When the Penis Changes: The Basics of Peyronie’s Disease

27:50But really the most important thing to me is when do I intervene with something invasive and invasive would be surgery. And the things that I do like is for guys to stabilize to the point where they haven't had much change in agulation for at least a few months. Because if I intervene too soon, I could either over or under correct those guys, right? If there's any chance that they get better. And by the way, you know, just to go back to me saying it never gets better, there is a very small percentage of guys, you know, maybe under 10 % that notice that Peyronie's can get a little bit better without doing anything.

28:25But again, we don't have those observational studies anymore because now we do have early interventions, which we'll get into over this course of this series. And so for somebody to walk into an office, we're Peyronie's and have a physician pat them on the back and say, hey, let's see how this goes in three months. That's not cool. You know, we have too many things we can do, even non-invasive things at all, that we give these guys a fighting chance at getting better before it turns into a three-month, six-month, two-year process before we get them care. those are two years where the guy's going to be psychologically emotionally and physically devastated by this condition and that's what i want to disavow of is that if a guy comes in the acute phase i have treatments available for them that we could start treating them immediately instead of waiting and saying oh let's see if it stabilizes and then we'll go from there we have to stop with that thinking what are some of those uh non-surgical treatments yeah so we're going to have episodes dedicated to this jordan but the way i look at peyronies in general from a treatment standpoint is pills, pokes, and procedures.

29:24And that's kind of a nice way to organize what we do. And the spoiler alert here is that even in 2026, we still have just one FDA-approved therapy for Peyronie's disease. And in full disclosure, the condition is treated with something called Xyaflex or collagenase, which is an enzyme that breaks down the plaques that we're going to talk about. and as in say in full disclosure, I was one of the principal investigators on the trial that brought that to market in 2013. So I have no stock interests in the company, but they do sponsor some fellowship and research for us. So that is my above board disclosure that I do have ties to the company, but none that I directly profit from.

30:11So I can speak marginally unbiased on this as a clinician. But yeah, the other things before we get to Zyaflex, which I'm going to have one of my friends and colleagues talk with me about here in the next few episodes at some point, is that there are medications that we think have properties that can help treat Peyronie's. And so the classic therapy is something we call antifibrotic therapy or triple therapy because there are three different things we try. And we use them in combination because they work differently. And again, none of these is FDA approved for Peyronie's. They're FDA approved drugs that we use for other things.

30:47One will be very familiar to the audience. It's something we call Tadalafil, which is a generic name of Cialis, or Sildenafil, which is Viagra. They work very similarly. And those are medicines we typically give to guys to improve their erectile function, sometimes their cardiovascular health for men and women both that have hypertension or high blood pressure within their pulmonary artery system. And the reason I mention that condition is that we know that these are not just boner pills. They're not just for giving us better erections, but they have multiple different channels that they can improve.

31:22And in the realm of Peyronie's, we know that they can decrease the amount of fibrosis or scar tissue that your body puts down. So if you see a guy and he develops Peyronie's and you don't want to treat him, even if you're a primary physician listening or a urologist doesn't treat Peyronie's, I would try them as you get them into my office or get a referral to your local Peyronie's expert to put them on a daily low dose of Tadalafil because it does have both in vitro and in vivo, meaning in the body itself, but also in lab tissue cultures, it can decrease the amount of scar tissue that forms. And so the idea is maybe we can intervene before this plaque becomes so dense that the only way we can get rid of it is either with an injection like collagenase or a surgery where I have to actually go in and either excise the plaque or counterbalance the plaque through surgery.

32:14we're going to have a whole episode on surgeries as well. So stay tuned for that. But Cialis is kind of, or to doubt, it was sort of the anchor of this antifibrotic therapy. The other two, one is actually an amino acid or a supplement called L-citrulline, which is a nitric oxide donor. It helps improve the amount of nitric oxide in a system. And we know the nitric oxide is important for dilation or opening up of blood vessels and relaxing a smooth muscle, both in the penis and everywhere. And so anybody that is a gym goer that enjoys pre-workouts, one of the big ingredients in pre-workouts is either something called L-arginine or L-citrulline.

