260 ‒ Men’s Sexual Health: why it matters, what can go wrong, and how to fix it

the survey found that roughly 40 percent of men that in the survey had some degree of sexual dysfunction right fifty percent of those men said I would love to get treatment but I don't know where to go but was very interesting The Clincher will has only 51 percent of those men told their doctor about it only 44 of those men told their partner or their wife about it that's suffering in silence and the main reason was they were embarrassed also clinicians don't ask about it hey everyone welcome to the drive podcast I'm your host Peter attia foreign thanks so much for making the trip over here from Houston uh 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 um there's a lot we want to talk about today um I will admit my insane capacity for ignorance in this domain so when one of our analysts was working on you know sort of the topics we were going to talk about it turns out I know as little about this as I know about the Contra positive in women's sexual health so uh you know a lot of times I go into a podcast having more knowledge about a substance and and and I can guide the discussion more thoroughly so I'll be kind of leaning on you heavily but um maybe we can just start by talking a little bit about your background your training uh and and how that leads you to doing what you're doing so so after medical school 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 and career path and I went to University of Texas San Antonio for medical school then after that I went to Baylor College of Medicine did a one-year internship in general surgery and did five years in urology then I did a one-year Fellowship in a Male Reproductive Medicine surgery where I really got into sexual health and infertility and I'm in a Baylor now since 2007 on faculty so tell me about what that means so you know when I did my general surgery residency the urologists I was working alongside with because one of my best friends Ted Shafer was 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 right so um the big things that we saw the urologist doing was removing prostate cancer removing bladder cancers removing kidney cancers those were big parts of it um because I was only limited in how much Urology I did I didn't really see much of any of the other stuff so I don't really know what constituted reproductive health or sexual health for men so what was that Fellowship like and what were the things that you sort of focused on it was great so listen you know Urology is multiple sub-specialties it could be Stones it could be cancer it could be female Urology but one sub-specialty is sexual medicine and another one is infertility and usually they're combined and so really what you're focusing on is Reproductive Medicine in terms of vasectomy of reversals doing procedures to help men recovers fromatogenesis varicocele repair sperm retrieval but also sexual medicine taking care of erectile dysfunction premature ejaculation Peyronie's disease and a big focus of that is also hypogonadism so that's really what I 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 okay sure so when people think about the penis they think just about one simple organ but there's actually a Confluence of three different organs it's really the urinary system it's the reproductive system and it's the sexual system together so the urinary system meaning the bladder next to the bladder comes the prostate from the prostate comes the urethra now in the prostate there are two ducts called the ejaculatory ducks and from those ejaculatory Ducks the testicles through the vas deferens will put some sperm into the ejaculatory ducts those ejaculatory Ducks mixed with the seminal fluid from the seminal vesicles and that gives a man his ejaculate above the urethra are two what we call called them tubes if you will these are called the corporate cavernosa essentially what it is is just smooth muscle inside so those two smooth muscle bodies corporate cavernosa are responsible for erections below the tube called the 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 is 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 uh it's a holistic system you think about it because every each of these can affect the others for example let's talk about the testicles you know when you talk about infertility that can also affect hypogonadism hypogonasm can also infect fertility right so patients also when you think about the urinary system patients can have retrograde ejaculation by taking medication for BPH well that may affect a fertility and that may affect their sexual function right so all three are interrelated so you think about it as a whole yeah well does it make sense to start with a certain set of problems uh and then maybe talk about how they change temporarily over you know in terms of prevalence by age and if so where would it make sense to start do you want to start with premature ejaculation erectile dysfunction let's start with ED and I think about sexual health in general I think you know I just want to put this into context you've want you to think about this so we know that 52 percent of men over the age of 40 suffer from erectile dysfunction some degree 52 percent of men even if you take conservative numbers that's 30 million men in the U.S 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 an erection or how do we think right so what we use is we use a questionnaire a validated questionnaire called the iief and this questionnaire there's several forms but there's a shorter version with six questions and essentially based on those numbers you can tell if someone has mild moderate or severe Ed so when they gave the original study in 1994 that when it came out there's 52 percent 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 forty percent of men at 40 had some degree of Ed 50 at 50 60 60 70 at 70. so it's an easy way to remember what percentage of men suffer from Ed now it's not necessarily aging I think that causes the Ed I think it's the acquisition of comor conditions as we get older and we'll talk about that but again it's a prevalent condition think about women I treat a lot of women for sexual dysfunction 43 of women in the United States suffer from some degree of sexual dysfunction 30 percent of men in the U.S some have some degree of premature ejaculation or ejaculatory dysfunction seven to nine percent of men have Peyronie's disease so this is how many seven to nine percent and men in the U.S have peyronies which will we should set aside time to talk about and they don't but the problem is that this population I call it suffer and silence they never talk about it in fact there's many studies showing they're completely silent they don't seek care and the issue is it has a significant impact on their quality of life right so we know that a third of men who have Ed have suffered from depression because of their Ed 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 sexual dysfunction and so when you you said suffering in silence you weren't just referring to Peyronie's disease you're talking about all sexual all sexual dysfunction so so there's there's reasons for that so one is if you look at surveys there was actually I got to bring this up because it wasn't a great survey that came out last year 1500 men survey between the ages of 18 and 80 and they asked about their mental physical and sexual health so in my world it's mental physical and Sexual Health it's it's a Triad not mental and physical and they're all related but the survey found that roughly 40 percent of men that in the survey had some degree of sexual dysfunction right 50 of those men said I would love to get treatment but I don't know where to go but was very interesting the Clincher was only 51 percent of those men told their doctor about it only 44 of those men told their partner or their wife about it that's suffering in silence and the main reason was they were embarrassed also clinicians don't ask about it they never when you go to a doctor's office and my wife is guilty my wife's a family practitioner and I said 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 so I'm not gonna 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 uh look one of the desired outcomes of this podcast of course is to empower um people of you know both sexes plus their Physicians to hopefully take a more active role in this um not to put you on the spot and ask you what those six questions are but just directionally what are the criteria for Ed in terms of severity frequency and such sure so I think one of the easiest ways to look at it is to use a question called the sep2 and the septiris so there's just two simple questions you have to ask the patient are you able to get an erection sufficient for penetration it's either yes or no and are you able to maintain that erection till orgasm 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 so that had then they had one episode of Ed so it's graded right by definition if someone says I can and the number one cause of Ed typically is I can't maintain it so they're gonna that's the first sign they say Doc I can get it but I can't maintain the erection they're telling you I have Venus leak which is the first sign of some kind of erectile 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 maintain an erection I can't ejaculate yeah yes that's right yeah that's not easy yeah okay so let's talk about the pathophysiology of this uh 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 mnemonic I teach them teach the medical students is vent what are the ideologies vascular endocrine neurologic and Trauma and Peyronie's degrees can be trauma as well so vascular endocrine neurologic trauma don't forget medications we'll talk about those beta blockers for example anti-androgens finasteride there's a lot of medications that can cause Imperial erectile function and then there's psychogenic Ed now psychogenic Ed typically is in younger patients right it's not common that a young patient has organic Ed but they have psychogenic Ed and psychogenic Ed is treated very differently than organic D and you you want to ask them some questions are you able to get interaction with masturbation if they say yeah no problem that's psychogenic they're telling you they have psychogenic Ed uh can you get a 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 probe for that because psychogenic Ed is treated with Sex Therapy I use daily Cialis and these patients It's very effective I think there's ways to treat that that's very different than organic edu okay so tell me a little bit more about what that means like what so do you refer out to Sex Therapy what are sex therapists doing in these situations 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 uh Telehealth so they can do televisits and before they have to go into the sex therapist office and they're a little bit more likely to use the Telehealth so but what has been very effective for some of the young patients is we will get a give them daily so when they take daily Cialis what they'll notice is that the erections are starting to get better and you'll do this at five milligrams five milligrams now what's interesting is that when a young person or anyone has erectile dysfunction one time we call it the Vicious Cycle what happens is the next time they engage in sexual activity they say to themselves as they're having sex I hope I don't lose my erection I hope and they will lose erection guaranteed because it's 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 the car follows the eyes same philosophy so what happens is and then when they engage it the next time the next time they say I can't believe it's happened two or three times so they get anxious it and they also undergo subconscious aversion they start avoiding sex because they're scared it's going to happen their partner thinks they have a low libido is it really a low libido or are they really anxious about getting an ed so typically daily Cialis when they engage in sexual activity start noticing hey things are working things are fine it's okay and then you can many times wean it off because you just want to show them that everything's working great again we also get we use a lot of peanut ultrasound in my office and it helps me look at the peak systolic velocity and diastolic velocity many times getting an ultrasound and showing them that everything is perfect is therapeutic let's talk I want to come back to the Pinot ultrasound into the um gain 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 induce an erection the other ultrasound you're referring to is shock wave therapy to treat erectile dysfunctions there's three areas here there's stem cells PRP and shock Whip and that's a treatment option uh we'll come back to that in a second but let's go back to this um maybe just for folks explain briefly how Cialis Viagra work you know what's the mechanism mechanism so the erections are caused or induced by the parasymph parasympathetic nerves and you can get stimulation oral I mean excuse me ocular Vision hearing sensory any kind of sensory stimuli or tactile can induce the nerves to secrete nitric oxide which will then go to the endothelium this is the key the endothelium will secrete nitric oxide which is really the on off switch once the nitric oxide goes up we get an increase in something called cyclic GMP cyclic GMP causes intracellular calcium to go down it causes the dilation of the sinusoids and increases the blood vessel diameter and the blood comes in now there's a bad thing there there's something called phosphodiesterase and phosphodiesterase eats up the cyclic GMP and therefore you will lose the erection so how does Viagra Cialis Levitra work it's a phosphodiesterase inhibitor so it blocks phosphodiesterase so you have more cyclic GMP so you can keep the erection around now there's 11 different phosphodiesterases in the body so for example 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 phosphodiesterases so you get side effects for example Cialis has more side effects with phosphatidosis 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 uh yes in my opinion the newest one of vanophil has the least correct cross reactivity with the other phosphodasterises so I think it has less side effects the only difference is that it is not generic yet so it's expensively expensive yeah so the generics now you can if you go to Cost Plus or you know more Cubans or you go to GoodRx it is so cheap to get Cialis today but avanophil is still not generic I see um you want to tell people the story of how Viagra was developed Survivor was developed to be a it was a 99 before 1998 but it was developed to be a blood pressure medication to control the blood pressure and they started noticing that everyone was getting or cardiovascular medication everyone was getting erections in the trial right and that's how everyone who got this yeah very interesting other drugs were the same way you may have heard of the drug Addy we use this to treat female sexual dysfunction or flip answering that was used as a medication for depression it was my born going on I'm in Germany and so they give it to women for depression and they noted these women wanted to have sex and that's how we got the development of Eddie yeah and and my recollection is Viagra was not successful as a systemic reducer of blood pressure in other words that trial failed right 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 the drug so as they're kind of tail is between their legs and they're saying well that sucks you know we just lost all 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 uh 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 you know a ho-hum blood pressure drug that would have had a market size of this yes to a market size of this and it was a game changer in my field so in our field sexual medicines we I'm part of the sexual Med side in North America game changer uh in the way we treat men for ED and really I mean we'll come back to this I suppose uh but 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 Addie the second drug was called violisi but not even close to the impact the Viagra had in men 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 Viagra you know yeah it might be that the single most potent agent for women's sexual health at least as a woman is aging is actually HRT yeah but there's a synergistic effect because if you use HRT and you use these medications because of different mechanisms of action that's right yeah they're accretive yes um okay so this phosphodized inhibitor which now we're into our third generation of them um basically saw the physiologic problem right so what is it the root of that problem I mean I understand that by inhibiting phosphod or asterase 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 