Courage, something shared by countless Americans, those that risked their lives, those that battle serious illness. When I was diagnosed with cancer, I was primarily concerned with ridding myself of the cancer, but secondly, I was concerned about post operative side effects like a rectile dysfunction ED, often called impotence. You know, it's a little embarrassing to talk about ED, but it's so important to millions of men and their partners that
I decided to talk about it publicly. And after all, it can be associated with many conditions, including prostate surgery, high blood pressure, diabetes, or even smoking. The point I want to make is that there are many treatments available for ED, so my advice is to get a medical checkup. It's the best way to get educated about ED and what can be done to treat it. It may take a little courage, but I've always found that everything worthwhile does.
I mean, none of it was wrong.
I love it. It's because it sounds more like a p s A than an advertisement. It does.
It totally sounds like I mean, they don't even say the name of the medicine, right, but it's very under the radar.
Uh huh. So that was from the infamous, really historic Bob Dole commercial from nineteen ninety eight. Bob Dol, Bob Dol.
Bob Dol. Do you know that was one of my brother's first words.
Was he born near like in the year leading up to a presidential election or what? I don't know.
I just remember during the presidential election. I'm pretty sure it was my youngest brother. It might have not even been him, but sitting there saying Bob Dol, Bob Dol, Bob dol, So it could him been the one who was nineteen ninety I don't know.
That's someone who's watching too much TV and too many political commercials, right.
Bob Dohl, Bob Dol, Bob Dol. Anyways?
Oh yeah, yes, Well, Hi, I'm Aaron.
Welsh, and I'm Aaron on an update and this.
Is this podcast will Kill You.
And today we're talking about viagra. We are can we say trade names? We're talking about Sildena, Phil, We're.
Talking about I mean, my part is mostly about biagra. Period Biographs is also not the first trade name that we would have said on this podcast.
Launched the Whole Allergies episode talking about EpiPens, like.
Yeah, exactly, epineph and auto injectors. Right, too much to say any episode, it's gonna be a great episode. I am so excited for this one. There's just it's a it's a rich topic. Yeah, who knew? Who knew?
Yeah?
We should have? We did, we did, they did, That's why we picked it. Yeah, but before we get into all of that, Aaron, what time is it? It's quarantin any time it is? And what are we drinking this week?
Nothing other than little Blue pills? Yep, it makes sense.
It makes sense. Pills, p I L s just one L just because because it's beer. It's a beer drink. It's a pill drink even and lemonade and blue curse out.
Sorry sorry, but not that sorry, because it clever.
I mean, we had to do the name and then the recipe was based on that, and so there you go.
Enjoy it or don't. Yeah, anyways, you'll find the full recipe so you can decide for yourself for that quarantine and the non alcoholic. We'll do it plusy Brita on our website This podcast will kill You dot com and on all of our social media channels.
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Aaron, can we get started? We can today's topic.
Right after a short break.
Still.
Dentaphil is the medicine that we're talking about today, and it is of course most famous for its use as a treatment for erectile dysfunction under the trade name viagra, but that is not its only use, so I want to give credit up front that this is also an important medication that is used for the treatment of things like pulmonary hypertension in both adults but also tiny babies. Off label use, and that's a condition where the pressure in your blood vessels and your lungs is too high
and it can make it really difficult to breathe. In babies, this is often because they're born premature. But I'm saying that now because that's mostly the last time I'm going to talk about it, because its use in other contexts is really overshadowed, of course by its fame as viagra. So to understand the use of this medication in the treatment of a rectile dysfunction, we have to start by
talking about erections. What are they, how do they work, what is happening when they don't work, and why does viagra help?
So we all love the questions that we should be asking exactly.
There is the potential, as evidenced by multiple like twenty to fifty page papers on the detailed biochemical reactions and the neurobiology and endocrinology of what's happening in a penile erection.
There's the potential to go into way too much detail, But for this episode I will link to all of those papers so people who want to dig deep can What we need to understand is really the broad strokes of what an erection is a penile erection is the end result of a pretty complex neurovascular process, which means that it involves a real web of our peripheral nerves as well as our brain and spinal cord. It involves both sensory and motor nerves, and both are sympathetic and parasympathetic,
so those autonomic nervous systems. It coordinates through tactile, auditory, visual, and other stimuli, and involves a pretty wide range of neurotransmitters as well as hormones. And all of this has to coordinate with our vascular system, which is what deals with blood flow in and blood flow out. And we don't have to get deep deep into the details to understand how this works and how viagrass soldeniphil can affect this process, but we do need to understand the anatomy
of a penis. So anatomically, the penis has some pretty specialized tissue creatively called a rectile tissue. Wow, okay, I know, such creative naming. So if you were to look at the interior of a penis, like in cross section, to me, it kind of looks like a fly with like an open mouth, going like ooh, okay, because like imagine a fly, a big fly eyes, but then they have like a human mouth going like, oh my.
Gosh, I don't like that image, but continue, but it's in your brain now.
So in cross section, it has these two big round almost really they're like tubes that are full of this spongy type of tissue that's called the corpora cavernosa.
And each of these.
Corpora cavernosa has an artery that flows through the center, and then these two sponges are surrounded by a pretty dense fibrous tissue that forms a sheath like a sword with a sheath. Right, it's a firm area, and that is what looks like the fly eyes, like this pair
of big wide eyes. And then beneath that, like on the dorsal underside of that, if you're looking at a cross section, there's another tissue, spongy tissue tube called the corpus spongiosum, and inside this tube is the urethru where pa is going to come out as well as ejaculate is going to come out, and that's what looks like
the mouth of the fly. This is surrounded by a thinner, fibrous sheath of tissue and then the whole thing is surrounded by a lot of different smooth muscle, not skeletal muscle, but smooth muscle.
So just like a lot of different types of tissue all laggered together.
A lot of different types of tissue in these three pockets of spongy area, okay, with a lot of smooth muscle tissue all up in there. And smooth muscle is the type of muscle that we have all of our bodies. It's what surrounds our arteries or is part of our arteries. It's what's in all of our internal organs, except for our heart, which has its own specialized kind of muscle.
