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 sep3 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 but 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 their action 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 we're going to talk it's a separate problem yeah yes that's right 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 mnemonica 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 if 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 in these patients It's very effective I think there's a 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 young patients is we will get a give them daily so when they take daily Cialis what they'll notice is that their 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 their 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 the 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 and 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 and 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 vanophil 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 that's the secret as opposed to the place yeah 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 flibe answering that was used as a medication for depression 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 were 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 mess side in North America game changer uh in the way we treat men 3D 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 that 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 phosphodis inhibitor which now we're into our third generation of them um basically solve the physiologic problem right so what is it the root of that problem I mean I understand that by inhibiting phosphod or esterase 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 or 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 pin press put pressure you'll notice that you'll get better and better erection because you're blocking the outflow 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 disappointing yeah it's circumvential but it's but but if you put your hand there and it gives you almost a 180 uh so then so circumferential but so it's not like the fingers where at about five and seven no it's all in 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 say it's fine just increase the inflow that's why we use intracavernosa 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 sick because it's 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 through 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 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 and so if you take five milligrams every day it's like having almost like eight milligrams in your system 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 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 man 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 uh 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 the FDA approved for pulmonary hypertension so absolutely 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 hypertension 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 fifteen or twenty dollars 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 five milligrams which was unbelievable so then we started going to the compounding pharmacies I said okay the compounding pharmacy 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 may 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 that 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 like 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 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 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 I would 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 a 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 lifestyle modification lifestyle modification has a huge impact on the quality of the man's reactions 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 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 it 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 arteries are 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 coordinate before the peripheral so that was the theory now it doesn't work very well because most of Ed is vino 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 exercise you lost weight it was a Mediterranean diet by the way I loved I really believe in mentoring diet if you lost weight and took the Mediterranean diet you saw three point which was significant increase on the iife 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 clinic clinical meaningful improvements 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 DD you want to see at least two moderate D5 and severe ed7 so it depends where they started see the way they started right but typically you want to see about a four but even just a three just on diet and exercise 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 our 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 physiological 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 people 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 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 Peaks a lot systolic velocity is less than 30 particularly if it's less than 25 milliliters per second he has arterial insufficiency that's important it 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 and itself it's filling and so you're measuring kind of backflow through the venous system right and that venous leak is important because remember that's the number one cause that's the problem the majority of the patients who have either will start out with venous leak so but then there's nothing just to be clear the venous leak is usually happening before you see arterial insufficiency in most cases foreign [Music]