Does Testosterone Boost Risk of Depression and Suicide?

For decades, scientists have known that men with unusually low blood levels of the male sex hormone testosterone (< 300 nanograms/deciliter of blood) suffer fatigue, depression, libido collapse, erectile dysfunction, weight gain, and loss of muscle mass. All these problems can be quickly reversed with supplementation that returns testosterone blood levels to the normal range.

Since the millennium, some physicians have claimed that men with normal testosterone levels can gain new vigor, muscle mass, and firmer erections by supplementing the hormone. Critics call these promises medically irresponsible, saying replacement increases the risk of mood disorders, heart disease, stroke, and possibly prostate cancer. A recent study bolsters critics’ argument. It shows that testosterone supplementation significantly increases men’s risk of depression and self-harm, including suicide.

A Colossal Study

Researchers at several American universities reviewed 70 million electronic medical records of men over age 18 who either did or did not take supplemental testosterone for any reason. True deficiency is rare (below). The large majority of those who supplemented T took the hormone in hopes of enjoying the gains advocates have promised and publicized.

The records search identified 17,838,316 men who did not supplement testosterone, and 263,579 who did (1.5 percent of the sample). Supplemental T doubled the risk of major depression, and increased the risk of self-harm, including suicide by 50 percent.

In research, the larger the population sample, the more credible the findings. The psychology journals are filled with studies based on samples as small as a few dozen participants, or a few hundred. This one tracked more than 18 million men. The enormity of this sample lends tremendous credence to its findings and should suffice to establish testosterone supplementation as a risk factor for depression and self-harm.

Thicker Blood

In addition to its mental health impact, supplemental testosterone also thickens the blood, making it more likely to clot, a risk factor for heart disease and stroke. The hormone may also spur the growth of prostate cancer, which is as common—and deadly—in men as breast cancer is in women. These risks have been well known since the mid-20^th century, and largely deterred doctors from prescribing it.

But toward the end of the 20^th century, based on small, short-term studies, some testosterone zealots argued that supplemental T is medically and psychologically benign. They have prescribed it to an increasing number of men complaining of vague symptoms like fatigue. Medical authorities estimate that testosterone supplementation is now a $1 billion-a-year industry.

An FDA Panel Overwhelmingly Urges Caution

Despite supplementation advocates’ promotion, men haven’t rushed to take testosterone. In the study, only 1.5 percent did.

But since the millennium, prescriptions for testosterone have increased sufficiently for the Food and Drug Administration to take notice. In 2014, the FDA convened an expert panel to investigate the increase in prescriptions. The panel voted 19 to one to impose strict new limits on testosterone supplementation. The panel cited several reasons for restricting testosterone prescriptions:

• Since the millennium, the number of American men taking the hormone has quadrupled to more than 2 million. But audits show that many received the hormone without sufficient blood testing to see if they really have what’s become known as “Low T.” As a result, many men taking testosterone may not need it.
• Safety issues remain unresolved, especially the hormone’s association with mental health problems and prostate cancer.
• Verifiable testosterone deficiency is rare in men under 65. But currently men 45 to 64 account for 60 percent of testosterone prescriptions.

As I write, testosterone is FDA-approved as replacement therapy only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain that cause a condition called hypogonadism.

Over-Prescribed?

The Endocrine Society echoes the cautions advised by the FDA panel. The Endocrine Society is the medical organization that specializes in hormones. It publishes authoritative guidelines for supplemental hormone therapy. The Endocrine Society recommends testosterone supplementation only for men who have unequivocally low levels, a finding that requires several blood tests. Multiple tests are necessary because men’s testosterone levels fluctuate during the day. Those who appear deficient in one test often show normal levels in others.

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Meanwhile, a report by researchers at the University of Texas (UT) Medical Branch in Galveston shows that 25 percent of the men taking supplemental testosterone had just one blood test prior to receiving prescriptions, which suggests that their doctors prescribed it carelessly.

In addition, even if multiple blood tests show a clear deficiency, the Endocrine Society guidelines insist that testosterone should not be prescribed unless men also report clear symptoms of deficiency, notably libido collapse—not low libido, but total loss of sexual desire. While T prescriptions have quadrupled since 2000, there is no evidence that the number of men reporting actual deficiency symptoms has risen anywhere near that much, another suggestion that doctors are over-prescribing the hormone.

Finally, the UT study shows that the fastest-growing group of men taking testosterone are in their 40s. But clear, symptomatic hormone deficiency is unusual before age 60, another indication that doctors are over-prescribing.

A Rerun of the Estrogen Replacement Debacle in Women?

The testosterone story looks like an ominous rerun of what happened forty years ago with estrogen replacement therapy for women. Doctors initially touted estrogen supplementation to preserve women’s youthfulness, femininity, and sexual function, while at the same time reducing their risk of heart disease. Small, short-term studies showed all these benefits.

But critics pointed out that most estrogen was taken by healthy women at low risk of heart disease, so it was unclear if the hormone actually reduced heart disease risk. Larger, longer-term studies showed that estrogen supplementation was clearly associated with an increased risk of heart disease and with the disease women fear most, breast cancer. When that research was published, women fled estrogen supplementation. We have no similar studies of supplemental testosterone, but the recent report linking it to serious mental health impact is a cautionary tale.

If you take testosterone and didn’t have multiple blood tests and clear deficiency symptoms before you received your prescription, you might want to rethink the use of the hormone.

And if you’re considering supplementation because of breathless claims about more libido, firmer erections, and boosted vitality, I suggest you think twice and get several medical opinions before opting for supplementation—especially if you have a history of depression.

If you or someone you love is contemplating suicide, seek help immediately. For help 24/7 dial 988 for the National Suicide Prevention Lifeline, or reach out to the Crisis Text Line by texting TALK to 741741. To find a therapist near you, visit the Psychology Today Therapy Directory.