But unlike most other smooth muscle in our bodies, the smooth muscle that surrounds the corpora cavernosa in the penis is tonic contracted, which means that it's always a little bit though not one hundred percent completely, but it's a little bit clamped down contracted, rather than relaxed. And what that does is it allows for only enough blood flow through to keep the tissues of the penis healthy without
allowing too much blood in. So what happens in an erection through again this complex series of neurotransmitters, hormones, blah blah blah. Is that this smooth muscle starts to relax and that causes the dilation of those arteries in the corpus cavernosa in those flies eyes, and that allows for increased blood flow. That blood flows out of the arteries into those tissues and fills up all of this spongy potential space. These are called sinusoids, and they're basically like
chambers in those spongy tissues. And as those tissues begin to expand, they actually compress the veins in the penis, which are all located outside of that fascial tissue or in between layers of fashion, but outside of those sponges.
So it's like let more blood in and prevent blood from leaving.
Exactly exactly, and that traps the blood in those sinusoids
in the sponge you have very little venus outflow. And the more that that process continues through this kind of positive feedback loop, then eventually you have a really significant increase in the pressure inside of the penis, and then you have a contraction of nearby muscles called the issio cavernosis muscles, and these are muscles like in the pelvic floor, not smooth muscles, but skeletal muscles, and that provides a further rigidity, so you have that's how you end up
with the rigidity of an erection. Does that make sense? Yeah, that's it. That's all it is, right. I can make it as simple as.
That more blood in, less blood out erection.
Erection, and to do that you first need a relaxation of that smooth muscle. So then if we understand that, then we can understand that there's a lot of ways that this process could go wrong, and that end result is called a rectile dysfunction. And for this I'm going to just rely on nih definitions limited though they may be. A rectile dysfunction is the condition in which somebody cannot either achieve or maintain an erection that is firm enough
for a satisfactory sexual experience. That's the literal definition. And there isn't one underlying cause of a rectile dysfunction. Erectile dysfunction is an end result, right, It's as satisfying sexual ability or the inability to have this satisfying sexual experience because the erection is not as firm as either it used to be or as you want it to be.
Now again, there's limitations to this, and one thing that I'm not probably doing a good enough job in this whole episode is going into the nuances of how we define sexual health in general, right, or.
What is the satisfactory sexual experience exactly? Right?
Yeah, yeah, yeah, right, So like that is that is beyond the scope of this. But if we're sticking with this definition, then what we're looking at really is that erection itself. And there's a lot of different things that can end up causing a rectile dysfunction or a lot of different risk factors that end up relating to this.
Right.
There are of course psychosocial issues, like we said, like what is healthy sexual function? What does it mean to that individual? What's considered disorder? But you accept that I've got a disorder or I feel like there's a disorder. There's a lot of different things that can end up causing this. There's things like neurologic issues, whether that's a spinal cord injury or peripheral nerve damage or either like demielinating disease like MS or a whole host of other
chronic diseases that can cause nerve issues. There's also endocrine issues like low levels of testosterone. There's also vascular issues, and vascular issues likely account for the majority of a rectile dysfunction, though it's a little hard to get great stats on this, but a lot of papers estimate like seventy percent or so. And vascular disease is not one thing, right, There's a whole bunch of risk factors that lead to vascular disease that can lead to a rectile dysfunction. Diabetes,
high blood pressure, high cholesterol. All of these affect the lining of our blood vessels, which is going to affect blood flow, which is necessary for an erection. Aging in general causes oxidative stress and endothelial dysfunction, and then of course the hospital can do it to you, which it sounds like was what happened in our first hand account because someone had treatment for cancer.
I was like, what do you mean.
Treatment for something like prostate cancer or other operations or medications that can sometimes cause erect how dysfunction?
Okay, Aaron, real quick, age? Why Like, I know you mentioned oxidative stress blah blah blah, but like, why what is the aging? Why does the aging process lead to higher rates of ED? Aaron This is.
A question that made like I already was, I wondered this, but looking at the statistics, I wonder even more because okay, this is jumping ahead. But statistically people say that anywhere from like fifty to one hundred percent of people with a penis over age seventy have a rectile dysfunction. Okay, again, meaning that they're not having a satisfying sexual experience because they're not able to achieve or maintain an erection.
Which real quick again, does that definition include frequency? Is that every time? Is that just once in a month? Is that once in a week? Like, it doesn't include any of that? It doesn't matter, right because it is subjective. It is it is a subjective experience that is meeting criteria for this dysfunction or disorder. Right, it's giving me menopause vibes.
Where we're calling this a disorder because it is causing impact on your life, which is valid, But is it a disorder like evolutionarily? Maybe not?
Right, I don't wait for it, just wait for it. There's more where that came from. We'll get you to it.
I can imagine, because again it is very individual, like what is the satisy finding sexual experience for one person is not the same as for another person. For some people, it might not even include an erection, it might not even include orgasm. Like, there's so much nuance to this.
What's the end goal here for Yeah, exact fixing, fixing, this, fixing, fixing.
This, fixing, this and this in the case of erectile dysfunction, is just the firmness of the erection.
But there is a real relationship between age and ED. So what is going on mechanistically? Like, what is the basis for this physiologically?
Great question. I don't have a one single answer for you. I don't have like an aging equals this. There's a lot. There's the fact that as we age, all of those other risk factors go up. Cholesterol goes up, blood pressure goes up, the rates of diabetes go up. Aging also, like I said, already is thought to be independently associated with things that end up causing endothelial dysfunction, which is blood vessel dysfunction. Is it just that there's a lot
of different factors. I don't think that there's one thing that aging causes that leads directly to a rectile dysfunction. I think it's a whole host of issues.
I just have so many questions, but keep going.