32:53They both essentially get converted to nitric oxide through either the liver or the kidney. But we also use it in peronies and in erectile dysfunction as a supplement that may have some evidence. And then finally, something called pentoxaphylene, which has been around for 50, 60 years. and that is another medicine that has a nonspecific pathway just like tadalafil where it can help improve blood flow to the penis and decrease scar tissue as well by inhibiting one of the inflammatory cytokine pathways and that is a big fancy word for essentially when a body feels that it needs to generate either an immune or an inflammatory response like you get kicked in the shin, you get redness, you get bruising.

33:37those are all inflammatory cytokines that run to the area to help increase wound healing. So pentoxifiline or Trento is its old brand name. It inhibits something called TGF beta, which is one of those inflammatory cytokines that leads to deposition of scar tissue. So it's a very, very indirect way that we think can decrease the amount of scar tissue that forms. So we only use that in guys that haven't had Peyronie's for a very long time, what used to be called the acute phase and even probably will always be called the acute phase. But as I said, I really don't like to use that term. But yeah, so those three things together, the literature is pretty sparse on a couple of randomized placebo-controlled trials that go back to about 2006 and prior that show maybe a 30 % chance that guys will get an improvement in their curvature if we do that within about the first six months of onset of conditions.

34:28So we'll talk about that with our other guests at some point to see what they do for it. Because again, non-FDA approved. So nothing on the label that says that those things treat Peyronie's, but we've cobbled together this little packet of pretty safe medications that may have some efficacy. One of the other things that we'll talk about a lot is penile traction or penile modeling. Because we do know that if you break your hand, then you get put into a cast or a splint. to break your arm, you get put into a cast. And so if you break the penis, and part of the reason that it doesn't work so well as an orthopedic injury is because again, as I said, this isn't really a fracture of the penis, it's more of a deposition of scar tissue.

35:10But what if we try to, if you're bent to the right, put on a device or something that can help redirect the penis to its more straight orientation that you remember before you develop scar tissue, that's called penile traction. There are multiple different brands out there that can do that. Some of them can actually work as a fulcrum or a lever to help re-bend the penis at the point of curvature so that if you bend 45 degrees to the right, then you bend the device 45 degrees to the left. So you're providing a counter traction and it kind of makes sense. And there's some data, especially if you combine that with a more aggressive approach, like some kind of therapy that we inject directly into the penis, either Zyflex or some of the non FDA approved injection therapies that we'll also cover at some point.

35:54But yeah, I mean, it kind of works. And it's something to do. One of the things that that we do think happens with traction is that you may be able to restore some length loss. And so even if a guy doesn't get much curvature improvement, maybe we'll restore a little bit of length loss. So, so again, something that we're going to unpack in in future episodes. But right, definitely some therapies we can do before we start getting too aggressive.

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39:45I'm sure you've been seeing people for, you know, you said this is the most common thing that you treat in your clinic. What's the biggest misconception you hear from patients in your practice? Yeah, one, that it's their fault that they did something to their penis. And so again, you know, we have to unpack the shame and say you didn't do anything. Even if you did do something, you know you you probably are well within your realm of what most guys can get away with their penis and so that is something that you have to walk out of my office and think okay you know i didn't do anything wrong my partner didn't do anything wrong you know if you want to talk about uh referred guilt it's when a guy comes in with a partner or sometimes the relationship doesn't survive the injury where where a person says that another person caused this to happen i've seen guys that have had had been sexually assaulted you know forcibly by by a sexual partner that did something essentially either a forcible bend during intercourse that set up this cascade of of inflammatory tissue that's a whole nother thing or if a couple is still together after the partner may have caused the injury that is another unpacking of guilt where you know they probably didn't do anything wrong unless they truly truly wanted to instill harm on on that partner, which I sadly have seen a couple of times, but really just a couple in the tens of thousands of guys I've taken care of.

41:06But yeah, you didn't do anything wrong. You know, it just happens and there is a genetic basis for this. And we do see it. And it's not, I should also say, the other major thing that we should dispel is that this is a condition, they call this in Scandinavia, the Vikings disease. And we thought that it had a much higher prevalence in men of northern European descent. And there is a little bit of a genetic signal for that. But I see men literally from all over the world, either living all over the world that come to see me for their condition, or that their ethnic origins are global. In fact, some of the things that I would love to disavow is that this is a disease that strictly strikes northern Europeans.

