If you鈥檝e never injected yourself with dog semen, don鈥檛 worry: someone has done it for you. Seventy-one years after the initial publication of听Frankenstein, the medical journal听The 尝补苍肠别迟听would dedicate three of its pages to听听that might have enticed Mary Shelley to take notes had she still been alive.
It was an attempt at finding the fountain of youth in the testicles of animals. The scientist at the centre of this weirdness would play a key role in the nascent field of endocrinology, the study of hormones and the glands that produce them. He was fascinated by the vigour men derived from their testicles and by the verve that was apparently lost in eunuchs.
In his听尝补苍肠别迟听paper, Charles-脡douard 叠谤辞飞苍-厂茅辩耻补谤诲 asserted that men who abstain from sex and from self-pleasure鈥攖he latter of whom modern scholars would call 鈥渘o fap鈥濃�斺�渁re in a state of excitement giving them a great, although abnormal, physical and mental activity.鈥� 叠谤辞飞苍-厂茅辩耻补谤诲 was 72 years old and weak. He thought that maybe the cure for old age was contained in some unknown substance inside the testes of the young.
Over a series of days, he injected himself in the fat of his left arm and legs using a number of preparations. The material came at times from a healthy dog, at times from young or adult guinea pigs. He injected himself with semen; with juice extracted from a crushed testicle; and with blood drawn from the testicular veins of the animal. The day after his first experiment, 叠谤辞飞苍-厂茅辩耻补谤诲 was, according to him and to his laboratory assistants, reinvigorated. His arms were stronger; his stream of urine was longer; but bizarrely enough, it was his 鈥減ower of defecation鈥� that he felt was the real radical change (perhaps a case of nominative determinism). 鈥淚 will simply say,鈥� he wrote, 鈥渢hat after the first days of my experiments I have had a great improvement with regard to the expulsion of fecal matters than in any other function.鈥� Move over, fibre supplements; the solution to constipation, at least in 1889, was a crushed canine testicle.
What 叠谤辞飞苍-厂茅辩耻补谤诲 was really onto is testosterone鈥攁lthough his animal preparations would听听of the precious hormone to do anything, and his experiments failed to be replicated later on. Testosterone would be isolated in the laboratory in听听and would begin to be given to certain patients two years later to boost their abnormally low levels.
Testosterone is a hormone that plays many roles in the body. In the adult male, almost all of the testosterone is produced by the testes under the control of a hormone made in the brain, and a tiny amount is made from a precursor squeezed out of the adrenal glands above our kidneys. Testosterone is one of many molecules that help regulate when genes are turned on in order to make proteins, and it plays important roles in libido, virilization, musculature, bone density, and mood. Yet, as we get older, our testosterone levels slowly decrease.
(Note: I will be referring exclusively to cis-gendered men here, as they are the targeted demographic for both the condition and therapy I am covering today.)
If you鈥檙e a man of a certain age, you have invariably heard of 鈥渓ow T,鈥� an ill-defined unease that is blamed on lower testosterone levels. (It was popularized as andropause, but the medical community has rejected this would-be equivalent to menopause.) The answer? Social media will bark it at you: testosterone replacement therapy. On听The Joe Rogan Experience鈥攖he most popular podcast in the world by all estimates鈥攖he word 鈥渢estosterone鈥� has been mentioned over 3,000 times in its 2,466 episodes, while 鈥渢estosterone replacement therapy鈥� and 鈥淭RT鈥� have been referenced 95 and 403 times, respectively. Rogan says he started supplementing with testosterone at听. In one episode, his guest, an MMA analyst, claims that Sylvester Stallone in听Rocky Balboa听(2006)听looks like he鈥檚 30 years old. 鈥淚t鈥檚 amazing what testosterone replacement therapy has done for him,鈥� Rogan听. 鈥淗e鈥檚 shredded. Incredible.鈥� Search for 鈥渢estosterone booster鈥� and you will find an infinite scroll of manly plastic bottles promising rejuvenation鈥攁t a price.
