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- [00:05]
Drew
I always knew that there was a problem, but every time I would go to a doctor, they wouldn't actually tell me that I had an issue.
- [00:12]
Thomas Goetz
This is Drew.
- [00:14]
Drew
I'm 38 years old. Currently I live in Brooklyn, New York.
- [00:18]
Thomas Goetz
Drew felt that something was wrong, but he didn't know what until the Internet gave him a hint. Maybe this wasn't a mental issue. Maybe it was his testosterone. So Drew made an appointment with his doctor.
- [00:32]
Drew
Then he ran the test, and my numbers were in the low 200s. But for some reason, he told me that that was fine. I don't need my numbers to be any higher. So he kind of gave me the runaround on that. But I know as a man, you know, the way I was feeling, it wasn't. I wasn't 100% there.
- [00:49]
Thomas Goetz
Right.
- [00:50]
Drew
So I didn't take his word for it at all because I knew that there was a bigger issue underlying that he wasn't helping me with.
- [00:57]
Thomas Goetz
Yeah, yeah, it sounds like he wasn't very sympathetic.
- [01:00]
Drew
Not. Not at all.
- [01:02]
Thomas Goetz
Drew was struggling, and he knew that his testosterone level was relatively low for a man in his mid-30s. So he started doing his own research on Reddit. There's a lot of talk about testosterone on Reddit. There's a whole subreddit called, well, testosterone, with 200,000 members, mostly talking about testosterone replacement therapy, or TRT.
- [01:26]
Drew
Reddit kind of gave me more of the information that I was looking for, because like you said, real world and real people actually giving you real advice or their situations.
- [01:37]
Thomas Goetz
Eventually, Drew decided that TRT was right for him too. So he found a men's clinic in his neighborhood in Brooklyn and scheduled a visit. Do you remember your first shot?
- [01:48]
Drew
Yeah, I do remember. And it's kind of funny, because when I. As soon as I got the shot, and I know for a fact this is a placebo effect, but my confidence boost was, like, sky high. I was walking around, like, I felt like the man everywhere I went. And I know for a fact that it was the placebo, but I think it was like a new beginning for me. I was fixing something that I had a problem with for a long time, and it felt good to know I'm dealing with it. Yeah.
- [02:14]
Thomas Goetz
Yeah.
- [02:14]
Drew
So, yeah, that first shot was, like, mentally, it was the best. The best feeling that I've had.
- [02:21]
Thomas Goetz
Drew kept going back every two weeks for his dose, and in a few weeks, he started to feel the effect for real this time.
- [02:28]
Drew
And as the weeks progressed, I started just getting emotionally, like, more confident. My self esteem would boost up, and that's when I knew something was happening. Because before I would have to fight for those feelings. This time it was I was just waking up with confidence and energy, you know, ready to tackle the day Prior to that. It was a battle for me to get to that point. So I knew around that six week mark that it was definitely doing something for me.
- [02:56]
Thomas Goetz
Drew made other changes too.
- [02:59]
Drew
I was a lot more cautious about things I would eat. I upped my protein intake a lot, lowered my carb intakes, and a lot of that was just removing things from my diet.
- [03:10]
Thomas Goetz
And workout wise, how did that change?
- [03:13]
Drew
I was a lot more focused. I knew what I wanted to get out of it. Because that's another thing is within that six week mark, I didn't stop working out. As a matter of fact, I worked out more. So when I started noticing its effects, that was another thing that came along with it was an increase in muscle mass. And I noticed that. I noticed it on the scale and I noticed it in the mirror. And that was another confidence boost right there.
- [03:45]
Thomas Goetz
How would you describe the impact on your life?
- [03:47]
Drew
I'm a lot more confident. My wife is happy. I'm finding myself putting myself in situations that I normally wouldn't put myself in because of my confidence boost. So, yeah, I just, I feel like it's definitely the impact of my life a lot better.
- [04:03]
Thomas Goetz
I'm Thomas Goetz, and this is Drug Story. Today's drug Story is about testosterone, or trt, testosterone replacement therapy. That's when it is prescribed to treat what is called low T. But first, let's be clear about what we're talking about here. Testosterone is a hormone that's produced in men in the testicles. I'm sorry, but I'm going to say that word testicles a lot in this episode, like a dozen times at least, maybe more. Women's bodies produce testosterone too, by the way, in the ovaries, but in much smaller amounts anyway. Testosterone gives men a lot of benefits. It helps our concentration, our energy, our mood and memory. And of course, it gives us a sex drive. But as we age, the testicles produce less of it. That's totally normal, or at least it was until TRT came along. TRT has soared in the past 25 years. Today, if you start a conversation with a man over 40 and you mention TRT, odds are they or one of their friends are on it. And they may not be at all shy about it because as many as 14% of men in this demographic have taken testosterone. They geek out on their numbers and their dosage and their regiment. It is a whole thing these days. And so what was once a taboo is now quickly becoming widely accepted. For many men, TRT is just a part of managing getting older. And increasingly, it's not just men over 40. Many younger men like Drew are turning to TRT to address a range of concerns like self confidence, depression or virility. Virility isn't just our sex drive. It describes the whole range of male characteristics like strength and health and potency. And so the growing use of TRT has created real questions around what manhood and masculinity should look like. We now live in a time when you can turn on masculinity with a switch or more precisely, with a shot. So in this episode, we're going to look at the idea of low testosterone and the creation of low T as a condition. We'll learn about how testosterone responds to winners and to losers. And we'll peek into the darker corners of Reddit and YouTube where TRT is routine, normal and encouraged. That's all coming up on today's episode of Drug Story. And here's a pump up song to get you in the mood.
