every, I could tell he was getting addicted. And I said, I can't do this anymore. So you just have to be careful on the tram at all. And then actually, alpha blockers, flowmax, second line therapy for premature ejaculation. Now, does that sometimes convert premature into retrograde? You can. So right, that's one of the risk factors for the afloboccus retrogate, but it prolongs the ejaculatory time.

So these are the treatment options that we use for patients, and they're quite effective, and you just kind of go through the algorithm for PE. Explain what a retrograde ejaculation is. So as I mentioned earlier in the prostate, there's something called the ejaculatory ducts. So think of it like a T. So the ejaculatory ducts are coming up. Moving forward is the urethra and it's coming out the urethra. Moving backward is the bladder. So when the sperm comes up and the semifluid comes up, the tendency is for the fluid to go back into the bladder. But as the man has an ejaculatory,

he closes off the bladder neck. So the fluid cannot get into the bladder, but as a man has an ejaculate, he closes off the bladder neck. So the fluid cannot get into the bladder. It's forced to go out. But when you take a medication like an alpha blocker or certain other medications, it can actually open the bladder neck. So what happens is the sperm comes up, semifluid then goes into the bladder. And so nothing comes out of the erythra. And when the man urinates or voids, then the seminal fluid will come out.

Is there any harm of a retrograde ejaculation? No harm at all. Just some patients find it annoying. Obviously would impair reproduction. For sure. So someone's trying to have a child. Huge problem. Yeah. Okay. At the other end of that spectrum is anorgasmia. Sure. And what's your workup for that? So anorgasmia, and we put this in the same is 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? And the same principles, are you bothered by it? Loss of control or inability to control? And more importantly, the timing. So what is the average amount of time that a man takes to a jackaline United States typically about six to seven minutes on average six to seven minutes is the norm that self reported in the numerous studies and it's interesting how we do that great question

So we look at something called the intra vaginal a jackatory latency time IELT and it's typically self reported but when it's self reported It's inaccurate. Yeah, it's. Because when we're keeping track of time. So what happens is when you ask a man who has premature ejaculation, he underestimates the time. If you ejaculate in two minutes, he says, I had 30 seconds. If you ask a guy who does not premature ejaculation, he overestimates the time. If you ejaculate in eight minutes, he says, yeah, that was 15 minutes. So it's a big discrepancy.

So how we do it is we give the partner a stopwatch. When he orgasms, she's supposed to click the clock. And that's the best way to get intra vaginal ejacular laser. IELT is best-wide stopwatch. And based on that gold standard, it's six to seven minutes. Six to seven minutes. Now look, certain countries have different numbers. So Asian countries, lower numbers, European countries, higher numbers, longer ejaculatory laser. What do you attribute that to? It could be cultural differences as well, but there's some differences, but when you look at, 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 SSRIs. Paxyl was number one by far, So Paxyls typically use the most. Zoll-off was number two. And you can see based on the dose, because it's dose dependent. So the higher the dose, the greater the ejaculatory time,

but at the end of the spectrum, it was 25x with Paxyl. So typically it's about 10x, you'll see in a delay. But without getting to the point of ED. So remember, if I'm using too much Paxyl, I bring it down. So one of the problems we'll talk about this delayed orgasmia, a lot of these patients are having it because they're on an SSRI.

That's why they have it. So if they're on 40 milligrams of Paxol, maybe we just go to 30, we still get the benefits of depression, but we improve the ejaculatory latency time, because it's very sensitive on those doses. There's no set number on delayed orgasmia, but typically someone will say greater than 15 to 20 minutes. If it's great in 15 to 20 minutes, that could be considered delayed orgasmia. We have no FDA-approved treatments

for this condition. There are no FDA-approved treatments. So everything I'm going to tell you today is off-label use for how we treat this condition. And what about the role of five alpha reductase inhibitors here? I would not use five alpha reductase inhibitors. I don't like to use them at all in my practice. Oh, I mean, as implicated in an orgasmia. In other words, is it possible that five alpha reductase inhibitors are amplifying? It is possible. There are patients that have had or taken five alpha reductase inhibitors that have had impaired

orgasm or an orgasasmia, because remember, it blocks DHT. And DHT is four to five times more potent than T when it comes to function for the receptor. So typically, and one of the treatments for delayed orgasmia is testosterone. So that's how you treat it, right? And so if you're using a five-outro, you're actually going in the opposite direction. What about the phosphidesterase inhibitors, the same drugs we talked about, to treat ED, how often do they induce delayed orgasm? They don't induce delayed orgasm. They just expose it.

They might make it such that you're gonna be able to do it. They expose it. But you bring up a very important point. If a patient presents with ED and premature ejaculation, you always treat the ED first. And that's a really important point because by two. Wow, that's an interesting thought. Let me wrap my head around it. A guy says, I have ED and premature ejaculation, meaning either I can't get an erection or when I can,

I have premature ejaculation. Those are my only two states. You got it. How common do you see that in a 50-year-old or 60-year-old man? It's not that common, but it does occur. I would be honest, but why do we treat the ED first? We treat the ED first because if you treat the ED, you can actually treat the... You can delay it, you can actually fix the... Fix the PE. And there's a reason for this.

Subconsciously, whether it's conscious or subconscious, it's a belief that the body is saying, if I don't ejaculate quickly, I'm going to lose this erection. I'm going to lose the erection before I ejaculate. And so if you're able to maintain your erection and not worry about it, you may prolong the ejaculatory time. So a board question we asked on the exams, patient presences at ED and PE, you treat the ED first, and you can't treat the PE at the same time.

I kind of want to talk shift gears a little bit and talk about testosterone replacement therapy. So let's 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 from LH and FSH to testosterone, SHBG, DHT, etc. And then let's talk about what deficiencies mean and what the consequences are and how we want to go about addressing it. Sure, so let's talk about the physiology because it's important. So GNRH is created from the hypothalamus. GNRH then goes to the pituitary. It's creates two hormones, LH and FSH.

And what's the signal for GNRH? Is it estrogen? And that's a negative feedback. So estrogen can't have a negative feedback on it. It's a pulsatile pulse, GNRH. 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, it goes to the LH cells. It goes to the LH cells. FSH has an S, it goes to the testicles. I tell the residents, remember that LH has an L ghostly cell. FH has an S ghostly cell. So LH ghostly cell and produces testosterone. FSH goes to the scertly cells and produces sperm. The two functions of the testicle are basically sperm and testosterone. So essentially, if a patient comes in and they have remembered that the majority of a man's testicles are comprised of certainly so. That's important because the exam is more of an indicator of his fertility status than his hormonal status. So that's important. Can you say exam you mean size? Size. So they should be four centimeters in diameter, twenty cc's and so when I'm looking at an infertility workup,

if the patient has small testicles, elevate an fSH and LH, I say there's a production problem, he's not making it. 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 is very important. So we talked about the fact that the testicles 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. Majority- By the way, is one of those stronger than the other as a signal?

I don't know if one's stronger than the other. I know that both are. I mean, we'll talk about serums and how serums work as they block that negative feedback on the estrogen. But remember that testosterone then is converted into estrogen, 0.3%, not much, 0.3%, and 6 to 8% is converted to the hydro testosterone. So you get two conversions. So the higher the testosterone, you should get greater estrogen and greater DHT. That makes sense. So what many clinics do is they try to block the conversions. They'll use a rheumatase inhibitor and they'll use five alpha reductase

and try to control it. And I'm not a big fan of that, but they do it. So that's really the big picture here. Let's double click on a few of those things and maybe just rehash that. So when you go to the doctor, it's pretty common that if the doctor knows what they're doing, they're going to measure FSH and LH in addition to testosterone. We're not measuring GNRH, right? It's pulsatile. Even if we had an

SA4, it would be useless, sort of like growth hormone. Let's talk about where SHBG fits into the mix because that is often measured. And let's talk about the concept of free testosterone, slash bioavailable testosterone, slash free endrogen index, all of these things that are not measurable, but are estimateable, and I want to understand if they mean anything. Most testosterone is bound. 2% is free. 50% albumin, 44% SHBG, 4% corticotropin, binding globulin.