I don't know that I'm going to answer any of your questions. But out of all the different things, be they neurogenic, be they vascular, be they psychological, be they hormonal, Very often the first thing that is used for treatment is one thing, and that is viagra. So, no matter the cause, that's not usually investigated, first thing, often not even second thing, the treatment is a blanket viagra for all your woes.
And so what percentage of cases of ED does viagra actually help with?
Most papers I read estimated sixty to seventy percent.
Wow, okay, it's pretty high.
It's pretty high. Why is that? How does it work? Let me tell you, sildentiphyl viagra. It's a phosphodiesterase or PDE inhibitor. What does that mean. PDE is an enzyme. It's not one enzyme. It's a whole group of enzymes. And these enzymes are present on a whole bunch of our tissues throughout our bodies. But there's one in particular
that viagra is very strongly like. It really only works on this one type of phosphodiastorse called PDE five and this particular phosphodiasterorate enzyme happens to be present in very high concentration in the corpus cavernosum of the penis. That's spongy tissue that's responsible for the majority really of an erection.
So through this again very complicated series of biochemistry, the end result of blocking PDE five, which is what sildentiphil and other similar drugs do, It blocks the action of this enzyme and that results in this cascade of events that causes increased relaxation of that smooth muscle, So that allows for blood flow into the corpus cavernosum to start, and that allows the further steps of an erection to
take place. That whole cascade of things can happen if you have relaxation of that smooth muscle and increased blood flow m H. And that's that's it. It can be as simple as that.
What about other ed drugs.
So Cialis is the trade name for tadalaphil, which you can tell by the A fill at the end that it's the same type of medication. It has like a different half life and blah blah blah, but it's still a PDE five inhibitor. So it acts in the same way. And there's a few other drugs that are really similar, just like different versions essentially but acting on the same end time. So all of those work in a very
similar way. There are other medicines that are used. Some of them are like injectable medicines that you inject directly into the penis. Some of them are you can put them in other ways. A lot of them still like predominantly we target this phosphodiestors pathway. The other ones might target different PDEs, so PDE one instead of five or whatever, but that's predominantly what they're doing is targeting this pathway.
Aaron, you said injectibles, and then you said and then put them in in other ways and you just try to skape right by that. Can you go back to that.
It wasn't that exciting of other ways? I just mean like sublingual orkay, yeah, injectable. I don't think that there are any that are just topical though, I think that that's been tried. Yeah, Okay, not that exciting. So yeah, that I mean that that is honestly, that's the that's the basis of it. That's how viagra works, and that's why it works. Interestingly, sildeniphil still requires the initial steps of erection, which includes sexual arousal, so you still need first this neurologic input.
Before you get.
That relaxation of the smooth muscle from sildentophil, because it's not like direct. The way that it happens is like the build up of certain like precursors and then the blocking of calcium and blah blah blah. So sildenophil itself, viagra itself does not cause an erection. It also doesn't affect libido or sexual desire. All it does is allow for increased blood flow so that in the context of an erection it can be firmer and or lasts longer.
Just opens the blood floodgates but waits for the signal from yeah.
It like it makes the floodgates easier to open. It allows for there to just be like a gentle push instead of like a big shove like of a heavy door.
Okay, So I have a bunch of questions. Okay, all right, you always see her on the commercials. If you have an erection lasting longer than four hours, et cetera, seek medical criapism. Right, Why is that happening. And second to that is kind of similar to that is like, what are some of the other side effects that we see with use of sildentophil and why do we see those things?
Great question. So, of course any medicine has the risk of side effects. Most common side effects with viagara are things like headache or flushing. You can have some dizziness or like stomach upset, also, weirdly, nasal congestion. I don't actually know why that one happens. Most of these have to do with the fact that because this is acting on smooth muscle, and while it is specific to PDE five and that is mostly found in the penal tissues,
it's also found in some other places. So this can cause relaxation of smooth muscle other places and then potentially drop your blood pressure and that might trigger some of these other symptoms. Really importantly, we see this happen if somebody is also taking a medicine that has nitrites in it, like nitroglycerin, which someone might take if they have angina, or like that pain in their chest that's from their
heart having blockage. Basically, if viagra and a nitrite is taken together, these drugs actually interact with each other and then cause really severe drops in blood pressure, like potentially deadly, really problematic to take these two medicines together. Otherwise, viagra and similar medications are actually pretty safe most all the time.
When priapism happens, so that like prolonged direction, that can be very dangerous because again with an erection, you're having a lot of blood flow through the arteries into the penis and very little blood outflow, so that pressure can really build up and end up. If it lasts for too long and you don't have enough blood outflow, you can increase the pressure so much that you can start to damage tissue in the penis. So priapism is very serious.
That generally only happens if somebody takes too much of this medication, Okay, at the doses that it's usually recommended. It's very very very rare to have priapism as a side effect. It's usually from doubling up on doses, or it didn't seem like it worked, so I took extra, et cetera.
And how is priapism treated?
A lot of times if it needs to be, it is treated by physically removing the blood from the penis with a large syringe. Any other questions.
That's it. Yeah, it's not great.
It's not great. There's other kind of trying to calm yourself to reduce that blood flow, because again, there's a lot of like nervous system input that's going into this. So if you can try and reverse some of that psychologically, sometimes that can help a lot with making that direction D two mess.
This is called how do you just be like, Okay, don't think about this erection, don't think about this direction that I've had for three and a half hours. Like, understandably, it's.
Very hard, it's very difficult to do. So, yes, so that's viagra, Erin, that's how it works. That's how you get an erection, and how you that's how it works. Erin, tell me how we figured this out. I cannot wait to hear the story, like the story of viagra.
Oh, there are so many stories to tell, Erin, and I can't wait to get to them all. Right after this break, step up to the plate, let the dance begin. Love life again. This is the age of man, this is the age of viagra. And of course, lest we forget ask your doctor.
Sorry your face, I cannot.
Oh yeah, really trying to embody all of these commercials.
You're doing such a sad job, literally such a good job.