- [06:42]
Dr. Charles Ryan
Got to be a macho I got
- [06:45]
Thomas Goetz
to be a macho, macho man I've got to be a macho Drug Story is sponsored by GoodRx. Every prescription has a story, and for many patients, affordability is a defining chapter. Goodrx makes it easier to find lower prices on prescriptions from GLP1s to flu meds, so cost isn't a barrier to care. Trusted by nearly 30 million Americans and over 1 million health care professionals each year, GoodRx offers savings at more than 70,000 pharmacies nationwide, helping people start and stay on the therapies that keep them healthy. To start saving, go to goodrx.com that's goodrx.com GoodRx is not insurance. Welcome back. Each episode of Drug Story has three parts. The diagnosis, the prescription, and side effects. This is part one, the Diagnosis, where we explore the underlying medical condition. In this case, that would be low testosterone, or more precisely, hypogonadism. That's the medical term for when your testicles don't work like they're supposed to. We're going to start our story on Mauritius, an island off the coast of Africa near Madagascar. And we're going back more than 200 years to 1817, when this little island was a long, long way away from practically everywhere else on earth. That's where and when Charles Edward Brown Sicard was born. Charles's father was An American sea captain, but Charles never knew him. He had been lost at sea before Charles was even born. So Charles was raised by his mother, a French seamstress. At 20 years old, Charles convinced his mother to sail for Paris in search of a better life. There, Charles enrolled in medical school. He was an ambitious but moody student, out of place and impulsive. But his timing turned out to be perfect. Medicine was just emerging as a legitimate science, and Brown Sicard began to make his name as a relentless scientist. He taught in Paris and London, and he spent years in the United States, taking a position at Harvard University as the medical school's physiologist and pathologist. The field of medicine was breaking wide open. Discoveries were waiting to be made, and the public was desperate for cures. Brown Sicard helped identify the basic functions of the spinal cord and the nervous system. He helped pioneer the field of endocrinology by establishing cause and effect of organs and hormones. There was so much to do. But as he entered his 60s, Brown Sicard began to slow down. By this time, he was back in Paris as the professor of experimental medicine and the College de France, where he used to bound up a flight of stairs. He now found himself clutching to the banister, taking one step at a time. Where he once enjoyed working on his feet in his laboratory, he now stayed seated for most of the day. And upon coming home from his work, he would eat a bit and go right to bed. When he was 72 years old, he
- [10:09]
Charles Edward Brown Sicard
wrote, my general strength, which has been considerable, has notably and gradually diminished during the last 10 or 12 years.
- [10:20]
Thomas Goetz
Being a physician, Brown Sicard was fairly certain what the problem was.
- [10:24]
Charles Edward Brown Sicard
The feebleness of old men, he later wrote, is in part due to the diminution of the functions of the testicles.
- [10:32]
Thomas Goetz
And being a scientist, he decided to undertake an experiment on himself. He created a mixture of three ingredients taken from guinea pigs and dogs. First, some blood drawn from the testicles. Second, it's semen. And third, fluid extracted from a testicle immediately after it had been removed from the animal and crushed. He mixed these fluids with some distilled water and injected it into his leg. Over the next three weeks, he injected himself nine more times. He was a changed man. His appetite came back. He ran up the stairs again. He lifted weights and found he could hoist more. He reported that he had a stronger jet of urine and more vigorous bowel movements.
- [11:26]
Charles Edward Brown Sicard
A radical change took place in me,
- [11:28]
Thomas Goetz
he wrote in the Lancet, the most prestigious medical journal of the day.