Oh, I didn't know that. I thought SHBG was the lion's share, but it's split relatively equally with albumin as well. albumin, 50% albumin, 44% and then 4% corticotropin, binding globulin, a small percentage, and then 2% free. I thought SHBG was the lion's share, but it's split relatively equally with the album as well. Abium, 50% album, 44% and then 4% corticotropin, binding, a lot of them, a small percentage, and then 2% free. But the body only cares what's free. If you look at correlates with symptoms, the free testosterone is the best correlate with

symptoms, but we're so fixated on this total testosterone. The best example, a guy walks in as testosterone is 450, 500. He says, I feel lousy. You say, what's going on? Check his SHBG. You get a calculated free testosterone. The best example of Guy walks in as testosterone is 450, 500. He says, I feel lousy. You say, what's going on? Check his SHBG. Get a calculated free testosterone. If his SHBG is elevated, the free T is going to be low. And there you have it. How accurate do you think the calculated free testosterone is?

I think it's much more accurate than the assay. So I calculate my own. So there are calculators that are online. And very simple, you put in the album, and you put in the SHBG, and you put in the T. You click, and it'll give you the calculated free T. It's more accurate, I think, than the assay. The goal standard is LCMS, but it's expensive and it's hard to get. So there is an LCMS assay for free testosterone. I don't know. I know it's for total. It's for total. That record does a total of LCMS. Yes. I don't think there's one free, but

I. But you're saying if you have an LCMS, if you're cost-insensitive and you have an LCMS essay for total, and you know albumin and SHBG, which are pretty easy to measure, you plug those three numbers in, you'll get an estimate, a pretty good estimate, that's a calculation, of course, of free tea. Yes. And I'll tell you, one of the things that has been the bane of my existence is that we have pretty good data age-wise for the

distribution of total T over a man's life. What does the normal bell shaped curve look like at 20, 30, 40, 50, 60? We don't seem to at least, I haven't found those data for free T. All I seem to find for free T is over 18, which is very difficult because when I have a 50 year old man who says, how do I stack up? I say, well, I can only tell you how you stack up to men over the age of 18. I can't tell you how you stack up to other 50 year olds. Yes. So I think there's two important points here.

One is, I always thought that this concept called Andropra's was real, meaning as we get older, our testosterone get low and lower due to age alone. That is not true. We know now that total testosterone levels don't decline very much in healthy males. What makes that testosterone go down is the acquisition of comorbid conditions. A 75-year-old really healthy male, he'll be having a normal testosterone. A total T. What does change is the SHBG. So as we get older, the SHBG does go up.

The total testosterone should stay relatively flat if you're healthy. And the free T will start to go down. So I've noticed and I'm sure we'll talk about this. Genetics seem to play a very big role in SHBG. I'm someone who just seems to have a very low SHBG. But I also have a very big role in SHBG. I'm someone who just seems to have a very low SHBG. But I also have a very low testosterone. So my testosterone is maybe 400, maybe 500, but my SHBG is in the 30s.

So my free tea is about 2.5% of my total tea. I have lots of patients who have very high tea, but their SHBG is in the 80s or 90s. But that's the body compensating. So the body is very clever. And that patient, if their T starts going down, the body starts offloading and lowering the SHBG to keep that hemostasis. It's almost like our reserves.

It's pretty fascinating. It's the body's reserves. It knows we have too much. It binds it. And what do you think is driving the age thing? Because we definitely see an amazing response to insulin. So as insulin comes down, SHBG tends to go up. As T4 goes up, SHBG goes up, and as estradiol goes up,

SHBG goes up. Yes. Which of those things, if any, are driving the age change? I can't tell you which one is to be honest with you. All I know is that it goes up. I don't know which factors. Might be something unrelated to you. All I know is that it goes up. I don't know which factors. Might be something unrelated to that. But I think genetics is a big part of it.

So it's definitely genetics. Obesity has an effect on that stage. There are comorbid conditions that affect the SHBG levels as well. But it's interesting. Usually with obesity, we see it go down. It's the opposite. It comes with hyperinsulinemia and it goes down. Okay, so you buy the idea that having a plasma measurement, pardon me, a plasma estimate

of free testosterone is valuable. One of the things that I've struggled with is trying to make the leap between what we can estimate, which is plasma concentration of free testosterone, and what is probably physiologically important, which is how much of that free testosterone. And what is probably physiologically important, which is how much of that free testosterone gets into a cell, how much then gets into the nucleus, how many androgen receptors do they have? How are they saturated?

How sensitive are they, and how do they lead to gene transcription? And I know that in the lab, you can probably do those things. I've talked with Ted Schaefer about that, but clinically, I can't do any of those things. I literally have this very crude estimate of free testosterone, and I struggle greatly

to make the link between that and what's happening. So instead, I just sort of say to pay, and I had this discussion with a patient yesterday, which was, this is a 55 year old guy, and pretty good health, his free testosterone is estimated at seven nanograms per desoleter. So he says, Doc, is this higher low?

And I said, it's low. You're about the 20th percentile for men over the age of 18. Again, I can't actually tell him what he is for a 55 year old because I don't have the data and it drives me bananas that that isn't published. But I tell him, yeah, you're at about the 20th percentile for all men over the age of 18. And he said, should we do anything about it? And I said, well, I gave him my soliloquy that I just gave you.

I don't actually know how much of that seven is doing its job. And by the way, if your Androgen receptors are already saturated, I don't know that giving you more is gonna do anything. So I said, let's go through the symptoms. So I asked him a whole bunch of symptomatic questions. I wanna hear yours.

You're gonna share yours, not mine. And sure enough, he didn't have one symptom that I asked him a whole bunch of symptomatic questions. I want to hear yours. You're going to share yours, not mine. And sure enough, he didn't have one symptom that I asked him about. And I asked him about 10 things. And he said, I don't have one of those. And I said, well, I would not treat you then. Let's revisit this in a year. And he said, great, no problem. So first of all, I want to hear, what would you say to that patient if he said, Mo, my free tea is seven, it looks low, what should we do? I'd say, first of all, I would completely agree with what you did because why are you so fixated on the numbers? It's not about the numbers. It's about how he feels. If a guy comes in with a level of 250, 200 total tea, very low, and he says, I feel fantastic, one could say, why are you treating him?

Conversely, if he has a level of 500, it has all the symptoms, we don't treat. So if he comes in and he has symptoms, then I will treat him. And tell me the questions you would ask to a little bit. So I say, these are the following, low energy, low libido, erectile dysfunction. I didn't ask that.

Increased fat deposition, decreased muscle mass, depression, poor sleep, okay? Those are the big ones. I also asked about recovery from workouts. Yes, you could. That goes with the muscle, but you're right. Yes, bone fractures are important. So they have bone fractures.

And then just look at them. Just look at them. Are they obese metabolic syndrome? No, this is a guy who's lost 25 pounds in the last year in our practice. He's exercising more. His bone mineral density is fine. If I was going to be very critical, I would say, his appindicular lean mass index is only at about the 55th, 60th percentile.

We want to see our patients within appindicular lean mass index above the 75th percentile. But I don't think he needs testosterone to get there. A little more training and protein will probably get him there. Aladazzy. 55. Right. So he's young. So think about this. So I say, you don't need testosterone today. A little more training and protein will probably get them there. Allodize. 55. Right. So he's young, so think about this.

So I say, you don't need testosterone today. I don't know about five or 10 years from now, but today, I'm not going to put you on it because the reality is if I do put you on it, it will suppress your endogenous access and you may need to be on it for life and you don't need it today. You have no symptoms. That's been my lazy excuse, which is I'm 50. I am a firm believer in the benefits of testosterone. I wouldn't be prescribing to patients if I didn't feel that way.