When viagra hit the market in nineteen ninety eight, it sent shockwaves around the world. Late night talk shows made countless jokes. Cultural commentators wrote article after article about how viagra would transform sex and relationships. Millions of men made long overdue appointments with their doctor. Hey, anyway you get in the door is great. Fizer counted their millions, and other drug companies got to work trying to create their own blockbuster drug. The impact that viagra has had is huge.
It changed the way drugs are marketed. It contributed to the medicalization of sex. It opened up discussions about a formerly taboo subject, sex and older adults. It highlighted gender bias in drug production and insurance coverage and research. I don't think the world had seen a drug like it before in terms of how much controversy and discussion it prompted.
Its release reminds me actually a lot of the chatter and hype around ozebic and related drugs, which we should really do an episode and this sort of like this will save us or this will be the end of us. Extreme perspectives like everything is so like, whoa, this is the end of relationships. Oh, this is the age of a new era, you know, like that kind of thing.
Wow, yeah, nineteen ninety eight. I don't think I realized it was so recent. Oh yeah, yeah, okay, I can't wait.
And it just slipped into like our cultural consciousness like right, yeah.
It's weird, weird, okay.
But before there was ozempic, there was viagra, and before there was viagra, there was nothing. That's the story that you've likely heard, and the story that Peiser seems to love to tell. Nearly every publication that references the origins of viagra uses the word serendipity or one of its synonyms. Okay, as the story goes, Pfiser was testing out a new drug for a heart condition and stumbled up to greatness by utter chance. That might be part of the story,
but it's certainly not all of it. The truth is that the hunt for an erectile dysfunction cure hadn't long been underway. And I'm not talking about like herbal extracts or animal glands, which like millennia people have been using
those or trying those out. I mean that there had been since at least the nineteen seventies and nineteen eighties, a real concerted effort in medicine to create a medication, a device, or a surgery to treat what had long been known as impotence but was getting rebranded as a rectile dysfunction. The history of impotence is a separate topic entirely, but relevant to this discussion is what people thought caused
it throughout that history, and that was your brain. For much of modern medicine, impotence, as it was then known, was considered a condition primarily of psychogenic origin, meaning it was caused by your brain. Anxiety, stress, depression, your wife's frigidity. Yeah, that was one of the leading causes. Rigidity, frigidity, cool, cool, And accordingly, it was treated by the folks who dealt
with your brain, psychologists and psychiatrists. This notion replaced the previous dominant concept that impotence was a normal part of aging, and it began the shift in seeing impotence as something to treat, as something to manage, as something to cure. It redefined what quote unquote normal looked like. People did recognize that there were some cases of impotence that seemed
to have a physical or organic origin. But the most commonly cited statistic, which by the way, no one can really figure out where the statistic came from up until the nineteen seventies or even the nineteen eighties, was that at least ninety percent of cases of impotence were psychological in origin. Yeah. Compare that to today, which is basically the reverse. Quote. Current medical consensus on a rectile dysfunction is ten to thirty percent psychogenic and seventy to ninety
percent organic. Quote.
And I don't know where they're getting those numbers.
Either, Pfizer, all of it.
Yeah, all of it is very interesting and doesn't even get into like female sexual dysfunction, which shows is still considered psychogenic and entirely in the rain. Right.
Yeah, but cool. What happened to cause this reversal? Yeah, it wasn't viagra, or at least it wasn't Viagra alone, since the tides began to turn at least a decade or two before the drug came on the scene. It was Viagra's predecessors that helped to transform impotence into a
rectile dysfunction. Devices, surgical treatments, or even injectable medications that were developed and tested in the nineteen seventies and nineteen eighties showed that for at least some a rectile dysfunction could be treated with medical rather than psychological intervention alone, and this led to a shift in who treated a rectile dysfunction as it was beginning to be known, from therapists to urologists, as well as increased interest in the
physiological basis of erections and ways to induce them via medication, which brings me to the story of Professor GS. Brindley. Okay, have you heard this story?
Nope?
Okay, name doesn't sound familiar. Nope, Okay should it?
It's going to add by the end of this I won't forget it.
Yeah, I think that's sort of how I feel. It's now scarred into my brain. Nothing could have prepared me for this. Oh dear, how might we set the stage? Yeah? Truly? The year nineteen eighty three, the location Las Vegas aka Sin City, the occasion the annual meeting of the American
Neurological Association hot stuff. On this fateful day referenced in every history of Viagra article and book, Professor G. S. Brindley made his way to the lecture hall, where he was scheduled to give an evening talk titled something along the lines of Vasoactive Therapy for a rectile dysfunction, Something innocuous, unremarkable. The audience was not substantial, around eighty or so people, mostly urologists, who dragged their partners along for one last
lecture before the evening reception began. The first sign that something was amiss appeared even before the lecture began. The audience watched as the fifty seven year old Brindley climbed the stairs to the lectern dressed in a blue tracksuit, not at all professional attire for this kind of meeting. It's not ecology, after all.
I'm very nervous right now.
You should be. And this track suit stood in sharp contrast to those in the seats who were in their evening best. If the lecture had followed a normal course, perhaps no one would remember the blue track suit. But from the very first slide it was apparent that this was anything other than a normal talk, because the very first slide was a penis. Yeah, okay, it's a urology meeting. Penis picks are to be expected. That's not abnormal, right, But This wasn't just any penis. This was Brindley's penis.
Brindley's penis, I knew it.
And not just one slide, but multiple dozens. Yeah, lot his own pen well, Brindley explained to his stunned audience he had no other choice. His hypothesis was that if you injected vasoactive agents like papaverine and pantolamine into the penis, you could induce an erection, But lacking easy access to an appropriate animal model, he decided to test it out on himself.
Uh huh.
It doesn't end here, unfortunately, because while a picture may be worth one thousand words a live demonstration, but you can't put a price on that.
No, you really can't. That's why you need a tracksuit.