- [11:32]
Charles Edward Brown Sicard
I found that I had fully regained
- [11:35]
Thomas Goetz
my Old powers, Brown Sicard urged other scientists to conduct their own experiments. And they took him up on it in droves. Soon, testicular extract was being tested around the world, from New York to Paris to Cleveland. Newspapers everywhere began to cover the news as if Brown Sicard had discovered the fountain of youth. By the end of 1889, more than 12,000 physicians worldwide were experimenting with Brown Saccard's fluid manufacturing Chemists were making fortunes selling what they called the elixir of life. Some pitched it as oyster juice. Now, who knows where all those guinea pig testicles might have come from? And honestly, it's unlikely that all those people buying all that elixir were actually getting bonafide testicular extract in time. After the frenzy of hype and bogus treatments, the medical establishment began to push back on Brown Sicard's elixir. They questioned whether the treatment had any benefit at all. Brown Sicard acknowledged as much. He himself raised the possibility that what he experienced was due to auto suggestion, what we would call today the placebo effect. Today, many experts say that's what was going on, the power of suggestion. But Brown Sicard was clearly on to something. He also speculated that extracts from female ovaries could provide relief to women in menopause. That turned out to be true. Here and there, reputable scientists continued to experiment with testicular extract, including two scientists who injected themselves with fluid from bull testes. They gained strength. They tested it curiously on the strength of their middle fingers. The unanswered question, though, was what was in those testicles that seemed to bestow vigor and vitality? Was it the semen? The blood? Something else? The answer would come four decades after Brown Sicard's experiment. By the late 1920s, scientists knew that our bodies were full of hormones, chemicals produced by glands that had specific functions in the body. In the 1930s, a German scientist named Adolph Butinand discovered the first sex hormone in women. Estrone. He had examined the urine of pregnant women. A few years later, he struck again. Boontinand somehow obtained 15,000 liters of urine from Berlin police barracks. Out of that prodigious volume of piss, he extracted 15 milligrams of the first known male hormone, androsterone. Not long after, the scientist and a colleague announced that they had effectively synthesized another male sex hormone, testosterone. In 1939, they were awarded the Nobel prize in chemistry for the discovery. The Nazi government, though they forced Butinant to decline the award. Synthesizing testosterone was everything synthetic hormone meant. No more animal extracts, no more guinea pig or dog Testicles. Now, chemical science could produce testosterone industrially in massive quantities, though in actual fact, at first, the uses were fairly uncommon. Hypogonadism was something severe and rare. It was diagnosed when someone failed to develop testicles or when someone had damaged or non functional testicles. Synthetic testosterone was also used in some cases of anemia and muscle wasting, but it was not a common treatment. But then, in 1945, a new argument for testosterone arrived in a sensational book by the science writer Paul de Kruff called the Male Hormone. This book was a celebration of synthetic testosterone, a manifesto for manhood. Like Brown, Sicard du Krouf believed that testosterone could rekindle the fire of virility in an aging body. And like Brown, Sicard Dukhruf was a willing subject of his own experiments. At 55 years old, he took testosterone supplements for a year before writing the book, and he testified that the benefits were enormous. He had more energy, more muscle mass, and more appetite for sex. The Male Hormone is a fascinating book, in part because for something written back in 1945, it is really honest and upfront about sex, and also because the book foreshadows the same argument and enthusiasm for TRT that exists today in the manosphere among the booming longevity movement. I mean, growing old isn't natural. That's the title of the first chapter. D' Khruuf even argues that taking testosterone will be as common as vitamins. He was truly ahead of his time. So it's something of a surprise that in spite of Dukhruf's popularity and passion, testosterone supplements did not take off in general use in the 1940s and 1950s. Instead, testosterone went underground. In the 1950s, bodybuilders in California began using synthetic testosterone to improve their muscle mass and lean physique. Around the same time, the Soviet Olympic team secretly used testosterone, a Soviet physician spilled the beans to an American team doctor, and so the US weightlifting team included it in their training for the 1954 Games. Testosterone use in sports was an open secret. In theory, the drugs were banned, but there were no valid tests to detect them. In 1969, the editor of Track and Field magazine called anabolic steroids the breakfast of champions. By the time the International Olympic Committee finally began effectively testing for the substances in 1976, they were already wildly abused throughout amateur and professional athletics. Even today, it's a cat and mouse game between steroids and testing. And just to make this clear, all anabolic steroids are either testosterone or they make the body produce more testosterone. That's the Whole game now. Back in the world of legitimate medicine, testosterone was still rarely prescribed for anything that might be considered a lifestyle purpose. For a long time, testosterone replacement therapy was just uncommon. But that would all change when the FDA officially approved AndroGel, a new kind of Testosterone supplement, in 2000. Soon the whole world would learn about something called low T, and the whole idea of masculinity and manhood would never be the same. We'll get into that coming up. But first, here's one of the original commercials that mentions low T. And no, this is not a sponsor or advertiser for Drug Story. This is. This is journalism, people.
- [18:37]
Low T Commercial Voice
Millions of men 45 and older just don't feel like they used to. Are you one of them? Remember when you had more energy for 18 holes with your buddies, more passion for the one you love, more fun with your family and friends? It could be a treatable condition called low testosterone or low T. Come on,
- [18:56]
Scott Flynn
stop living in the shadows. You've got a life to live, so
- [19:00]
Low T Commercial Voice
don't blame it on aging. Talk to your doctor and go to isitlowt.com to find out more.
- [19:10]
Thomas Goetz
Welcome back to Drug Story. This is part two, the prescription. We're going to look at the emergence of low T as a novel condition and the rise of TRT as a routine therapy after testosterone was first synthesized back in the 1930s. For more than 60 years, the only way to take the hormone was by injection, a syringe filled with the stuff, pretty much the same method that Brown Sicard tried back in the 19th century. This was likely one reason testosterone supplements were rarely used outside of people with serious testicular problems or athletes looking for an edge. You had to be really in it to win it, to get that needle stick. That all changed in the 1990s when a patch was developed that delivered testosterone through the skin. That was much easier than an injection. The only trouble was that patch had to be affixed to the scrotum, and it often caused skin irritation, which sounds like an uncomfortable combination. A few years later, things got better. In 2000, a new testosterone product was approved by the FDA. AndroGel, a topical gel that could be applied anywhere on the body, typically the shoulders. Suddenly, it was a whole lot easier to get supplemental testosterone. The only trouble for Solvay Pharmaceuticals, the company that made Androgel, was that the FDA approved it to treat hypogonadism. As I mentioned earlier, that was understood as a serious and rare condition where the testicles don't work properly to produce testosterone unless the company could find a Way to expand on how doctors understood hypogonadism. Solvay would have a very easy to use drug for a very small market. Their first answer was andropause, a term used to describe so called late onset hypogonadism. The term andropause had been floating around in medical circles for a few years. It suggested a male equivalent to menopause. That's when older women stop menstruating and levels of estrogen decline. Menopause is of course a natural process for women and hormone replacement therapy can help alleviate symptoms. So drawing a parallel in men, well, that seemed logical. Other terms made the comparison even more obvious. Male menopause was floated out there, or even manopause. You get it. Solvay worked hard to get andropause to stick. A few months before Androgel hit the market, the company sponsored the first medical conference dedicated to this new condition. They paid physicians to conduct research into hypogonadism that fortuitously suggested that waning testosterone in older men. It led to other health problems. And they promoted the ADAM test. ADAM stands for androgen deficiency in aging males. The test was a short questionnaire that would help doctors diagnose andropause in their male patients. And Here are the 10 questions.
