Is testosterone therapy safe and effective? What we know

Could testosterone be the next breakthrough in medicine? An expert panel organized by the US Food and Drug Administration (FDA) in December seemed to think so. The panel advocated for significant policy adjustments to broaden access to the hormone for individuals with various conditions. Members of the committee described testosterone replacement as “a cornerstone of preventive health” and “a multibillion-dollar preventive-care opportunity.”

In the United States, testosterone is already prescribed for individuals with low hormone levels due to known medical issues, such as testicular damage. However, increasing evidence suggests that a wider demographic, including both men and women, might benefit from testosterone delivered through injections, patches, subcutaneous implants, or gels. (This article uses ‘men’ and ‘women’ as per the language used by the panels and studies referenced, acknowledging that trans, non-binary, and intersex people are also impacted by this issue.)

The panel’s suggestions have intensified the ongoing debate about who could benefit from testosterone therapy. Some clinicians argue that many men with low testosterone, particularly younger ones without underlying medical issues, do not require supplemental treatment and can increase their levels by adopting healthier lifestyles and shedding excess weight. Others contend that men experiencing symptoms like low libido, fatigue, and irritability could benefit from the therapy.

On supporting science journalism

If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription, you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.

More enthusiastic advocates, including many members of the FDA panel in December, propose a third approach: testing all cis men for low testosterone and treating them even in the absence of symptoms. “You could make a very strong argument that having a normal testosterone level is important for health and prevention of illness,” says Abraham Morgentaler, a urologist at Harvard Medical School in Boston, Massachusetts, who participated in the panel.

Morgentaler and other panelists emphasized that testosterone is not merely a ‘lifestyle drug’ for muscle building and mood enhancement. However, it is increasingly marketed as such. Podcasters like Joe Rogan and his guests have praised the hormone. Numerous testosterone clinics are emerging globally, promising improved fitness and energy levels, even to those who may not have low testosterone.

High doses of testosterone can pose risks, including infertility and increased mortality. The hormone is classified as a controlled substance with potential for abuse in the US and other countries, partly due to doping scandals from the 1990s and 2000s. FDA commissioner Marty Makary, who expressed enthusiasm for testosterone during the December panel, suggested re-evaluating this classification.

What evidence supports the safety and benefits of testosterone replacement?

Safety record

The reputation of testosterone has fluctuated since its synthesis in the 1930s. Initially hailed as “one of the most potent drugs recently introduced to medicine,” it lost favor due to cancer concerns. This fear stemmed from the work of urologist Charles Huggins, who discovered in 1941 that prostate cancer depends on testosterone, and reducing the hormone could shrink tumors. This breakthrough won him a share of the Nobel Prize in Physiology or Medicine in 1966.

Morgentaler recalls that when he trained in the 1980s, the prevailing belief was that testosterone therapy could cause prostate cancer, based on Huggins’s findings. Despite these concerns, Morgentaler believed testosterone could aid some patients with low levels and sexual issues, so he began treating them under close observation.

Morgentaler reports that his patients did not develop cancer and greatly benefited from the therapy. His clinical findings, along with the realization that Huggins’s warnings were based on one individual’s case, revived interest in testosterone therapy. Although some clinicians disagree with Morgentaler about the extent of benefits, he is recognized for his work on testosterone safety. He has previously consulted for testosterone-selling companies but claims no current financial interests.

Additional risks emerged over time. Retrospective studies in 2013 and 2014 indicated an increased heart attack risk for men on testosterone therapy, prompting the FDA to add a warning to product labels in 2015.

However, the TRAVERSE randomized clinical trial, with about 5,200 participants, found no higher incidence of severe cardiovascular events in middle-aged and older men with low testosterone and high cardiovascular risk taking the hormone compared to those on placebo. “This study only picked very sick people, the greatest-risk population, and nothing bad happened to them,” says Mohit Khera, a co-author and urologist at the Baylor College of Medicine in Houston, Texas, who was also part of the FDA panel and consults for testosterone companies.

Following the TRAVERSE findings, the FDA removed the cardiovascular warning from testosterone products last year.

The TRAVERSE trial’s safety data pertains to men with confirmed low testosterone levels — below 300 nanograms per decilitre of blood serum — treated to restore levels to the normal range of 350–750 nanograms. Higher doses that elevate levels beyond the natural range entail significantly different risks.

High doses of testosterone can thicken the heart muscles, impairing its blood-pumping ability, a condition known as cardiomyopathy. Elevated testosterone levels can also cause infertility, shrunken testicles, reduced sperm count, and erectile dysfunction, explains Channa Jayasena, an endocrinologist at Imperial College London. Neuropsychiatric effects, including irritability and psychosis, may increase the risk of violent crimes and domestic abuse, Jayasena adds. He advises testosterone-selling companies but refuses payment to avoid conflicts of interest. “For reasons we don’t fully understand, very high doses of testosterone do something that therapeutic testosterone doesn’t do,” he notes.

A Danish study tracking about 500 men using high doses of anabolic steroids — including approved testosterone products and other hormone variations — found their mortality rate was three times higher than non-users over roughly seven years. Jayasena compares this risk to cocaine use. The study’s participants were identified through a doping control program inspecting fitness centers in Denmark and testing suspected steroid abusers. Authors acknowledge that steroid use has been linked to risk-taking behaviors, which may partly explain the higher mortality rate.

This misuse form is also addictive: about 30% of men on high doses develop dependence. “They are flooding our clinics,” Jayasena says.