Mmm. Brindley was worried that the audience wouldn't believe that the erection featured in these pictures was induced by the injection alone, and so prior to the lecture, he had injected himself with popuvererin and deliberately wore his loose tracksuit so that he could pull his pants tight against himself, which is exactly what he did after stepping out from behind the podium. As to what happened next. Let me read you this quote from one of the audience members. Quote.
At this point, I and I believe everyone else in the room was agog I could scarcely believe what was occurring on stage. But Professor Brindley was not satisfied. He looked down skeptically at his pants and shook his head with dismay. Unfortunately, this doesn't display the results clearly enough. He then summarily dropped his trousers and shorts, revealing a long, thin, clearly erect penis. There was not a sound in the room. Everyone had stopped breathing. The sense of drama in the
room was palpable. He then said, with gravity, I'd like to give some of the audience the opportunity to confirm the degree of two messens. With his pants at his knees, he waddled down the stairs, approaching, to their horror the urologists and their partners in the front row. As he approached them, four or five of the women in the front rows threw their hands up in the air and
screamed loudly. The screams seemed to shock Professor Brindley, who rapidly pulled up his trousers, returned to the podium and terminated the lecture.
He didn't realize that maybe this was inappropriate until people screamed, I mean, okay, So I have so many thoughts on this, so many thoughts on this.
I was processing this story for days. It's so many, it's so many.
You're at a conference, a meeting, and you I mean, I don't have the right.
This is a guy who doesn't have friends to tell him, Hey, man, maybe not.
You can't drop trow on stage at a scientific conference.
I mean, and let's be real. You shouldn't need to have friends who are your moral guideposts like that, Like that should be something that you know to not do right.
You can't do that.
You cannot, you cannot do that. But he did, Okay, he did. And so what can we take away from Brindley's lecture One? And this is the thing that's most often referenced when you know this is mentioned in any article or book about viagra, is that his demonstration showed
that you could induce erections with a vasoactive compound. This was fifteen years before viagra came on the market, and so this is why the story is often mentioned because it's like, oh, this is proof that people had been working on medications for a rectile dysfunction long before Peiser got into the game, and sort of the same physiological basis was used as like how to induce an erection? Yep, okay, fine,
that's the first thing. But the second thing that we can take away and this is the thing that I didn't see mentioned in any articles or books that included the story is excuse me, but like what what?
Yeah?
What?
Like?
How was this allowed to happen? How was this not disciplined afterward? And who has no one commented on how messed up this was?
Yeah?
Like, not only that, but people generally write about Brindley as this quirky, eccentric guy whose lecture was unique, dramatic, paradigm shifting, and unexpected. This is a quote right from unique. It is difficult to imagine that a similar scenario could ever take place again. End quote. I mean, I yeah, certainly, hope not no kidding. I mean it's the same thing we see time after time with certain people getting away with anything if their work is seen as valuable, right, like.
Literally exposing your erect penis to an entire room without consent, yes, or even warning. I mean not even warning much, not.
Even warning, not like, hey, what you're about to see is pictures of a penis on whatever, Like that's yeah, we can even Okay.
I would honestly expect it at a Eurologic Society conference, though I would still expect in the eighties some kind of warning like in the eighties. I guess you're.
Right today, I think that's generous of you. Yeah, sorry, yeah, but it's just it's it's amazing. Like the article where I pulled these quotes from is titled how not to Communicate New Scientific Information, and it was written in two thousand and five, and it's still Brintley is like, what a quirky guy. This was so unforgettable. Wow, he goes down in history as a really eccentric dude.
So wait, sorry, this is an article about how not to communicate things. Are they lifting him up as an example of good job?
Or like it's mostly like cheeky, like wow, what a guy. I can't believe he did this. What a scoundrel. So I mean the reflection still not there. I mean two thousand and five was twenty years ago, but still yeah, all right, okay, so I've already given enough airtime to Brittanley, Let's get back to viagra. The nineteen seventies and nineteen eighties saw a number of developments that set the stage
for Viagra's introduction. Injections with phasoactive compounds that gave people erections, a rectile dysfunction perceived as a deviation from the norm rather than a normal part of aging, and the switch in thinking of a rectile dysfunction's cause from psychogenic to organic. All of these things opened the door to reframing ed as a medical condition that affected quality of life and
thus was a therapeutic target. It's true that Phiser didn't set out to make an erectile dysfunction drug, but this reframing made it possible for them to seize the opportunity when it presented itself, which it did in nineteen ninety two. Phiser had for a few years been working on a medication to treat angina, experimenting with a few different compounds, including one called saltentiphil citrate, which had been synthesized by
fire in their sandwich labs in the UK. Essentially, they were looking for an alternative to nitrates, which worked in the short term but became less effective over time as tolerance developed. Early studies showed that sildenophil dilated the blood vessels, lowering blood pressure, a good thing because it meant sending more blood to the heart, but it could also lower blood pressure too much when used in combo with nitrates, as you mentioned, Aaron, and that was a common prescription
for their intended consumer group. Plus the short half life of sildenophil meant you had to take it three times a day, which was not ideal, and it was associated with a few adverse events like indigestion, headache, and erections, specifically more frequent and longer lasting erections, and that's how it was described like erections were labeled or were described as an adverse event. Despite what later versions of the story would have you believe, there was no light bulb
moment where Pfizer scientists proclaimed finally an erection drug. Initially, this side effect was just kind of noted down along with the rest of them, and even if someone did spend a few minutes of thought on it, sildoniphil didn't seem like it would be the best ed drug. The increased erection didn't happen until a few days after taking the drug, which you had to do three times a day, and the clinical trial involved young men, so there was no reason to think that it would have the same
effect in older men who had ED along with vascular disease. Okay, so if you wanted an erection on Saturday, you'd have to start taking the meds on Wednesday and not skip one of your three daily doses.
Interesting, yeah, based on their studies as an based.
On right, right, because this was not like at this point, sildoniphil had not been tested specifically for exrections.
Right right, right right.
