TODAY'S GUEST: Dr. Johanna Hannan, sexuality researcher

I'm extremely happy to welcome Dr. Johanna Hannan to Hard Conversations!

Dr. Johanna Hannan is an assistant professor at East Carolina University Department of Physiology, Brody School of Medicine. She did her post-doctoral fellowship at The James Buchanan Brady Urological Institute and Department of Urology, Post-Doctoral fellowship with the Department of Physiology at Georgia Regents University, and earned a Doctor of Philosophy in Pharmacology and Toxicology from Queen’s University in Kingston, ON, Canada.

Dr. Hassan is currently apart of a research group at East Carolina University, studying the pathophysiological mechanisms of genitourinary dysfunction in men and women to help discover new therapeutic strategies to treat and prevent sexual and urinary dysfunction. Her work with PDE5 inhibitors (like Viagra or Cialis) exposes that they do not cure the underlying disease and treatments for female sexual dysfunction are lacking.

Dr. Hannan has also studied the vasculature supplying the genital organs, its pathological vascular remodeling, fibrosis and endothelial dysfunction, and has characterized the unique properties of this vascular bed in models of aging, cardiovascular disease, diabetes, obesity and radiation to find treatments that can improve both sexual dysfunction and cardiovascular disease. Her work is also interested in the role of neuronal dysfunction and degeneration of the pelvic ganglia and cavernous/pelvic nerves in neuropraxia, diabetic neuropathy and aging related to pelvic organ dysfunction.

• WEBSITE:

  https://physiology.ecu.edu/research/johanna-hannan/

• TWITTER:

• https://www.twitter.com/hannan_lab

YOU'LL LEARN

• How laboratory erectile dysfunction research is done

• What comes up during erectile dysfunction

• How studying rats helps us understand blood flow and erectile dysfunction

• How Viagra works

• The role of pudendal arteries in sexual functioning

• What scientists actually do when studying penises

• The role of nerves in sexual functioning

• How nerve injuries occur in a laboratory (poor mice!)

• How studying rat diets and exercise helps us understand erectile functioning

• We also learn about penis functioning from studies with rabbits and mice

• “Normal” testosterone levels

• And more!

THANK YOU FOR LISTENING to my male sexuality and sex therapy podcast!

To get more hard conversations sent directly to your device as episodes become available, you can subscribe on iTunes or Stitcher!

Also, reviews on iTunes are extremely helpful and greatly appreciated! I read each and every one of them, and feel free to share your URL there so I can contact you later on and say thanks!

And lastly, if you have any questions (or would like answers to previously submitted voicemail questions!), head on over to Tim’s website.

About the Show

Introducing Hard Conversations, a podcast about male sexuality, and all things erectile, from the latest natural erectile dysfunction treatment to the best ed medical treatment. Therapist Tim Norton expands the conversation about male sexuality, adds context to why we struggle as a society to have hard conversations and breaks down how in a sex-positive environment there really is no room for taboos, judgment, or shame when it comes to penises.

YOUR online sex therapy and couple’s therapy HOST:

Tim Norton is a sex positive sex therapist working in private practice. He offers online therapy, online sex therapy, online sex coaching, and therapy and coaching for somatic symptom disorder.

Tim obtained his bachelor’s and master’s degrees from the University of Southern California. Tim is a proud member of American Association of Sex Counselors, Educators, and Therapists (AASECT), the Los Angeles Sexological Association, and works part-time with the Pain Psychology Center in Beverly Hills.

Hard Conversations Podcast Transcript

Tim: Hello, and welcome to hard conversations. My next guest is Johanna Hannan, an assistant professor at the Brody school of medicine at East Carolina university. She did her postdoctoral fellowship at the James Buchanan Brady neurological Institute and department of urology. And studied medicine at Johns Hopkins.

Her research focuses on the internal pudendal arteries. Those are the arteries that supply our genitals and their impact on aging, cardiovascular disease, diabetes, and obesity. She and her fellow researchers are searching for treatments that will [00:01:00] improve both sexual dysfunction and lower rates of cardiovascular disease.

She's received multiple honors and awards for her research and urology and sexual medicine. And I'm interviewing her today at East Carolina university. Hi Joanna. Hi Tim. Hi. Was, did, did that intro and capsulate? Yes. 

Dr. Johanna Hannan: Yeah, so we do both,  vascular dysfunction and renal dysfunction. 

Tim: Okay. Okay. And we're, we're going to get into that.

So what,  what got you into this? You're a lot of your, a lot of your research ends up covering erectile issues. 

Dr. Johanna Hannan: So when I was an undergraduate student at Queens university, I, we did research projects in our senior year and I was looking for a project and I got involved with a researcher who I. Who mainly did cardiovascular research.

And,  I thought I'd be getting involved in one of those projects. And when I came to the lab to start [00:02:00] learning techniques, I found out I was going to be doing behavioral responses and rats and counting erections. And it did involve cardiovascular disease, but it just wasn't the type of study I was looking for or thought I'd be involved in initially.