41:48Because if anybody is listening, that is not of that origin, and they think, well, I've got this bend to my penis. But they, you know, I've heard this is always something that normally affects white guys it doesn't it can affect anybody so that's the other thing is that you know if you are a person that has a penis you can get this i can this is one of the diseases without tmi-ing my guys and say look i can wake up tomorrow and have this condition there's you know i know i know how to prevent erectile dysfunction i eat right i sleep i exercise you do all the things that mills tells me to do because i listen to his podcast i read his book and i'm like i'm not going to get erectile dysfunction until you know i cannot keep up anymore with the cruel hands of age, but Peyronie's does not have that every day I wake up.

42:29And I think this could be the day that I developed this. And so you can't live in fear of it. If you're sitting there listening to this show and think, well, man, I'm really glad I don't have that. But boy, you know, do I have to be careful of something? You really don't, you know, but the point is, is that this can happen to anybody. There is really not a lot of predispositions. And I, you know, the goal of this whole podcast is to spread joy and joy and love and peace and love, peace and love. And not a, I know Ringo. Yeah. So if we all listen to him a little more, but, but really the goal is, is to just, you know, not worry about developing these things.

43:06But if you do, then we got treatments for it too. That's the other myth is that, Hey, you really, you know, this is something that just happens. You can't do much about it. I cannot believe in 2026, I still get guys that come into my office that really had to go past what their local doc told them to either get on the internet or just seek out Peroni's experts and end up in my office with the misconception that there's really nothing we can do to get this better. It still happens today. It has been now 13 years since the FDA approved collagenase for the penis or Xiaflex. 13 years and so this is not a cutting-edge novel novel therapy by any means it's something that that again we're going to dedicate an episode to but it is something that still that the majority of urologists actually don't use this medication for reasons that we'll unpack later but there are plenty of guys that are very well trained in fact you know two every year i train two urologic surgeons in how to administer that drug in a safe and effective way so there are lots of guys out there that have excellent training in this.

44:12And so, right, don't go in, if you are listening and you think, geez, I do have this lump on my penis I didn't have before. I had this curvature, I don't know what to do about it. And you're listening to the show, then don't give up. You know, don't give up and think there's nothing I can do about it because we have all kinds of treatments. We have pure fellowships now for the last many years that have been dedicated to training surgeons and providers how to treat guys that have this. So yeah, that's a huge misconception. There's so many things we can do for these guys. It sounds like you've taken care of our you're probably gonna be okay segment for this episode.

44:46Yeah, you know, that is true. And I do think that that's very helpful is that the other thing I will talk about is that the mental health component of this, because we really hit this hard on the show, is so important. I collaborated with some colleagues from Karolinska Institute in Sweden. Sweden and Scandinavia in general has amazing patient databases because it is a system that has universal health care. And people, it turns out they really enjoy living in Scandinavia, so they don't move that much. They're not that transient of a society. And so they can have amazing longitudinal records because they have many touch points over the patient's life from when they were born to when they die.

45:29And so we had a database of over 9 ,000 men that we looked at with Peyronie's. And this was published, I want to say about 2022 or so in the Journal of Urology. So one of our premier journals that looked at the mental health aspect of men that had Peyronie's disease when they had this painful or painless curvature deformity to the penis. And the number of guys that had mental health issues as really, whether as a result of the Peyronie's or whether it was just an association, we weren't really powered to look at. But essentially the association is about a three to one fold history of guys that have had touch points with mental health providers.

46:06There's a huge increase in guys that are on antidepressant medications that have Peyronie's disease. And really tragically, and this is something that I hear, Jordan, not frequently, but it happens, is guys with suicidality that have considered ending their life because of this condition. And so one of the things I love, as you know, being funny and humorous and light, but this is where I'm not going to do it because I've had men that have come into me where their urologists have made fun of it and said, ah, you know, it's, it's just a bend to the penis. It's funny. You got a banana between your legs, not the right thing to say.