right so that you nailed it to the main issue is Venous leak what we call a vinocclusive dysfunction so you have to think of the 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 sinusoids down the center of the tube is an artery okay and think of the wall of the tube as a thick casing called the Tunica albuginea okay right under the Tunica albuginea are veins we call subtunical 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 press against the wall and prevent the blood from coming out of the penile tissue the problem is as we age we get atrophy of the muscle right and we get fibrosis of the muscle 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 right on the Venus wall that's right and so how do you overcome that there's several ways one is that you can actually if so it's a simple outflow inflow game so if the inflow is 10 and the outflow is 15 you're not going to get an erection right but if you give someone Viagra and you make the inflow 25 you can overcome the venous leak by increasing the inflow that's one way the second way is actually some people use something called a penile 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 a man so you haven't fixed the inflow problem but you've increased the back pressure on the outflow that's exactly right so and so if a man took his hand while he's having erection and placed his hand and grabbed the penis at the five and seven o'clock position and press put pressure you'll notice that you'll get better and better erection because you're blocking the outflow but you can't keep your hand and tell people why you said five and seven o'clock well it's that's typically well well it's circumferential oh it is so conventional I thought the I thought the veins were disproportionate yeah it's circumvential but is but but if you put your hand there and it gives you almost a 180 uh so then it was so circumferential but so it's not like the fingers where at about five and seven no it's all the majority it's all the way around okay yeah so if you that's why if you plan a tourniquet you actually prevent Venus leak or but most people say I don't want to use a tourniquet I said it's fine just increase the inflow that's why we use intracalvanosal 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 a Venus leak we know that lower testosterone levels have been implicated for causing being six is atrophy the penile muscle you know so we when I do a lot of a procedure called a penile prosthesis and I have a lab so what I do is we have a a protocol where we can take the tissue the penile tissue at that time we send it to the lab and then we'll look at it high high density of Androgen receptors within the p l tissue right so as the androgens go down you can start getting atrophy of the penal muscle that is very interesting and I do want to come back to the um intracellular and nuclear uh distribution of Androgen receptors testosterone and DHT so again we'll I'm trying to keep track in my mind of all the things I want to come back to um if you said to me Peter how can an aging person prevent atropy atrophy of their muscle the most obvious thing that comes to my mind is use it right it's a use it or lose it system right is the same true of the penis it's very true so if you look at patients who are not using the penile 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 penile tissue you will start getting atrophy of the muscle just if I put your arm in a cast today right so regular erections so nocturnal erections are very important also right so that's how we get our oxygen into the penile tissue through the nocturnal erections due sexual activity there are studies suggesting that daily pd5 Inhibitors see house Viagra can help with hypertrophy of the cavernoso 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 eaten 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 yep right but daily Cialis has been shown to cause hypertrophy of the cavernosa smooth muscle keep the tissue healthy so in many ways I look at daily Cialis 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's starting to show up for Ed that's when I want you to start taking the daily Cialis not only to help you with what your issue is but I look at to me as a preventative measure you've talked about daily Cialis my recollection is that you there were basically two dosing strategies right there was 20 milligrams you you know 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 you know have sex on demand alternatively it's having five in your system every single day produces the same tissue level is that directionally right not close so the conversion is 1.6 is the multiplier okay so if you so if you take five milligrams every day it's like having almost like eight milligrams in your system that's the conversion is 1.6 so so 8 is obviously less than 20 but some men really don't need 20. you know so that so that five daily remember there's other benefits five daily has been FDA approved for BPH and let's we'll talk about it FDA approved so you can give someone Flomax uh or you can give them daily sales well the problem with Flomax is retrograde ejaculation got it so so so think the young men if they had a choice they'll say I'll take the cials and and the side effect will be better erections yeah right so FDA approved for p BPH why what's the mechanism so ice mechanism unknown right and that's what's a little bit interesting that so so so all we do know uh it even says in the mechanism I know 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 a Cialis and a Flomax medication not to take them too close together there's a warning because you can get a hypotensive so we have to separate them but daily pd5 Inhibitors are also um if FDA approved for pulmonary hypertension so yeah so so so 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 systemic and they were looking at uh blood markers il-6 so you react to protein not so specific they were looking at flow median vasodilation brachial artery and they were shown that even if the patient stopped this was a study by a versa even if the patient stopped the daily Cialis versus the on-demand those patients who took the daily still had persistent Improvement so maybe maybe there may be something going on in the endothelium as well so I think about endothelium I think about pulmonary potential I think about BPH Ed it's five milligrams daily very affordable okay maybe maybe we can you know what would you say is the biggest downside of Cialis so there are I used to say cost and it was unbelievable how much did Cialis cost it was almost 15 to 20 uphill so the history 15 or 20 for a five well it was a 20 milligram pill so but they but it was still absorbent it was almost four hundred dollars for a 30-day supply of five milligrams which was unbelievable so then we started going to the compounding pharmacies I said okay the compounding pharmacies said we can make it for a dollar pill that's great it's hard to trust the quality right some are better than others and some compounding farmers are FDA approved so that makes it a little bit better but then the generics came out and it was shocking if you now if I give a patient who goes to HEB they can get 90 pills of Cialis for 17 with no insurance 90 pills five dollars are you concerned you know I've I've become very concerned with the quality of generics yes and realizing that not all companies are the same you know like Sandos is a good company but you know some companies are sure do you have preferred brands of generics don't you fancy I don't have a preferred brand although I haven't seen the generic significantly less effective than the brand when it comes to pd5 Inhibitors right and so um so that's I think that's that's one thing that I think I have not seen it less effective that's great to hear okay so um I know this isn't this is sort of indirectly related to Ed but what about refractory period so sure 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 you could have intercourse 27 times in a day and then something happens when you get older those days are done right like you might get two a day sure um is that considered a lagging or leading indicator of Ed is the fact like what's different about that 20 year old yeah versus the 50 year old yeah so there's no question that the refractory period goes up as we age one of the uh implications for refractory time is Prolactin so when you have an ejaculate your orgasm your prolactin levels go up okay 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 and The the refractory times go out right and I'm sorry is there anything different about the prolactin secretion I've never I I've never seen a study showing that although it intuitively think the prolactin may be along for a longer period of time but I have not seen any study so that might be the that might be the indication basically that even if you don't have Ed you know things are changing your Anatomy your physiology is changing absolutely absolutely and I think the majority of it is it is more difficult to get an erection uh as we get older and therefore that contributes to the refractory time it's so interesting how Evolution simply you know you you would argue that you know not that we want to spend too much time speculating on Evolution given that as Andrew huberman would say neither of us were there for the design phase but um it's interesting in that you can you can certainly understand I think in the case of women why based on the change in reproductive State Evolution didn't care as much about their sexual health as they got older is the same true for us where Evolution sort of thought eh the older you get the more genetic mutations in your sperm I actually don't want you reproducing as much when you're 50 as you are when you're 20. yeah I don't know about that you know I we have patients who are older that have great semen parameters I think it's based on your quality of your health right so healthier Men by the way would make sense you know it makes sense because you're more likely to produce so when you look at men who are in their 80s 80s who are in great shape they're having sex no issues no even unassisted you know meaning they don't even require they use a bit of eyebrow yeah but some do some don't I mean I have patients at 70 80 years old great shape no issues having uh erections the patients that come to me who are older 60 70 who are also trying to conceive they marry someone younger and you'll be surprised typically sometimes you will see patients with sperms metagenesis 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 poor quality erections terrible semen parameters so I don't know if age is like the main driver no I think that makes sense um and I think I talked about this with Sharon on the podcast but um the I almost wonder if the greatest motivation for a patient especially a male patient with respect to insulin resistance is actually erectile function because definitely one of the things I've seen in my practice is that patients who go from having a higher hemoglobin A1c to a lower hemoglobin A1c will often notice an improvement in erections yes and and again I'm not talking about a one point change but if someone goes from having a hemoglobin A1c from you know 5.9 to 5 which you know represents probably about a 25 milligram per deciliter reduction in average blood glucose that's a person who says I used to need Cialis for every erection to I'm totally fine so you bring up a really important point it's a lifestyle modification lifestyle modification has a huge impact on the quality of the manager actions 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 erections and your quality of life right and there's other manifestations that would improve as well but you're talking about insulin resistance and when you improve insulin resistance when you prove 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 heart attack or a stroke 15 it's the first sine of cardiovascular disease numerous Studies have shown that and just to be clear this is not psychogenic Ed this is organic so and say that again how many what percent physics of 2004 uh Ian Thompson had the prostate 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 at 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 montoursi that same year showed that if you had a cardiovascular event uh you had 50 of those men had Ed 39 months prior to having the cardiovascular event it is the Sentinel sign of course that's it now so so it's a real Canary in the coal mine when it comes to microvascular health particularly if it's arterial insufficiency you know so so the question is what's the relation so one was one theory was arterial diameter Theory and doesn't make a lot of sense but there was this is the theory if you look at the penile arteries they're one to two millimeters the coronaries are three to four millimeters the peripheral artery is a six or seven millimeters and if you get fifty percent occlusion of an already you know you get any organ damage so you're more likely to include the penile 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 you know occlusive disease and really it's the potential artery not the cavernous 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 urologists we just copy them well two of the three biggest risk factors for cardiovascular disease are taking aim at the endothelium right so the three big ones APO B 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 elimination would mediate Ed for sure obesity diabetes is one of them also so this is called reversal the 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 okay 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 loved I really believe in Mediterranean diet if you lost weight and took the Mediterranean diet you saw three point which was significant increase on the iiff score this is on that six point scale uh well on the six questions after 25 you know but a three point and so and on the iief with no Viagra no living no intervention except diet and does that does that does that three-point increase translate to a cleaning clinical meaningful Improvement close yeah because 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 D5 and severity D7 so it depends where they started where 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 in terms of il-6 they lost weight I mean just diet and exercise alone reversed or had an improvement in Edie so lifestyle modification is very important when we talk about sexual dysfunction so let's go back to what you're 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 trimix which is a medication that's compounded you can actually also inject alprosidil which is commercially available like edex and you're injecting this into the Corpus into the corpora and it will cause a vasodilation right and and just because every guy listening to this is freaking out saying that you're sticking a needle in my penis right but you'd be surprised not in the urethra not in the urethra at the base of the penis we inject it at the two or ten o'clock position and within five to ten 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 peak systolic velocity if the pixel is systolic velocity is less than 30 particularly if it's less than 25 milliliters per second he has arterial insufficiency that's important that means not enough blood flow is coming into the penile tissue if the end diastolic velocity is greater than five millimeters per second then he has a 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 let's start with systole systole 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 numbers the majority of the patients who have Ed will start out with venous leak so but then there's just to be clear the venous leak is usually happening before you see arterial insufficiency in most cases 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 Albertina so think about the two two Albertina coming together as they 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 right so it actually goes upwards so 80 and so these patients will have a curvature of the penis when it's erect it's important when it gets greater than 60 degrees because that's prohibitive for intercourse right and it is 60 degrees so patients can have 90 degrees they can have almost 180 degrees it can be very significant wow so so when so but that is a very that is a very significant disease the patients who have Peyronie's disease really suffer from depression they've disfigured they feel like there's a disfigurement um there's a treatment now uh 2015 the first FDA approved treatment in the world came out for peyronies which is called xiaoflex 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 we until 2015 we had no medical treatment everything was off label you know and what would that include so people used to give vitamin E and they used to give um colchicine so in 2015 