When a man is considering if TRT is right for him he must consider the potential side effects he may experience. For context, anecdotally, most men on TRT find the benefits of therapy to far outweigh any potential risks but it is still important to be aware of what those risks might be. The most common side effects of TRT are acne, accelerated balding (in those who are genetically prone to it), increased red blood cell production, fluid retention, estrogenic effects, testicular atrophy, and infertility. More serious but less common risks of TRT include potential accelerated growth of prostate cancer and risk of cardiovascular events. Let’s take a look at each side effect and risk individually…
Acne. This occurs due to the effect of androgens on oil production in the skin. Acne will occur in about 10-30% of testosterone users. Whether someone falls in that category is heavily influenced by their individual susceptibility and how the regimen is dosed and administered. If in his teenage years, a man had acne, he is more likely to experience it when starting TRT. If acne is a concern, utilizing testosterone cream may be a good choice as it tends to produce less acne than injections. There are also a variety of ways to manage this unwanted side effect ranging from skincare routines to topical products to oral medications (in extreme cases). It is also important to note that for most men this is a temporary reaction and as their body adjusts to the higher androgen levels the prevalence of acne should subside.
Accelerated balding (in those prone to it). Male pattern baldness is largely hereditary and will only affect users of TRT who have the existing genetic predisposition to it. A certain amount of testosterone is converted to DHT (dihydrotestosterone), a more potent androgen that plays an important role in maintaining male characteristics but also, unfortunately, negatively impacts the hair follicle. As a byproduct of TRT DHT increases, potentially accelerating male pattern baldness. This will occur in about 10-30% of men who are genetically predisposed to the condition. It is important to note that TRT does not cause baldness in men who do not have the genetic predisposition but rather can accelerate it in those who would inevitably experience it at some stage regardless. Additionally, there are many treatments available to help restore hair growth if needed including specially formulated shampoos, PRP (plasma-rich platelet) therapy, hair transplants, and more.
Increased red blood cell production. Red blood cells play an essential role in oxygen and nutrient delivery to cells. Most men on TRT will experience some increase in red blood cell production due to testosterone's effect on the bone marrow (where blood cells are produced) and EPO (erythropoietin, a hormone that stimulates blood cell production). Modest increases are often welcomed side effects of TRT as they can improve endurance and athletic performance due to the enhanced oxygen delivery. If levels climb too high though, there is a risk that the blood becomes viscous, increasing the risk of blood clots. This can be closely monitored with lab work and if the levels start to increase too much therapeutic phlebotomy (blood donation) can be used to bring them back to a more optimal range. Alternatively, this is another place where testosterone cream can be used in place of injections as it tends to have less effect on blood cell production. Additionally, men can do their part by maintaining adequate hydration to help mitigate this effect as it works as a diluting agent in the blood.
Fluid retention. Testosterone causes fluid retention because of its effect on the kidneys and other hormones. Testosterone increases sodium reabsorption in the kidneys, ADH (antidiuretic hormone) release, and estrogen levels all resulting in increased water retention. Fluid retention can increase blood pressure, so this side effect is most concerning for men with existing high blood pressure who are starting TRT. Additionally, albeit not typically needed, there are medications like diuretics that can help manage this side effect if necessary. Again, maintaining adequate hydration can also combat fluid retention by promoting an optimal fluid balance in the body.
Estrogenic effects. In men, all estrogen comes from testosterone so increasing testosterone will likely increase estrogen. Old-school TRT providers would start all patients on an “estrogen blocker” to mitigate this effect but newer research suggests there are many benefits of letting estrogen levels increase a bit. Estrogen plays an essential role in bone and cardiovascular health and much of the research coming out suggests that low testosterone is an indicator of heart disease, likely due to the reduction in estrogen. So, more up-to-date providers typically take the stance that absent any bothersome effects, it might be optimal to keep estrogen levels on the higher end of normal. That being said, if a man is experiencing unwanted symptoms like breast tissue growth, nipple sensitivity, mood swings, or decreased libido an estrogen blocker may be indicated. These types of symptoms occur in around 20% of patients and are typically seen when estrogen levels exceed the upper limit of normal. Carefully balancing the benefits of estrogen without producing unwanted side effects is essential to a good TRT regimen.
Testicular atrophy. This is a side effect that almost all users of TRT will experience to some extent. Endogenous testosterone is produced in the Leydig cells of the testes in response to signaling hormones released by the brain. When testosterone is given exogenously (as it is with TRT) it signals to the brain that there is enough testosterone present, decreasing the signal to produce more. This decreases the production in the testes leading to some atrophy. Most men can expect their testicles to shrink by about 25-35% although it can vary significantly from individual to individual. There are some medications available to prevent this side effect if it is particularly bothersome to an individual.
Infertility. Sperm is produced in the Sertoli cells of the testes, and the same negative feedback loop as mentioned above is at play. Because the body senses increased testosterone levels the signaling molecules from the brain to produce testosterone and sperm are diminished. This reduction in sperm can cause infertility. The estimates are highly variable but anywhere from 40-90% of men experience either no or very low sperm counts in their ejaculate when on TRT. If desired, fertility can be maintained by adding a medication to mimic the signaling molecules which will preserve endogenous production. If TRT is stopped fertility is generally restored in 6-12 months. There are rare cases of permanent infertility but typically in the context of using exceptionally high doses or in the case of an underlying medical issue. It is important to note that despite testosterone's typical effect on fertility it should never be used as a primary means of birth control.
Accelerated growth of prostate cancer. Testosterone’s effect on prostate cancer is complex and still not completely understood. The theory that testosterone can accelerate prostate cancer growth stems from the idea that androgen deprivation therapy is an effective treatment for prostate cancer; but just because something is an effective treatment does not necessarily mean it is a causative factor. Checking a PSA (prostate-specific antigen) level before and regularly during treatment is a good way to identify if prostate cancer may be present and if treatment needs to be either reconsidered or discontinued.
Increased risk of blood clots, heart attack, and stroke. These are a collection of issues that often fall under the umbrella term cardiovascular disease. The potential risk stems from issues already discussed including increases in blood counts, blood pressure, etc. Individual medical history and health status also significantly impact these collective risks. As previously mentioned, there is evidence that lack of testosterone increases cardiovascular risk as well so risk/benefit calculations here will be highly individualized. Additionally, if your provider is monitoring the typical causative factors (e.g. blood counts, blood pressure, etc.) issues can generally be identified and mitigated before an event occurs. It is also important to note that cardiovascular disease is the leading cause of death in the United States so is likely any given person's greatest risk with or without TRT.
Beneficial side effects. It is important not to forget the many beneficial side effects of TRT like weight loss, athletic improvement, sexual enhancement, improved mood, increased motivation, etc. These are the aspects that tend to tip the scale in favor of TRT for so many men. It is not without risk but the improvement in overall quality of life appears to be a worthwhile trade.
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