But it was,  the first paper that I published and he was a big part of the reason why I ended up doing research, but we pretensive animals and the impact of different antihypertensives to remodel the vasculature and not only lower blood pressure, but also improve rectal function. 

Tim: Okay. So that was the first time that that happened.

And it sounds like you liked it. 

Dr. Johanna Hannan: I liked it. I was hooked. It was, to me, it was a very interesting field to get involved in because we can apply a lot of the things that people were studying in cardiovascular disease. To a widely understudied problem, like [00:03:00] erectile dysfunction, so that in urology,  there's fewer researchers, there's less competition.

And so you can really make big contributions to the field. I think.

Tim: Why is that? 

Dr. Johanna Hannan:  I think there's fewer basic scientists who are purely PhDs that are researching it and I'm not sure. Y exactly.  I think since there's been a boom in basic science research since Viagara yeah. And overall everybody's more comfortable talking about erectile dysfunction. There was more research funding available for it.

 but still primarily the, a lot of the research is being done by primarily urologists to dabble more so in the basic science. And so,  I really enjoy this field because I feel like I can really [00:04:00] dive in deep and contribute. 

Tim: Okay. Now, My next question. I feel like I knew the answer to at when I took my high school biology final, but why, how can we study rats and learn about human erections or human cardiovascular systems?

Dr. Johanna Hannan: Well, there's. Benefits and disadvantages to working with Rodin models. So there's always pros and cons. We find it beneficial to work with rats because when we're looking at erectile dysfunction, they do have very similar anatomy when it comes to the vascular supply and the neuronal supply. It's very similar to humans.

 the nice thing about rats is that they're fairly inexpensive to work with.  they are. There's a variety of different disease States. [00:05:00] Again, some of them actually will mimic human conditions. So we try and take what we can from the rat and then try and make it relevant to what's happening clinically and what we see clinically.

Tim: Okay. So how is their vascular system similar to humans? 

Dr. Johanna Hannan: So when we're talking about the internal pudendal artery, which you referenced earlier,  it has the same branching and,  it takes the same pathway as it does in the human. And so we've actually done some studies where we've characterized this vasculature in rats and then compared it to human cadavers.

And we see similar paths vagical remodeling in these vessels in both. Clinical situation and in the animals as they age. 

Tim: Okay. That is really fascinating. Isn't it? Okay. Cause, and you would have to study a cadaver to do that. So have you gotten to [00:06:00] study human cadavers or was that already done? And you can just read the study.

Dr. Johanna Hannan: So we, when I was at Hopkins, during my postdoc, we collaborated with,  West Virginia university medical school and they had some students over the summer who were prospecting cadavers and they would send us,  coronary arteries and pudendal arteries. What does 

Tim: prospecting mean? 

Dr. Johanna Hannan:  it's a fancy word for dissecting cadavers 

Tim: damn hazy Prosek thing.

Okay. So you were 

Dr. Johanna Hannan: pro sexy for medical students who were dissecting cadavers and removing coronary arteries and internal pudendal arteries. And they would ship them to us so that we could look at the histology and the vascular remodeling in these 

Tim: vessels. Okay, fascinating. And you're sitting there looking at them under microscopes and saying, wow, these are just like rat arterial systems.

Dr. Johanna Hannan: Right? So the big thing that we believe is important [00:07:00] with this vascular bed, a lot of people focus their research on the penile tissue itself, which of course is very important for erectile function. But we believe that if you can't get blood into the penis, The function of the P and L tissue becomes a little bit less critical.

 if we can't deliver blood and so. What we found is that these vessels are actually quite susceptible to vascular damage. And we'll often find damage to these vessels prior to other vessels in the body. Such as we've looked at aorta, we've looked at renal arteries, we've looked at mesenteric arteries, and these are in different disease States like hypertension, or, and we believe that the.

The Pew dental artery, because the only time it really sees high changes in blood flow is during an erectile response, but it can be susceptible to damage. And that's where you'll see [00:08:00] cases where. And prior to cardiovascular disease, and we believe it's comes down to these, this vasculature, that seems to be more sensitive to damage.

Tim: How many of them, those, how many rat penises do you see in a week? Is it, or is it just like during the. Portion of the study where that's that's happening. It 

Dr. Johanna Hannan: depends. It depends. Cause sometimes the castration studies we're doing now, they go on for they're castrated for over eight weeks. So at the end, when we're doing a whole bunch of experiments is when we will well, and luckily now I have students that do this for me.

So. But yeah, towards the end, we'll have some crazy days. Cause we'll do we also measure sexual function in vivo in the animals. So we'll do a surgery that we stimulate the cavernous nerve and measure the pressure in the penis. And so then we'll when we're done that surgery, it's a terminal surgery. Then we take everything out and [00:09:00] then it's an eight to 10 hour experiment afterwards where we put everything into tissue baths and run all the curves.

