Study finds testosterone injections carry greater risk of adverse effects than gels, patches

May 11, 2015

A recent study led by faculty at the UNC-Chapel Hill Gillings School of Global Public Health has found that testosterone injections are associated with a greater risk of cardiovascular events, stroke, hospitalization and death compared with testosterone gels or patches.

Testosterone use has increased considerably in the United States (U.S.), United Kingdom (U.K.) and other countries. Many of those using testosterone lack clear medical indications for treatment, and there has been considerable use contrary to recommended guidelines.

One prior clinical trial of testosterone gels was halted when the participants – older men – began to experience more cardiovascular events while using the gel. While other studies have suggested that testosterone use has no adverse effects, there are ongoing concerns.

Dr. Bradley Layton

Bradley Layton, PhD, research assistant professor of epidemiology at the Gillings School, worked with Til Stürmer, MD, PhD, and Alan Brookhart, PhD, also from the epidemiology department, as well as Julie Sharpless, MD, from the UNC School of Medicine, and other colleagues at the University of Basel, Switzerland and Boston University to study the comparative cardiovascular safety of gels, injections and patches.

Pharmacokinetics differ among the three delivery methods: injections cause spikes of super-normal testosterone levels, while transdermal patches and gels cause more subtle but sustained increases, potentially resulting in different safety profiles.

The paper on the research team’s findings, titled “Comparative safety of testosterone dosage forms,” was published online May 11 by JAMA Internal Medicine.

The researchers examined new users of the three forms of testosterone by reviewing databases of U.S. private insurance claims, U.S. Medicare billing claims and U.K. general practitioner records.

They identified middle-aged and older men who were newly initiating testosterone use following a minimum 180-day period free of documented use. The researchers tracked these subjects for up to one year to observe health outcomes.

The study findings suggest that testosterone injections may increase short-term risk of cardiovascular events, stroke, hospitalization and death compared with gels. The risks profiles of patches and gels are similar, and in both cases are lower than the risks associated with injections.

Layton and colleagues observed a trend over the study period, in which use of testosterone gel increased and use of injections and patches declined.

The U.S. Food and Drug Administration recently narrowed the indications for testosterone treatment, and regulatory agencies around the world are currently considering adding warning labels to testosterone products.

“There has been considerable interest in testosterone products lately, especially from regulatory agencies, as testosterone use has increased steadily over the past decade and some studies have suggested increased risks associated with their use,” explained Layton. “We investigated testosterone risk in multiple settings and populations where it is used very differently, and we consistently observed increased risks with the injections compared to the topical forms.”