- [22:15]
Charles Edward Brown Sicard
Do you have a decrease in libido sex drive? Do you have a lack of energy? Do you have a decrease in strength and or endurance? Have you lost height? Have you noticed a decreased enjoyment of life? Are you sad and or grumpy? Are your erections less strong? Have you noticed a recent deterioration in your ability to play sports? Are you falling asleep after dinner? Has there been a recent deterioration in your work performance?
- [22:48]
Thomas Goetz
I mean, come on. You could ask any men over 35 those questions and they're going to answer yes to at least half of them in the Adam test. The this was developed by Dr. John Morley, an endocrinologist at the Saint Louis University School of Medicine. A pharma company donated $40,000 to his school in exchange for the test, which he admitted to the New York Times a few years later. He had drafted in his bathroom in 20 minutes. As he told the Times, I have no trouble calling it a crappy questionnaire. It is not ideal. The ADAM test remains to this day a widely used way to screen for low testosterone. The andropause campaign worked. Prescriptions for TRT doubled after Androgyl hit the market in 2000. But the FDA, well, they were flummoxed by the rise of this new term. An FDA director told the new Yorker at the time that the FDA never approved AndroGel for Andropause. We're not sure what Andropause is. The intention was that Androgel would be for people with conditions like Klinefelter's and pituitary dysfunction. Then executives at Solvay came up with something even better than Andropause. They opted to skip the whole idea of a medical sounding term, the whole comparison to menopause. Instead, they latched onto a term that had been floating around the bodybuilding community for years. Low T. T, meaning, you know, testosterone. Low T is much easier to say than hypogonadism. And it didn't have that, you know, gonad in the middle there. And it also created a whole new concept around testosterone, that it's just a number easily measured by a blood test and something that could be readily optimized. Low T was a revolution, especially after a 2002 study found that testosterone rates in American men were trending down historically. And it shifted what science considered hypogonadism instead of low testosterone caused by poorly functioning testicles. Increasingly, hypogonadism was understood as simply anyone with low T by that definition. A 2006 study found that a staggering 40% of men over 45 could be diagnosed with it. That study, by the way, was funded by Solvay Pharmaceuticals. All this research suggested that low T was a much bigger problem. It seemed increasingly clear that something was medically wrong in older men with lower levels of testosterone and that TRT could be the cure. Soon, commercials spreading the word about low T were appearing all over television. A new website appeared online, isitlowt.com and that helpfully offered the Adam test to curious visitors. The site was developed by Solvay Pharmaceuticals. Ghostwriters wrote stories about low T for leading magazines, including Women's Day and Businessweek, that were published under the names of well known physicians. But neither the ads nor the site mentioned andor gel by name. Quite deliberately, they were just raising awareness, not selling a product. This wasn't modesty. It was a clever way to socialize the idea of low T as a common problem without running afoul of FDA rules that prohibit marketing of a drug for unapproved purposes. So by spreading the idea of low T as a medical issue that men should talk to your doctor about, well, that was legal so long as the ads didn't directly connect the dots to a specific drug or treatment. And thus the stigma around low T&TRT began to fall away.
- [26:47]
Low T Commercial Voice
Feeling like a shadow of your former self.
- [26:49]
Thomas Goetz
Michael, get in the game.
- [26:50]
Low T Commercial Voice
Don't have the hops for hoops with your buddies. Lost your appetite for romance and your mood is on its way down. You might not just be getting older. You might have a treatable condition called low testosterone or low T. Millions of men 45 or older may have low t. So talk to your doctor about
- [27:08]
Thomas Goetz
low t. Hey, Michael.
- [27:09]
Low T Commercial Voice
And step out of the shadows.