I've spent not as much time as you, but more time than most people in the literature. And I completely buy the efficacy and safety of it, but I'm like, I don't need it yet. And I know that once I started, I'm going to be on it indefinitely. So I'm going to hold out as long as possible until I need it. That's what I wish most people would do. The problem is a lot of these young men go into the T clinic at 30 years of age, and they get started, and they're on it, then they come see me, and they say,

I didn't know I could be infertile. And now I have to reverse them, which is a protocol we use, they never were informed, they could have fertility. Let's talk about this. Maybe we'll talk about all the different ways that we could have fertility. Let's talk about this. Maybe we'll talk about all the different ways that we can replace testosterone. So the three ways that we have historically

done it in our practice, I guess technically four, one is, and we don't do this anymore, we used to use clomaphing. It had the advantage of several things. One, it's a pill, very convenient, take it three times a week, two, it preserved function, meaning you preserved both testicular volume and spermatic function, so you preserved fertility.

And actually, it was quite efficacious because you could titrate the dose and get to almost whatever you mean. The drawback is, if the man didn't have testicular reserve, he wasn't going to get much of a bump. There were some guys who had kind of peripheral hypogonadism as opposed to central. This was a great treatment for central, but you were at the limit of what the testes could do. 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. HCG is just a memetic for LH, luteinizing hormone, which you talked about, of course, is the direct stimulant of the lay dig cell, which makes testosterone. Lots of disadvantages, it's pretty expensive, it's an injectable, it's a very delicate injectable, so it has to be refrigerated. If you drop the bottle, the protein misfolds, and it's crap, so lots of problems associated with it. But again, it seems to preserve testicular volume,

which young men care about, maybe older men do too as well, not clear if it's as good as clomid at preserving fertility. I would love to hear your opinion on that. But again, it feels less problematic to men in the sense that it's less permanent. Of course, we then use the main stay as injectable testosterone sipionate or its derivatives. And again, we'll talk about all the pros and cons of that. And then lastly, pellets.

So testosterone pellets, don't do that anymore. Now that we've switched to being more of a remote practice, so I don't see patients in person to put the pellets in them. And also for men, pellets are a much bigger deal than for women. The pellets are so much bigger. For women when you're putting little estrogen and testosterone pellets in it, it's a walk in the park. They don't even notice you've done it.

For men, they notice it. Great topics. So this is really important. So you talked about two. So let's talk about endogenous ways to raise testosterone first. And you can use clomid. You can use HCG.

Some people use an astrosol. I don't recommend that, but we'll talk about that. So clomid first. It's a SIRM, negative feedback to the estrogen receptor. The problem with clomid is the following. We get a discrepancy effect, and this is what happens. You get a very nice bump in the testosterone level. That's true. But roughly 40% of patients say, I have no desire for sex. I have no erections. I don't feel any desire. Because the way the clomid works,

it blocks estrogen receptor centrally. Men need estrogen. It is critical. You need estrogen for libido and sexual function. So they have these beautiful 800-900 levels. No desire for sex. You take that same patient and put them on exogenous testosterone. And 800, he says it's working. So the way clomid works is that it blocks, and so that mechanism is not conducive for many men. Yes, it's easy. There's a national backwater.

So now we're starting to use a little bit more N-clomid. Is N-clomid legal in the US? It is compounded. Remember, repro and try to get it through in 2015 at the FDA never made it through. You know, it's the trans-ISomer of clomid, as you clomid. So, and essentially, it is available compounded

and you can get it, but it's hard to get clomid now even because there's a national back order. Is this just due to all these T-shops opening up on every corner that are? Well, they're different. So they're more into giving the T and the injection and you come in and get the injection for a fee, but this still is on the endogenous side. If Klomit's not bad, I mean, it does work.

Why is there such a run on this stuff? Because what happened was HCG wasn't for many years compounded. Recently, the FDA has said that HCG cannot be compounded, so everyone dropped the HCG and went to Comet, and now there's a mad rush to get the Comet. You can still get HCG commercially, but the price is due to the roof. But it's due to the roof.

So what happened was that everyone started going to Comet, and so now we're back ordered on Comet, and you can still get HCG, but it's pricing. And did the FDA say no more compounding HCG because it's too complicated and they couldn't do quality assurance? I think it was a patent infringement. I think it was more to the fact that I think Merck still had rights to the patent on HCG and it was too similar because a compounder can make something, but it has to be different. That's my understanding. I think it's going to start coming back, but there was a national shortage on HCG,

and that's why people started going to clomid. But clomid, it's not, the 60% will say my T goes up, you gotta give it every other day, or you can get a tacky phlaxis. So 7% can get tacky phlaxis if you give it daily. Some patients, they say, I can't remember every other day, I say fine, take it every day, and there's a percentage of you make

become resistant to the seven percent. Okay, so that's fine. We tell people to get a pillbox when we use to use it, so it was just Monday, Wednesday, Friday, and don't have to think about, load the pillbox. If you forget, take it every day, and cloned when we give it every day.

And what doses do you use? 50 for cloned every other day, and cloned 25 a day, or if they forget on 50 every other day We use 25 Clomid daily. Okay fine It's not a great, but it does help we use it for fertility so patients were coming to me for fertility to help them achieve a pregnancy We use it you can use H CG H CG is expensive and it is pricey typically it depends on what dose you want to use But it's 1500 three times a week up to two thousand three times a week. It can be effective

It's nice for patients who have pituitary pathology because I bypass the pituitary, go straight to the testicle and they can start making testosterone. And then in patients who have an elevated LHNFSH initially, client filters can't really use HCG or Clomix because they're already maxed out. They're already maxed out. So you've got to use NASA's all because I'm trying to increase the TDE ratio, increase the T, and typically I'm using this medication to improve from adogenesis so that I can then do a biopsy or a test-y to receive sperm.

I've never seen a man with client filters. When a man presents with client filters, what are his typical T, D-H-T, and E levels? So the E's are typically high, the T's are typically there. How high are the E's? 40, 30, E. I also know that, right? They're not super high, but they are. And it depends on how far long you see them along.

The F-sation L-H are typically already elevated, pretty high. So if the F-sation L-H are already elevated, I can't use Clometer ACG. What's the prevalence of client filters? One in 500, so it's quite common. Really, that high? Yes. Just tell people what client filters is.

It's a genetic abnormality where you have an extra X chromosome, X-X-Y. So phenotypically you're a man. So phenotypically you're a man. Phenotypically you're a man, but there are issues in fertility. You can have gynecumacia. They're typically long stature in nature. They have normal sexual function. They have no issues with ED, but the T is low, so that may affect the ED.

But we treat these men with medications to raise the T. And why can't you just give them to start a room? We can, but what if they won't have a child? So that's the only thing. So what we made use, I see a lot of these patients when they're 14 or 15 when they're first diagnosed. How are they usually diagnosed? I mean, I know the diagnosis is genetic, but what brings them to presentation?

A lot of times what you'll see is that there's no facial hair development. So they're delay in development. I see. No shaving. And so what you'll notice. And so the, and there's a suspicion, long stature, small testicles on exam, the pediatrician may say, let me just check a curiotype and just see what's happening.

And then you see two X chromosome. And then you know. One in 500. That means there's a lot of people listening to this podcast that have client filters, presumably they know it, but they may not. And if they know it, they might be wondering, is testosterone an option in what you're saying is not necessarily first line unless you can block estrogen as well.

And of course, it depends on the fertility status. Right. And some of these patients will start testosterone. And then when they're ready to have children, we will do a procedure called a micro-tessie at that time. And what we'll do is we'll stop the testosterone. And so my reversal dose is HCG 3000 units three times a week. And we'll either give them GONAL F or CLOMAD with it.

There's three ways to look at it. There's patients who have taken testosterone and they're abusers, and they come in now and they want to have children. That's the type number one of patients. That patient stops the testosterone HCG 3000 units three times a week, plus recombinant FSH or GONAL F, 75 units three times a week. And that actually does help reverse. Anywhere from three to seven months, you can see recovery of some adogenesis in these patients

who are asospermic. So that's great. And tell me that guy shows up having been on testosterone for how long to be a year. A year's. And many times they may have gotten the testosterone from a gym or some, and they didn't want to get monitored. And they're at super physiological level. So this is how long you've been on it and how high was your dose?