Given that this hormone is in the social water, it鈥檚 no wonder that testosterone prescriptions in the United States听听from 2000 to 2011 (despite the fact that many of the men receiving these prescriptions have normal testosterone levels via blood testing). At its peak in 2013,听听of men aged 30 or older in the U.S. had a prescription for TRT. A听听by the Food and Drug Administration two years later as well as a couple of studies reporting potential cardiac effects seem to have chilled the market a bit.
Is TRT really the fountain of youth? Not quite.
Define normal听
Testosterone replacement therapy is meant to treat a very specific medical condition called male hypogonadism, which is when the body produces too little testosterone (or none at all), leading to testes malfunctioning. Sometimes, the problem originates in the testicles themselves, either as something present at birth or acquired later in life (like being infected with vaccine-preventable mumps or getting your family jewels in a twist); other times, the cause is in the brain, and the testes don鈥檛 receive enough hormone from it in order to make testosterone.
Doctors who suspect male hypogonadism will look for signs and symptoms, and they will ask for your blood testosterone levels to be measured. These levels vary during the day. They are at their highest right after waking up, which is why testing should include drawing blood in the morning (or a few hours after waking up if you do shift work) on听two or three听separate occasions, ideally in a fasting state, to measure testosterone levels using a reliable test.
But what should these numbers be measured against? What is a normal level of testosterone? There is no widespread agreement. The U.S. Endocrine Society鈥檚 2018 guidelines uses the results from this听听to define 鈥渘ormal:鈥� total testosterone is measured in nanograms per decilitre, and the normal range from this study was 264-916 ng/dL. Quite the gamut. Meanwhile, the Canadian Society of Endocrinology and Metabolism听听a threshold for low testosterone, presumably letting testing laboratories decide.
Things get even more nebulous when we move into 鈥渓ow T鈥� or late-onset hypogonadism, i.e. what Joe Rogan was concerned with. This alleged condition is meant to affect men of a certain age who naturally produce less testosterone because of ageing and who complain of symptoms, many of which are not specific and could have other explanations. Men will report feeling depressed, having difficulty sleeping, lacking energy, as well as seeing their sexual desire (and accompanying erections) go down. It can be hard to disentangle which symptom is simply the result of getting old, of an unhappy marriage, of changing life circumstances, and of low testosterone.
Older men who want to supplement with testosterone because they are experiencing sexual dysfunction will be disappointed by the conclusion reached by听听two years ago. Its authors reviewed 43 studies on the subject and concluded with moderate certainty that, in the short term (as most studies fail to follow patients for decades), testosterone replacement therapy probably has little to no effect on erectile dysfunction or sexual quality of life. A听听of TRT鈥檚 impact on men thought to have low T failed to see an improvement in brain skills like thinking and memory, but there was enough evidence to state that testosterone听might听improve muscle strength, vitality, and mood, as well as help with blood sugar levels鈥攂ut these alleged benefits are still debated. We are a far cry from 叠谤辞飞苍-厂茅辩耻补谤诲 sticking himself with crude extracts and noting 鈥渁 radical change.鈥�
While TRT鈥檚 benefits are commonly exaggerated, its risks have been the subject of much discussion, and there too, early data have overstated the case.
The heart of the matter
Testosterone supplementation takes many forms: gels, patches, pills, tablets meant to be kept against your gums, as well as injections and surgical implants. Each formulation has pluses and minuses that doctors and patients have to weigh. Those buccal tablets can irritate the gums and alter taste; that gel can irritate the skin and transfer testosterone into the body of someone who rubs up against you; and injections have a low adherence rate, with听听of men prescribed a short-lasting testosterone injection giving up within a year. In fact, any drug that we have to take long term has a major adherence problem, with on average听听of all people dropping off.