So. Tends to be a long day. That's a long day, 

Tim: right? That's a 

Dr. Johanna Hannan: lot of fun. I,  we don't have a urology,  department here at the medical school. So any of the students that want to go into urology usually come to see me to try and get on some papers and things like that. So it's fun working with them.

That's really 

Tim: cool. Interesting. So, There was a, I had a urology just on recently and he did explain that system of,  of tissue in the penis and gorging with blood. And can you distinguish the difference between in case everybody hasn't listened to every single episode?  what, what that process is?

Cause I think maybe the, the layman just thinks, well, [00:10:00] there's arteries in my penis and when there's blood in my penis, I'm hard. It's not quite that is it. 

Dr. Johanna Hannan: Right. And I did listen to Dr. Gonzalez, his podcast. He was saying that there's, there's two different aspects of erectile function that clinicians are interested in.

And one of them is whether or not blood can get into the penis. And the penile tissue can relax to allow that blood to expand. And then the other type of dysfunction that can occur is a result of being weak. So the veins that are on the perimeter of the penal,  erectile tissue, when the penis fills with blood and expands, The tissue will actually pinch those veins and close them off and prevent the blood from escaping the penis.

And so this is a different type of dysfunction that can happen as a result of the changes of the penile tissue itself. So if it [00:11:00] becomes. Too fibrotic with age or diseases, then it will not be able to expand enough to pinch off those veins and completely occlude the blood and cause of rigid direction.

So I'm not so much interested in that aspect of erectile dysfunction, but more so getting the blood into the penis. 

Tim: Okay. And then once it's in the penis, what does it do? 

Dr. Johanna Hannan: So then it, the PNL, so she will relax and expand. And then as long as we can get that, what we call it, you know, occlusion or the complete blockage of those veins, then it will maintain, interact rigid.

Tim: Okay. And does it do the same thing in rats? 

Dr. Johanna Hannan: It does the same thing in rats. 

Tim: And what is rat sex like? It's very quick. Is it quick? It's very like how quick is quick. 

Dr. Johanna Hannan: It's about three to five seconds. So one of the [00:12:00] ways that we can assess erectile function behaviorally is we administer April morphine, two rats, and then watch them over a half hour observation period.

And,  One of the unfortunate side effects that they were morphine. Wait, what is 

Tim: April morphine? It just is. It's like morphine. 

Dr. Johanna Hannan: So it's a dopamine agonist. So it's going to act essentially in the hypothalamus and the areas of your brain to act on dopamine receptors and trigger a erectile response neurally.

Okay. For us, it's an interesting tool because. You're initiating erections in the brain. And if there's any vascular defects in these animals, then there'll be a parent because they will not be able to have interaction. Now it's also,  causes vomiting. And the nice thing about working with rats is rest don't have a gag reflex or a vomit reflex.

And so it's a little bit less messy than if we were to decide to [00:13:00] do these with let's say with dogs. Okay. 

Tim: So, so the rats. Now does that mean that they'll be able to have more sex in that time? Or it's just, it's more controlled. You can just induce the erection when you want it. 

Dr. Johanna Hannan: So we use it as a tool to measure the amount of erections they can have in that happen.

And so if they're potent and they have good erectile function, they'll typically have three to four erections. And if they have dysfunction, they'll usually have less than two. 

Tim: Okay. And then, and, but these are pretty small erections, right? Are you looking with a microscope or can you spot one net with the naked eye?

No, 

Dr. Johanna Hannan: we can spot it with the naked eyes. So we typically have them sitting on plexiglass platforms with cameras underneath and when the rats have an erection, they have a very specific behavioral response in which the public thrusts. There penises [00:14:00] at emerges and then they'll groom. And so we can, we have a very specific response that we're looking for.

So this will allow,  to, to monitor the animals. And because it's, it's a non-invasive procedure. If we want to look long-term at the effects of a treatment or effects of diet or exercise, then we can monitor them weekly to see if things improve. 

Tim: Okay. Yeah. And when I was going through your. Body of research.

You had looked at a lot of those things,  at diet and exercise and,  yeah. Okay.  now you, you said I learned so many words going through. These, these papers neuronal  you? So the brain, the brain is similar in structure to in rats. So,  and I imagine you're probably focusing on specific aspects of the brain, [00:15:00] especially ones that are linking to.

 sexual processes and that kind of thing. So what, what, what's similar about rat brain and people brain when we're, when we're sexual? 

Dr. Johanna Hannan: So I'm not sure if I can answer that we're much more interested in the peripheral nervous system. And so we look at changes that can happen to the nerves that are supplying the penile tissue.

So we'll use different models,  that can mimic nerve injury. And then that is similar to the nerve injury that would happen for patients who are undergoing,  prostate removal for prostate cancer or radiation therapy. 

Tim: Okay. Okay. Yeah. You're more focused on. The penis itself on, on the 

Dr. Johanna Hannan: public areas, everything in the pelvic 

Tim: area.

Right. And we'll, we'll leave the brain stuff up to the other doctor. So. Let's dive into it. What can you tell us about what have you found with diet? 