Dictates. How far along, so for you? We tell patients and we use physiologic doses. So typical dose for us is 50 milligrams of Cipianate twice a week. That's what we do. Okay. So we would say, at physiologic dose, you don't want to be on this for more than two years. And we are really hyper-vigilant and say, I wouldn't be on this for more than a year

unless you're willing to be on it. What do you say? You're talking about younger patients, though? Yeah. So someone who's like in his 40s. So in his 40s, I still try to, the second, so the category two is a young man who just wants to use HCG alone. And that's not 3,000, and three times, that's 1,500, 3 times a week as a dose.

And then there's the last one, and this is a study that we did at Baylor, where there's a patient who wants to take tea, and we give them HCG with it to protect the access. And that's 500, so 500, 15,000, there's three different patients, the preservation of, you know, and this also is a- Is this 500 of HCG three times a week. It's not doing anything to boost endogenous production. Protection. It's just protection.

And the best study, this is the best study I can, the guy named Koviella. This is how we got the idea of Baylor. Koviella had a study in 2005 where he gave patients 200 milligrams of testosterone I am every week. It's a big dose. Big dose every week. And what he was measuring was intratesticular testosterone levels. 200 I am every week. The intratesticular went down 94% of patients were down to zero in three weeks.

So that's a good number to remember. 94% decline in intratesticular testosterone in three weeks, 94% decline. Then what he did was he gave these patients different doses of HCG, was he gave these patients different doses of HCG, 250, 500, all the way, 1000. And what he found was between 250 and definitely 500, there was no significant decline in inter-testicular testosterone. Very interesting. So he was giving 500 every other show in 2013.

2030 by partner, Larry Lipscholtz said, okay, if that's true for inter-testicular testosterone, what is it doing for fertility? So let's do the same thing. Let's give these patients testosterone 500 units of HCG every other day. And what we saw was there was a decline, but it wasn't a significant decline.

And now that was the median. So there are patients who can have it. I don't want people to think, hey, if I do this, it's completely safe. But it does help protect the increased from the amount of genesis. But why is that the case, given that HCG is acting on the latex cell,

you would think you would need recombinant FSH to get the protection of sperm agenesis. Because it has some FSH properties. If you give a man for fertility just HCG, you actually see improvements in sperm agenesis. Now, there is some of the fact that some of the testosterone is being used by the Sertoli cells for production, a sperm production.

Has someone done the study of giving clomophine or mclonophine with testosterone to maintain sperm production? I have not seen that study, but people do it off-label. And it would seem to me that that would be even more efficacious. Yeah, people do it off-label. The only issue is that you got now two things working in opposite directions.

Because you got the estrogen problem up top. Yeah, and also that you know that when you're given the tea, you're suppressing the LH and FSH and Clomance trying to raise the S. I said, giving recombinant FSH would be the better thing to do. Yes. How expensive is recombinant FSH? Extremely expensive. So I would say it's really only used for fertility, right? That's its unlabeled use is in fertility with what? Yeah, up to $500 a month. I mean, it's very expensive. Wow. This is insanely expensive proposition once you start going, and what is HCG cost? It depends now because now you can't get a compound. No, if you're getting Pregnill brand about 300 to 400, 300 dollars a month. Insane. Yeah. You can understand why

unfortunately men, especially younger men who might not have the disposable income, are basically just getting testosterone because it's very cheap. and especially if they're getting it in an illicit fashion, you're keeping them out of the doctor's office where they can't be monitored, and you're pushing them into the gym locker room where God only knows what they're getting. There's one thing I forgot to mention on the fertility preservation side,

besides the in-assets all, clomaphine and HGG. There is some data that just came out suggesting that the intranasal testosterone does not significantly suppress surmata genesis. And this was interesting. So it's done three times a day. This was out of the group at a university Miami. Three times a day. It's called nattesto. It's commercially available. You got a wall. You can buy it. I've never even heard of this. I was just about

to ask you about the oral testosterone, but we'll explain. So nattesto is a nasal testosterone that's implied, it's 11 milligrams is implied in each nostril and you do it three times a day and essentially what happens is it has the fastest rapid onset and then it declines. And I always thought when I was... 11 milligrams TID. So 33 milligrams daily. So in other words, the bioavailability is much lower than injection.

Yes, but the interesting thing is this, I looked at the pharmacokinetics, I said, how can this be effective? Like how it's in and out so quickly. And then doing some deeper work and talking to some endocrinologists, I said, look, Mo, you don't have to have it around if it's bound to the receptor and it's doing its work. It doesn't have to physiologically be there all the time in the serum. And it's interesting, these patients do feel better. They feel better.

And because of the rapid onset, some of them do say they take it before sex, they take it before a workout because very quick, they say they feel better when they take it. How is this not become the drug of choice? But no significant suppression in surmata genesis. That was interesting. Now more studies need to be done, but that was a proof. Why is this approved? It has to, I think, has been out for at least six or 70.

It's been for a while. Is it cost prohibitive? Insurance does cover it. It can also be compounded. But it's used by a lot of young men. That's so interesting. So, 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 endogenous route. How are you deciding between pellets,

which we should explain what they are, topical, like androgel are compounded, injectable, such as sippinators, Iostead, or intranasal, or oral now. I go through all the options, first of all, say, because a lot of times it could be cost prohibitive and we find out which is the most affordable. Although I would tell you that injectables,

cash price from a compounding seat is $25 a month. We have them inject sub-Q, either a nantate or sippingate. It's based on AHU sippingate for younger patients and nantate for older patients. I think sippingate's more anabolic, it has more sodium retention. And so I teach the residents that sippingate has a C for child and nantate has E for elderly. I typically use like 50 or 60, but look at the patient. But I think that it has a little more sodium retention. So I try to stay away from the swelling and the edema in older patients.

So that's how I make my decision. And where do you make that cut off age wise? It's typically a 50 to 60 around there. I just, you know, if they're using injectables. So I'll say, okay, now what I like about the injectables is, okay, we use subcue, always subcue. And we have 25 gauge needle, short needle. Yeah, 5.8 inch, one CC syringe, 25 gauge.

It's big enough to draw it up. It's small enough to inject out or part of the butt or belly. belly. And pinch the fat. Pinch the fat. And we do it Sunday Thursday because these drugs peak in 24 hours. So you do it Sunday. You're ready for Monday. You do it Thursday. You're ready for Friday and patients like it. It's $25 a month. And tell me why you pinch. I know you want to get more tissue up, but don't you worry about inducing trauma, you get more vascular surgery. It decreases the pain. So the harder you pinch, the less pain you feel.

And why belly is opposed to upper outer gluteal fold? I tell patients, you can do wherever you want. Okay, okay. Most patients just think fat. And I'm able to see it. It's easier. And less pain and the fat. Most people, I have like 10, 20% say,

it's less painful in the muscle. I say, great, doing the muscle. Wherever you prefer, although there's a conversion, the conversion is the following, that you have a higher blood level if it's in the fat. For example, I think the conversion is about 20%. So if you give someone 80 milligrams sub-Q, it's about giving 100 milligrams I am roughly,

is what I'm seeing. So if you look at the Zyastead, the starting dose is 75 milligrams, not 100, it's 75. So you do get a slightly higher blood level, I think, when you give patients a subcute. So my favorite is Sunday Thursday, 0.25, 0.25, no insurance. It's easy. But there's patients that are needle phobic. I get it.

So Zyastead's a great option. Zyastead, of course, is still a needle, but it's preloaded. They don't have to see it. It's just a test. 27 gates. It's unbelievably tiny. Has a high speed. How do they get it out? Is the pressure just so because? So if you look at the, it's a high spring. So it's not a new drug. They're just using an

antate. It's just an antate in a very clever spring loaded device. Well, I haven't they come up with a CIPI and a equivalent. I think an antate is what they used to get through the FDA. It's a good point. So that's what they use. But the ticket is the 27 gauge needle, which is unbelievable tiny, with a very powerful spring. Very long spring. So it gets it in with less pain and the patients just throw it away. They don't even know it. For a month, it's easy.

