Edward C. Geehr, M.D.

Are testosterone products safe?

In January 2014, the Food and Drug Administration announced that it was investigating the risk for stroke, heart attack and death in men taking FDA-approved testosterone products. The investigation was prompted by reports of increased risk of those outcomes in middle-aged or older men after starting testosterone supplementation.

The announcement coincided with publication in the journal PLoS ONE of a study of nearly 56,000 men who had been prescribed testosterone between 2008 and 2010. The rate of heart attacks was measured before and during the first 90 days of testosterone therapy. The study authors observed that the risk of heart attack more than doubled in men older than 65 and nearly tripled in men younger than 65 with a history of heart disease.

The PLoS study findings confirmed previous observations from smaller studies, including those published in 2013 in the Journal of the American Medical Association and the journal BMC Medicine.

In June 2014, the FDA announced that testosterone products had to carry a warning label about the increased risk of thrombosis – blood clots in the veins.

Not so fast

Now a new study of more than 25,000 Medicare patients, recently published online in the Annals of Pharmacotherapy, has reached a very different conclusion. Researchers from the University of Texas found that testosterone users were no more likely to suffer a heart attack than nonusers, and for men considered at highest risk of heart attack, testosterone use cut the risk by nearly 30%.

Testosterone prescriptions for older U.S. men have increased threefold over the past 10 years, according to the Annals article.

Why the spike? There's been a huge climb in direct-to-consumer marketing, a rapid expansion of clinics specializing in the treatment of low testosterone and the development of new drugs, including gels applied to the skin – the most popular form of use.

Testosterone and the heart

The link between testosterone therapy and heart disease is complicated because the cardiovascular system responds to testosterone supplementation in ways both positive and negative.

The up side is that testosterone may improve health by decreasing fat mass, increasing sensitivity to insulin and reducing inflammation and thickening of the artery walls. It's possible that these positive effects are most beneficial to older men with increased cardiovascular risk.

The down side: Testosterone increases salt and water retention, which can lead to high blood pressure and heart failure. The hormone may also increase the risk of blood clotting, which can lead a greater risk of stroke or heart attack.

Why the conflicting study results?

There is no such thing as settled medical science. For example, one previous study published in JAMA found a connection between testosterone use and heart risk; critics pointed out that nearly 10% of the 1,100 study subjects were women. Several groups have called on JAMA to retract the study.

The Annals of Pharmacotherapy study was a review of Medicare data, not a controlled clinical trial. Researchers tracked only outcomes in men who received testosterone injections, not those who may have received gels, patches or oral drugs.

Until the FDA provides clearer guidelines for changes to labeling of testosterone therapies, I recommend that men who are interested in testosterone therapy follow this advice:

If you have signs and symptoms of low testosterone – hot flashes, loss of sexual desire, poor sleep and loss of muscle mass – seek a physician with experience and training in the field of hormone therapy.
Undergo a full checkup to rule out other possible causes of low testosterone and to see if you have medical reasons to avoid therapy.
Get blood testosterone levels to verify the presence of low testosterone.
If other reversible causes of low-T are present, such as obesity, poor diet, inactivity or thyroid disorders, correct those conditions first and then reassess testosterone levels.
Start treatment only if your symptoms are confirmed by low serum testosterone levels and if your condition hasn't improved after correcting reversible causes of low-T.
Get periodic tests to make sure your dosing is not bringing on too-high levels of testosterone, and to check other blood values, such as your red blood count.
Inform your doctor if you experience chest pains, trouble breathing at night or frequent and persistent erections. Dosing may need to be adjusted or therapy ended.
Undergo regular prostate exams and serum PSA level tests to check for prostate cancer, an indication to stop testosterone therapy.
Partners and children should not be exposed to gels or patches, or to skin or clothing adjacent to where gel has been applied. Testosterone easily transfers via skin contact and can cause serious side effects in children in particular.