Dr. Johanna Hannan: In our case, we've [00:16:00] done mainly things in the lab where we've either manipulated what the rats are eating,  in terms of giving them a more higher fat diet to see how that impacts on erectile function.

And then we've also taken animals that are overweight and sedentary and given them a restricted diet where we've restricted. 40% of their caloric intake daily to see how that improves function. Now there's a lot of parallel studies that others have done clinically. So a lot of the data that we're seeing, we're seeing improved vascular function.

We're seeing weight loss as well as improved erectile function. A lot of these correlate to what we see clinically as well. 

Tim: Okay. What does a rat get fat eating? Is it ice cream or what 

Dr. Johanna Hannan: is it? I mean, they would love to eat ice cream. Unfortunately, the, the rat diet's pretty boring. So a high fat diet that,  [00:17:00] Is more high in cholesterol and that will cause them to get fat, but we have animals.

The rats are very,  social animals since they're typically their house together. When I was in graduate school, we had a bunch of brats that. Had been housed separately in aged. And I don't know if there was rat depression going on with them, but they ate just a lot of the regular bland food that they had access to and they become, they became quite overweight.

Tim: Hmm. Just eating more of the boring stuff that they 

Dr. Johanna Hannan: eat, like any more of the boring stuff and just sitting in their cage and not really doing a whole lot. 

Tim: Okay. So, so you do. Get them fat. And you, you see like fewer erections in these studies where you've put the, the dopamine agonist inside of their brain, and they've got a [00:18:00] half hour to have as many erections as they can, and they have fewer correct.

And we're able to pretty confidently generalize that to what might happen in a human. 

Dr. Johanna Hannan: Right. So we, in addition to just looking at the behavioral response at the end of the study, we can also look at the actual vascular function of both the penis and the, the vessels that supply the penis. And so we can see that they don't relax as easily to, to things like nitric oxide.

 and they typically have an increase in. Basal constriction. So if they constrict more than the blood is going to have more trouble getting to the penis. And so we see these vascular changes that correlate with a lower number of erections and these animals. 

Tim: Okay. And that's, that's something you're not going to be able to see with the naked eye.

So you, but you're able to [00:19:00] obviously then get right in there with the rat and. Go is it wouldn't be like a camera study where you're going inside and looking at it. If they're flowing, how do you test to see vasoconstriction in an IRAT? So in this 

Dr. Johanna Hannan: case, these are all experiments that are done at the end of the study.

So we'll actually collect the tissue and then take small little,  rings of the vessels. So we'll section the vessels into two millimeter rings, and then we can take these rings and put them in a tissue bath and administer different drugs. To determine how the physiology has changed. 

Tim: Okay. At the end of this study and they've, they've died at that point.

Dr. Johanna Hannan: Right. They're done. 

Tim: Okay.  which 

Dr. Johanna Hannan: is another benefit of using animals because unfortunately we can't get these same types of studies to understand the actual mechanistic things that are happening with humans, because not [00:20:00] many humans are willing to donate their vasculature or their penis. So it's a challenge.

Tim: Right? Right. That, that wasn't even a,  Box that I could check on the organ donation list. Was it,  huh. Maybe that would be something for us to lobby for.  okay, so that's that's diet and then I guess an exercise study would be pretty similar they're they're running on wheels or, or how does a racket exercise?

Dr. Johanna Hannan: So they actually make small. Size rat treadmills. So the rats can run on these treadmills and there's different things that will encourage them to run because it's, unfortunately we can't do this with humans sometimes, but they'll have a little thing that can shock them. If they slide back on the treadmill or a little burst of air to encourage them.

Cause the rats. Need that extra motivation. They're not, they're not very enthusiastic to run, especially if they're overweight and sedentary. 

[00:21:00] Tim: Okay. So a little, a little boost of air, even my just kinda, yeah, no, they'll 

Dr. Johanna Hannan: start to get them going. 

Tim: And so then they run and they run and then they, they eventually lose weight and, and then they die and then you look at their arteries and they're there.

They're wider or they're presumably that 

Dr. Johanna Hannan: are they relaxed better. So we try and look at different,  molecular pathways to try and see what other type of drugs would potentially work clinically in humans to improve vascular function. Or if we can understand how exercise is benefiting humans, then it'll help us try and come up with more cures for.

That's disease. 

Tim: Okay. So you can say then with a fair amount of confidence, that exercise would help erectile function. 

[00:22:00] Dr. Johanna Hannan: Exercise definitely helps erectile function.  there's a study that came out this past week saying that not exercising is just as bad as smoking, having high blood pressure or being diabetic.

And it was a study where they looked at over a hundred thousand patients and found going through their stress tests and then their eventual,  mortality that patients who exercised independent of other things were better off. And so it was quite remarkable to hear that that, that no exercise there were equating to.

Worse than being sedentary or worse, you know, worse than smoking and having high blood pressure. So I thought that was quite interesting, just a small amount of exercise and essentially not being sedentary. It had such a benefit 

Tim: how small and amount of exercise. So 

Dr. Johanna Hannan: that's something where I think there's, there's a [00:23:00] variety of studies that looked at it,  or that I've looked at the amount of exercise and how critical it is.