- [27:11]
Thomas Goetz
Hi, how are you? Learn more@isitlowt.com these ads were incredibly effective. A study in Jamaica, the journal of the American Medical association, it found that every time a commercial played in a Metro market, local TRT prescriptions went up almost 1%. And those commercials played a lot. All over the United States, prescriptions for Androgel took off. They grew by 55% in 2012 alone. That year, AndroGel sales brought in more than 1.3 billion. Billion. In 2013, the marketing team behind Andergel was named the all star marketing team of the year by the trade publication Medical Marketing and Media for their work in, quote, convincing men with low or no testosterone that their condition wasn't abnormal or anything to be ashamed of. In 2015, the FDA issued a public warning. It cautioned against using testosterone products for low testosterone due to aging. The warning insisted on the stricter definition of hypogonadism as a true disorder of the testicles. And it reasserted that declining testosterone in aging males was a normal process. But all of that was just too little, too late. The idea of low T was already out of the barn. Loti was here to stay. But what exactly is low or even normal when it comes to testosterone? For this, we turn to Dr. Charles Ryan, a physician at Memorial Sloan Kettering in New York and the author of the Virility Paradox, a great book about testosterone. What is considered a normal range? How is that chosen?
- [28:59]
Dr. Charles Ryan
Great question. Because normal blood tests, right? You go and you get a blood test from your doctor and they say it's normal, it's abnormal. Whatever a total testosterone level is for a male who is generally healthy is somewhere between about 250 nanograms per deciliter in your blood to maybe 750, 800 nanograms per deciliter in your blood. Now, it's highly skewed by your age. If you pull a group of 21 year old college students into a lab and test their blood, they're going to skew a little higher. If you pull a group of, you know, 75 year old men and test their blood, they're going to be skewed towards the 250, 350 range.
- [29:42]
Thomas Goetz
So that is a huge range, 250 to 800 nanograms. And as Dr. Ryan explained, it can vary widely from day to day or hour to hour. So you might take a test and get a 500 normal and then try again in a couple days and it's 200 boom. Low T. These variations can arise from all sorts of things. Hormones ebb and flow. But one of the amazing things is that testosterone rises when good things happen. This, as Dr. Ryan explains, is called the winner effect.
- [30:17]
Dr. Charles Ryan
So the winner effect is something that has been talked about in anthropology as a relationship between success and testosterone levels. Testosterone in the winter effect has something of a positive feedback loop, which is an event happens, an individual does something successful that could be they're hunting and they kill an animal that's going to feed their family or something like that, and their testosterone level will go up. And the idea of the feed forward is that having a higher testosterone then may drive improved performance and further winning. And you can think about the obvious evolutionary impact of that, which is if you're the successful hunter who comes back with a food and B, a higher testosterone, you're going to be seen as more attractive by potential mating partners. And that may multiply through the millennia of evolution, thus sort of compounding this winter effect.
- [31:16]
Thomas Goetz
Right. And I, I get it for hunting, but, but like it happens in daily life in like Minnesota or, or San Francisco.
- [31:27]
Dr. Charles Ryan
Yeah. Or Wall Street. Right. There was an interesting study that looked at a few years ago at day traders. And what they did is they collected testosterone twice a day. Once was at 11am at the beginning of the trading time period and at the end. And what they found was that the people with the higher testosterone levels tended to have a greater profit and loss than those who didn't. Now, it wasn't that there were people with high testosterone who were great traders and there were people with low testosterone who wasn't. All traders had high days and low days. And what they found was that the high days associated with better financial outcomes of their day trading. We can also see that there is testosterone rise may be tied to other reward circuits we have in our brains, like dopamine, et cetera, such that success in other areas, you know, making a sale, if you sell cars, having a successful surgery, if you're a surgeon, you can see how those could happen on a micro level many times a day
- [32:27]
Thomas Goetz
in all of us. It's not necessarily that people with high testosterone do better. No, it does become a loop where, where success in Theory raises testosterone level and that increases confidence, which might improve your chances of success. Again.
- [32:44]
Dr. Charles Ryan
Correct.
- [32:45]
Thomas Goetz
There's a positive feedback loop. And where there is a winner effect, you may imagine that there is also a loser effect.
- [32:53]
Dr. Charles Ryan
Right. So maybe there is a really interesting study. It's old. 1994 Went to the World cup, the soccer World cup, and there was a. I think it was the final match between Brazil and Italy. What they did is they followed fans and they measured the testosterone levels in fans of both teams. So Brazil won the match. And within minutes of the game, 11 of the 12 Brazilian test subjects showed elevated testosterone levels. Not huge, a bump. Most levels increased by about 15 to 35%. But two of the men experienced an almost 100% spike. So they had a doubling of their testosterone level just from watching Brazil win. The Italian fans experienced a decrease in testosterone, every one of them. And the reductions were similar in magnitude to the increases seen in their counterparts, you know, 15 to 20%. But there were two Italian fans who had a more than 50% drop. So I think there probably is a loser effect.
- [33:58]
Thomas Goetz
It turns out that married men also have lower rates of testosterone. So do frequent marijuana users and people with depression. People with insomnia or obesity have lower testosterone levels. It's difficult to tease out cause and effect here because of the winner effect and the loser effect. Does being obese give you low T, or does having low T make you less active, which leads to obesity? Depending on the who and the why, it could be either one or both at once. Hormones are complicated, but you can see how to a great many men, TRT might seem like a reasonable treatment for all sorts of conditions. Taking a testosterone supplement starts to sound like a pretty easy answer to a lot of complicated problems, including self esteem and lack of confidence and depression. It seems like an elixir for life. And to be clear, I don't want to suggest that many men are not struggling, that they are not experiencing real challenges, or that TRT does not work to help some men. I spoke with Scott Flynn. He's a psychiatric physician's assistant with a mental health practice in Georgetown, Texas, about 30 minutes north of Austin.