46:39And there are lots of things to have fun and make light of, but, you know, I would challenge any guy out there that if one day you woke up and you had a bend to your penis and it wasn't a penis that you knew, uh, that, that would be anything that would be funny about it. And it has, you know, it's, it's been on, it's been on Saturday Night Live. It's been lampooned that this condition. And so, so can you find humor in it? Sure. And, and I'm hoping we'll, we'll bring a guest on at some point that can, that has had this condition that maybe can, can look at this with a humorous light. But as a provider, you know, for me to discount, this is like, Hey, at least you're not going to die from this.

47:15Not cool at all. And there are guys that come in and feel a lump in their penis. And that's the first thing they think is that, Oh my God, I have cancer. And I will tell you in the years and decades I've been practicing, I've never misdiagnosed cancer for Peronis disease or Peronis disease for cancer. They're very, very different manifestations. They don't look alike, they don't feel alike. And so again, get evaluated, but most likely you don't have cancer and it just doesn't present that way in the penis. But yeah, I mean, the things that have really changed in terms of how guys present is wonderfully and delightfully they're presenting much earlier than they were before.

47:54So we had another, and maybe we'll bring this up with one of our guests as well. But when we were looking at the original trials for Peyronie's disease, which, gosh, those clinical trials dated back to, I want to say around 2006, 2007. And we published a subset analysis, meaning we looked at a lot of different ways. We looked at the data and how guys presented. and in the clinical trials that brought Ziaflex to market, we excluded men that had not had Peyronie's disease for greater than a year. And the reason for that was not scientific in terms of thinking that it would be less efficacious, but unfortunately, insurance companies have weaponized us on that and said, look, it's not studied in guys under a year.

48:36So that's why they make people wait. Thankfully, with a lot of advocacy and a lot of pushback, I haven't really had that problem for a number of years now, but it's still something that I hear frequently. But what we found is that the average age of presentation for Peyronie's in the old days was guys could have it four or five years before they really sought any kind of definitive therapy. And what we also found, which is kind of good for you're probably going to be okay, is that if you are listening to this and you've noticed this curvature for a while and you haven't found the right physician or urologist to treat this, that your treatment course is going to be just as effective.

49:14And we found that even if a guy had Peyronie's plaque for a year or even 10 years, that if we initiated therapy with intralesional injections, in this case, Zyflex, that the outcomes were about the same. Guys still can benefit from therapy even a year out. But I'm not seeing guys that have had this now for 10 years anymore. In fact, I've had guys that immediately they see it, they get on the Internet, they find out, they define what it is, and they come see a provider within days to weeks to months. and so again those are the guys that that what we know is and we have a couple of nice papers out in the literature recently that treating guys in the acute phase but again i hate to use that term but guys that have had this for less than six months they do just as well as guys that have had it for you know for years and so why make a guy suffer and wait you know for some magic time to kick in before you can start actually treating them for their condition so another thing we have to break down is that acute versus chronic phase should not affect a treatment course if you think a man's a candidate for intralesional therapy the only thing i would say is that if you're a patient listening and you see somebody and you have this acute phase where you've had it for three months six months and they want to operate on you i would that's where i would slow the roll a bit because i don't typically and it's not a set in stone again we'll talk to some of our our other providers will get on the show.

50:35But for me, I want things to be really stable for at least six months, maybe even a year. And again, because we have things we can do before that time, like Zyaflex, then we can see potentially an improvement that we can either decrease the amount of surgery we have to do in a guy or obviate the need for surgery in general. We looked at our data not too long ago and found that about 80 % of guys will get a durational good response to intralesional therapy or the injection therapy. with Zyflex and only about 7 % of my men that had gone through a course of Zyflex end up actually needing surgery.

51:11And so that's a pretty good number. It means you have a 93 % chance of finding a non-surgical solution to this condition. So those are the kind of numbers that we want to keep posting. And as we get more and more familiar with this compound and we change and refine our techniques a little bit more, as well as adding on additional therapies potentially, one of the things that we know that Peronis is associated with, for example, is hypogonadism or low testosterone, which we have talked a lot about on this show, but that's also optimizing testosterone levels, optimizing blood flow. And however we do that to the penis through diet, exercise, and stress reduction, all those things, they all help, you know.