I think it depends on how sedentary you are, but in general, a very small amount of exercise, whether it's you start walking 30 minutes a day,  it will have benefits. So there's definitely more exercises better, of course. But even that small amount might really help. 

Tim: Hmm. I don't know if I'm, I'm repeating an anecdote.

But I heard this the other day and that,  a friend was talking to a friend who is a cardiologist and he was telling her that. The only way he gets men to exercise is telling them that it will help their penises that yeah. That when he puts it in those terms, that, you know, cause if you just say, you know, it'll lower your chance for heart disease, that, that, that, that does nothing.

 but [00:24:00] yeah, if you can say you're going to be much better in the SAC,  you might, you might get them. I'm out walking. And so I guess that would be a difficult thing to generalize from the rat study. Like how much do they have to exercise to see an improvement in? 

Dr. Johanna Hannan: Yeah, so we were giving them, they were, they probably doing a moderate amount of exercise, so it wasn't just walking is a little bit faster than walking and it was half an hour, a couple of times a week.

I think the big thing it depends on is. In rats, it always gets to the point where the disease has progressed so far that we can't come back from it. So a lot of the treatments that we're doing, we're trying to either improve blood flow. We're trying to,  make sure that nerves are. Regenerated, but frequently in these conditions, the penis becomes hypoxic.

It's not getting adequate blood flow, hypoxic, hypoxic, so not enough [00:25:00] oxygen. Okay. And so it's,  as a result of that, it will start to remodel and it can become very fibrotic. So there's a lot more colleges. It becomes stiffer, which you might think would be a good thing for the penis, but when it's stiff like that, it can't relax and expand to allow the blood to come in.

So it seems with a lot of these as the disease progresses,  there comes to a point where. We can't really reverse this. So you really want to get patients in to see their doctors early, when they're first getting signs of erectile dysfunction, because at that point, exercise and diet can probably fix.

Everything that they've got going on. Whereas if they wait too long and it progresses, then it could be that their penises become more fibrotic and things like PD five inhibitors won't work for them anymore. And they might be on the track to then eventually having to get a penile implant or [00:26:00] something more serious to have erections again.

So we're really looking at that initial window. I'm trying to determine. What the mechanisms are and where can we target that to be able to revert, to reverse the disease before it gets to that late stage where there's really not a whole lot we can do about it. 

Tim: Hmm. Yeah. So take away from that is get into your doctor as soon as possible.

Especially if, if you have a sedentary lifestyle or, or, or poor diet. Yes. Yeah. Okay.  and you are not basing that on just the, the studies that you've completed because when you do research, you know, I don't know the last time any, any of my listeners have used Google scholar and actually read a study, but the whole first page of a study or more talks about all the research that's been done beforehand.

[00:27:00] And so, and you've, and you've got to know that then you, you don't want to repeat. Repeat stuff or are you sometimes you repeating it, but you don't want to be redundant and you want to grow the literature suit. So you're familiar with it. And you know, the research that's out there that,  is in contrast to what you're saying.

So, and if you've been doing this for a while, so you've, you've got a pretty good handle on, on,  what we know. 

Dr. Johanna Hannan: Yeah. So everything we're doing, we're aware of what other basic science studies have been done. But I think more importantly, we have to be aware of. What's been done clinically are where the holes are clinically.

Cause that's where basic science really fits in is to try and answer a lot of those questions that we can't address clinically in patients. And so we work really closely with urologists and other clinicians to try to really understand what's happening clinically and then take those holes that are.

That we can't understand because we can't [00:28:00] dive into it as deep with human patients and go to our rodents and try and understand what's going on in that and understand the mechanism behind the disease state. 

Tim: Right. Okay. And have we ever. Done those kinds of studies where we would actually go in and, and study,  a live person and cut open their penis or anything like that, like it, or that's just maybe before, back in the day when we did shady or things or no.

Dr. Johanna Hannan:  I think, I mean, back in the day today, they would definitely dissect cadavers to try and understand how blood came into the penis and things like that. One of the tools that we, that we can do is when men are getting implants done,  there's a lot of tissue that's removed from the penis. Right. And so we can use that tissue in the lab to look at it and put it in [00:29:00] the tissue baths and look at contractility to different drugs or relaxation, or we can look at it histologically to see how things have changed.

The big issue with that tissue is it's starting to reach that end stage disease that I was talking about where at that point. It's not normal. It's very, very diseased. You start to see strange responses with it. And then the other side of that is that we don't frequently get normal tissue from young, healthy men, but we get a lot of tissue from these very, very diseased men with erectile dysfunction, but then we have nothing to compare it to.

Tim: Right. And so it would be nice if there were a bunch of guys out there with great erections who would just donate their tissue, but that's pretty unlikely. 