I was involved in the American neurological Association Peyronie's guidelines first guidelines and we said do not give vitamin E it's not indicated colchicine doesn't work but the only medication that's indicated are anti-inflammatories the way pronies works this is administered locally or systemically so that's what we give think about this the way Peyronie's disease works there's an active phase and there's a quiescent phase so the day you have an injury for about 12 months it's constantly changing we have the rule called the 15 40 45 rule 15 of patients will get better within the first year that's awesome sorry does this mean that Peyronie's disease is always born of trauma it's the prevailing Theory so we think that we in sexist trauma by the way so and so when a patient engages in sexual activity if he has 100 rigid penis less likely to injure if he's 70 80 or 90 rigid he's going to penetrate and he's going to injure so Ed many times precedes PD Peyronie's disease interesting and so and but we do think it's due to trauma during intercourse that buckling trauma will then cause a plaque so I tell patients think about this you have a balloon I put a piece of duct tape on the balloon I blow up the balloon what's going to happen everything's gonna expand except the duct tape and you're going to curve in the direction of the duct tape right and the greater the duct tape the greater the curve so how can I treat this I can use medications to remove the duct tape or the plaque and you can't in size put it 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 second thing you can do is actually surgical you can put stitches on the opposite side and placate it to make it straight or I can cut out the plaque and put a patch a graft to the plaster human pericardium 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 yeah so we in that case I would put a penile prosthesis and does a patient know if if trauma is the predisposing factor is it is it apparent to him that he is induced trauma sometimes majority no oh wow so 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 penile fracture a penile fractures when they're engaging in sexual activity and there's a sudden pop a sudden injury that occurs significant swelling that occurs in the penile 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 say doctor could we think he has a penile fracture we'll go in and people taking the surgery and will show up the fracture and the fracture is what a break in the Tunica alvirginia so in the in the casing I was talking about swelling is now because the fluid is leaking it's all blood he's it's a hematode 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 does affect so it's more prevalent as men get older but I do think so in 2009 I wrote a paper looking at testosterone as a possible implicator so we found that 74 percent of men had low testosterone and that's interesting because you know when you have low testosterone you have decreased rigidity the penis so I think you're more likely to injure but testosterone has been implicated for wound healing merely in the dermatologic literature as well so it's almost like a double hit you're more likely to be less rigid and injure you're less likely to heal but as you get old 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 right so these patients will have an injury but then with the way they heal is it's a plaque that forms fifteen percent of men have this or sorry seven to nine percent of men have this um 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 they say that don't you know 40 of patients stay the same 45 percent 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 gonna have to operate on you again because it hasn't finished has a stable is it remodeled 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 more better battery or I say have you noticed any changes that have occurred no Doc it's pretty stable is there any more pain with an erection 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 a favor is traction devices so that's been very commonly used and these devices are devices that I use one on my neck but I'm guessing it's different but it's the same concept any part of the body is pliable you 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 so it's a there is a a portion of the device that goes around the glands and basically clamps the glands and then you have spray ability to extend the uh the uh directions and and the uh base that goes or at the base of the penis as well and you can extend it uh 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 taken gotten the most uh um interest is 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 flat to say it actually bends so if you're curving up you can bend it down you're going left you bend it right and you hold it there for 30 minutes at least twice a day for three months has been shown at about 30 to 40 Improvement in curvature so penis larger wider and straighter but you got to do the work they're about 500 a little pricey um but they are effective and I know somebody listening is going to think well wait a minute if you don't don't have peyronies 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 today what percent so 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 yeah it feels like a lot to me two centimeters you know at the maximum you know so and is that a permanent change or is that only a change that you know lasts as long as you continue to use the device so we know that patients have to it's uh 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 once a week or twice a week just for periodic use but some studies will show up to two centimeters uh you can gain in length so it's not negligible yeah but um so we get patients to come all the time and say can you do penis enlargement surgery I don't do that surgery um but I think that the stretcher is a safe way without doing surgery to gain some length and the the guy will use this for how long I mean it's every day twice a day for at least 30 minutes up to three months the old stretching devices were two to six even up to six hours a day uh 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 um for at least three months but the restaurant because it's the ability I think to bend in the opposite direction you could shorten the time that you have to wear it 30 minutes twice a day wow um is there a critical window in which that works going back to Peyronie'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 quiescent 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 right in the active phase right so because if he's greater than 60 it's prohibited for intercourse so typically I like to uh at least the stretching device now the AUA guidelines I want to be clear will say we should probably wait until the patient is in the quiescent phase the treatment is to give them anti-inflam Laboratories have them come back from the requisite phase and then start therapy and then the AOA guidelines we did not put in any stretching devices as well you 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 yeah you know it's potentially worth it depending on your extent of the damage um okay so going back again to the Diagnostics so you induce the erection chemically you look for arterial inflow and outflow venous outflow um you diagnose let's just say the problem is purely on the arterial side so venous problem no issue you mentioned you can still use the phosphodiesterase inhibitor to compensate 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 venously because it's RTL insufficiency right and it tells you how bad it is also so if I see that the venous leak is end isolic of 10 15. it just tells you the severity of Ed which is very tell me what normal is again so you want less than five on the end diastolic you want at least greater than 25 or 30 preferably on the peak systolic 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 you know who had no issues whatsoever what would you literally see as a pizza like a 40 and I saw like of less than one yeah yeah so nothing and and and what's important is that remember each corporate cavernosa will have a different number both sides you have to do both sides and what 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 this is and so you can say you know look you're having some peaks of stock a low Peak systolic on the right but not on the left you know so it just gives you another diagnostic remember what's interesting about the penis is it's fenestrated right so that whatever you have on one side compensates on the other so if you inject a medication on the right it also gets relaxed right so it's fenestrated so it does make it very easy but the you mentioned something important you know this Peaks systolic velocity if it's low in a young man I am worried right because I think it's a marker for cardiovascular risk you know when you know you there was this machine I was using in my fellowship I was a fellow and we got this machine called the Endo Pat 2000 and it would check endothelial function what's it called endopath 2000 was it caught by Israel I love that it has the 2000 at the end of it reduces any credibility of the machine if it was just the Endo pattern I'd be like oh yeah that's pretty cool yeah endopath 2000 just it came out it was by an Israeli company but we used to put a uh blood pressure cuff in one arm and then it would have a probe on the finger and then a probe on the controller finger and we put superficial logic pressures we'd 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 a cult uh a cardiovascular blockage and so they found that if you had poor endothelial function in the finger it was a marker for potentially a cult blockage so as a fellow I did the same thing I would do the machine take the these results then I'd take them into the ultrasound room and do a penal ultrasound and if they had poor arterial poor endothelial function on the endopath you would see a poor inflow of blood in on this pixystolic artery so there is a a correlation between the endothelial function and you know cardiovascular disease but it's not common that we see we see much more end diastolic dysfunction than systolic function okay now let's talk about some of those therapeutic options you mentioned so um when is a man a candidate for an injection and how long does that last so let's think about it we used to have in the 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 Viagra Levitra Cialis or Stendra 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 the in medication is no longer worked we'll go into penile injections and these injections are extremely effective it's just what are you injecting so either trimix which is infantolamine and prostaglandin it's three medications into the penile tissue and it dilates the arteries and it's very effective it lasts for how long it's dose dependent so you got to be very careful because if you inject too much you have a priapism they have to go to the ER and I may have to surgically bring it down so the first injection should always be in the office and taught how to inject and usually I asked to bring the partner because 50 of the partners inject for their uh you know 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 this you reject every time you want to have sex I got it you inject every time you have sex within five the base of the penis at the base of the penis two and ten o'clock position and what we teach you how to do it and we have you slowly titrate up to finally get to 80 rigidity because you'll get the other 20 rigidity with foreplay and once you find your number whether it be 0.2 MLS 0.25 MLS you use that number the problem again remember is Ed is a progressive disease so many men will start having to use higher and higher 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 a new paradigm we don't have the first second and third we offer the patients all the options we use something called share decision making if a patient says I don't want to start with a pill I want to start with injection that's fine we don't use the urethral suppositories anymore they we used to use them quite a bit in the past it's a prostaglandin suppository that you place into the urethra and it causes a vasodilation in the penis I thought in my opinion they didn't work very well they were good for combination therapy isn't that uncomfortable it can cause significant urethra burning that is true through some bleeding as well and they cause a little bit of hypo tension in some patients as well so so we stopped using those but the penile prosthesis has been around now for 50 years this year was 50 years invented a Baler in 1973 and it is a phenomenal treatment option and what does it look like in its current form there's been many iterations uh there are two main suppliers as Boston Scientific coloplast and this device essentially is a a procedure where we place two cylinders or balloons into inside those casings the Copa cavernosa there's a small pump in the scrotum and there's a small Reservoir behind the pubic bone typically or underneath the rectus muscle that holds the normal saline and all you're doing is when you want to engage in sexual activity you reach down you press the pump and it brings normal saline into those cylinders and Deuces an erection and when you finish engaging sexual activity you release it and all the fluid goes back so just 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 going to go away he deflates exactly so some men find that very favorable so so essentially you get had the erection whenever you want as long as you want yeah so in other words even if he ejaculates prematurely he can still finish and please his partner if and the same goes with the injections so a man who uses an injection the injection just goes away when the when it wears drugs so some men do use that recreationally so what happens is even if you ejaculate with an injection you're not going to d2s yep um how risky is that surgery is that uh surgery I would say it's not very risky at all how long does it take you to do this 45 minutes uh well we operate and we do these under general anesthesia general anesthesia and um you know I think IV surgery has risk so let's be clear there are some risks associated with there's a small percent of risk for infection there's malfunction um uh you know 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 one a year yeah what what 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 you know at least 50 to 60 a year I think is very reasonable uh just to make sure that there are no issues and 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 you have to do something else yeah so typically uh the infection rate's less than two percent but now typically we'll say closer to one percent so it's not very common use a prophylactic antibiotic I do so typically I use several things I use uh uh vank gent and I'll use a anti-fungal as well because we know that 10 of these infections can be fungal and then we use a new arrogant called bank and gent why such big big guns because we're so worried about getting up if you get a prosthetic infection yeah no it's a disaster it's over yes in other words we're not going to just use first and second generation cephalosporins and cover skin yeah we're going all in yeah now listen if I so the bank has to be in an hour before okay the event cannot get in an hour before I'm okay with Sometimes using ancef and gent okay I'll use an anti-function yep and Jen for sure and then what we'll do intraoperative is I now use iricept iricept is what the a lot of the orthopedic surgeons use an intercept is chlorhexidine essentially but it's very good for fungal anaero aerobe and it's very it's a very effective Medicaid it's cheap so we use iricept intraoperatively uh the benefit of some of these uh Prosthetics is they're antibiotic coated so the Boston Scientific was antibiotic code of Minocycline or fan bin the coloplast device is hydrophilic and you can dip it into the antibiotic and it takes it in you the key is a short operative time there's many things in the operating room that we do to mitigate the risk of infection um do you wear the spacesuit like the orthopods do we don't uh 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 you know the light handles above you I don't have more than one person at the table across from me um you know it's it's very important because if they get an infection because it starts 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 know but you just have if you catch it early if they're septic they have any kind of purulence no Salvage you're not going to do it you know so it's you know and if if 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's but it is much more challenging to get another one in and it's going to be shorter typically that's maybe even thinner also so we sometimes