Who can benefit?

Advocates for broader testosterone use often share compelling anecdotes about its transformative effects. Morgentaler recounts that when he began treating patients with low testosterone in the late 1980s, they reported positive changes such as improved relationships and patience. Many express feeling rejuvenated, with enhanced mood, energy, and libido, Morgentaler states.

However, many patients discontinue treatment. The TRAVERSE trial revealed that around 61% of participants on testosterone stopped treatment. While reasons for discontinuation are not well-documented, Morgentaler speculates that some dislike the delivery method, while others do not perceive the benefits, potentially due to incorrect dosing or unrealistic expectations.

Clinical trials validate only a fraction of the benefits often attributed to testosterone. The most evident impact is on sexual function. A TRAVERSE trial subanalysis of approximately 1,100 men with low libido found that both the treatment and placebo groups increased their sexual activity, but the increase was 25% higher in the treated group. Testosterone therapy also boosted sexual desire, though not erectile function.

A meta-analysis commissioned by the Endocrine Society, based in Washington DC, found that testosterone was linked to a “small but statistically significant” improvement in sexual function, satisfaction, and libido among men with low testosterone. Contrary to the TRAVERSE trial, it also noted a small improvement in erectile function. The review found no significant differences in energy, mood, or cognition.

Other studies have demonstrated testosterone’s effectiveness in treating anemia and enhancing bone density. Interestingly, men on testosterone in the TRAVERSE trial experienced more fractures than those on placebo. “It must be that these inactive men were becoming more active,” which could imply increased exercise, Jayasena suggests.

Smaller trials indicated that testosterone also promotes an increase in fat-free body mass and muscle strength, in both younger and older men.

Potential benefits for women

As testosterone use increases in some groups, many potential beneficiaries remain largely overlooked, such as trans men, for whom the hormone is part of gender-affirming care, and postmenopausal women.

For women, the only condition with clear evidence of benefit is distressing low sexual desire after menopause, as shown in a systematic review and meta-analysis of 36 randomized controlled trials.

Susan Davis, an endocrinologist at Monash University in Melbourne, Australia, and a co-author of the review, reports a wide variation in women’s responses to testosterone therapy. Just having a physician listen, validate, and care for them is enough for some women to feel better. “I’ve now studied testosterone in thousands of women and probably done more clinical trials than anybody else with testosterone,” says Davis, who consults for testosterone-selling companies and has received grant funding from one. “What we’ve seen over and over again in all our studies is an incredible placebo effect.” Testosterone shows better outcomes than placebo in sexual function but does not significantly affect well-being, cognitive health, or body composition.

Recommended doses — aimed at restoring testosterone levels to those of premenopausal women — are generally safe, resulting in side effects like acne and increased body and facial hair.

High doses, however, can lead to more severe side effects, such as hair loss, weight gain, voice changes, and an enlarged clitoris, which some patients find distressing, Davis says.

Davis has encountered patients previously prescribed high doses who report agitation and aggression. Some experience road rage for the first time. “One woman told me she woke up in the middle of the night with her hands around her husband’s neck from a dream,” Davis shares. Discontinuing treatment can be difficult. Women who abruptly stop after high doses “can feel very flat and miserable,” Davis explains.

Only four countries have testosterone products approved specifically for women: Australia, New Zealand, South Africa, and, as of last year, the United Kingdom.

Elsewhere, women use testosterone formulations made for men, which might pose risks, Davis notes. This off-label use is prevalent in the United States. “It would seem to me that the FDA would actually be protecting women by approving a female dose-specific formulation,” she states. The December FDA panel did not address testosterone use for women or trans men.

Regulatory hurdles

The FDA currently restricts testosterone product approval for treating ‘classical hypogonadism,’ where low testosterone results from genetic conditions or disorders of the brain or testicles. In the United Kingdom, Europe, and Australia, testosterone is approved for men with laboratory-confirmed low testosterone accompanied by symptoms, without needing an identified cause. This aligns with most clinical guidelines from global urology and endocrinology associations.

However, the stricter regulatory environment in the United States is gradually changing. In April, the FDA invited pharmaceutical companies to apply for testosterone therapy approval for men with low testosterone and low libido from an unknown cause.

No regulatory changes have yet followed the expert panel’s discussions, such as removing testosterone’s controlled-substance classification or recommending routine testosterone testing for all men. Further changes may still occur.

Helen Bernie, a urologist at Indiana University in Carmel, argues for including testosterone testing in routine preventive care due to its association with various health risks. For instance, Bu Yeap, an endocrinologist at the University of Western Australia in Perth, and colleagues have linked low testosterone in older men to higher stroke risk. Extremely low levels increase mortality risk from any cause and cardiovascular disease. Their research also connects low testosterone to higher dementia and Alzheimer’s disease risks.

“We are really aware from the work we’ve done that low testosterone is quite a robust biomarker for poorer health outcomes, particularly in older men,” says Yeap, who has advised and received research support from testosterone-selling companies. However, he cautions that the data do not justify testing asymptomatic men. “If you treat all men with low testosterone, will it actually prevent ill health? We haven’t proved that.”

To answer that question, Yeap suggests a large randomized clinical trial involving 10,000 older men with low testosterone and increased health risks, followed for at least four years. His team is seeking funding for such a study, which he anticipates will be costly and complex. “But you’ve got to get the evidence,” Yeap says. “You can’t just pre-emptively make assumptions, which is what some people might be doing.”

This article is reproduced with permission and was first published on May 5, 2026.