But even with all these odds stacked against sildeniphil, researchers still thought it might be worth a shot. They had the molecular action of sildenophil mostly figured out, so they reasoned that maybe seldenophil in the absence of sexual stimulation equals no erection, but sildenophil plus sexual stimulation equals erection. And so Pfizer put together a couple of pilot studies in nineteen ninety three and nineteen ninety four testing sildenophil
for the treatment of ED. They recruited volunteers with ED gave them sildenophil or placebo, put them in a private room with erotic materials, and then monitored their erections using a device called the Ridgie scan. Yes that's the actual name.
Rigie Scan.
Love Reggie Scan. A note on the Ridgie scan. Sixty percent rigidity was considered successful, which corresponded to the amount of rigidity for vaginal penetration. So quite a heteronormative measurement.
There, not surprising, it's not at all. I just thought that, how this function is ormative?
Interesting? Yeah, the results of these pilot studies were promising. Sildenophil seemed to work, and what was even better was that it worked after a single dose. This opened the door to larger clinical trials involving thousands of individuals, which were also successful. Participants allegedly didn't want the trial to end, so Pfizer got permission to keep them enrolled in a long term trial. This is from someone affiliated with Pfizer,
so you know, grain of salt. In fact, actually a lot of the papers, a lot of the papers both about the history but especially about the effects of viagra or sildenophil, are like you can look and you're like, oh, Pfiser Labs. Yeah, oh yeah, Pfizer, Oh, Pfizer, Siser Fresher. Yeah. There did seem to be a few worrying side effects which you touched on a little bit aarin, but by and large it seemed relatively smooth sailing for Pfizer and Sildenophil in large art because its safety had already been
assessed in previous years. So in nineteen ninety seven, Peiser filed a new drug application for Viagra as it was now known with the FDA. The FDA gave Peiser Priority Review status, which is used for drugs that quote represent major advances in treatment or fulfill a significant medical need. And wow, okay. Within a year, the FDA approved Viagra for treatment of a rectile dysfunction, and the first oral medication for ED landed on the market in nineteen ninety eight.
Viagra's launch was anything but a quiet slipping onto the market,
and it drastically changed the marketing landscape for pharmaceuticals. You might think that an erectile dysfunction drug kind of sells itself, but in fact, at the time similar medications or devices were considered kind of CD, and so Pfizer had to carefully strategize their marketing campaigns, and one way they did this was to make it clear that viagra was for only certain kinds of people, essentially the straight, married, middle class, older white men that they featured in their early ads,
many of which didn't necessarily say or focus on erectal dysfunction or viagra outright, or if they did, they made it very clear that a rectal dysfunction was entirely a medical issue, not a psychogenic one. These ads also portrayed viagra as a relationship drug, promising to restore happiness, as
well as masculinity as narrowly defined in these ads. Pfizer was also one of the first to use celebrity spokespeople like Bob Dole in advertisements and paid consultants like urologists to appear on daytime talk shows or in commercials, and importantly, these consultants didn't readily reveal their connection to the company,
instead portraying themselves as un by experts whoa shade. This direct to consumer advertising seems super familiar to us now, although still bizarre and icky and dystopian, Like I don't have regular TV and so when I'm like in a hotel and they're commercial after commercial after commercial.
For every single commercial is for a drug, and it really drives me crazy. It's horrible, especially because very much like the ad for viagra, where they didn't even say viagra, Like now they all say the drug, but a lot of times they won't say the condition. Even so it'll make everyone who's listening think, well, I need to go talk to my doctor about this medicine. I have no idea what it's for, no idea what it's treating, but everyone on the TV needs it and they're so happy.
Right look at me, I can eat yogurt happily again, Like.
Right, look at me, I'm playing in the sunshine fly height what pushing my grandchildren on a swing?
Like it's just yes, uh, we laugh so we don't cry. But yeah, at the time that Viagra was released, this sort of direct to consumer marketing was super new. The FDA had only lifted the ban on these types of ads six months before the drug was released.
Also, they used to be banned and then they were lifted. I'm so curious. We need to do a whole episode on that.
We yeah, we really, we really really need to. The World Wide Web, which was relatively new in nineteen ninety eight. Also provided another avenue for people to gain more information about viagra and to try to buy the drug online without a prescription. Viagra was the butt of a million and one late night talk show jokes. It made appearances in storylines on TV shows, and soon everyone knew the name of this drug.
Yeah.
Many men took the logan ask your doctor to heart, and there were some reports that visits to doctors' offices actually increased for some groups of men who made their first appointment in years to ask about viagra. Erectile dysfunction went from a disorder treated in the nineteen sixties by psychiatrists to then be treated by specialist psychologists to one
treated by general practitioners. Within the first three months of its release, Viagra made four hundred and eleven million dollars in sales.
Is that in nineteen nineties dollars.
I believe so Yeah, Holy guacamole, and two point seven million prescriptions were written in the first three months.
Wow.
It became the fastest selling drug in history, grossing over one billion dollars in its first year and netting seven point four billion in total sales for Pfizer in its first five years. I am aghast, I know agg I'll just like the audience in Brindley's lecture. Some commentators sung the praises of viagra, like Bob GUCCIONI, which I don't know if I'm saying that right. The publisher of Penthouse who wrote that quote, feminism has emasculated the American male,
and that emasculation has led to physical problems. This pill will take the pressure off men, it will lead to new relationships and undercut the feminist agenda. And QUI I'm going to lose it. I'm gonna lose it. Uh, less
sexist and more reasonable. People pointed out that viagra had made sex, especially for older adults, more of an open topic of conversation, and it reduced the stigma attached to erectile dysfunction, but there were some many even critics of the drug, mostly centered around fears of how viagra would
change relationships, lead to addiction or recreational use. From an article in Time before Viagra's release, quote, doctors are concerned that an anti impotence pill could be subject to widespread abuse. Reports indicate that some Hollywood bedroom athletes have already tapped into an underground market for an injectable erection drug. The danger is that otherwise healthy men will take seldentifhil to bolster their sexual performance and then become psychologically addicted, unable
to achieve an orgasm without it. End quote. Bedroom athletes, athletes, A Hollywood bedroom athlete love that what. Prior to Viagra's release, Pfizer anticipated this opposition and quote sent a delegation to the Vatican to find out how the Roman Catholic Church would respond to the pill. The Vatican gave its blessing on the basis of Viagra's contribution to improving family relations.