you we call this a penile 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 priapism you know if someone has priapism after 36 hours uh the new guidelines will suggest that you can put a penile implant in and I strongly suggest let's tell folks what priapism is yes so priapism 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 it around your finger numerous times I'm cutting off the blood supply well how long does it take for that finger to start having necrosis and damage in the penis 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 but let me understand what that guy is going through what is it I mean wouldn't he be in pain having had an erection from Friday till Monday exactly but is he just not seeking care because he's ashamed he's ashamed or he 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 penile prosthesis in because if you try to get that in later on down the road I cannot tell you how much fibrosis and scarring is in that tissue I see and for me to get the penal implant can 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 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 corpora and try to detomest them and then you get arterial to Venus connection right so if that happens I don't want to put an implant in right away because you have a risk of erosion slightly and you have a slightly affection possibly because someone's manipulating the tissue so I said let it calm down let's come back in three weeks and this gives us more time to get the implant you do an ultrasound to make sure there's no shunt uh so 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 say wait a minute it's the exact opposite he presented with a low flow right venous outflow obstruction right and you converted them but the president 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 other sound it's a high flow you leave them alone right so high flows tree is a little bit different high flow is typically someone and what what is the etiology of priapism I know it's a side effect so there's many causes of phosphodiesterase Inhibitors right but it's experience it's extremely rare the most common cause typically is when someone is injecting a trimix or an agent and injected too much but you can get medications like trazodone cocaine and there's a lot of medications that can induce a an erection that won't go down so but but interesting trazodone which is ubiquitous now as a sleep agent right right and it can cause a priapism and so is it dose dependent um I don't know if it's dose dependent and I've typically most patients like 50 milligrams when they go to bed but um I I would assume that it could be interesting um okay so the moral of the story here is if you have erection for four hours go to the ER absolutely and when that patient comes to you in the ER you you make an incision to good points things the first thing I do is I put in phenylephrine so if it's less than four hours I'll inject the antidote the antidote so the antifenylephrine and it'll usually work if it's less than four hours as it's if the hours are greater and greater out what I'll do some aspiration irrigation to try to get the old blood out and phenylephrine if that doesn't sorry aspiration irrigation to the penis at the base of the penis so we're using 18 gauge butterfly needle put it in and I'm asking injecting normal saline and I'm aspirating many times we'll use cool saline we're just trying to get the the sluggish blood out of the tissue wow do they ever develop like clot venous venous clot it is Venus that's what it is oh it has already clogged it's already closed it's already clotted I didn't realize that okay so you're basically trying to get all that caught and sluggish blood out and and so you'll ever run Heparin in it or anything like that we don't run Heparin in it although if I do a shunt uh sometimes people have advocated we starting to happen or Plavix post-op to keep the shunt open yeah yeah right I usually typically use a little aspirin but that's one thing you can do but so we aspirate irrigate then we put the phenylephrine if it doesn't work then my favorite is a T-shirt and a t-shirt 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 I'm doing this under local well this time I'll take them to you or yeah and you can't it hasn't been described under local but I think it's just better to take them to the or that's traumatic less dramatic and um and you have to counsel them you know if I do this Hagar and disrupt the muscle uh there's a high chance you're going to have erectile dysfunction and we'll have to deal with it you know uh how often do you induce peyronies in treating priapism where you after treating the priapism there's now going to be a scar that results in the safe yeah so I think the the question is you know when we use trimix if you use trimix regularly that is a risk factor for peyronies so because any repetitive trauma to the corporation physical corporate cavernous is going to actually in injure the the tissue when 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 them to inject opposite sides every other day so you can't do it every day inject opposite sides to mitigate the trauma that you're causing to the corporate cavernosa um okay last thing on Ed I wanted to talk to you about is this uh device that a couple of my patients have talked about I think it's called gainswave sure what is it so gainswave is just a company uh but that uses devices for Shockwave therapy okay so I just have to give you a little bit of history about Shockwave therapy in 2010 Dr vardy European study was the first to start using shock waves to treat Ed and you shock waves are not new to urologists we use high intensity Shockwave for kidney stones right it's called high intensity shock wave this is called low intensity Shockwave therapy or list right and when I first saw that I'll be honest with you I thought it didn't make a lot of sense I said this is ridiculous he's shocking the penis two to three times a week three weeks 2500 shocks what is he doing but the science is actually quite clever the science is you're inducing trauma when you reduce trauma you bring in neoangiogenesis right you actually recruit stem cells right you help with nitric oxide synthase so it actually is helping improve the condition we weren't the first cardiologists have been doing it for years if you look at cardiologists they were shocking the heart and they look at the reperfusion and it was reperf using the heart Orthopedics do it for uh 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. so since then and again pardon my ignorance how is the device applied so it is think of it like a probe and what happens you have to have someone doing performing the procedure we divide the penis in six zones so it's shaft hilum and cruise and in in two sides so six zones and we will typically and sort of just explain where each of those is so the hilum is the shaft is obviously the shaft of the penis the hilum is where the at the base of the penis and the cruises underneath the scrotum okay because those peanut tissues go underneath the scrotum so we will deliver 2500 shocks uh in these six areas and it takes about 25-30 minutes and the patients will come in and they'll come in at least one or two times a week for three or six weeks so six and you may have to have a booster so when we've already 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 necessary when vardy did it he showed that there was Improvement in uh peanut blood flow and men were having better erections okay great 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 okay 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 and but they're not dangerous so the FDA has called this a type 1 medical device low risk anybody can buy it so you could be any profession anyone on the street though going great for these is 500 to a thousand dollars a shock cash so you and I sorry 500 to a thousand dollars for the machine one treatment for one tree one treatment one treatment machine but you said a guy needs two of these a week for three months a two for three weeks oh so six treatments let's say so anywhere from three thousand to six thousand dollars okay for a machine that's a Pneumatic that does nothing in my opinion yeah but the patient doesn't it can be bought by somebody at Costco you got it you could go to the gas station and the guy the guy could fill your tank and give you and you can buy scrotals out you nailed it and he can make 500 to 6 000 okay and the problem is that the Ed population is very vulnerable right 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 right 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 thirty percent of men will get the best erections of their life off the sugar pill right and then of course they're going to tell their buddies that this is the best sugar pill you've ever 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 shock waves that are very effective the machines these are called Electro hydraulic machines electromagnetic machines these are called Class Type 3 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 gainswave is a class three whereas games wave is is just the the 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 yeah but I know that they at least one of the patients mentioned to me at only a doctor's office can have this thing so I assumed it was a class three class three so whatever the device they were using and those those machines are more expensive the electro hydraulic is exactly what the shock wave is for the kidney stone if it's a low intensity electromagnetic is by storts and but again I just want to be fair you know we this this is where the device took off greater than the science yeah the science is coming up and I would say that it may be beneficial for patients who have mild to moderate Ed but I just be careful on the ads that are given on you if you look at these ads they say you'll get a great erections today you'll have great erections by tomorrow and I mean the ads are unbelievable so there's really you know so I'm part I'm part of the sexual mess side of 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 were put out in 2018 it's been five years there's been new data but I just want to say use it with caution don't tell everyone it's the best thing to sliced bread it has potential it has potential and more studies need to be done Okay so we talked about Ed does it make sense to now talk about premature ejaculation sure I just want to mention two more things it's stem cells and PRP oh yeah because that's the that finishes the service and so stem cells um the problem with stem cells and we published the paper we did use stem cells we had a we had an IDE there's no FDA approval for this yeah there's no FD approved 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 said you cannot use stem cells so just in general for any therapy we I had a I use a machine that had an IDE by the FDA so investigational device exemption and this was the exemption was for specifically Ed for stem cells I see so we conducted 30 patients uh we use adipose derived stem cells we take the fat we wanted to use it fresh so we put them in a machine we would get 37 to 50. so you would literally this was autologous you would take a man's fat issue get the stem cells and then reinfuse you got it but so what I my 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 120 cc's of fat and put it into a machine that had the IDE for uh making stem cells so the machine after two hours would give me anywhere from 37 to 50 million stem cells and then I would inject those stem cells into the penile tissue at the base of the penis 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 tourniquet off and did you have a 30 Placebo men this was non-placeable controlled and this is important because up to today there's not a single placebo-controlled trial with stem cells 3D not one right 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 of four on the iief no Placebo control but it was only durable for six maybe nine months and started tapering off so 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-controlled trial because you know people swear by stem cells and some companies will say 15 000 will give you stem cells for Ed where's the placebo-controlled trial right it doesn't exist right so you have to be careful well the other thing I guess is at fifteen thousand dollars in Costa Rica why we would have to believe it's significantly better than daily Cialis at uh what seventy dollars a year yeah so so I would say look there may be some benefit I do think there's some benefit in stem cells for Ed and I I was the number 15 000 I don't know you know some people have different numbers but yeah but 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 share the efficacy and the question is if I'm spending a lot of time doing the liposuction for and it lasts for six months I can't do this for a life I mean that's not a practical way to do it you know one might argue oh my God that's fantastic I'm getting free liposuction every six months at some point I'm gonna you're gonna take all those subcutaneous fat on my body but no it's not a viable solution but exosomes may be the next way what are exosomes so basically this is it's basically the secret home what's coming out of the stem cell so people are looking at exosomes and I think that may be another alternative to look in the future how are they harvested so that's basically you can look at placental uh and you can look at also look at 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 going to 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 we got our first randomized placebo-controlled trial first one until 2020 21. before then there was one case report one case Report with five patients out of Wake Forest showing that there may be some benefit and this was sold like it was the best thing since sliced bread they call it the P shot which is the prior per shot basically take stem cells it costs about fifty fifteen hundred to three thousand dollars now honestly to really make it cost fifty dollars you take blood you spin it you get the supernate and you spin it again as some calcium chloride you have PRP you know they inject it um Into the 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 with Placebo arms 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 in April next month so that's going to be interesting okay 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 so we'll link to that sure yeah um okay so my takeaway from everything on Ed just to summarize is uh easy way to remember the prevalence is it's matched by age yeah so amazing to think that at 40 which is pretty young 40 of men are impacted at my age 50 percent of men at 60 60 Etc um second thing to consider is you know if if men listening to this or their partners are listening go and get help don't don't suffer in silence uh the third thing to consider is that daily phosphodiesterase inhibitor I took away from you is a very viable solution that there shouldn't be a stigma attached to that and there shouldn't be a fear that I'm becoming dependent on it or something like that in the sense that these are valuable drugs they can also sometimes break the Vicious Cycle if there's a psychogenic component exactly you want to rule out psychogenic before you proceed to pharmacologic uh as the only therapy you have the diagnostic side on the arterial venous um and then I think this idea about PRP stem cells exosomes and shock wave it's still a little bit too soon to know a little bit too soon promising yeah but too soon and of the four would you say the most promising is stem cells I like Shockwave okay I like soccer you know why because when I do Shockwave therapy it recruits the stem cells because stem cells go to area of damage yeah so essentially I'm getting the stem cells I'm getting in the ogenesis it's not invasive it's quick it's not so we're probably most optimistic on uh Shockwave leased on PRP so far and maybe there's a combination and we'll see that with the results of this anyway so okay so let's let's pivot now and talk a little bit about uh the sort of states of ejaculation so so inorgasmia delayed orgasm Etc um how does the prevalence of this differ by age yeah so ejaculatory dysfunctions are important we know that 30 percent of men 30 of men are likely to have some type degree of ejaculatory dysfunction more prominent is premature ejaculation right so premature ejaculation uh 30 of men up to 30 will have it only nine percent of that 30 percent 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 three percent of men in total are doing anything about it nine percent of the nine percent that's exactly right which is very small but in you know two years ago the guidelines came out the new guidelines came out so what is a premature ejaculation 