AACE Responds to FDA Testosterone-Replacement Statement

Miriam E Tucker

September 29, 2015

The American Association of Clinical Endocrinologists (AACE) has issued a position statement on the use of testosterone-replacement therapy in response to the US Food and Drug Administration's announcement earlier this year regarding cardiovascular effects of testosterone, placing more emphasis on potential benefits and emphasizing the uncertainty about the FDA's advice.

The statement is published in the September issue of Endocrine Practice by the AACE Reproductive Endocrinology Scientific Committee, led by Neil Goodman, MD, of the University of Miami, Florida.

The AACE panel recommends:

  • Testosterone-replacement therapy should be considered for symptomatic men who have unequivocally low total and/or free testosterone levels that are assayed on at least two samples drawn before 10 am.

  • Clinicians should be especially cautious in the use of testosterone therapy in symptomatic elderly men with demonstrably low testosterone levels, and such treatment should be avoided in frail elderly men until better outcome data are available.

The AACE statement was written in response to the FDA's March 3, 2015 drug safety communication and prior hearing about study findings suggesting increased cardiovascular risk with testosterone-replacement therapy. The FDA cautioned that testosterone be prescribed only for men with confirmed low testosterone levels and advised that clinicians alert patients to the possible increased CVD risk.

Dr Goodman and colleagues note that epidemiologic studies strongly support the association of low testosterone concentrations and hypogonadism with cardiovascular events and mortality — in elderly men in particular — so low testosterone could be a marker of illness rather than a causal factor.

Moreover, they say, testosterone-replacement therapy is associated with favorable changes in cardiovascular risk factors, including reduced fat mass, increased muscle mass, and decreased insulin resistance.

AACE Agrees With FDA That More Trials Are Needed

The AACE committee also points out that randomized, controlled studies have not been powered to adequately characterize the relationship between testosterone-replacement therapy and CVD outcomes.

While two retrospective studies have raised concern, another has suggested no effect. But, the committee notes, all of these studies are flawed, precluding meaningful conclusions.

The panel called "unclear" the FDA's recommendation that "testosterone is an FDA-approved replacement therapy only for men with disorders of the testicles, pituitary gland, or brain that cause hypogonadism" and that "it should not be used to relieve symptoms in men who have low testosterone for no reasons other than aging."

Rather, Dr Goodman and colleagues write, "It is our opinion that any patient being considered for [testosterone-replacement therapy] must undergo a thorough diagnostic workup. The decision to replace testosterone should be guided by the signs/symptoms and testosterone concentrations rather than the underlying cause. These men should be told that we do not have definitive studies demonstrating efficacy or risk for treating men with these conditions."

The AACE panel members say they agree with the FDA that the risk/benefit ratio of testosterone-replacement therapy is not well established in aging-associated hypogonadism. And, as the FDA did recently, they call for large-scale prospective randomized trials to answer the question.

Dr Goodman is on the AbbVie speaker bureau for AndroGel. Disclosures for the other panel members are listed in the article.

Endocr Pract . 2015;21:1066-1074. Article

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