And so at 100 milligrams, what's your monthly cost on cash price on Zio? On Zio State. On Zio State, $150 cash price. So considerably more than Cipianate. Because even more than Cipianate, but some people say it's worth it because I don't have to deal with the pain. I don't have to it because I don't have to deal with the pain. I don't have to travel. I don't have to draw it up on my trip.

It's easy. And there's no user error associated with how much you're drawing. It's easy. If I tell you have a dollar for a time of patient, made a mistake on the math. Yeah, so it's easy. Now, the O'Rolls are very fascinating. And just approved last year. Well, 2019.

So Undecco08 has been approved all over the world since 1970. It's been around for numerous years as called Andrial. So, when I went to China, when I give, in Australia, Europe, Andrial is available, can't it, but never got approved in the US. In 2019, the first testosterone undecan-08 got approved wise and decomant important, because oral historically caused a patotoxicity. But these go through the lymphatic system,

so they don't cause a patotoxicity. Do you swallow them? You have to take it with a fatty meal. But the newer they don't cause a padatoxis. Do you swallow them? You have to take it with a fatty meal. But the newer ones don't have to be with a fatty meal, they just have to be with a meal. If you take it fasting, no absorption. Zero. So if you're intermittent fasting, it makes a little tricky.

So you have to take it. But you could just commit to taking it dinner every night. It's B-I-D. Oh, boy. So not bad. So what happens is, you're supposed to take it at breakfast in dinner. So off label, I do give my patients a breakfast and lunch because what happens is you superimpose the first curve on the next so you get a really nice level on the day and it goes on and

it mimics the diurnal variation. So I like it better, breakfast and lunch. Again, that's off label. Most people use it. And what's the dose? So it depends. So Jitenzzo, which is the one that first came out in 2019, the first one, 237 milligrams BID. Tulando came out in 2022. So now we have two, and that's 225 BID. And 225 BID.

Which tells you how inefficient the oral conversion is relative to the injection, right? Right. But you're getting still to the blood level. So, yes, it's wise. But now in 2022, the third one just got approved. So, chisate tracks, the new drug by Marius Pharmaceuticals, is now the third oral. So now we have three orals that are FDA approved. So it's getting very popular, but all of the BID, the only difference is

to land, oh, has no titration. So essentially it's 225 and 80% of patients should be in the normal range, but there's no titration. The other two, you can titrate if you're not high enough. So, orals are popular. Look, Americans are used to taking pills. They have pillboxes.

They put them in their pillbox. But there are patients who are injectables that just love doing it once a week or twice a week. Very convenient. I do do a lot of palates, a lot of palates in men and in women, I think they're very effective. But the only issue with palates is that the following, you'll peak in 72 hours, but by that third to four month, and this was our paper

We showed that there's a sharp decline. It actually just goes very quick So patients it's kind of weird. I live great for three months and kind of allows you for the fourth and then I come in I live great so we can shorten the interval to three months. You know, that's fine So the key is I call putting the balloon in the air We want to put the balloon in the air and catch it before it gets too low and put it in the air again. But you know, it can do some logistic problems. I mean, if you got a trip and you got to get in the, my clinic quickly, so a lot of patients do like the injectables

because they're autopilot. I don't have to deal with it. And, you know, just show people how large a tract you're making for a male to put testosterone in him. Like it's not a trivial size. It's not a trivial size, although I would tell you, so we were taught initially that you should make a W, go one, two, or a V.

Or a V, yeah, that's what I used to do. But I don't do that, so we invented a technique called stacking. So basically, we put it in, and basically, it's just like a column, we put them up and down together, because you want to keep the distance far away from the incision, or you'll get expulsion. And every time you do a V, it's a whole new track for blood or trauma.

So we would do a stacking technique and it's worked quite well. And the pellets, you know, three stacking vertically or stacking on top of each other, on top of each other, uh, literally like a column. And so, you know, it works very well. These patients, patients who do it, like it. And so they keep coming. There's a lot of people that travel and they don't want to have the hassle or their needle phobic. So they come in. And how long is a guy inactive for you after putting pellets in? No exercise for 72 hours. The bandages stays on for 48 hours. You can share with it, but no exercise.

So some people say, I like to work out. I can't work out for 72 hours. I got to come see you every three to four months. I have pain, so I'm discomfort, not much, but you have some. And I say, what about the injectable? It's once a week. When you consider the track record of how long these drugs have been around in each of their various forms and the challenges of using endogenous versus

exogenous, if a man is committed to being on testosterone therapy, so you're no longer worried about preserving endogenous function, do you favor the injectable over all others right now? I do. I worry about a Rithrocytosis also. We did a study showing that, I think the worst thing you can do is give 200 milligrams I am every two weeks. That doesn't make a lot of sense to me.

In the drug, we'll ask about 10 days. For about four days, you're not even having any medication on board. You have a higher Rithrocytosis rate because it's the spiking that causes that a Rithrocytosis. If you have a man and you drop to 50 milligrams twice a week, the arithositosis rate goes down. It's more physiologic. So as long as they don't mind doing it twice a week, it's my favorite.

It works the best and it's the cheapest. And it produces a better physiologic level. We didn't talk about topical. I have never been a fan of topical for men. I think it's acceptable for women because our options are limited, but tell me what your views are on topical. I don't favor topicals for several reasons. So we did a paper in 2009 that showed

that 20% of men won't even absorb a topical. So that's poor absorption. Because there's a- Same in women, by the way, it's really problematic. The formula is milligrams times percent penetrance. So- And that's variable. It's variable. And it's even. It's variable.

Anything variable day by day on the same person. So, if I happen to... How clean is the skin? What part of the skin do you apply it on to? Has the skin been exfoliated? How are these things? Yeah. So, if a patient, I give him a thousand milligrams of testosterone, he has zero percent penetrance,

because it's nothing. So, I said, patients, don't get fixed to it on how many milligrams I'm giving you. Let's look at the end result. What is your level? So, the problem is that if you look at the attrition rate, if a man starts on a gel today, only 20% are on that gel at the end of one year, it's the convenience.

It's having to do it every day. It's the levels. It's the levels. It's once a day. It's once a day, okay. Gels are once a day. You can do up to twice a day, but it's once a day. But the issue is this, I can't even get the levels

that men want to be on sometimes on a gel that I can get on an injectable. So there's many reasons why the cost, you get the insurance, right? The cost, you can get a compounded cream which has even less penetrance, so I'm not going to go there. So I've never been, and don't forget about transference. It's a big problem with men because they're covering so much of their body surface area to get... If you have a pregnant woman at home, if you have a child at home, you want to be careful as well, then you get to travel for the TSA. So there's a lot of issues with the gels

that I really, really don't think you should do. I mean, for women, you mentioned women injectables and pellets work fantastic. pellets are great. The injectable, you have to kind of compound it to get the delusional. It's easy. So it's 50 milligrams, if we go 50 milligrams for ML,

it's .1cc. How do you go 20 per ML? And go .1 CC is a week. It's easy. And they find it very effective. 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? So we talked about the breakdown to testosterone going into Estadial, testosterone going into DHT. Testoshrone has numerous effects on different party parts at different levels. So we know that erectile function typically is around 200 nanogram per desk leaders. 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. So in other words, what's the highest? What has the greatest sensitivity to falling to testosterone?

The way to cover yourself is just being that record tall. If I'm in that record tall, I know I'm covering because everyone's different. But again, you're saying when you said 200 nanograms for desolate, that's total. How do we determine free the cutoffs? That's important. Everyone's different. So I have to say this, I never understood why we used this number 300. What are you telling me? 300 nanogram is a 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.

Not even close. That's what 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 antigen receptor. So, when I was a fellow, in my lab, very beginning, we would take the blood, we'd go back The reality is that there are many patients at lower levels that feel good. It's based on the sensitivity of the antigen receptor. So, when I was a fellow, in my lab, very beginning, we would take the blood, we'd go back and count the C-A-G repeats. Patients who had longer C-A-G repeats would have more sensitive receptors.