- [35:12]
Scott Flynn
I started noticing that in some of my older gentlemen, these guys were just not getting better. They were coming in with very classic run of the mill depression symptoms. Low energy, low interest. What we call anhedonia, for example. Just a lack of joy, a lack of interest. You know, there's not much motivation. A lot of these guys were coming in just convinced that they had adhd. They can't focus, they're struggling to make decisions. They feel their work performance over the last five, ten years or so has, has really, you know, started suffering. And so I started ordering more labs, which we rarely ever do in psychiatry. I was seeing just shocking numbers coming back in the 1000s and 2000s. And there's just absolutely no reason whatsoever why somebody should be so low. But I, you know, I started thinking to myself, this is, this is a testosterone issue.
- [36:15]
Thomas Goetz
So he started prescribing TRT for them, and it worked.
- [36:19]
Scott Flynn
So what happens? Well, you know, I, I often use the analogy of like the low gas tank. You know, if our body is, is just simply kind of running on fumes and not just for a week, not just for a month like myself, you know, I, I spent a good five, six years running on fumes, let's say. And when you fill the gas tank up and you know, you've got high octane fuel running through your body, you are going to feel like a new person. Whether mentally, cognitively, these things all just, they get significantly better. These gentlemen fill up their gas tank, they feel fantastic, they feel rejuvenated.
- [37:05]
Thomas Goetz
And as you may have guessed, as he hinted at there, this is something Scott knows personally. He has himself been taking TRT for more than a year with great success, he says. So what's the downside? What could possibly go wrong if millions of men decide that taking testosterone works for them? Where is the harm? We will get into that coming up in part three after the break. But first, here's another ad for Androgel, which is not a sponsor of this podcast. This commercial is from 2013 and it does a great job of making it seem like TRT is just a normal thing to do.
- [37:45]
AndroGel Testimonial Voice
I have low testosterone. There, I said it. How did I know? Well, I didn't really see. I figured low testosterone would decrease, increase my sex drive. But when I started losing energy and became moody, that's when I had an honest conversation with my doctor. We discussed all the symptoms. Then he gave me some blood tests showed it was low T. That's was a number, not just me.
- [38:06]
Thomas Goetz
Today, men with low t have AndroGel 1.62% testosterone gel. The number one prescribed topical testosterone replacement therapy increases testosterone when used daily. Women and children should avoid contact with. Welcome back to Drug Story. This is part three, side Effects where we look at what happens when you start treating a disease with a drug. Except in this case is low T. A disease is low T just an inevitable part of life. But now there's a drug, a hormone, a supplement that makes it maybe not so inevitable anymore. Over the past 25 years, taking steroids or testosterone has gone from being a shameful scheme for cheating athletes to to being perceived as a reasonable, maybe even outright healthy way for men to get back to normal or even better than normal, to live your best life to make the most of your manhood.
- [39:01]
Tom Costello
It's being called a landmark study that could affect millions of men who suffer from low testosterone. Low T as the ads call it, has been linked to everything from loss of energy, muscle mass and sexual function to to increase vulnerability to illness. And now, as NBC's Tom Costello tells us, new research sponsored by the National Institutes of Health shows testosterone replacement therapy may have some benefits.
- [39:27]
Thomas Goetz
And it worked for Androgel. It was a huge hit. At the same time this idea of low T, it was up for grabs. Anybody or any company could try to grab a piece of this action and soon enough, lots of companies found that there was money to be made in low T, whether they had an FDA approved prescription drug to sell or not. Hi Jose Canseco. Have you noticed as you've gotten older that you don't have the energy or strength or sexual performance you had when you were younger? Maybe you have more stomach fat. It may just be the low testosterone. Frank Thomas, AKA the Big Hurt used to keep pretty busy on the baseball
- [40:05]
Low T Commercial Voice
field, but now he's busier than ever.
- [40:08]
Thomas Goetz
After I turn 40, it wasn't easy to keep up. Everything changed.
- [40:12]
Dr. Charles Ryan
My energy, my drive. And then I found Nugenics just like millions of others.
- [40:17]
Low T Commercial Voice
Why should every man try Ageless Mail Max because it has KSM66 to help
- [40:22]
Thomas Goetz
increase testosterone and Knox perform to boost nitric oxide. These are all ads for supplements, non prescription treatments that fall outside of the FDA's oversight or jurisdiction. Many sold herbal concoctions with things like Ashwagandha, Coleus, dhea, fenugreek and zinc. But who knows what is actually in them? Who knows if they actually work? There is just not a lot of solid research on these supplements. And where there is, the sample sizes are typically small and the products lack long term safety and efficacy data. So take the supplements with a grain of salt. There has also been a boom in men's health clinics. Some of these clinics offer comprehensive medicine and clinical care for men while others are focused exclusively on low T and erectile dysfunction. They offer easy appointments and cash only prescriptions for Viagra or trt. There are hundreds of these clinics across the country. Ageless Men's Health and Renew Vitality Clinic and Prime Performance. There's even a new chain called Game Day Men's Health. With more than 300 clinics open from Texas to Manhattan to Florida and 1,000 more franchises in the pipeline, GameDay offices are designed to look like well man caves. There are big screen TVs playing ESPN and issues of Motor Trend magazine on the coffee table. Plus there's in office lab testing and sticking with the latest wellness trends. They also offer GLP1s peptides and vitamin injections. And you too can open a Game Day franchise if you have a net worth of $450,000 and are ready to invest $200,000 in a new location. Okay, this boom in men's clinics has pros and cons. For one thing, men are notoriously bad at going to the doctor, getting a checkup, caring for their health. So if these clinics make it easier for men to see someone about their health, that is all to the good. But these clinics are not really a substitute for a proper doctor's visit. They don't even have a doctor, an MD on duty full time. Here's Dr. Ryan again.