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 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 ejaculatory time now when it's lifelong it's typically now less than two minutes right so it's less than two minutes it used to be less than one now it's less than two but it has 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 and says I ejaculate in 30 seconds and I'm happy look 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 it's 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 right now acquire it's 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 percent of your typical time so let's say I used to ejaculate in 10 minutes and now it's five okay that qualifies it's fifty percent of what man so these are the two definitions of so you want to break it down now why is that important because how I treat somebody is very different right if someone's acquired we start looking at hormones that's important we look at prolactin we look at thyroid we look at testosterone we look at some more diagnostic if it's lifelong we don't do a lot of diagnostic work up you're not supposed to it's the acquired where you start figuring out you know the four reasons for this premature ejaculation one is the biological the theory that there's increased sensitivity of the glands right so if they're born with increased sensitivity that's why one of the therapies is using lidocaine or some of these numbing agents on the glands they're over the counter there's sprays that actually lidocaine on the penis 10 minutes prior to engaging sexual activity if it doesn't then put lidocaine onto the partner you wipe it off before you engage in sexual activity I see and so and and but be careful because if you spray too much it causes Ed right so that's one so it's the biological there's about there's a neurobiological essentially meaning the neurotransmitters so essentially that there's too little serotonin um the neurotransmitters are causing an impairment for the ejaculation there's some belief on genetic uh we don't have an assay right now but they're four four genes that have been implicated um the some genes but these genes are only implicated in lifelong or in acquired uh and acquired that's sorry it should be lifelong I'm sorry and there's polymorphism of the the and they're they're they they're the receptor neurosteroid receptor genes right and they're 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 and uh the last one's important it's psychological right if you have um a new relationship stress um any kind of uh that causes some psychological impairment that can actually cause premature you have a sense of why stress can have opposite effects why is it that in one man stress us might result in Ed and in another man it might result in no difficulty with an erection but premature ejaculation yeah I think it's how you interpret I don't I can't answer that I don't know the answer I don't do know that stress though significantly in effect you in all sexual function I call it sad it's stress anxiety and depression patients suffer from those so stress it can have a significant impact on all forms of sexual dysfunction right and so but stress stress has a huge impact when it comes to sexual dysfunction a lot of men when the stress have difficulty getting an erection um and so it 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 promescent 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 um I say okay you don't have to take it every day although it 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 counter-intuitive right because one of the side effects of an SSRI is reduction in libido right and Ed both and Direction libido so you're right uh so so you just have to realize that those are and then first line therapy should always be Sex Therapy this is one area where Sex Therapy is very effective and sex therapists are what what is the formality of training to be a sexist they are certified you have to have a certain certification so basically a psychologists or psychiatrist typically psychologist not psychiatrist but psychiatrists can be uh certified in Sex Therapy but um these uh they're very helpful because there's two techniques the start stop 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 I mean but if they did the work that's a cure right that's a cure for PE um so so those are the first line therapies there are second line therapies the two second line therapies are Tramadol a narcotic right right and actually has been shown if you look at the ejaculator time less than one minute a lot of so up 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 as the risk of addiction or exacerbation of very high yeah and so that's why I had a patient once that started using you know five a month and you're 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 want it every I could tell he's getting addicted right and I said I can't do this anymore you know so so you just have to be careful on the tram at all uh and then actually uh alpha blockers Flomax premature ejaculation yeah right so now does that sometimes convert premature into retrograde you can so right that's one of the risk factors for the Alphablocks retrograde but it prolongs the ejaculatory time you know so so these are the treatment options that we use for patients and they're quite effective you just kind of go through the algorithm uh for PE explain what a retrograde ejaculation is so think about what happens when the uh so as I mentioned earlier in the prostate there's something called the ejaculatory ducts so think of it like a t Okay 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 seminal fluid comes up the tendency is for the fluid to go back into the bladder but as the 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 seminal fluid then goes into the bladder and so nothing comes out of the urethra 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 yep obviously with impair reproduction so for sure so someone's trying to have a child yeah um okay at the other end of that spectrum is an orgasmia sure and uh how what's your work up for that right so an orgasmia 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 same principles are you bothered by it uh is there a nobility loss of control or inability control and more importantly the timing so what is the average amount of time that a man takes to ejaculate the United States typically about six to seven minutes on average six or seven minutes is the norm so that's self-reported uh in numerous studies and it's interesting how do you do that great question so we look at something called the intravaginal ejaculatory latency time ielt and it's typically self-reported but when it's self-reported it's inaccurate yeah 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 it was 90 30 seconds if you have to ask a guy who does that premature ejaculation he overestimates the time he says if he ejaculate an eight minutes he says yeah it's 15 minutes right so it's a big discrepancy so how we do it is we give the partner a stopwatch and when they engage in such when he orgasms she's supposed to click the clock right and that's the best way to get intra-vaginal ejacent control line so ielt is best why 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 later what what do you attribute that to cultural right there could be cultural differences as well but there's there's some differences but when you look at uh for example these medications like ssris they are very effective in prolonging the ielt very effective and there was a study in 2004 by waldinger he was looking at the different different ssris Paxil was number one by far so Paxil is typically used the most Zoloft was number two and you can see uh based on the dose 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 right with Paxil so typically it's about 10x you see energetic delay but without getting to the point of Ed without without getting so use remember you can dose if if I'm using too much pack so I bring it down right so one of the problems we'll talk about this delayed orgasmia a lot of these patients are have it because they're on an SSRI yeah that's why they have it right so if they're on 40 milligrams of Paxil maybe we just go to 30 we still get the benefits of depression but we improve the ejaculatory latency because it's very sensitive on those doses right so when there's no set number on delayed orgasmia but typically someone will say greater than 15 to 20 minutes if it's greater than 15 20 minutes that could be considered delayed orgasmia we have no FDA approved treatments for this condition there are no FDA approved 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 a five Alpha reductase Inhibitors here I would not I I would not use five Alpha reductase but I don't like to use them at all in my practice oh I mean as implicated in uh an orgasmia in other words it's possible that five Alpha reductase Inhibitors you're amplifying it is possible there are patients that have had or taken five Alpha reductase Inhibitors that have had impaired orgasm or and orgasmia uh because remember uh it blocks DHT and DHT is four to five times more potent than T when it comes to uh function for the receptor so so typically in one of the treatments for delayed orgasmia is testosterone right so that's how you treat it right and so if you're using a five after you're actually going in the opposite direction what about uh the phosphodiesterase Inhibitors the same drugs we talked about to treat Ed how often do they induce uh delayed orgasm yeah so I think that they don't induce delayed orgasm right so they just expose it they might make 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 that's an interesting thought let me 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 why do we treat the Ed first we treat the Ed first because if you treat the Ed you can actually treat you can delay you can actually fix fix it right and there's a there's a there's a reason for this subconsciously whether it's conscious or subconscious it's a belief that the body's saying if I don't ejaculate quickly I'm gonna I'm gonna lose this erection right I'm going to lose the erection before I ejaculate right and so if you and so if you're able to maintain your erection and not worry about it you may prolong the ejaculatory time so we it's a board question we asked this exam on the exams patient presents the Ed and PE you treat the Ed first and you can treat the P that can treat the people at the same time okay I kind of want to talk shift gears a little bit and talk about testosterone replacement therapy sure so let's um maybe give folks a little bit of an explanation of how the hypothalamus pituitary testes and adrenals all play a role in the generation of the hormones that we're about to talk about which means let's talk about everything from LH and FSH to testosterone shpg DHT Etc and then let's talk about what deficiencies mean and but sure what the consequences are and how when I go about addressing it sure so let's talk about the physiology because it's important so GnRH secreted from the hypothalamus generation then it goes to the pituitary secretes two hormones LH and FSH and what's the signal for GnRH is it estrogen uh well and that's a negative feedback so you can't have a negative feedback on it it's a pulsatile pulse GnRH you know that pulse goes down as we age that's important part of aging we'll talk about as well the LH FSH will then go to the testicles I tell the residents remember that LH has an L goes through those f is s it goes to Sir totally cells right so LH goes to latex cells and produces testosterone FSH goes to the sertoli cells and produces sperm right the two functions of the testicle are basically sperm and testosterone so essentially if a patient comes in and they have um remember that the majority of a patients a man's testicles are comprised of sertoli cells that's important because that is the exam is more of an indicator of his fertility status than his hormonal status right so that's important when you say exam you mean size size so they should be four centimeters in diameter 20 CC's and so when I'm looking at an infertility workup if the patient has small testicles elevated FSH and LH I say there's a production problem he's not making it 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 uh making testosterone but there's a negative feedback that negative feedback testosterone goes back and feeds back negatively on the pituitary and also on the hypothalamus but also estrogen goes back and feeds back negatively testosterone can be broken down but majority by the way is is which is one of those stronger than the other is 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 serms work as they block that negative feedback estrogen um but remember that testosterone then is converted into estrogen yeah 0.3 percent not much point three percent and six to eight percent is converted to dihydrotestosterone 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 aromatase Inhibitors and they'll use five Alpha reductase and try to control it and I'm not a big fan of the but but they do it um so so that's really the big picture here so let's let's double click on a few of those things right 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 um we're not measuring uh GnRH right it's pulsatile sure even if we had an assay for it it would be useless sort of like growth hormone um 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 Androgen index all of these things that are not measurable sure but are estimatable and I want to understand if they mean anything yeah so uh most of testosterone is bound two percent is free and so 50 albumin 44 shbg four percent corticotrope and binding globulin oh I didn't know that I thought shpg was the Lion's Share but it's split relatively equally with albumin 50 albumin 44 and then four percent cortical and binding small percentage and then two percent free okay but the body only cares what's free right that's what they 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 is testosterone is 450 500 he says I feel lousy say what's going on check his shbg get a calculator free testosterone if shpgs 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 if they're calculators that are online and very simple we put in the album menu put in the shpg you put in the T click and it'll give you the calculator free T it's more accurate I think than the assay uh the the gold standard lcms but it's expensive and it's hard to get so there is an lcms assay for free testosterone not uh I don't know I know it's for total yeah it's for total total CMS yes not for I'm not just I don't think there's one for free but yeah but you're saying if you have an lcms if you're cost insensitive and you have an lcms assay for total and you know albumin and shpg 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 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 yes what it means what does the normal Bell shape 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 yeah all I seem to find for free T is over 18. yeah 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 andropause was real meaning as we get older our testosterons get low and lower due to age alone that is not true we know now that test 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 it a total T what does change is the shpg so as we get older the shbg does go up the total testosterone should stay relatively flat if you're healthy and the free tea will start to go down right and the shbg goes I mean so I've noticed and I'm sure we'll talk about this genetics seem to play a very big role in shbg I've seen people I'm I'm someone who just seems to have a very low shpg you're lucky uh you know it's but I also have a very low testosterone so my testosterone is maybe 400 maybe 500 but my shpg is in the 30s so my free tea you know is about two and a half percent of my total tea I have lots of patients who have very high tea but their shpg is in the 80s or 90s but that's the body compensating right so the body is very clever if you start if that and that patient if their T starts going down the body starts offloading and lowering the shb gene to keep that hemostasis it's almost like our reserves right it's almost like the bodies 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 we definitely see an amazing response to insulin so as insulin comes down shpg tends to go up uh as T4 goes up shpg goes up and as estradiol goes up shpg 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 but I think genetics is a big part of it so it's definitely genetics but there's also other environment look obesity has an effect on this there are comorbid conditions that affect the SHP G levels as well but it's interesting usually with obesity we see it go down yeah it comes with paper and it goes down yeah um okay so you you buy