And the more sensitive... Why is that? In sensitive, excuse me. Because everyone's different. Your receptors and my receptors have different sensitivities. Genetically, how we're made. 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 sensitivity, interceptor,

sexual function. So sometimes people need more to feel better. And I think that's a misconception because a lot of times people say, well, you're in the normal range or at 400, something else may be going on. And invariably, if you can raise them to the upper quartile normal, cover them, you may see symptomatic improvement.

Do you think we're ever gonna get to the point where TRT can be customizable based on a more broad view where a patient comes to see you, and you do an Androgen Receptor ass assay on them and you couple that with what their free tea is and make decisions based on that as opposed to just sort of flying a little bit blind and having to guess. That would be amazing. So we did that in our lab and so I had some of my colleagues say, Hey, can you have this patient? I don't understand. Can

you look at the sensitivity and receptors? My lab is not clear certified. So I couldn't give you that advice. I can't give you advice, but I can look at different assays, but I think that would be amazing. So there's got to be other factors I can predict, because right now it seems very okay. How complicated is the assay? It's so easy to run, but the only thing is it does take a little bit of manual labor. My technician, we have to sit there and he's living up there. Like it's an aliza, or what's this?

It's an aliza test that you see. We have to count C-A-G and circle it. C-A-G live in it. Like it's an Eliza or what's the... It's an Eliza test that you see, we have to count C-A-G and circle it. C-A-G and circle it. And then he would then say, Hey, Cara, I have C-A-G repeat of 28. So you know, he's extra. Do you not get the impression like LabCore or somebody like this could generate that

or even just a proprietary lab could get the clear certification and go... What's the ROI? So the thing is, it's about how much money will they make if they do it? Yeah, and you're saying the market might not be there because the majority of the TRT market is wildly unsophisticated and their answer is just give more testosterone.

And that's what they do. Not titrate testosterone. They do the right sensitivity, right? How dare I assume that people wouldn't care about the level of new on-site would, right? Now let's talk about DHT. So you mentioned that testosterone gets converted, I think you said about six to eight percent of it

gets converted. Presumably, there's quite a DHT. So you mentioned that testosterone gets converted, I think you said about six to eight percent of it gets converted. Presumably, there's quite a bit of genetic variability there. I mean, five alpha reductase activity is really quite genetic. Sure. And what is the purpose of DHT? So DHT is the most potent antigen we have on our body. In terms of sexual function, it's extremely important. When you remove the DHT, it can have a significant impact on someone's sexual function.

So that's typically what I look at. I look, DHT is implicated for prostate. In terms of prostate growth, it's implicated for hair as well. So these are medications that are used to take away the DHT because they can cause a jalapetia. So 5F are ductase. It's located all over the body. There's type 1, there's type 2.

So type 1 can be in the scalp, it can be in the brain, it can be in the prostate, it can be in the adrenals, it can be in the kidney, they're all over the body. The finasteride is predominantly type 2. We do test rides, type 1 and type 2. We may talk about that later, but it's important to realize that these enzymes are throughout the body, have multiple functions throughout the body. Go over that type 1 type 2 again. So finasteride, was that the first drug used to treat BPH? So, yeah, finasteride came out in 1992. As a proscar.

As a proscar. Five milligrams of finasteride. You got it. To treat BPH. Yes, then in 1997, the 1 milligram dose came out as propitia. And then later on, I believe 2012, was deutastoride. And when you look at the graph. And deutastoride was brought out to treat BPH

Avadart, avadart, but wasp for BPH BPH, okay, so when you look at five alpha reductase Activity there's type one and type two two iso enzymes if you look at where they are type one into is in the scalp Type two is predominantly more in the prostate, but also is type one. They're in the adrenal glands They're in the brain as well. They're also located in the epididimus all over the body. So it's not just affecting just one location. You're affecting numerous parts of the body when you're taking away the DHT and that can have detrimental effects. About an hour ago, you said you do not like to use five alpha reductates inhibitors in your practice at all. I don't. So that means if a guy comes in with BPH,

and you want to treat him medically, not surgically, what would you use as first line? Alpha blocker or daily C-Alice? That's it. And you're seeing as good a response with daily C-Alice as you would see with de-tasteride or proscar? I'm seeing a much better chance with an alpha blocker and then I would then use. And the alpha blocker of choice is? I usually use alpha zoosin only

because alpha zoosin has the least rate of retrograde ejaculation. You can use tam salosin or you can use salidosin but alpha zoosin has a... So for younger men... And what's the brand name on that one? Your oxytrol. So it tends to have the least rich.

So for younger men they prefer to have that. So typically that's the medication choice. I think? Your Oxytrol. So it tends to have the least switch. So for a younger man, they prefer to have that. So typically that's the medication choice. I think finasteride is a very bad drug and I think it has very detrimental effects. You were the second very prominent urologist to raise this to me. The first being Ted Schaefer, which has got me and my team trying to wrap our minds around this thing called post-finasteride syndrome. You want to tell people what it potentially is. I know there's a ton of controversy and confusion around it. trying to wrap our minds around this thing called post-fenasteride syndrome. You wanna tell people what it potentially is?

I know there's a ton of controversy and confusion around it. So, finasteride, they're patients who have taken finasteride who develop irreversible sexual neurologic symptoms. For example, permanent ED, Ilebito, psychological problems, depression, suicidal ideations. And I believe it's a real syndrome. I don't believe everyone who takes finasteride gets post-finasteride syndrome, but I do believe that there's a subset of patients who take finasteride, who develop this condition.

I'm the minority. Most people do not, and I accept that. So the official position of the American urologic, what is it, AUA? Association is what? Well, if you look at the package, it states there are patients who have prolonged side effects with this drug. It says it. It's there.

But the true definition of a statement on post-fenastryde, there's no statement. Essentially, most clinicians don't believe it exists. I do believe that there's a subset of patients who take finastryde that have a significant adverse effect. There's a plausible mechanism for that. finasteride that have a significant adverse effect is a plausible mechanism for that. I won't explain what that is. But the key thing is this, we were taught in medical school that finasteride blocks the conversion from testosterone to dihydrotestosterone.

And that's it. That's all we were told. But that is only one fraction of the story. Because each one of those steroids then goes into something called a neuro steroid. DHC goes into the answer to the dial, that's the neuro steroid. Then you multiply that by six. So six steroids are blocked, and those six steroids then have a decreased conversion into their neuro steroid.

I'm sorry, the six steroids are blocked because five alpha reductase acts on more than one. Exactly. Progesterone, aldosterone, there's a whole linear, it's not just testosterone. Uh, I see. I see. So the problem, the biggest problem is when you block progesterone, getting into its neuro steroid called alopregnano

loan. Why is that important? Because alopregnano loan is an implicated for depression, anxiety, cognition, right? So some of those neuro steroids are very important when it comes to depression, anxiety, depression, right? So some of those neurosurids are very important when it comes to depression, anxiety, depression, cognition. So much so that there has been an increase in suicide rates in men who've had this post-financial search engine. If you had to guess what percentage of men who take finasteride experience negative side effects that persist upon the cessation of the drug.

I don't have a denominator, but I will tell you this. In the package insert, it says less than 5%, I think it's more than 5%, and I think many men get these symptoms, but they're taking it when they're 60 or 65, and they think it's a normal part of aging. They say, oh, I'm so sick of ED, but a 30-year-old knows this is not normal A 20-year-old knows this is not normal. But the key is this, let's say you do or do not believe in post-finasterite. I believe in. Let's say you don't believe in it. Okay, you say it's not true.

What you cannot deny is that there's an increased risk of suicides in this population of men. Irrespective whether you believe it's true or not. There's an interest in this. And I'm sorry, this is an all men who take finasterite or just young men. Irrespective whether you believe it's true or not. This is an all men who take finasterite or just young men. Certain men who have post-finasterite syndrome, who take finasterite. So for example, I had a study at 25 men who had post-finasterite, 25 men who had controls. In my 25 minutes. The controls are men who took finasterite but had no symptoms. Who never took a finasterite at all. And the reason I did that was the reason because

I was looking at gene variation. I would take skin biopsy at both populations and I was looking at genes, upregulation to outreg certain genes between the two populations, just normal controls and a finasteride. But two patients out of my 25 committed suicide in my trial. And I'm sorry, the men who were taking finasteride in your trial were taking it for what reason?