51:50And so again, we have to treat this condition holistically. We have to treat it not just as I have a chunk of scar and my penis and I need a surgical solution. But no, if we treat a guy holistically, we treat their mental health, we treat their hormonal health and we treat their physical health or the plaque directly, that's the winning combination. So there's really got to find a provider that can do all of that for you. Well said. I mean, I know one of the questions I had my final question for you was what's changed most in Peroni's treatment during your career? It sounds like you've been actively involved in a lot of those changes from both how it's treated holistically and also the medications that are used, the injections that are used to help the non-surgical options.

52:32So that's incredible. Yeah, I mean, I will say, so I started practice, my fellowship ended mid-2008 and then Zyaflex was FDA approved in 2013 and I was involved in the clinical trials throughout. So I had a few years where we didn't have Zyaflex except for on an experimental basis. and I will say something kind of surprising that comes up. In fact, it just came up at a national meeting in D.C. a couple weeks ago is that my surgical practice has exploded at the advent of Zyaflex and there's this thing in medicine when a new drug comes out called, there's two things, one is good and one is bad and the good thing is called disease state awareness or DSA and pharmaceutical execs like to talk about DSA where you have something that maybe not so many people knew about because Peyronie's is an amazing case study, you know, for an MBA in disease state awareness.

53:33If you look at old textbooks that the overall incidence of guys walking down the street that have Peyronie's is about 0.9 % up to 3%. That goes back to fallopius and looking at cadavers and saying, hey, here's a scar tissue in the penis. and I found this, you know, in one out of a hundred cadavers, then that's the incidence of pronies, 1%. Well, now that we've had a disease state awareness, because we have a drug, that incidence is pretty practically, and I think realistically gone up to about 10%. So 10 % of guys walking down the street have this condition. So we used to call this an orphan condition.

54:10It's not an orphan disease. It has lots and lots of guys. And I always tell people, you know, when they come in and they're waiting to see me in that in that waiting room there's you know i practice male fertility i practice sexual dysfunction of all kinds and hormone management but really almost 40 of my practice is devoted to peyroni's disease and 100 of my practice is devoted to men's health and so there's a really good chance that you're going to be in a waiting room with somebody else that has that condition as you're waiting to see me so my peyroni's career has exploded uh for sure over that time.

54:43But the surgeries I'm doing, because I'm seeing so many more guys that have this, and because Zyoflex is not a miracle drug, and despite what, you know, we would want people to say, and again, I'm not a speaker for the company that produces Zyoflex, so I can say this, and in fact, I said that in the New York Times, maybe 10 years ago, when it was first coming out, and I said, this is incredible drug, because we had nothing before, now we have an FDA-approved therapy. But again, not everybody, 20 % of guys or so don't get a satisfactory response to Zyaflex and a percentage of those guys are going to want to operate.

55:19And if I see conservatively, you know, tens of thousands of patients in my clinic sees thousands of guys a year on a new patient basis, we probably see four to 5 ,000 men a year. And if 40 % of those have peronies and 80 % of those guys get a good response to Zyaflex, if I think they're a candidate, then that still leaves me in the OR quite a bit. And so I'm still once or twice a week operating on men for Peyronie's disease. And so now you have a medical condition that has a surgical solution that we're really gonna get into in future episodes. And I think that's really important to know. And so you're right.

55:52I love that you're probably gonna be okay because my goal is to say, look, we're gonna find a solution. I don't know how yet. I don't know if it's gonna be, it'll get better on its own, but I can almost guarantee that's not it. But we'll start you on some medications. We'll optimize your hormones. we'll get you on a good nutritional regimen you know make sure you're eating well exercising doing all the things to make you live a long and healthy life and potentially help improve your peronies and then we'll start talking about medications and then we'll we'll eventually have the discussion about surgery but yeah we're gonna we're gonna figure out how to get some degree of functionality back the other misconception though that i think is really important is setting and i'd have this discussion always when i'm when i'm talking or training younger physicians is that you do have to set the expectation that there's a good chance that that man will not get the penis he had back before this condition.