One clear downside of TRT is that you are听听while on it. Supplementing with testosterone feeds back into the brain, which produces less of certain hormones, and this causes a low sperm count. If you are trying to have babies, TRT is not for you.
Meanwhile, the two scariest claims about TRT鈥攊ts uneasy association with prostate cancer and its alleged cardiovascular risk鈥攈ave thankfully been shown to be untrue or, at the very least, likely to be quite rare.
Because testosterone helps most prostate cancer cells grow, there was a fear that TRT might increase the risk of prostate cancer. But while TRT is听, no study has linked TRT to the development of this cancer.
Also, even though early, inconclusive studies reported a potential increase in strokes and heart attacks, the two-year听, which recruited enough participants to resolve this question, failed to show this increase. It should be noted that TRAVERSE was not perfect: it was funded by a consortium of testosterone manufacturers and the increase in testosterone in the group that received TRT was modest. The men who participated in TRAVERSE were also not representative of every older man courting a testosterone prescription: everyone either already had cardiovascular disease or was at high risk of developing it, and most also had obesity and diabetes.
The flip side is that if TRT really did a number on the heart and blood vessels, these men were predisposed to experience it; and yet, the number of heart attacks and strokes (and deaths from those) was nearly identical in the TRT group and the placebo group. TRT thus appears to be safe in the short term from a cardiovascular perspective, but there is an asterisk: TRAVERSE found in its TRT group more cases of very specific adverse events (pulmonary embolism, acute kidney injury, and atrial fibrillation) than in its placebo group. Is it a fluke? More studies can answer that.
Fool鈥檚 gold on sale
What we are witnessing is a gold rush filled with pyrite. Yes, testosterone has helped countless men who have genuine male hypogonadism and it has probably conferred some benefits to some older men worried about low T; but this genuine treatment has undeservedly been heralded, by both direct-to-market service providers and social media influencers, as a cure-all for old age in men. On top of this, companies have piggybacked on this hype to sell not prescription testosterone but over-the-counter 鈥渢estosterone boosters鈥� as unregulated dietary supplements. These boosters are said to contain all sorts of plant-based derivatives, like extracts from rhodiola, gingko, ashwagandha, fenugreek and, yes, horny goat weed, and they don鈥檛 have to prove clinical benefits and may not even contain what they say they do. Don鈥檛 be fooled.
Actual TRT is relatively safe, although it comes with side effects and some men are not eligible because of preexisting risk factors. If you believe that TRT might help you, there is a lot for your physician to rule out first. If your symptoms are fatigue and decreased libido, you may also have to look at what you eat, how often your exercise, and whether or not you smoke. And before you get a prescription for testosterone, you should be run through a questionnaire, sent for multiple blood tests, and followed up by your doctor. Even then, you may think testosterone is helping when it鈥檚 not: the brain can witness improvements that aren鈥檛 there because of placebo effects. See 叠谤辞飞苍-厂茅辩耻补谤诲 himself. 鈥淒o I feel a bit better today?鈥� you might think. 鈥淢ust be the testosterone.鈥� Testimonials don鈥檛 tell the full story.
Following 叠谤辞飞苍-厂茅辩耻补谤诲鈥檚 experiments in the late 1800s, thousands of men were injected with animal testicular extracts. The benefits of TRT may still be overblown in the 21st听century but today鈥檚 therapy has come a long way in terms of consistency and safety. At least we鈥檙e no longer reaching for our canine companion in a bid to reverse the arrow of time.
Take-home message:
- Many older men are prescribed testosterone replacement therapy even though their testosterone levels are normal.
- The benefits of testosterone replacement therapy in older men are still debated, with a systematic review concluding that the therapy is unlikely to do anything about sexual dysfunction.
- 鈥淭estosterone boosters鈥� are not supposed to contain testosterone; they are plant extracts that do not have to prove benefit, and these types of herbal supplements are not infrequently contaminated and adulterated