End quote and barf. I get the Pope approved, Pope approved. Yes, the Pope's seal of approval stamped on every blue pill.
Oh my god, I have so many feelings I can't express them.
I mean, I not enough time in the world for me to process all of the thoughts and feelings.
I have the Pope approved viagra.
Improving family relations.
Yeah, family relations, that's what viagra improves.
Absolutely aarin. Others drew attention to the manner in which Peiser had branded a rectile dysfunction, accusing them of creating a disease or problem, and then inventing and marketing a solution classic capitalism. Then there was the question of normal. Even before viagra, medicine had sought to create a baseline for what was considered normal and what wasn't in terms of erections, arousal, masculinity, femininity, aging, sexuality, relationships, and bodies
in general. By constructing boundaries around what is quote unquote normal or acceptable, medicine can other people and make them feel like there is something wrong with them and they should be striving to achieve that normal. We've talked about this before in our Menopause episode, sort of the medicalization of a normal part of aging and some of the
issues that come with that. But like we also said in our Apause episode, that doesn't mean that we should completely reject these drugs that might make some people's lives a little easier, a little better, or a lot better. Just because something is a normal part of the aging process doesn't mean that we can't or shouldn't do something about it if we want to, and if it doesn't harm us, right, if.
It's causing problems in your life, like you seem, like we talked about with menopause, like is that totally a normal part yes, is some of it very uncomfortable and impacts your quality of life? Yes, do something about it. Same thing with Edah.
Absolutely, yeah. And so I want to push back a bit on this idea that a rectile dysfunction is solely a problem invented to sell a solution. Yeah, because clearly millions of people around the world have benefited from the use of viagra and related drugs and have reported that their quality of life has improved because of them. And the last criticism that I want to discuss is not about viagra itself, but about what Viagra highlighted when it came to gender bias in medicine and what is considered
medical necessity. Ah.
Yep.
Within a few months a Viagra's release in nineteen ninety eight, most major American health insurance carriers covered it. Also wow, Yeah, well because there were a few lawsuits pending, and so they quickly were just like, all right, we see this, we see this coming in our future, let's just cover it.
Within a few months, do you know how many insurance companies still won't cover ozempic and other similar I mean wigovy more like not ozempic, but the ones that are marketed just for weight less. That's a whole nother thing.
It's a whole other thing.
Yep, wow, okay, all right, cool cool.
But this was not the case for birth control pills. Right when Viagra came out, most people still had to pay for it out of pocket. The year Viagra was released nineteen ninety eight, women paid sixty eight percent more out of pocket health expenses compared to men because most reproductive health services were not covered.
Well, Aaron, birth control is not approved by the Pope, right.
It's absolutely not.
It's very much not.
The reasoning was that viagra is a medical drug intended to treat a legitimate medical condition, while birth control was and is seen as a quote unquote lifestyle drug. Oh my god, and therefore optional. I'm never mind the fact that many people use birth control to treat medical conditions, never mind the fact that birth control was approved by the FDA in the first place to treat menstrual disorders.
Viagra also brought to light other differences. For fifteen years after its initial release, the birth control pill could only be prescribed to married women, who often had to obtain their husband's permission. Only in nineteen seventy two were unmarried women allowed to obtain the pill. Can you imagine any law prohibiting an unmarried man from getting viagra or requiring that he get his wife's permission right so that she knows what he's up to? M hm, and I acknowledge
that it's a bit apples and orange comparison. Here is it, though, But swap out viagra with male birth control and the point remains. And finally there's the sheer existence of viagra, which was made possible only by years of studying the decline and erections over a man's life. Similar studies in women happening at the same time were few and far between, tinged with sexist assumptions, and kind of came to the conclusion, well, who even knows? There's just too much going on here?
Women are just too complicated. The switch from impotence is a psychogenic disorder to a rectilenction is an organic condition happened lightning fast. Compare that to the long, long tradition of women being told that it's all in their head. Even when it comes to quote unquote female viagra, it's the same thing. Quote is it a mind or body problem? End quote. Read the cover of a two thousand copy
of Newsweek. In early studies of vasoactive drugs for female sexual dysfunction, participants were required to see a sex therapist first. Who quote evaluates the context in which the patient experiences her sexuality, her self esteem and body image, and her ability to communicate her sexual needs to her partner. End quote. Oh it's hormonal. Oh it's about blood flow. Oh it's all in her head. Oh it's about her partner. Oh
it's about the general state of the world. Oh. Maybe it's a combination of all of them, and we'll never figure it out. How about arousal is not the same for everyone? But part of the issue seems to stem from the fact that the study of female sexual dysfunction takes the blueprint from male a rectile dysfunction. Researchers are looking for a direct parallel What is the female equivalent of an erection? But what if there isn't one in these studies? What is the outcome that the researchers are
looking for and how are they measuring it? Is it vaginal lubrication, is it clatoral engorgement, is it perceived arousal? Is it orgasm? Or is it some mix? Why has it taken so long to develop a female viagra. Great question, let's tell that story someday.
Also erin it hasn't changed. I mean, first line on up to date for female sexual arousal disorder is see a sex therapist, right, And.
It's never considered like, oh, a rectile dysfunction is so simple because we've been studying it for so much longer and we've put so much more funding into answering this question. But female arousal, female sexual dysfunction is so complicated because we don't really care about it, and we haven't cared about it. It's such a mystery.
It's also like it doesn't just service to everyone because like, yes, therapy is great.
And that's exactly what I have here. Yeah, because what viagra did is that it reduced male arousal to one dimension, right, and it led many researchers to do the same for female arousal. This is not good for anyone, right, Like, and I think that this is a really undertold part of the story where it's like viagra is great and if it works for you, whether you're whether the ultimate cause of a rectile dysfunction is psychogenic and viagra is working because it's whatever helping.