56:40You know, you'll get some degree of functionality. The best case scenario is that you will correct the curvature. You may regain some length, if not all length, but that you have to accept the fact that you had an injury, you had a disease state that led to a permanent change in your penile architecture, but we're going to make it better. you know we're going to figure out a way to get to the point where you're functional again and i think that that may be the most important thing to walk away from this podcast is that you're going to be okay don't know how yet don't know when you're going to be okay but you may not be who you were before you're going to have to learn to adapt a bit and have that conversation well to be continued i know we have uh some folks coming on some fellow uh folks in the field and some people who have dealt with this with bravery and humor.

57:28And yeah, I'm really excited to dive into this. I have to say, I was one of those people who was really not familiar with this before I started speaking with you about it. And it's really shocking to me to hear that, you know, as many as 10 % of men are dealing with this. And so it's good to get the word out there. Yeah, no, I mean, I was, I think in medical school, I had exactly zero lectures on this. And so this is not something that medical students probably are really exposed to unless they're going to a center of excellence or a medical school that has providers that spend a lot of time treating this.

58:02And, you know, thankfully, UCLA, I have a lot of medical students either in my research group or come through my office. And so we are getting the word out. And I think it is becoming even those students that don't go into urology but go into a field that where they are taking care of men in some fashion, they at least have a bit of that disease state awareness. Oh, yeah. I just have foreclosure. The other thing is that we don't like is a term disease mongering, where you're trying to muster up a disease that a guy may not have. Peronis, you can't fake it. You just can't fake it. And so when people are surprised at just, you know, the amount of guys out there with Peronis disease, nothing has changed.

58:40There's nothing in the water. It's just the fact that it's way more common than we think. and nobody wants to come in and say, hey, give me that drug for Peyronie's because nobody wants this condition. And so I think that's the other thing about this is that it is very, very distinct and it is a very real condition that has very real therapies. But yeah, just because you see the ads on TV, the only people that ever respond to those, the guys are like, oh man, I had no idea that this is something that I had or that I had a treatment for. I just kind of figured it was a normal part of getting older.

59:16And so that's where I think disease state awareness is great. It allows guys a little bit of a vehicle and a mechanism to reach out and find somebody that can take care of you. And so there are good finders online, Peronis disease finders, where you can find providers that specialize in this. A plug for one of the groups I'm a part of, the Sexual Medicine Society of North America or the International Society of Sexual Medicine, ISSM. both have great websites where you can get good patient information on and also often find providers that specialize in this and so so those are good resources very well vetted that patients can reach out to for uh for information in addition to the mailroom with dr jesse mills which i hope also will be a good source of information for guys dealing with this the mailroom pod at gmail.com bam there it is so yeah let's uh you know let's call it a wrap for today and then say TBC and have guys come back and figure out, you know, how I engage my friends in treating this condition and spreading the word.

1:00:21Let's bring it on, my friend. Thank you for all you do. Dude, thanks for calling me the Jimmy Page of Peyronie's disease. I don't think I don't know how I'm ever going to live up to that, but I can die a happy man now. Put that on your website. Put that on your business card. Boom. There you go. vetted by by uh rolling stone correspondent jordan rumpel i'll take it all right man hey dude have uh we didn't get to catch up but uh hope things are going well for you and uh and i'll see you next time i'll bring a buddy of mine and uh we'll we'll uh we'll hash this out some more heck yeah looking forward to it sir all right bro be good see you next time

1:01:02Let's talk about it.

1:01:25The Mail Room with Dr. Jesse Mills was a production of iHeartRadio. It was executive produced by Jordan Runtog. It was edited, mixed, and mastered by Bahid Frazier. And the theme was provided by Long Transit. If you liked what you heard, please subscribe and leave a review. For more podcasts from iHeartRadio, check out the iHeartRadio app, Apple Podcasts, or wherever you listen to your favorite shows. This program is intended for educational and informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Consult your health care provider for any medical or other related questions or concerns.

1:02:05The views and discussions aired on this podcast are those of Dr. Mills and do not represent the official positions of UCLA or UCLA Health.

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