If you’re a man struggling with erectile dysfunction, fatigue, or anxiety and depression, a quick Google search might lead you to believe that there’s a one-stop solution for all these ailments: testosterone replacement therapy (TRT). For men who are truly testosterone deficient, TRT can provide symptom relief. But it’s not a quick fix, and there are risks men should be aware of before they get started on testosterone therapy, says Alexander Pastuszak, M.D., Ph.D., a urologist specializing in male infertility at the University of Utah Health.
One of those risks: If you decide to come off of TRT, you might feel worse after stopping the therapy than before you began. For some men, that effect is temporary. For others, it’s permanent. “It’s not withdrawal,” says Pastuszak, “it’s a new normal.”
Normally, testosterone levels are regulated by a cascade of hormonal checks and balances called the HPA axis. The hypothalamus monitors testosterone levels — if they’re low, it tells the pituitary gland to produce luteinizing hormone, a chemical that travels down to the testicles and kick-starts testosterone production. But when the hypothalamus decides there’s enough testosterone circulating in the body, it tamps down the whole process.
That’s what happens when you start taking testosterone replacement therapy: At first, the synthetic testosterone supplements what your body is already making. Over time, however, your body’s HPA axis decides that its work is no longer necessary because your body has enough testosterone, and it causes your body’s natural production of the hormone to slow.
That’s not a problem, so long as you stay on TRT, Pastuszak says. But for men who want to stop — perhaps due to side effects or because they no longer want to depend on medication — coming off testosterone therapy can be extremely difficult.
After stopping TRT, many men see their testosterone drop to levels lower than when they began treatment. For example, a guy whose natural testosterone hovered around 300 ng/dL — on the low end of normal — might see those levels drop down to 150 ng/dL after stopping TRT. Men who experience this dropoff can expect to experience the same symptoms as before they started TRT, or worse, including “lower sex drive, low energy, maybe some issues with erections if those existed before, brain fog, maybe difficulty sleeping,” Pastuszak says.
The severity of these symptoms, and how long they last, depends on how long you were taking TRT, Pastuszak says. “The longer a guy has been on hormone therapy, and the higher the dose, the worse they will feel after stopping,” Pastuszak says. Men who stop TRT within three-to-six months might not see any kind of decrease in their natural testosterone production.
When men do see a dropoff, it can take weeks to months for the HPA axis to kick back into gear, Pastuszak says. For some men, particularly those who have been on a higher dose of testosterone for many years, those effects can be lasting. That’s because over time, testosterone therapy causes the testicles — which produce the majority of the body’s testosterone — to shrink. As a general rule, the smaller the testicles, the less testosterone they produce. This shrinkage is permanent.
How willing patients are to stay on TRT indefinitely — or to come off it and deal with its after-effects — is something Pastuszak discusses with everyone who considers starting the treatment. He also encourages his patients to consider options that are much less likely to permanently alter their natural testosterone production. “TRT isn’t the only thing that can raise testosterone levels,” Pastuszak says.
For example, lifestyle changes and supplements are enough to naturally boost testosterone production in many men. Other options include taking off-label hCG and Clomid, two medications that stimulate the body’s own production of testosterone, although this isn’t what they’re approved by the FDA to do.
hCG is a gonadotropin — a hormone that stimulates the gonads (the ovaries or testes). Normally, you only see hCG during pregnancy, when it tells the ovaries to produce more estrogen and progesterone, and to stop producing eggs. (In fact, most at-home pregnancy tests come back positive only when they detect the presence of hGC.) Taken as a medication, hCG can also work on the testicles, telling them to produce more testosterone. It has the side effect of actually increasing the size of the testicles and is sometimes taken alongside TRT to keep the testicles from shrinking.
Clomid works a bit differently. Estrogen blocks the pituitary gland from making luteinizing hormone, the chemical messenger needed to produce testosterone and sperm, and Clomid blocks estrogen. This allows the pituitary gland to make more luteinizing hormone, triggering the body to make more testosterone.
However, if you do have low testosterone and are feeling the effects of it, lifestyle changes like exercising more, reducing stress, and prioritizing sleep are usually the first step.