- [42:42]
Dr. Charles Ryan
If you walk into a testosterone clinic and complain of those things, you are a nail walking into a hammer shop, right? You're going to get the treatment. That is not to say that the loss of confidence and the depression or the other factors are contributed to by low testosterone, but to say that that's the only cause is illogical and it is not consistent with how a clinician should think. And you know, just because you have a symptom and you have a low testosterone does not mean that the low testosterone has caused the symptoms. It could be that somebody has had a series of events in their life, psychological or physical, that have culminated in a psychological state or a psychiatric state where they are and low testosterone. But it's not a cure for the underlying disorder. Fundamental principle in medicine is you try to treat the underlying disorder, not just the symptoms if you can. Some people might hear what I'm saying and say, well, yeah, but if I feel better, who cares? And I would say that might be part of it. But if you leave an underlying disorder uncorrected or unaddressed, you miss the opportunity to improve the whole health of the individual.
- [44:00]
Thomas Goetz
This goes way beyond storefront clinics. The testosterone boom has gone online in a big way. There are now dozens of telehealth companies that cater to Men's Health. Hims and Hone and Ro and Rex and Dudemeds and Peter, MD and Titan and Maximus. Yes, that one is a little on the nose. My name is Maximus Decimus Meridius, Commander of the Armies of the North, General of the Felix Legions, loyal servant to the true Emperor Marcus Aurelius, father to murdered son, husband to a murdered wife.
- [44:41]
Low T Commercial Voice
And I will have my vengeance in
- [44:44]
Thomas Goetz
this life or the next. These are all actual companies and they make it super easy to get TRT or all sorts of other so called lifestyle medications. They are all about helping you achieve a better you Increase testosterone, lose weight, improve sexual function, enhance performance, live longer. Seriously, they promise that too. You can sign up, do an online assessment and get a prescription, cash or credit. No insurance in about half an hour. Visit one of these sites and you are on the periphery of the manosphere. That's stew of websites and forums and podcasts that promote a hyper masculine, super super stoked version of manhood. The manosphere gets pretty dark pretty fast, but you can stay in the mainstream and find Joe Rogan talking openly and enthusiastically about trt. Hormone replacement therapy exists for a reason, and that reason is it makes you feel way better.
- [45:51]
Tom Costello
It makes your body work way better.
- [45:53]
Thomas Goetz
You can avoid a host of ailments and conditions that are related to your body breaking down due to age with hormone replacement therapy. Or visit Reddit and the testosterone subreddit. There you will find guys sharing advice on dosages and syringe sizes and side effects. Back acne is a big one. They are geeking out on their numbers and their routines. There are a lot of before and after pictures, many of them guys in their 20s or 30s who start a little chubby and then six months later jacked. TRT has clearly gone way beyond older men feeling they have lost their pep. There's a clear overlap here with bodybuilding culture and all the maxing and bro science they're in. Reddit is a rabbit hole. If you take a peek, make sure you do not fall in. Most of these guys don't even seem to be using Androgel. The most common way to take TRT these days is the old fashioned way, an injection every few days. Here's Dr. Ryan so the problem with
- [47:03]
Dr. Charles Ryan
the manosphere ethos is that manosphere doesn't encompass the rest of the world. We live in a world with others. There are other people here. And if your goal of taking testosterone replacement therapy is to have a better social media pose, or to show that you've got more muscle or lean muscle mass or whatever, you may win on Reddit, you may win in the social media, but are you winning in life when you do that? Because you're going to compromise things like your empathy and your compassion and your patience for others. Maybe you're getting laid more, but are your relationships healthier? Are you a better person in society? Does society need more people like that? And I think that at the extremes, the answer is obviously no.
- [47:50]
Thomas Goetz
So that's the extremes. But what about the original use case for TRT and low T? Older men whose testosterone levels have indeed dropped below normal levels? What's the benefit for them?
- [48:02]
Dr. Charles Ryan
The New England Journal of Medicine in 2016 published a randomized placebo controlled trial of 790 men 65 years or older and had low serum testosterone. And they had to have symptoms suggesting that the testosterone would work. And what they did was they replaced the testosterone. They were pretty diligent about maintaining levels within a normal range. So these are people who started out low, you've replaced it, you've put it up into the normal range. And in this group of symptomatic patients, raising testosterone for one year from moderately low to the mid normal range had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms, but did not benefit with respect to vitality or walking distance. Vitality is a term of art, if you will, in medicine that has criteria like energy for doing various activities of daily living and seeking pleasure and things like that. But when I read that paper, I said it wasn't the home run for everybody. The enthusiasm needs to be tempered because moods got better, sexual function got better. But maybe overall quality of life was not the big win that they thought it was going to be.