the idea that having a plasma measurement pardon me a plasma estimate of free testosterone uh 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 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 right and I know that in the lab you can probably do those things I've talked with Ted Shafer about that but clinically I can't do any of those things right I literally have this very crude estimate of free testosterone and I struggle greatly to make the link between that and what's happening yeah so instead I just sort of say to pay and I have this discussion with a patient yesterday which was and his so this is a 55 year old guy uh in pretty good health his free testosterone is estimated at seven nanograms per deciliter so first thing I can so he says Doc is this high or low 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 them 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 going to do anything so I said let's go through the symptoms so I asked him a whole bunch of symptomatic questions I want to hear yours so I'm not gonna I'm gonna you're gonna start mine um and sure enough to a T 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 yeah let's revisit this in a year he said great no problem yeah so um first of all I want to hear what symptoms would you what would you say to that patient if he said Mo yeah my free tea is seven yeah it looks low what should we do I'd say first of all I would completely agree with what you did because why are we so fixated on the numbers it's not about the numbers it's about how he feels right if a guy comes in with a level of 250 200 total T very low and he says I feel fantastic one could say why are you treating them conversely if he has a level of 500 feels great I mean it has all the symptoms we don't treat so if he comes in and he has symptoms then I will treat and tell me the questions you would ask so I say these are the following low energy erectile dysfunction I didn't ask that okay increase fat deposition decrease muscle mass depression poor sleep okay those are the big ones now I also asked about recovery from workouts yeah you could and that goes with the muscle but you're right yes uh bone fractures are important that they have you know bone factors um and then just look at them just look at them are they obese metabolic syndrome like you know you know this is a you know this is a this is a guy who's lost 25 pounds in the last year in our practice he's exercising using more his bone mineral density is fine if I was going to be very critical I would say his appendicular lean mass index is only at about the 55th 60th percentile we want to see our patients with an appendicular 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 how old was he how old is he 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 ten 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 yeah that's that's been my lazy excuse which is I'm 50 and I I am a firm believer in the benefits of testosterone I wouldn't be prescribing it 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 yeah 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 tea 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 but it takes seven but they never were informed you know that they uh they could have infertility yeah so let's talk about this I'll um 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 um one is and we don't do this anymore um we used to use clomiphene so we would give Clomid it had the advantage of several things one it's uh it's a pill very convenient you take it three times a week uh two it preserved uh function meaning you you preserve both testicular volume and spermatic function so you preserved fertility um and actually it was quite efficacious I found it to be because you could titrate the dose and get to almost whatever you mean the drawback is if the man didn't have testicular Reserve uh he wasn't going to get much of a bump sure so so you know 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 are 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 mimetic for lautenant hormone which you talked about of course is the direct stimulant of the late egg 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 it's crap so lots of problems associated with it but again 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 um but again it feels less problematic to men in the sense that it's less permanent sure of course we then use the Mainstay is injectable testosterone cypionate 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 in to put the pellets in them sure and also for men pellets are a much bigger deal than for women the pellets are so much bigger sure for women when you're putting little estrogen and testosterone pellets in it they're it's a sure it's a walk in the park they don't even notice you've done it for men they notice it sure great topic so this is really important so you talked about two so let's talk about endogenous ways to erase this awesome first and you can use Clomid you can use HCG some people use an astrozole I don't recommend that but we'll talk about that so Clomid first it's a serm negative feedback to the estrogen receptor 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 percent of patients say I have no desire for sex I have no erections I don't feel any desire because the waste this Clomid works it blocks estrogen receptor centrally men needed estrogen it is critical you need Estes for libido and sexual function so they have these beautiful 800 900 levels you take that same patient put them on exogenous testosterone at 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 back order so now we're starting to use a little bit more n Clomid is n Clomid legal in the U.S uh it is compounded remember Repro and try to get it through in 2015 that the FDA never made it through but it was it's you know it's a trans isomer of Clomid and so of a zucchromid so and essentially it is available compounded and you can get it but it's hard to get home and now even because there's a national backorder and and is this just due to all these tea shops opening up on every corner that are well they're different so they're more into giving the tea and the injection and you come in and get the injection for a fee okay but this still is on the endogenous side if Club is not bad I mean but why is there such a run on this stuff because what happened was HCG wasn't for many years compounded and recently uh the FDA has said that ACG cannot be compounded so everyone dropped the HCG and went to Clomid and now there's a mad rush to get the Clomid you can still get HCG commercially yeah so what happened was that everyone started going to Clomid and so now we're back ordered on Clomid and you can still get HCG but it's pricey 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 uh rights to the patent on HCG G and it was too similar because the compound can make something but it has to be different that's my understanding so I I for some reason our compound you know so I think certain com 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 it's not the 60 will say my T goes up you got to give it every other day or you can get a tachyphilaxis so seven percent can get tachyflaxis if you give it daily some patients I say they say I can't remember every other day I say fine take it every day and the seven percent chance you may become resistant to the seven or seven percent yeah okay so that's fine we want people to get a pill box when we used to use it yeah it was just Monday Wednesday Friday and don't have to think about it right if you forget take it every day and like and clone would we give it every day and what doses do you use uh 50 for Clomid every other day or nclema 25 a day right or if they forget on 50 every other day we use 25 chroma 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 use it you can use HCG HCG is expensive and it is pricey typically it depends on what dose you want to use um but it's 1500 three times a week up to 2003 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 it can start making testosterone and then in patients who have an elevated LH and FSH initially Klein filters yes you can't really use HCG or clone because they're already maxed it's already maxed out so you've got to use Anastrozole or because I'm trying to increase the TD ratio increase the T and typically I'm using this medication to improve spermatogenesis so that I can then do a biopsy or a Tessie to achieve spermine and how I've never seen a man with client I've never seen a man with Klein filters if when a man presents with Klein filters what are his typical T DHT and E levels so the E's are typically High the t's are pretty typically 40 30. they're not super high but they are and it depends on how far along you see them long way efficacion LH are typically already elevated did pretty high so if the FSH and LH are already elevated I can't use Clomid or HCG right so that's the prevalence of Klein filters uh one in 500 so it's quite common really that high yes just tell people what kleinfelter is it's a genetic abnormality where you have an extra X chromosome xxy so phenotypically you're a man phenotypically you're a man but there are issues infertility you can have gynecomastia uh they're typically long stature in nature um normal you can live in a normal sexual function uh 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 right and so we see that and why can't you just give them testosterone uh we can but what if they want to have a child right so so that's the only thing so what we made you so I see a lot of these patients when they're 14 or 15 when they're first diagnosed so we have the power they usually die 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 right no shaving and so what you'll notice and so the if there's a suspicion long stature uh small testicles on exam the pediatrician may say let me just take a karyotype and just see what's happening and then you see 2x chromosomes and then you know yep you know so so it's one in 500 that means there's a lot of people listening to this podcast that have kleinfelters presumably they know it but they may not and if they know it they might be wondering is testosterone an option and what you're saying is not necessarily first line unless you can block estrogen as well right 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 microtessy 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 then we'll either give them go no F or Clomid with it so there's three ways to look at it there's patients who've taken testosterone and they're abusers and they've 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 uh recombinant FSH or going off 75 units three times a week and that actually does help reverse anywhere from three to seven months you can see recovery of spermatogenesis and these patients who are azospermic that's great okay and tell me that guy shows up having been on testosterone for how long to be in the years and and many times they may have gotten the testosterone from a gym or something and they weren't getting monitored and they're at Super physiological levels so this is how long have you been on it and how high was your dose dictates how far along you know so so for you you tell patients that and we use physiologic doses so typical dose for us is 50 milligrams of cypionate twice a week that's what we do yeah okay so so we would say that 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 yeah but what do you say so typically it depends on you're talking about younger patients though yeah so someone who's like in his 40s right 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 three thousand three times a week that's fifteen hundred three 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 three times so 500 1500 3 000 there's three different patients the preservation of you know and this also is about 500 of HCG three times a week it's not due doing anything to boost endogenous production protection it's just protection and the best study this is the best study came out a guy named koviella this is how we got the idea at Baylor koviella had a study in 2005 where he gave patients 200 milligrams of testosterone I am every week okay it's a big big dose every week and what he was measuring was intra-testicular testosterone levels at 200 I am every week the inter testicular went down 94 of patients were down to zero in three weeks so that's a good number to remember 94 decline in inter-testinal testosterone in just three weeks 94 decline then what he did was he gave these patients different doses of HCG 250 500 all the way a thousand and what he found was between 250 and definitely 500 there was no significant decline in intra-testicular testosterone very interesting so he's giving 500 every other so in 2013 amazing 2030 by partner Larry lipschultz uh said okay if that's true for intertesticular testosterone what is it doing for fertility yeah so let's do the same thing let's give these patients testosterone and 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 I don't want people to think hey if I do this it's completely safe but it does help protect decreasing somatogenesis but why is that the case given that HCG is acting on The Late egg cell you would think you would need recombinant FSH to get the protection of spermogenesis right because it has some FSH properties if you give a man for fertility just HCG you actually see some improvements in spermatogenesis now there is some of the fact that some of the testosterone is being used by the sertoli cells for production of sperm production would you has someone done the study of giving clomiphene or mclomaphene with testosterone to maintain sperm production I have not seen that study but people do it off label yeah and it would seem to me that that would be even more efficacious people do it off label the only issue is that you got now two things working in opposite directions yeah and also that you know that the when you're given the tea you're suppressing the LH and FSH and clomid's trying to raise the SL so but giving but giving recombinant FSH would be the better thing to do this yeah how expensive is recombinant FSH extremely expensive so I would say it's really only used for fertility right that's it's on label uses infertility yeah up to 500 a month I mean it's very expensive wow this is insanely expensive proposition once you start going and what does HCG cost it depends now because now you can't get a company no if you're getting pregnant about 300 to 300 a month insane yeah yeah these are you know these are 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 uh and especially if they're you know getting it in an illicit fashion yeah uh so so you're 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 Anastrozole clomiphene and HCG there is some data that just came out suggesting that the intranasal testosterone does not significantly suppress somatogenesis and this was interesting so it's done three times a day this was out of the group at a University of Miami three times a day that's how in the text called natesto it's commercially available you go to Walgreens you can buy it I've never even heard of this I'm just about to ask you about the oral testosterone yeah so the Testo is a nasal testosterone that's implied it's 11 milligrams is applied in each nostril and you do it three times a day and essentially what happens is it has the fastest rapid on onset and then it declines and I always thought 11 milligrams tid said 33 milligrams daily right so in other words the bioavailability is much lower than an injection yes but the interesting thing is this I thought look if I looked at I looked at the pharmacokinetics I said how can this be effective like how it's in and out so quickly right and then you know doing some deeper work and talking to some endocrinologists 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 right 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 it's very quick they say they feel better when they take it this is how has this not become the drug of choice but no significant suppression is fromatogenesis that was interesting now more studies need to be done but that was when was this approved uh the test show I think has been out for at least six or seven years it's been it's been for a while is it inhibit is it cost prohibitive uh it's it it you insurance does cover it uh it can also be compounded but um it's used by a lot of young men that's so interesting so um when a if a guy comes to you and you go down the path and decide you're going to go down the exogenous route not the endogenous route how are you deciding between pellets which we should explain what they are topical like AndroGel or compounded injectable such as you know cypionators is dead or intranasal or oral now yeah oral so there's so 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 