Predominantly alopecia. So you could technically argue that there's another issue going on, that whatever it is that's driving someone with alopecia to take finasteride for hair loss speaks to a difference in emotional state that might be predisposing them to some. In other words, it would be more interesting to see if you had 50 men who were all taking finasteride for the same indication, but you isolate the 25 who are experienced negative symptoms. I think that would be very important. I agree.

Or do a randomization. I agree. In either case, it has to bring some attention that we... Eight percent suicide is a alarming rate. And that was over what period of time? It was over five period, but my study was just a point in time. They'd come and visit, we would do that. But after they left, we fall up these patients, 8%.

So if I told you any drugs. And just to be clear, again, to push back, because this is so important that we think through this rationally, do we know what the history was of mental illness in those patients? Did they have a history of depression before taking the drug? None.

We don't have significant mental illness before they come in. They weren't on SSRIs. They weren't have a history of depression before taking the drug? None. We don't have significant mental illness before they come in. They weren't on SSRIs. They weren't have a history of depression when they came in. So that's important to know that. They weren't diagnosed with depression prior. But any drug, if I told you drug X,

it doesn't matter what you believe the cause or is, is associated with the higher suicidal rates. I would say, okay, let's take a closer look. And see what's happening. There's a matter. That's what I'm saying. I mean, it seems to me that a random assignment trial would address this. And if you didn't want to do randomization, you would at least be able to do a post-hoc analysis in the way that I've described it. And it's amazing that that's not being done. Do we see the same effect of detest ride?

Patients have taken detest ride, but it's not as prominent. And I think probably it's because a, you know, a lot of patients who were taking this, were taking it for alopecia, so they were taking finasteride, but there have been reports of due test ride symptoms the same way. I think that's important. So, you know, I think more attention has to be given

to this condition. And that's why my personal bias, I do not give. So when men come to you on those products, you'll say, if the guy's coming to you on that product for BPH, we've got the alpha strategy and the Seattle strategy. If the guy's coming to you on that product for hair loss, you'll tell him what? I tell both men if they're coming to BPH or Alpegian, I tell them that there is a condition that's been associated with this, men taking this medication that can cause an impairment in sexual function and actual depression and anxiety. Many countries, Canada, France, UK have put on their package insert. can cause an impairment in sexual function and actual depression and anxiety.

Many countries, Canada, France, UK have put on their package insert. Black box. Not black box, but it's warning saying that, hey, there's increased risk of suicide ideation. This is not trivial. Technically SSRIs have that warning as well. And it's never clear to me that SSRIs are causing an increase in suicide. It's in part, I think, that we were looking at a demographic that's more susceptible to suicide.

I think that's the thing I'd always struggle with. What I find most interesting about this, and I'm not doubting that there's something there, is why does it linger after the drug stops? That's the part that is undoubtedly most disconcerting. It's, if this is real, how is it that a guy can take this drug for a year, stop it, and two years later, he is still suffering the sexual side effects associated with it. That strikes me as epigenetic. I can't come up with another explanation. That's exactly right.

So there are many plausible mechanisms, one being that could be epigenetic, one is silencing of the five ARI gene through DNA methylation. So that's been the most common prevailing thought. Okay, but we don't know, but that's one of the most common thoughts. Again, it needs to be studied. Let's talk a little bit about the role of testosterone in prostate cancer, because when I bring up testosterone replacement therapy for men, the question I get asked the most is about prostate cancer. Now, I've documented and discussed this in so much detail. I think I've probably done two, if not maybe three podcasts on the subject, including a dedicated AMA podcast on all things that relate to testosterone as far as risks and benefits. And I would say we've

spent more time on this than just about anybody, perhaps not as much as you. We came away from this analysis with the belief that there was no evidence that exogenous testosterone application was increasing the risk of prostate cancer. And there was actually some evidence that hypogonadism may not be increasing the incidence of prostate cancer, but may have increased the incidence of high grade prostate cancer. Furthermore, we saw virtually no evidence that exogenous testosterone therapy was leading to an increase in atherosclerotic cardiovascular disease, though there was one study that suggested in the short run, i.e. within one year, highly susceptible men might see an increase in the risk of AACVD, but that risk decreased at two and three years post treatment. So,

with that being my current state of understanding, can you fill in the gaps? This is a great topic. So, this thought that testosterone causes prostate cancer started in 1941, Huggins and Hodges, Nobel Prize based on one patient. One patient in 1941, when they gave exogenous testosterone, the prostate cancer got worse. If you look at the different paradigms, the American Eurologic Association in 2018 came out with the testosterone guidelines. Guideline on that intersection. Patient should be informed that there's no association between testosterone and prostate cancer. Strong recommendation. So finally, patients say,

I googled it, I heard I can get prostate cancer. So no, the guidelines are very clear. Based on the evidence, no data supported. Contrast that for a moment with the guidelines on estrogen therapy and breast cancer in women, which we're not going to go down that rabbit hole because I get way too fast-foralated. But talk about the difference between men and women and how differently they're treated with respect to hormone therapy. I think a lot of that started with the WHO. WHO, 2003. So you get this big news and everyone's off hormones and later on you get a re-evaluation of

the WHO and say, hey, maybe we made some mistakes. But all that knowledge. But the damage was done. And so we're going to talk about the traverse trial. So I've been one of the involved in the traverse trial. The traverse trial is coming out in June. This year, it'll be coming out at the endo meeting about cardiovascular. But that was very similar.

The impetus part of the traverse was, hey, we have no large trial men. You know, we have something in women. We have nothing in men. The traverse, 6,000 6000 patients randomized placebo control trial, largest of its kind will be coming out pretty soon. But I want to finish about prostate cancer. So there's a paradigm shift. And the paradigm shift is that maybe testosterone may not only be safe, but it may be protective against the development of prostate cancer. So I just want to give you an example. In 2015, the Hopkins group published a very

interesting study on a concept called bipolar androgen therapy. They called it BAT. Who was the lead on that? It's Schwarzer and the senior was Denmead. In 2015, and it did something very unconventional. You walk in with metastatic prostate cancer into Hopkins and what they do is they give you high doses of testosterone to treat your metastatic prostate cancer. Which is mind-boggling because the standard care for that patient is the exact opposite. It's to give you androgen deprivation. It's to chemically castrate.

Right. And the way they would do it, they would give you Lupron first to shut you down, and then they would give you high doses, 400 milligrams every month, and it would go up and down, and it would basically convert the castrate resistant prostate cancer to castrate sensitive. And so essentially the PSA went down by 50% and what they saw was a radiographic disease, a metastatic disease went down by 50%. That is unheard of to give that metastatic prostate cancer patient to testosterone. The same group published numerous really impressive studies, but my favorite was the one that came out

in 2021 called the Transformer Trial. This is mind blowing. So they took about 200 patients who had castrate-resistant metastatic prostate cancer and they said, okay, and if they became resistant to abiotorone, the treatment of care is Enzoludomide, which is an Androgen receptor blocker. This is instead of giving everyone Enzoludamide, we're going to give half the men high doses of testosterone. Okay, so let's see what happens. So they gave them insoluteamide or high dose of testosterone. They found that the overall survival between the two groups was the same, no different.

But the difference in quality of life was significantly better on the basis of the course. But it got even more interesting. You were allowed to, if you took bipolar engine therapy, you were allowed to switch over to end zeludamide, if you came resistant and vice versa. The patients who did bipolar engine therapy and then did end zeludamide had significantly greater survival, 37 months versus 28 months, then end zeludamide, which is the standard of care. The cost of endoluteamide is 8,000 a month. The cost of 400 milligrams of testosterone is about 100 a month. And it had significantly greater survival. This is published in 21. 21. So we're three years, two years after

that. Yes. How many men with metastatic prostate cancer are receiving that care now? I think minuscule. Why? I don't know why attention was not given, more attention was given to this study. It's called the Transformer Trial. It was really impressive as using Extandard to Care, which is Enzylutamide versus Bipolar and Enzylutamide. So, I think you're going to see a lot more of therapeutic use of testosterone. I also, you're going to see a lot of studies. There have been some recent studies suggesting that giving testosterone to men after radical

prostatectomy may be potentially protective against biochemical recurrence. That was Tom Ollering's group. Look, I'll tell you what. So I have a lab. In my lab, we do a lot of basic science work with testosterone and prostate cancer. One of the studies we did was we took P2D. We put LYNCAP cells, prostate cancer cells, and those P2D. And we gave each one of those P2D.

