Panel Members Question FDA Stance on Testosterone Replacement Therapy

The benefits of testosterone therapy outweigh the risks, according to experts, and the FDA may need to rethink its stance.

NASHVILLE, Tenn. — It may be time for the U.S. Food and Drug Administration (FDA) to rethink its position on testosterone replacement therapy, as the treatment’s benefits outweigh its risks, according to speakers at the American Association of Clinical Endocrinologists (AACE) 24th Annual Scientific & Clinical Congress. 

The FDA has approved testosterone replacement therapy only for men with disorders of the testicles, pituitary gland or brain that cause hypogonadism, said Sandeep Dhindsa, MD, associate professor of medicine and chief of the division of endocrinology and metabolism at Texas Tech University Health Sciences Center in Odessa.

The agency has said, however, that testosterone therapy should not be used to relieve symptoms in men who have low testosterone as a result of natural aging.

Dhindsa, who was a member of a panel of researchers who spoke on the topic of testosterone therapy at this year’s meeting, said there is no evidence that the response to testosterone replacement therapy is dependent on the cause of hypogonadism. In addition, he and other researchers reported that the benefits of the testosterone replacement therapy for treating low testosterone in both men and women substantially outweigh the risks.  

“The FDA is recommending that the treatment of hypogonadism should depend on the underlying cause. However, this does raise many concerns for the practicing physician,” said Dhindsa. “Testosterone therapy can provide significant benefits for hypogonadal men. There is no compelling evidence that testosterone therapy either increases or decreases cardiovascular risk. Risks and benefits of testosterone replacement therapy in elderly men are not well defined. In patients with vascular disease and minor symptoms of hypogonadism, a more cautious approach towards testosterone therapy is prudent.”

FDA Safety Alert for Testosterone Therapy

The panel’s comments were in response to the FDA’s March 2015 safety alert cautioning that the benefits and safety of testosterone medications prescribed for age-related low testosterone levels have not been established. In that statement, the FDA also called for manufacturers to include labeling about a possible increased risk for heart attacks and strokes.

However, Dhindsa said that the FDA provided no meaningful definition of aging, leaving it unclear whether or not age restrictions for testosterone therapy also apply to middle-aged individuals.

Further, the safety alert does not address the role that testosterone decline itself plays in common comorbidities, such as obesity and type 2 diabetes, at all ages, including adolescents and young men, he added.

“Several recent publications have raised concern that testosterone replacement therapy in men increases cardiovascular risk. There have also been reports of decreased mortality with testosterone treatment. However, all these studies have significant methodological limitations and do not permit us to draw any firm conclusions. There is no compelling evidence that testosterone therapy either increases or decreases cardiovascular risk. Meta-analyses of short-term randomized controlled trials do not show an effect of testosterone on cardiovascular events or mortality,” Dhindsa told Endocrinology Advisor.