- [49:21]
Thomas Goetz
And what are the side effects? Well, your testicles shrink, for one thing. With all that testosterone in your body, testicles don't need to produce as much, so they atrophy. You can stop TRT and see if they kick back in. Sometimes they do, though. Sometimes they do not. Which means you're going to have to keep taking TRT for life. Pretty much. If you have prostate cancer, TRT can make it worse.
- [49:47]
Dr. Charles Ryan
Testosterone does not cause prostate cancer. It is what's called a tumor promoter. It drives it, it fuels it.
- [49:53]
Thomas Goetz
But outside of that, there is not a lot of evidence that TRT is hugely dangerous, provided you stay in the normal range. There have been concerns around heart disease and stroke over the years. In fact, back in 2013, the FDA required warning labels put on testosterone. But they reversed that in early 2025 after a new study found no evidence of increased risk over time. But even if we don't call them side effects, there are well known things we associate with testosterone. Aggression and anger. Short temper, Selfishness. These are traits of manhood that all flourish with trt, and they are not always positive for the man on TRT or for the people around him, which is something that Dr. Charles Ryan knows about, because, remember, his book about testosterone is called the virility paradox, meaning there are trade offs to being virile.
- [50:49]
Dr. Charles Ryan
Well, the paradox is essentially that this role has two sides. Testosterone as a hormone, virility as a construct is to our benefit. Virility shapes our desire to build, to survive, to explore, to procreate. We wouldn't be alive as individuals nor as a species without virility. It gives us strength. It gives us togetherness. It's driven evolution. But the paradox is that we don't need it all the time, and that there are times when it begins to do negative things, perform negative things. Violence, crime, unstable relationships, compassion, empathy, generosity. All of those are counter to virility in some respects. And so when we think about being a whole human, we want to have compassion and empathy and all of those things, but we also want to procreate and be strong and be builders and be explorers. And so it gives with one hand and it takes away with another.
- [51:55]
Thomas Goetz
And here's the thing. Dr. Ryan knows this because his specialty is prostate cancer. And one common treatment is to use other hormones and medicines to turn the testosterone in men off. That can reduce the spread of cancer. And when he does that, Dr. Ryan has noticed something.
- [52:13]
Dr. Charles Ryan
What I discovered in talking to my patients over the years was that many of them complained about it, they didn't like it, and that was understandable. But there is some nuance to that. And I had some patients who would talk to me and they would say, you know, I feel like I'm a little bit nicer, I'm maybe a little bit more patient. And I remember more than one person, I think, said to me, you know, I got space in my mind for other things now that I'm not thinking about sex all the time. I found my way all the way back to Plato, actually, which was kind of satisfying because I was an undergraduate philosophy major. There's a nice passage in Plato's Republic, of all places, where they have a dialogue between an older man and a younger man. And the younger man is saying, basically, I'll put it in 20, 25. You know, language. Isn't it a bummer that you can't be with a woman anymore because you're so old? And he says, he says, no. He says, you know, I've since I've lost that lust factor of my life. It's like I've been freed from the enslavement of a demented master, and it has opened up space in my mind for the building of character.
- [53:22]
Thomas Goetz
Now, we may not all want to be Plato's old man. We may want to get get our lust back, our passion and drive. Apparently, many, many men prefer that. But let's not kid ourselves that this is always a medical problem. TRT may make us feel better and younger, but it's not an actual fountain of youth. It's not really turning back the clock. You're still getting older. And if you stop trt, well, you just might find that belly fat returns, your confidence slips a bit, and your energy level drops. There's a term for that. It's called getting older. Okay, that's it for this episode of Drug Story. For an annotated list of our sources for the this episode, visit Drugstory co. Drug Story was created, written and hosted by me, Thomas Goetz. Molly Warner is our research director from Reasonable Volume. Rachel Swaby produced and sound designed this episode with assistance from Audrey Ngo. Elise Hu was the editor. Mark Bush is our engineer. Voice acting by Colin Borden. Drug Surrey was produced with support from the University of California, Berkeley School of Public Health. Special thanks to Claudia Williams and Michael Lu. Thanks also to Drew Scott Flynn and Dr. Charles Ryan, who has his own podcast. It's called the Good News About Cancer and it's great, geeky, inspiring stuff. Give it a listen. Drug Story is an independent production. If you'd like to support our work, contact us at Drugstore Co. You can also subscribe to our substack there and be notified when new episodes come out. And if you like this episode, help us spread the word. Rate us and subscribe on Apple or Spotify or wherever you get your podcasts. Next up on Drug Story, we go deep into chronic pain. It's one of the most persistent problems in human existence and also maybe the biggest screw up in the history of medicine. Will there ever be a way to fix it without complications? That's next time on Drug Story. Thank you for listening. Listening to this episode of Drug Story may cause you to spend too much time browsing Reddit. Catch yourself flexing in the mirror and say the word testicle 17 times in one hour. We recommend that you embrace your feminine side, accept that you aren't 19 anymore, and always think of yourself as a winner. The building, everybody.
- [56:28]
Dr. Charles Ryan
Hands go up.