Dr. Johanna Hannan: It's a challenge. I think it's, it's much more challenging here in the U S to, to have it done. There's one researcher in Spain, who's [00:30:00] done a. Really nice series of studies where they've, they have quite a bit of young control tissue, and I'm not sure if they get it from organ donors or,  younger patients who've donated their bodies who died in a motorcycle accident or something like that, but they have a.

With their system there, they have more access to,  control normal tissue from patients that we just don't have here. 

Tim: Okay. So this is a call out there for, to donate your penises to science so we can learn more about this. Okay. And so another. Big part of the research that comes up. And then I see in headlines and on, Oh, what's the one that I'm thinking of.

Well, it'll come to me, but I keep seeing headlines about testosterone and I noticed,  a couple of your studies had gotten into [00:31:00] testosterone and, and I think the general lay person thinks that, okay, well, If your testosterone's high, then you're gonna have more erections. And,  when I talked to Gonzalez, he, he kind of broke that down in a certain way.

And then I also had a neuroscientist guest on, and then she had other things to say about that. So, so what have you seen and what have you studied? Whereas with regards to SaaS throne, 

Dr. Johanna Hannan: So in where our interests in testosterone are more so focused on,  the lack of testosterone. So when. One of the most common treatments for men with prostate cancer is the first thing that their doctors will do is often put them on some sort of anti testosterone producing or binding drug.

And so they want to deplete them of testosterone to starve their prostate cancer of testosterone. And that helps the cancer shrink because quite [00:32:00] often, prostate cancer is very dependent on. The testosterone that these patients produce in their bodies. And so unfortunately there are adverse effects from these men who have a testosterone inhibition things such as,  they have a higher risk of cardiovascular disease.

 recently there's a study that just came out that showed there are high risk of fracture and. Erectile dysfunction is a huge problem for them and testosterone.  For the vasculature to relax and respond to nitric oxide, it needs to be present. And so what happens is you'll get a lot of vascular dysfunction.

So your blood vessels will become more. Contractile and will constrict more and impair blood flow. And then you'll also have a lot of fibrosis and atrophying happening. So the [00:33:00] penis will become more stiff and it won't relax as well. And so these men at times will be on this,  anti testosterone therapy for months and years.

I mean after their prostate cancer has been in remission. And, and there's this fear that if the testosterone comes back, that it's going to feed the prostate cancer and they're going to have recurrence. And unfortunately there was one study that was published.  I can't remember if it was in the fifties or the sixties, but it showed that if you gave it.

Testosterone back to prostate cancer cells that were growing in a Petri dish, it caused it to grow rapidly. And so now we have this fear that is men who are deprived of testosterone. If we get them back any testosterone, then it will be bad. And so. There's we're trying to [00:34:00] do more studies now to see if giving back very small amounts of testosterone is enough to improve their erectile function, improve their cardiovascular health without having a big impact on prostate cancer recurrence.

So we're doing this in the lab by castrating animals, and then we're examining what that castration does to their sexual function, so that their vasculature to the nerves that supply the penis. And then we're also trying to get back testosterone to see if we can improve function in those animals faster.

Tim: And you said animals, is this other animals other than rats? 

Dr. Johanna Hannan: No, we, I mean, we were mainly using rats, I'm just using it. 

Tim: Okay. Okay. Are there other animals that also have similar 

Dr. Johanna Hannan: vasculature structure or is it people will also use,  rabbits and mice as well? I try to [00:35:00] shy away from mice because a lot of our peripheral nerve experiments that we do.

 the ganglia is very, very tiny in a rat. So if you go all the way down to a mess becomes even smaller. So we use rats for the ease of collecting tissue and having enough tissue to do our studies.  but a lot of people have used rabbits as well. Again, we're even bigger. So,  It's a lot easier to do some of the experiments, but again, with the bigger animal comes a bigger price tag.

So it depends what your budget is like. 

Tim: Ah, right. And that would probably explain why there's not more primate research and that kind of thing. Okay. Well, I guess as you were describing what you're studying with testosterone, one thing that both of the other guests definitely agreed upon was when it's really, really low.

It's absolutely bad. It's absolutely. There's nobody disagreeing about that. What we run [00:36:00] into is there are,  varying opinions on what normal level of testosterone is and what high testosterone is. And if like, I suppose if the difference between normal and high would actually see an increase in erectile function.

And would that be something that you'd. Run into, 

Dr. Johanna Hannan: I mean, how high testosterone are we talking? People who are trying to become like Arnold Schwartzenegger using steroids to increase muscle mass? Is that the type of high testosterone you're referring to? Yeah. Yeah. So in that case,  I don't think. It's going to benefit erectile function.

We know that those men end up with a lot of testicular atrophy.  and as a result, they become infertile and actually may begin to develop erectile dysfunction. So too much testosterone, it's [00:37:00] not a good thing.  but yeah, if it's just indogenous levels of testosterone, I don't know if they have, I don't think that they would have a greater sexual function per se.

Necessarily.  

Tim: okay. And then how does it interact with the blood flow? Like how, why, why does it affect it? 