It's a different amounts of testosterone. And it is true when you initially give testosterone, you see prostate cancer cell growth, no question. But when you give higher and higher doses of testosterone, you see greater and greater suppression of prostate cancer cell growth. We called that the inverted U, where maybe castrate may be protective,

the urchinato protective, but hypo-ginato is dangerous. So then we said, okay, let's do it in animals. 200 mice. Castrated 50 mice, we gave castration, we gave 50 controls, we castrate and give low doses of testosterone, and then we gave castrate and high doses of testosterone. These are pellets in the mice.

We published both these articles. What we found was that if you castrate the mouse, you get a decrease in prostate cancer growth. No question. It helps. Low doses of testosterone, you start getting increased in prostate cancer growth. High dose, you get a statistically significant decrease and inverted you. So if I have prostate cancer...

And that high dose compares how much to the castration. Essentially, it's a eugenadal range, essentially castrate. So castration behaves almost the same as... Slightly better, but in certain cases, in the animal case, in the petri dish, it was better. It just varies, but the key is this. If I have prostate cancer, either castrate me or put me in the normal range, but do not, I think personally put me in the hypergonnaughtal range. I think it's the danger zone. Yeah, except I would say having watched men get castrated chemically, it's awful. I mean, I generally advise men

to undergo surgery whenever possible. If surgery is an option, if you're that gleecin, three plus three or three plus four or whatever, and it's just a question of having the best surgeon operate on you, yes, there is a lot of downside of surgery, but I think it pales in comparison to the downside in what I see from men that undergo chemical castration, the metabolic syndrome, and the metabolic derangement that follows from being hypogonatal, beyond hypogonatal. They're basically you gonatal, not to mention the complications of bleeding that follow with the radiation.

So, again, I'm sure there's lots of medical oncologists and radiologists that are listening to me now wanting to put arrows into the back of my head, but I don't think I'm speaking with just a surgeon's bias. I think I'm speaking from watching men in the years that follow undergo complete metabolic destruction. And even if they're still alive, their quality of life is so poor. So that's why I would say, like, gosh, if there's a medical way to do this with high dose testosterone, you're right. And certain patients do benefit better with radiation, just based on gleece and score. But the end of the day, yes, if it's moderate, we give them six months, if it's severe, we

give them two years of interdegreesion therapy, but we do in my practice treatment after radiation with testosterone. It's controversial. We'll get into this. And what dose are you using? 100 a week. So typically, I will use gel first. I want a short acting so I can stop it if it PSA.

Then we'll move on to an injectable. But treat them just like I normally would treat any other patient. Whether they have the... You treat them to a level of total tea or free tea at the top quartile. Just like I would at someone in the normal there, but it's a range. But there's no date of support that it causes cancer. And what kind of consent form do these men sign to undergo something that is erotic and do you need an IRB for this?

If you look most clinicians or urologists, there was a recent survey looking at urologists, 96% of urologists will treat men after radical prostectomy with testosterone. 86% of urologists. Yes, after radical. After 86% after radiation therapy. Look, there has to be some to consent here. There has to be some informed decision making.

The American Urologic Association made it very clear. The risk-benefit ratio after prostate cancer surgery radiation is unknown. We don't have the randomized placebo control trial. So I tell them, look, we don't have a randomized placebo control trial. These are the risks, these are the benefits, and we have a shared decision making model. But there's something important you have to understand something called the prostate saturation model. It's really important. We were taught in medical school that the higher the testosterone, the greater the PSA, we were taught it was linear higher the test australian, the greater the PSA, we were taught it was linear.

And the higher the test australian, the greater the good. That is not true. At some point, it saturates. We did a study in 2011. We said the saturation was around 250 nanogram per desolate. So if you take a guy who is at- That's pretty low. That's pretty low.

But that's where the satin inflection point was. And others have shown the same thing roughly around 250, we're all different but why is that important because if you have a man who starts out with a test optional level of 190 and you put them on testosterone this PSA should go up it should go up if he's at 290 and you put them on testosterone it should not go up and if you take the guy from 290 and taken to 3000 should not go up because it's saturated it plateaus So that's why if I give someone a loop run, that test option goes down, but the PSA goes down. But if you raise the test option, it's not the more I raise it, the more the PSA goes up.

So the tricky part for me is when patients come to me after radiation therapy, because they've been given an ender-in-geparation therapy, the test option's 50. They're oncologists spend all this time taking away the test option. That's right. And when you get it from 50 past 250 you're going to see that rise until you get it's natural. Right.

And so the oncologist says, what are you doing? Patients says, what's going on? I have to set the expectation. It's going to rise. It's going to plateau. I just have to have the understanding with you based on the saturation model. You just have to have this understanding. What about testosterone and breast cancer?

This is a topic I have become very fascinated with. I want to do a dedicated podcast on breast cancer and all things that have to do with it because it's obviously such a comprehensive and such an important topic given its obvious impact on women. But while I have you here, does anything you do focus on from a research perspective, the effects of testosterone as an adjunct to therapy, especially in the estrogen-sensitive breast cancers. Yeah, so I do treat women who have a history of breast cancer. We may treat them with testosterone.

It's working with the oncologist. Many times though, I will typically use drugs that are not hormone-based, like adi, particularly, because that will give me the same benefit of libido, but with using dopamine. Oh, but you're using it for sexual function. Sexual function. No, I meant for, I've been reading a lot of case reports that have suggested that testosterone replacement therapy with a romptase blockade in women with breast cancer

is a therapeutic option. In other words, testosterone is protective against breast cancer. And I don't know if the aromatase inhibitor is necessary. That's an even more controversial topic. But at least the thinking there would be, you're going to prevent testosterone from becoming estradiol. Sure. So the studies I've seen are giving testosterone without the aromatase inhibitor. And letting both go up and showing that it's still protective. But I don't have a lot of experience in treating women with breast cancer.

Yeah. I mean, I hopefully find somebody that can. Well, we've covered a lot here today. This is a really interesting topic. And even though I came into it knowing very little, I feel like I've learned a lot, both in terms of pathology and the treatment. So, Mom, I want to thank you very much for this. Thank you. My pleasure.

My hope, of course, is that everybody listening to this, who's impacted by anything on the spectrum that we've talked about, is at least a little more empowered to kind of realize that there are people like you out there and presumably you do have a sense of how many doctors in the country would have your degree of certification so the urologists who have been some specialized. Sure. So I'm part of an organization called the Sexual Men Society of North America, and this is exactly what we do. It's a great organization. We'll 1200 strong and urge you to go to the website, look at it. Which is very interesting. That's almost, if I remember correctly, that's about the same number Sharon said that there's about 1200 or so doctors that are kind of doing

what she's doing as well. In that group, there's a lot of APPs and nurse practitioners. So that 1200 encompasses all of us. But all of us have the same passion and desire in this space. So sometimes someone's looking for and desire in this space. So sometimes someone's looking for a provider in their area. You can go to the website and find a provider in that area. Sometimes you work via telemedicine.

In state of Texas is only can be in Texas. So I can only do telemedicine in Texas, do Baylor. Yep. What percentage of those 1200 are at major academic institutions like you are versus in private practice? Yeah. So I'd in the majority are in academic institutions. Let's say about the 1200, 400 or 450 are yourrologists. Majority are in academic institutions. Well Mo, thank you very much. I hope you enjoy the rest of your weekend here in Austin playing tennis. The weather looks to be a little warm. Thank you so much for the invitation. Thank you Peter.

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