These Two Testosterone-Boosting Drugs May Help You When TRT Can't
Testosterone replacement therapy can come with undesirable side effects. These are alternatives.
Over the past few decades, testosterone replacement therapy (TRT) has surged in popularity among men seeking relief for aging-related declines in energy, libido, and muscle tone. In fact, between 2003 and 2013, use of the treatment increased four-fold — and its growth isn’t predicted to stop anytime soon.
For men whose symptoms truly stem from low T, TRT provides real relief — but can come with unwanted consequences. Chief among them: Long-term use can cause sperm count to dwindle and the testicles to atrophy, harming the body’s natural production of testosterone.
But TRT isn’t the only option available for men whose hormone levels are off-kilter. Two lesser-known drugs — hCG and clomiphene (Clomid) — can stimulate your body’s own natural testosterone production, potentially preserving your fertility and testicles.
Here’s what to know about these two therapies.
What Is hCG?
If you’ve tried for a baby at any point, you might have heard of hCG — it’s the hormone for which pregnancy tests check. During pregnancy, the body starts producing it as soon as an embryo implants in the uterus.
So what does hCG have to do with testosterone? The hormone doesn’t naturally occur in men — but it looks a lot like one that does, says Braden Barnett, M.D., an endocrinologist at Keck School of Medicine at the University of Southern California.
hCG’s male doppelgänger, luteinizing hormone, is crucial to testosterone production in cisgender men. When the pituitary gland senses there isn’t enough testosterone in the body, it produces luteinizing hormone. This chemical messenger travels down to the testes, signaling them to ramp up production.
“Luteinizing hormone and hCG effectively look similar enough that hCG can bind to and activate the same receptors that luteinizing hormone can,” Barnett says.
hCG is FDA-approved to treat low testosterone on its own or alongside TRT. The thinking behind the latter approach is that hCG stimulates the testicles, keeping natural testosterone production going even as you supplement it. This helps prevent the testes from atrophying, keeps sperm count up, and may make it easier to come off TRT later if you so choose.
However, very few clinical trials have investigated this treatment, and those that do exist have been small, Barnett says. A 2012 retrospective analysis published in The Journal of Urology studied 26 men in their 30s who received hCG at the same time as TRT. After six months, the men’s testosterone levels had increased, on average, from 207.2 ng/dL to 1,055.5 ng/dL. (Normal values fall between 300 ng/dL and 1,000 ng/dL — but it’s typical to have high levels of testosterone during testosterone replacement therapy, especially immediately after a new dose.) Meanwhile, their semen levels hadn’t changed after one year, and nine of the men had gotten their partner’s pregnant.
In a 2019 study published in the International Brazilian Journal of Urology, 20 men experiencing low libido, lack of energy, and erectile dysfunction received hCG only. After eight months, testosterone increased, on average, from 362 ng/dL to 519 ng/dL, and half of the patients saw their symptoms improve.
How Does Clomiphene Work?
Unlike hCG, clomiphene, also known by the brand named Clomid, is synthetic. But it does look a lot like a chemical the body naturally produces, Barnett says: estrogen. (Yes, men produce estrogen too — just at lower levels than cisgender women.)
In men, estrogen levels are important because they’re a proxy for testosterone. “All estrogen in the human body starts from testosterone, so men who have higher testosterone levels also have higher estrogen levels,” Barnett says. Remember how the pituitary gland checks the body’s testosterone levels? Well, it’s actually looking for estrogen.
Clomiphene blocks estrogen receptors in the pituitary gland, preventing them from “seeing” actual estrogen. The pituitary gland assumes the body doesn’t have enough estrogen, and therefore testosterone, so it tells the testes to ramp up production of T.
Studies on clomiphene for testosterone replacement, similar to those on hCG, are few and far between. A 2014 study published in the Journal of Urology found no difference in testosterone levels between men on clomiphene alone compared to those on testosterone replacement therapy.
A 2023 study published in the journal Endocrinology, Diabetes, and Metabolism followed 153 men who received clomiphene for low testosterone. After one-and-a-half months, their testosterone had increased from nine to 16 nmol/L (normal is 10-35 nmol/L). Eight years later, patients who continued taking clomiphene still had raised levels.
The Pros and Cons of hCG and Clomiphene
The main reason a doctor might recommend hCG or clomiphene alongside or instead of TRT is the preservation of fertility, says Ranjith Ramasamy, M.D., an associate professor of Clinical Urology at the University of Miami Miller School of Medicine.
“While TRT provides direct replacement, it also leads to decreased production of natural testosterone in the body and negatively impacts fertility,” says Ramasamy.
That said, these alternative therapies aren’t for everyone. If your testes are injured, atrophied, or otherwise not functional, neither of the drugs will work. Think about it: They can’t boost testosterone production if the testosterone factory isn’t in operation. Similarly, clomiphene also won’t work for men who have a damaged or non-functional pituitary gland.
Another con is the fact that neither drug is well-studied. Not only are the studies out there small, but also very little research so far has looked at long-term safety, Barnett says. “For that reason, it’s not my first-line treatment for low testosterone.”
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