Dr. Johanna Hannan:  so on our blood vessels, we have receptors. That testosterone will bind to. And so when testosterone binds these receptors, it's actually going to trigger a cascade of molecules being activated and the release of nitric oxide and the vessels will relax.

So it can act directly on the vessels to cause them to relax. But then it's also important for general vascular health. So it's believed that,  [00:38:00] it will prevent without it you'll have more inflammation that can lead to damage to your blood vessels.  so in general, it's, it's going to promote vascular health, improve relaxation without getting into really, really boring.

Nitpicky cascades of signaling molecules.  that's, that's in general what it's going to do. 

Tim: Okay. Okay then. And that, that obviously, that makes sense. Hmm. And, and so is that pretty much the spectrum? What else are you studying besides diet exercise testosterone? Pew dental arteries. 

Dr. Johanna Hannan: And so, so I'm interested in a nerve injury.

And so, as I mentioned, these men who have prostatectomies their prostates removed or radiation to their prostates, [00:39:00] it frequently results in a neuronal injury leading to erectile dysfunction. And so one of the things that we do is that we're trying to understand. That progression of neuronal injury from the time of injury.

So we will mimic,  the prostatectomy injury by taking rats and we'll actually crush the nerve, their pelvic nerve or their cavernous nerve that supplies the penis. And so we'll do this bilaterally. And so this crushed mimics the same type of nerve entry that can happen when,  clinicians are performing a radical prostatectomy and.

So when clinicians are performing prostatectomies, they will use the retractors and they'll push the nerves out of the way in attempt to preserve them. But even this manipulation of the nerves can lead to crush or a stretch injury and resulting in erectile dysfunction. And so [00:40:00] by mimicking this and the rats, we can do a time course and we try and understand what's happening at that early stage, because if we can distinguish.

 certain pathways or drug targets that are up or down, then this is something that we could potentially turn into a treatment that you could apply to the nerves directly. When the patients are having their prostate removed in the hopes that you would prevent that whole damaging cascade of events from here and preserve erectile function.

Tim: That's really interesting. Well, first I'm sitting here wondering, so how do you crush that tiny little. Thing without what are you 

Dr. Johanna Hannan: use? Use microscope and very small, fine forceps. And so we'll just take our forceps, we'll find the nerve and then we'll close the forceps as hard as we can on the nerve for 15 seconds at a time, three different times.

And so we're in, we're done. You'll [00:41:00] actually, the nerve is typically. This little white line, but when we're finished crushing it, there'll be this little clear part within the nerve. Almost like a little dent with no white, but it'll still be attached. So then we can look and see how the nerves can regenerate back across this little gap that we've created 

Tim: and is anybody getting them to do that?

Dr. Johanna Hannan:  the basic science experiments have actually been very successful. I think. The problem is they haven't translated into clinical success as well. So commonly when we're using rats, we, because it's more cost-effective we tend to use very young animals. And so one of the issues is in these young animals, when we do these very specific nerve injuries, If we were to leave them long enough, they will regenerate their narrows on their own.

So a [00:42:00] lot of these studies where they're doing different types of,  neuro regenerative therapies that are trying to. They get to the clinic like injecting STEM cells or using shockwave or,  amniotic fluid or whatever. Your favorite type of regenerative medicine is hemp.  they're very successful in that, but the rats are young.

They it's an ideal. Controlled environment. The frequently we are seeing that we're able to recover function. And I think the issue is we're not doing these in older animals or animals that have underlying disease like diabetes or hypertension though. The experiments in the lab are working really well, but they really haven't translated clinically.

Tim: So I meet a bunch of guys who. Say [00:43:00] that they have,  pudendal nerve injuries and something. When I, when I read about that, I have noticed that there is a disagreement on how to test for that on how to see that. Is it something that we can. Definitely see with some kind of an ultrasound. 

Dr. Johanna Hannan: So when you say pure dental or nerve injury, do you mean more from a like hip fracture or bicycling or?

Tim: Yeah. Bicycling is one of the common ones where it sounds like sometimes that conclusion is. Inferred versus actually seen. Is there something that when there's that kind of nerve damage that would show up and we can say, Hey, that's a damaged nerve. 

Dr. Johanna Hannan: Mm I'm not sure. I don't know what the tools are for that.

Tim: Okay. Okay. But, but in a rat. You could see it. And it's just, it's really clear. [00:44:00] Okay. That forcep 

Dr. Johanna Hannan: worked. Right. So it's, I mean, it's different. Have you actually done the injury? If it's, if it was a stretch injury or if it was something that we weren't opening the animal and doing to the animal and seeing where we were doing it?

I don't know that we would actually recognize.  that there's an injury there. And so this is a little different because we're actually opening them up. We know exactly where we're doing the entry. 

Tim: Right. And so if, if they had that kind of an injury coming into the experiment, you might not even be able to spot it like, right.

Yeah. It'd be unlikely. Cause you've had them since birth presumably and you would've known if they would have fallen or something like that. 