You overcome easier than you're less in your own head.
Whatever it is, right, whatever it is, but it's like, shouldn't we consider the whole picture instead of being like, it's blood flow, right, it's blood flow. It's blood flow, and for women, I don't really know, it doesn't seem to be just blood flow for you. So sorry, best of luck. I think this is why the story of viagra is so fascinating to me, is because of all
of these dimensions. Is because of the huge legacy that it has had on marketing, on sexuality, on the way that we talk about drugs, and I'm like blockbuster drugs, I mean everything, And so I'm really curious, Aaron, what you can tell me about viagra today.
I don't know, not much. I think we've covered it all, but I'll try and wrap us up right after this break, Aaron. We already talked about a lot of the statistics when it comes to the prevalence of a rectile dysfunction, which again mirrors one hundred percent in those over age seventy fifty or more percent. As you like, it increases, it's estimated to increase with each decade, usually over age forty so starting from like forty to fifty percent around age
forty and kind of going up from there. Exactly how are these statistics determined, It's a little bit unclear from all of the papers that I read, and that is not too like we've mentioned, undercut the importance of a rectile dysfunction in a person's sexual health, because we already underappreciate sexual health, especially in US healthcare, like it is just ignored across the board for a lot of people, and viagra and similar medications are often seen as this
kind of easy fix, a blanket fix for any kind of a rectile dysfunction. When is that the fix for everyone? Maybe not. There's also statistics that I saw in a number of papers that I don't know where these came from, and they weren't good. But also that estimate that a large proportion of people who maybe have a rectile dysfunction or are suffering in some way with their sexual function don't actually ever access even a drug as ubiquitous as viagra.
So there's again just a lot of it comes down to the way that we communicate about sexual health and the taboos that are still in existence about sexual health. Even though viagra has become sort of the butt of so many jokes and is so easy to come by these days. It's also estimated that in the US, the the cost of treatment for a rectile dysfunction is fifteen billion dollars a year.
How much do we.
Spend on female sexual health? Almost nothing, probably in comparison.
I have a question, did you come across any studies looking at the effects of viagra on women?
Great question, I didn't. I know that they do exist.
I didn't.
I probably should have spent more time looking for them specifically. But I know that they do exist, and I know that there are other there are other medicines that are targeting like female sexual dysfunction specifically. The one that I know of the most is not like a vasodilator. It doesn't work in that way. It's more closely related to
like the SSR rise. It like works I think in relation to seratonin, which is another neurotransmitter that is very much involved in like the a rectile process as well. But yeah, it is an area much less explored.
Okay, but in terms of like women taking viagraph women taking.
Viagra, it is a thing that has been done. I don't know the stats on it. Oh okay, yeah, yeah, I don't know the stats on it. There are, though, also a lot of other treatments for rectile dysfunction aside from viagra. There's similar medicines like the sialis or tadalaphil and others, some of which are now approved to take on a low dose daily basis rather than an as needed basis, which is how viagra has always been taken
and marketed. There are also other things like vacuum devices which use negative pressure to stimulate blood flow that helps the process along. There's injectable medications, there's suppository medications. There's other surgical interventions, especially depending on the cause of the rectile dysfunction to begin with, and you might need a surgical intervention. Some of these are like semi rigid all
the time. Some of these have pumps that you physically pump up when you need but there aren't, as far as I could tell, at least as of twenty nineteen, any new oral medicines that are targeting like very novel biochemical pathways to treat a rectile dysfunction. There's also a lot of supplements and nutraceuticals that are at your own risk entirely unregulated see our Supplements episode. And then there's newer therapies like shockwave therapy or PRP. All of these
very I don't know. I have a couple of papers if you want to go in detail on what the evidence of these are. They're all still very much in trials and not anything that's available on the market, But there is still a hefty amount of research going on on new and better ways to treat a rectile dysfunction.
It's a profitable business. It really really is one thing that I want to add just I know that someday we will do a female via episode because I think
that is really needed. But I think that like if we demand equal funding to find a female viagra, we should also demand equal evidence that what we find is therapeutic and not full of side effects and is as easy to take as viagra, that it actually does what it claims to, rather than just paying lip service to equality in medicine capitalism masquerading as feminism, which is I think some of the problems that are associated with some of these female viagras today, where it's just like, look,
we did it right, this is what you've been asking for. It's the equivalent oh, don't mind those side effects. Oh, don't mind this, don't mind that the evidence is kind of, you know, a little bit vague and leave something to be desired.
Well, And to do that we would need to do a lot more research on sexual health in general.
Yes, yep, but yeah, sources, sources. I have a bunch I didn't really like. I honestly, I feel like a lot of these were grain of salt. And again, like I mentioned in terms of where they came from, which was people who were working with Peiser at the time or were kind of one dimensional in other aspects. Anyway, there was a book called The Rise of Viagra, How the Little Blue Pill Changed Sex in America, And this is from like shortly after, just a few years after
its release, by Micah Lowe. And then if you want to read more about like the detailed how Feiser found this or how Piser like decided to shift their focus to seldeniphil as a treatment for a bactyl dysfunction. There's a book titled simply Sildentophil, and there's a chapter about the discovery of seldeniphil. Yeah, a whole.
Book, all right. I have a lot of papers that go far more into the detail of the neurobiology, and like Bioka, i'mal pathways of erections. There was a paper that I found really helpful by Dean and Lou from two thousand and five called Physiology of Penal Erection and path of Physiology of a rectil Dysfunction. Another by Grotski at All from twenty ten Anatomy Physiology and path of
Physiology of a rectil dysfunction. A few others that are specific to stildentophil, and like the pharmacology more of sildentiphil and other medications, and at least one on other ways that we use it, because again we use this medicine for other things too. But you can find the list of our sources, all of them from this episode and every one of our episodes, on our website, this podcast Weekilli dot com and it's under the episode stub that's where it is.
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