uh cash price from a compounding pharmacy is 25 a month we have them inject Sub-Q either an antide recipient it's based on age I use cypionate for younger patients and then they for older patients I think it's more anabolic has more sodium retention and so I teach the resin size cypionate has a c for child and Anthony has e for elderly I typically is like 50 or 60 but look at the patient but I think that you know it has a little more sodium retention so I try to 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 to typical of 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 Sub-Q always Sub-Q and we have a 25 gauge needle short needle 5 8 inch one cc syringe 25 gauge it's big enough to draw it up it's small enough to inject in the butt outer part of the butt or belly belly yeah and pinch the fat right 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 to I know you want to get more tissue up but don't you worry about inducing trauma you get more vasculature I think it decreases the pain so the harder you pinch the less pain you feel you know and why belly as opposed to Upper outer gluteal fold you can do I tell patients you can do whatever you want okay okay if you like the gluteus of most patients just think you want to be able to see it and less pain in the fat you know most people but some people I have like 10 20 say I it's less painful in the muscle I say great doing the muscle got it wherever you prefer although there's a conversion the 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 to roughly is what I'm seeing so if you look at zystad 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 uh Sub-Q so my favorite is Sunday Thursday 0.25 25 a month no insurance which is it's easy and you like but there's patients that are needophobic I get it so the highest it's a great option and Zaya state of course is still a needle but it's pre-loaded they don't have to see it it's just 27 Gates it's unbelievably tiny has a high how did they get it out is the pressure just so because so if you look at the the yeah it's a high spring so it's not a new drug they're just using an antide yeah yeah it's just an end date in a very clever spring-loaded device why haven't they come out with a cypionate equivalent uh you know they all I think an answer is what they used to get through the FDA uh that's a good point but they so that's what they use but the the ticket is the 27 gauge needle which is unbelievably tiny with a very pretty long spring yeah so it gets it in with less paint and the patients just throw it away I don't even know it four months it's easy and so uh at 100 milligrams what's your monthly cost on cash price so considerably more than cypionate consuming more than cypionate but some people say it's worth it it's worth it because I don't have to deal with it I have to deal with it I don't have to travel I have to draw it up on my trip you know I just it's easy you know so and there's no user error associated with how much you're drawing if I told you have a dollar for every time a patient made a mistake on the math yeah so it's easy now the orals are very fascinating so and just approved last year Well 2019 2019. so undecan 08 has been approved in the all over the world since 1970. it's been around for numerous years it's called andreol so when I went to China when I give in Australia Europe Andrea's available Canada but never got approved in the US in 2019 the first testosterone deck anyway got improved why isn't decorate important because orals historically cause hepatotoxicity that's right 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 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 right so you have to take it so if you're intermittent fasting it makes a little tricky you know so you have to take you could just commit to take it with dinner every night that what's bid oh boy so it's be it no it's still but so not bad so what happens is you're supposed to take it at breakfast and 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 in the day and it goes down it mimics the diurnal variation so I like it better breakfast and lunch again that's off label most people what's the dose so it depends so jatenzo which is the one that first came out in 2019 the first one 237 milligrams bid okay talando 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 then but you're getting still the blood level so yeah of course of course yeah yeah but now in 2022 the third one just got approved so of Kaiser tracks the new drug by Mary's Pharmaceuticals is now the third world so now we have three orals that are FDA approved so it's getting very popular but all are Bid the only difference is talando 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 uh if you're not high enough so orals are popular look Americans are used to taking pills they have pill boxes they put them in the pillbox so I think but 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 pellets a lot of pellets in men and women I think they're very effective but the only issue with pellets is that they're falling 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 patience it's kind of weird I live great for three months it 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 the key is I call it 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 in the air again but you know it can buy do some logistic problems I mean if you've got a trip and you got to get into the my clinic quickly um so a lot of patients do like the injectables because they're autopilot I don't have to deal with it you know and um you know just show people how large attract 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 we we do a technique um so we were taught initially that you should make a w go one two three or a v or V yeah that's what I used to do so but I don't do that so we invented it we started this is 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 it trauma so we would do a stacking technique and it's worked quite well and the pellets stacking vertically or stacking on top of each other on top of each other literally like a column yeah you know and so uh you know works very well these patients patients who do it like it and so they keep coming and they you know so they don't worry about there's a lot of people that travel and they don't want to have the hassle or they're needophobic so they come in and how long is a guy inactive for you after putting pellets in no exercise for 72 hours yep the bandage stays on for 48 hours you can shower with it but no extra so some people say you know I like to work out I now can't work out for 72 hours I got to come see you every three to four months I have pain some discomfort not much but you have some and I say what about the injectable just 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 you know 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 really feel so I I worry about erythrocytosis also so we did a study showing that if you know I think the worst thing you can do is give 200 milligrams I am every two weeks that that doesn't make a lot of sense to me and the drug will last about 10 days so for about four days you're not even having any medication on board but you have a high erythrocytosis rate because it's the spiking that causes that erythrocytosis so if you have a man and you drop the to 50 milligrams twice a week the erythrocytosis 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 yep and it produces a better physiologic level we didn't talk about topical I have never been a fan I've never been a fan of topical for men um I think it's acceptable for women because our options are limited but tell me what your views are on topical yeah so the problem I'm not a favor 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 right so that's poor absorption because there's so many women by the words the formula is milligrams times percent penetrance so and that's variable it's variable and it's even variable day by day on the same person right so if I have again how clean is the skin what part of the skin do you apply it onto has the skin been exfoliated these things yeah so if I'm if a patient I give them a thousand milligrams of testosterone he has zero percent penetrance he gets nothing so I said patients don't get fixated on how many milligrams I'm giving you let's look at the end result what is your level right there's 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 ear it's it's the convenience it's having to do it every day it's the level twice a day right uh 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 yeah right so it's not not and so so there's many reasons why it costs you know so it's because most of these are you have to get with 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 right yeah because they're covering so much of their body surface area I think if a pregnant woman at home if you have a child at home you want to be careful as well then if you have to travel with a TSA so there's a lot of issues with the gels 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 delusions so it's 50 milligrams we go 50 milligrams per ml so and it's 0.1 CC it's usually go 20 per ml yeah angle 0.1 CC's a week yeah it's easy and they find it very effective if okay let's now talk about physiology so how does testosterone work how does DHT work how should we think about testosterone DHT and estrogen and why do they all matter right so we talked about the breakdown testosterone going into estradiolence testosterone going into DHT testosterone has numerous effects on different body parts at different levels right so we know that erectile function typically is around 200 nanogram per deciliters when you start falling below 200 nanogram you start losing nocturnal erections right muscle tends to be higher bone tends to be higher so different body parts I guess call it turn on at different levels right so the issue is that so in other words what's the highest what has the greatest sensitivity to Falling testosterone right so the way to cover yourself is just being the upper quartile that's why if I'm an avocado I know I'm covering everything because everyone's different so but again you're saying when you said 200 nanograms per deciliter that's total how do we determine free right and that's the cutoff that's important everyone's different so you know I have to say this I never understood why we use this number 300. what are you telling me 300 nanograms is the definition for hypogonadism so are you telling me that 290 we must all feel bad and at 310 we must all feel good that is not true right but that's what that's what it's it's it's it's it's come to so the reality is that there are many patients at lower levels that feel good it's based on the sensitivity of the Androgen receptor so when I was a fellow and in my lab very beginning we would take the blood we go back and count the CAG repeats patients who had longer CAG repeats would have more sensitive receptors and why is that insensitive or Subs 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 zitzman in Germany showed that depression can be associated with sensitivity Interceptor sexual function so so sometimes people need more to feel better yep and I think that's a misconception because a lot of times people say well you're in the normal range you're at 400 something else may be going on and invariably if you can raise them to the upper quartile normal cover them you may see symptomatic Improvement do you think we're ever going to get to the point where um trt can be customizable based on a more Broad View where a patient comes to see you and you do an androgen receptor assay on them and you couple that with what their free tea is and make decisions based on that as opposed to just sort of flying a little bit blind and having a guess that would be amazing and that's what we started so we did that in our lab and so I have some of my colleagues say hey can you have this patient I don't understand can you look at the sensitive to anti-receptors my lab is not clear certified so I couldn't give you that give advice I can't get your advice you know so 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 how complicated is the assay it's so easy to run but then the only thing is it does take a little bit of manual labor my technician would have to sit there and he literally gets an Eliza or what's this Eliza tested 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 Kara I have uh CAG repeat of 28 so you know he's he's extra do you not get the impression like LabCorp or somebody like this could generate uh that or even just a proprietary lab could get the CLIA certification and 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 not 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 based on sensitivity yeah right that's fair yeah how dare I assume that people would care about the level of nuance I would right um okay 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 uh presumably the very there's quite a bit of genetic variability there I mean five Alpha reductase activity is really quite genetic sure um and what is the purpose of DHT so DHT is the most potent Androgen we have on our body right it has a very 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 now 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 alopecia so so so five Alpha reductase is located all over the body there's type one there's type two so type one can be in the scalp it can be in the brain uh it can be in the prostate it can be in the adrenals it can be in the kidney they're all over the body right um the finasteride is predominantly type two detast type 1 and type 2. we may talk about that but it's important to realize that these enzymes are throughout the body have multiple functions throughout the body and go over that type 1 type 2 again so finasteride yes is was was that the first drug used yes so to treat BPH so yeah finasteride came out in 1992 as proscars five milligrams of finasteride you got it to treat BPA yes then in 1997 the one milligram dose came out as Propecia uh and then later on I believe 2012 was dutasteride and when you look at the graph and dutasteride was brought out to treatment it was for BPH BPH okay so so the the when you look at five Alpha reductase activity there's type 1 and type two two ISO enzymes right and uh if you look at where they are type 1 and 2 is in the scalp they can be type 2 is predominantly more in the prostate but also is type one they're in the adrenal glands they're in the the brain as well they can they're also located in the uh epididymis they're different 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 now about an hour ago you said you do not like to use five Alpha reductions Inhibitors in your practice at all I don't so that means if a guy comes in with BPH you would and you want to treat him medically not surgically what would you use as first line uh Alpha blocker or daily cios yep that's it and you're seeing as good a response with daily Cialis as you would see with dutasteride or proscar I'm seeing a a much better response with an alpha blocker and then I would then use the alpha Blocker of choices uh I usually use alfies ocean only because Alfy's ocean has the least rate of retrograde ejaculation you can use tamsulosin or you can use solidocin but alphysosome so for younger men and what's the brand name on that one uh your Oxytrol okay yeah so it tends at the least sweat so for younger men they prefer to have that um so typically that's the medication choice so I I just I I ABS 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 Shafer which has got me and my team trying to get wrap our minds around this thing called post finasteride syndrome um you want to 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 I libido uh psychologic problems depression suicidal ideations and I believe it's a real syndrome I don't believe everyone who takes finasteride gets post-phenasteride syndrome but I do believe that there's a subset of patients who take finasteride who develop this condition now there I'm the minority most people do not and I accept that so the official position of the American Urologic uh what is it AUA yeah Association is what there well if you look at the package there are it states there are patients who have prolonged uh uh treat side effects with destruct it says it it's there but the true definition of a statement post finasteride there's no statement essentially most clinicians don't believe it exists I do believe that there's a subset of patients who take finasteride that have a significant adverse effect and there's a there's a plausible mechanism for that I'll explain what that is but the the key thing is this we were taught in medical school that a finasteride blocks the conversion from testosterone to dihydro testosterone 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 