Dr. Johanna Hannan: Okay. Yeah. I mean, I think the rats are pretty resilient, so we don't have any of them cycling yet. So.

Tim: All right. So do you have any. Any, any,  [00:45:00] insight as to the future of this kind of research and what we can expect to see 

Dr. Johanna Hannan: that there's a lot of potential in the regenerative therapies. So there are clinical trials going on for,  STEM cell therapies. That are happening across the country. I think we're, we're still in the early stages for a lot of them.

The nice thing about them is that you can take, you can isolate STEM cells from those, from those patients, whether they're bone marrow derived, or from there. Fat tissue and give them back to the patients. So you don't have to worry about immune responses and they're their own donor. And I think that there's a lot of potential there for these therapies too, to,  give him more of a curative treatment to erectile dysfunction, because a lot of the treatments that we have currently, like the Viagra's there.

More of a band-aid than a [00:46:00] cure for erectile dysfunction. So I think that STEM cells are something that could really benefit these patients, give them a cure, uh long-term  improvement in erectile function. The other one that I think is very interesting and don't think that we have enough data on to really know.

How well it's going to work yet is shockwave therapy. And so the low end energy shockwave therapy, it's similar to the therapy that a urologist would use to break up a kidney stone. And so it just gets, it sends these little shock waves. Through the penis. And what they believe is happening is that these shockwaves are causing a little tiny bit of damage to the inside of,  the smooth muscle within the penis.

And this is going to cause an inflammatory response and then initiate all of these [00:47:00] growth factors that are responsible for going in and repairing the penis. It will also activate what we believe are these. STEM cell populations that are within the penis. And so they think that by giving these shockwave treatments, which are very noninvasive, the patient will come in and they'll just apply some ultrasound jelly to the penis.

And they'll barely feel anything as the shockwave is growing over their penis.  this is something that we hope has the potential to. Repair the damage that is present in the penis leading to better erectile function. 

Tim: Okay. And I've actually seen the video or videos for that, where. I guess a urologist would have been selling that service and giving a demonstration of, of what the process is actually like.

So this is being done and there, there are human volunteers for this 

Dr. Johanna Hannan: research, right? So [00:48:00] it is being done.  but I would caution patients that it is not yet FDA approved. So until we have clinical trials where patients are not paying for the service. Where they're either receiving placebo or they're, you know, a well-controlled double-blind appropriately run trial that can say without a doubt that this treatment is efficacious, it works that it,  that it's not something that people are just selling as a hoax.

Until we have that data. I would caution patients to be careful because there are a lot that are trying to take advantage of patients by trying to sell STEM cells or perform shockwave. And if you're not sure if it's not a re if, if it's something that's not FDA approved, there's no saying what it is that they're injecting into these patients penises, but they just need to be very careful.

[00:49:00] Tim: Okay. And that's a really good thing to know.  because I know what happens with a lot of guys is they get pretty desperate and willing to try anything. And,  You know, when you watch the video, it looks like no big deal. Like, Hey, there, that's certainly a lot less scary than a penile implant. And it's certainly a lot,  smoother than an injection.

And it's nice to not have to take a pill. That's gonna make you see your red and give you a headache. And,  it's, it's compelling, but let's be clear. There haven't, there has not yet been enough research. It's not yet FDA approved and we don't know, hopefully that's as promising as the science would imply, but it might turn out to not be an actually good treatment.

Dr. Johanna Hannan: Right. And we still don't know how, what the effects are going to be long-term. Is that something that [00:50:00] you're going to have to get done every six weeks? This is something that's going to last for six months. So there's still a lot, a lot of clinical research being done that hopefully we'll get the answer to that soon.

Tim: Okay, well, thank you so much. That's a, this is all very interesting. And I think, you know, I think there's a certain kind of guy out there who just wants to know that there is hard science behind some of these things that, that we report and share. And, and then I wanted to get into the nitty gritty of what it's like to, to study a rat and it's sex.

And, and so. People could have a little bit more confidence that know the science behind this is taken very seriously and it's, it's replicated and, and there are dedicated academics out there who are, who are doing this research and doing it well. So it it's,  you know, it's cause you, yeah. I mean, anybody ever, everybody's going to tell you, Hey, you should have exercise more.

 yeah, [00:51:00] but, but no, you really should. 

Dr. Johanna Hannan: Yeah, it's the same thing with the smoking campaign. When you told men that smoking gives you erectile dysfunction and they put all the nasty impotent like pitchers on the cigarette cartons, I think that has more of an effect than telling them you're going to die of lung cancer, or you're going to get.

High blood pressure. 

Tim: Right? Right. Absolutely. Okay. So,  thank you very much for this. This has been really interesting. And,  thank you for contributing to this hard conversation. 

Dr. Johanna Hannan: Thank you very much, Tim.

Shout outs to the sex positive community, including sex educators, sex therapists, sex coaches, other fellow sex, podcasters, sex, surrogates, academics, sexual health, medical community, sex workers, the tantric community, and everybody else with having hard conversations. Bye-bye.