neurosteroid right so DHC goes into Anderson a diode and it's an interest in diol that's the neurosteroid then you multiply that by six so six steroids are blocked and those six steroids then have a decreased conversion into their neurons sorry the six steroids are blocked because five Alpha reductase acts on more than one exact steroid uh progesterone aldosterone uh you can look at there's a whole linear it's not just testosterone so the problem the biggest problem is when you blocked progesterone getting into its neurosteroid called allopregnanolone why is that important because aloe pregnant alone has been implicated for depression anxiety cognition right so some of those neurosteroids are very important when it comes to depression anxiety depression and cognition right so much so that there has been an ink increase in suicide rates in men who've had this post-financial syndrome if you had to guess yes 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 fought less than five percent I think it's more than five percent 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 right they say oh I'm supposed to get Ed but a 30 year old knows this is not normal this isn't the 20 year old knows this is not normal but but the key is this let's say you do or do not believe in post finasteride I believe and 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 this is in all men who take finasteride or just young men certain men who have post finasteride syndrome who take finasteride there so for example I had a study I had 25 men who had post finasteride 25 men who controls in my 20 the controls are men who took finasteride but had no symptoms who never took a finasteride 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 I was looking at genes upregulation downward external genes between the two populations just normal controls and a finasteride but um two patients out of my 25 committed suicide in my trial okay and so to me 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 and again I'm that there's another issue going on right that whatever it is that's driving someone with alopecia to take finasteride for hair loss speaks to a difference in you know 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 the negative symptoms I think that would be very important I agree or do a randomization I agree yeah but but in in either case you know it has to bring some potentially yeah eight percent suicide is a alarming rate and I I'm sorry for what period of time uh well it was over a five year period but it was my study was just a point in time they'd come and visit we would do this but after they left we follow up these patients eight percent so how this is I mean if you if I told you anything just to be clear again to push back because this is so important that that we think through this rationally do we know what the history was of mental illness in those patients do they have a history of depression before taking the drug so we we do have history that none we don't have significant mental illness before they come in they weren't on ssris they weren't to have a history of depression when they came in right so that's important to know that you know they weren't diagnosed with depression prior but but any drug if I told you drug X it doesn't matter what you believe the cause is associated with higher suicidal uh rates I would say okay let's take a closer look yeah yeah and see what's happening it doesn't 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 dutasteride so there have been uh dutasteride um patients have taken due tests right had symptoms but it's not as prominent right and I think probably it's because um a you know a lot of the patients who were taking this were taking it for Alopecia so that we're taking finasteride but there have been reports of due to asteroid um uh symptoms the same way right so that's I think that's important so so you know I think more attention has to be given to this condition um 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 Cialis strategy this guy's coming you on that because coming to you on that product for hair loss you'll tell him what I tell both men if they're coming to a BPH or alopecia I tell them that there is a condition that's been associated with this men taking this medication that can cause an impairment uh in sexual function and acting actual depression and anxiety some you know there's so many many countries Canada France UK have put on their package insert Black Box not black box but this warning saying that hey there's an increased risk of suicidal ideation this is not trivial you know yeah yeah well I mean again I think it's very interesting again I mean 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 in part I think that we're looking at a demographic that's more susceptible to Suicide so I 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 yeah that that strikes me as epigenetic right 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 uh but we don't know but that's one of the most common thoughts again it needs to be studied yeah 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 so 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 um I would say we've spent more time on this than than just about anybody perhaps not as much as you um 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 um 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 ascvd 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 let's talk about this is a great topic so so look this 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 Urologic Association in 2018 came out with the testosterone guidelines guideline on that under Section patients should be informed there's no association between testosterone and prostate cancer strong recommendation so finally patients say I Googled it I heard I can get prostate so no the guidelines are very clear based on the evidence no data support it 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 phosphorylated but talk about the difference between men and women and how differently they're treated with respect to hormone therapy and I think a lot of that started with the Whi Whi of course 2003 so you get this big news and everyone's off hormones and later on you get a reevaluation the Whi and say hey maybe we made some mistakes but all that no damage was done right all that noise so we're going to talk about the Traverse trial so I've been one of the involved in this reverse trial the Traverse trial is coming out in June of this year will be coming out the end meeting about cardiovascular but that was very similar the impetus part of the Traverse was hey we have no large trial in men we have a uh you know we have something original we have nothing in men the Traverse 6 000 patients randomized placebo-controlled trial largest of its kind will be coming out pretty soon but I want to finish about the prostate cancer so so so listen so many 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 bats who was the lead on that uh it's Schweitzer and the the senior was denmead and so in 2015 and they 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 right it's to give you Androgen deprivation it's too chemically castrated 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 it's a sensitive right and so and so essentially the PSA went down by 50 and what they saw was a radiographic disease medicine went down by 50 that is unheard of to give that metastatic prostate cancer patient testosterone the same group published numerous really impressive studies but my favorite was the one that came out at 2021 called the Transformer trial this is mind-blowing so they took about 200 patients who had castrate resistant metastatic prostate cancer and and they said okay and if they became resistant to abiodarone the treatment of care is enzolutamide which is an androgen receptor blocker they said instead of giving everyone enzolutamide we're going to give half the men high doses of testosterone okay so let's see what happens so they gave them enzolutamide 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 patient course but it got even more interesting you were allowed to if you took bipolar antigen therapy you're allowed to switch over to angelutamide if you came resistant and vice versa the patients who did bipolar antigen therapy and then did enzolutamide had significantly greater survival 37 months versus 28 months then enzolutamide which is the standard of care the cost of enzolutomide is 8 000 a month the cost of 400 milligrams of testosterone was about 100 a month right and they had significantly greater survivalist 1021 21. so we're three years two years after that yes how many men with metastatic prostate cancer are receiving that care now I I think minuscule why I don't know why that's why I did I don't know why attention was not given more attention was given to the study I mean it was it's called the Transformer trial it was really impressive you know as using a standard to care which is enzolutomide versus bipolar energy therapy and then the angelutamine so I think you're going to see a lot more of therapeutic use of testosterone you know um I I also you're going to see a lot of studies there's been some recent studies suggesting that giving testosterone to men after radical prostatectomy may be potentially protective against biochemical occurrence that was Tom alleren'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 Petri dishes we put Lin cap cells prostate cancer cells and those Petri dishes and we gave each one of those Petri dishes 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 call that the inverted U where maybe castrate may be protective eugenatal protective but hypogonadal is dangerous so then we said okay let's do it in animals 200 mice castrated 50 mice we gave a castration we get 50 controls if we castrate and give low doses of testosterone and then we get castrate and high dose of testosterone these are pellets in the mice we publish 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 increase in prostate cancer growth high dose you get a statistic significant decrease an inverted use so if I have problems high dose Compares how much to the castration essentially it's a eugenatal range essentially Castor if you do so castration behaves almost the same as slightly better but in certain cases in the animal case in the petri dish it was it's better but 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 hypogonal range I think it's a danger zone yeah except I would say having watched Men get castrated yeah chemically it's awful I mean I I generally advise men to undergo surgery whenever possible if surgery is an option if you're that Gleason three plus three or three plus four or whatever and and you know 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 in what I see from men that undergo chemical castration the metabolic syndrome yes and the metabolic derangement that follows yeah from being hypogonatal Beyond hypogonadol they're basically eugenatal um not to mention the complications of bleeding that followed the radiation so um again I'm sure there's you know lots of medical oncologists and radio oncologists that are listening to me now wanting to put arrows into the back of my head yeah but uh 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 right and even if they're still alive their quality of life is so poor sure so that's why I would say like gosh if there's a medical way to do this with high-dose testosterone you know certain you're right there's certain patients do benefit better with radiation just based on Gleason score and but at 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 energy deprivation therapy but we do in my practice treatment after radiation with testosterone is controversial we'll get into this and what dose you're using so typically I will use gel first because I want a short acting so I can stop it if the PSA then we'll move on to an injectable but I treat them just like I normally would treat any other patient I don't whether they had you treat them to a level of total tea or free tea just like I would at someone in the normal therapeutic range but there's no data to support that it causes cancer and what kind of consent form do these men sign to undergo something that is so radical and do you need an IRB for this so if you look most clinicians or urologists it was a recent survey looking at urologists 96 of patients of urologists will treat men after radical prostatectopy with testosterone 86 percent of your own yes after radical after 86 after radiation therapy right now look there has to be some consent here there has to be some form decision making the American Urologic Association made it very clear the risk benefit ratio after prostate cancer surgery radiation is unknown right 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 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 and the higher the testosterone 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 in the underground per deciliter so if you take a guy who's that's pretty low it's pretty low but that's where the satch inflection point was and others have shown the same thing roughly around 250 but we're all different but why is that important because if you have a man who starts out with a testosterone level of 190 and you put them on testosterone his PSA should go up it should go up if he's at 290 and you put him on testosterone it should not go up and if you take the guy from 290 and take him to 3 000 should not go up because it's saturated right so it it plateaus so so that's why if I give someone Lupron that testosterone goes down but the PSA goes down right but if you raise the testosterone 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 Android deprivation therapy the testosterone is 50. and their oncologist spent all this time taking away the testosterone that's right and when you get it from 50 past 250 you're going to see that rise until you hit saturation and so the oncologist says what are you doing patient 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 we just have to have this understanding what about testosterone and breast cancer this is a topic I have become very fascinated with um 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 you know it's it's obvious impact on on women um but while I have you here do you does 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 uh and we can't 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 right because that will give me the same benefit of libido but with using dopamine but you're using it for sexual function sexual function I got it no I meant for um I've been reading a lot of case reports that have suggested that testosterone replacement therapy with aromatase blockade in women with breast cancer is a therapeutic option in other words testosterone is protective yes Against Breast Cancer and I I think the aroma 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 want to prevent testosterone from becoming estradiol sure so the studies I've seen are giving testosterone without the aromatism and letting both go up and showing that it's still protective but I don't have a lot of experience I'm going to hopefully find somebody that can well we've covered a lot here today this is a really interesting topic and uh even though I came into it knowing uh very little I feel like I've learned a lot both in terms of uh the pathology and the and the treatment so Mo I want to thank you very much for this my pleasure uh My Hope of course is that everybody listening to this who's impacted by any anything on the spectrum that we've talked about is at least a little more empowered to to kind of realize that there are people like you out there um and presumably you have a sense of how many doctors in the country would have your degree of certification so the urologists who have then sub-specialized sure so I'm part of an organization called the sexual medicine Society of North America and this is exactly what we do it's a great organization with 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 and it's but in that group there's a lot of apps nurse practitioners so that 1200 encompasses all of us yeah um but all of us have the same passion 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 going to be in Texas so I can only do telemedicine in Texas do Baylor yep and uh what percentage of those 1200 are at Major academic institutions like you are versus in private practice Yeah so I'd say the majority are in academic institutions let's say about the 1200 to 400 or 450 urologists and their majority are in academic institutions got it 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 oh [Music]

Channel: Peter Attia MD

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Id: GNCpG1fkMBA

Length: 162min 2sec (9722 seconds)

Published: Mon Jun 26 2023