FDA Explains Its Position on Testosterone Prescribing for Age-Related Hypogonadism

Urology Practice Management - October 2015, Vol 4, No 5 - Hypogonadism
Rosemary Frei, MSc

In recent years, according to the FDA, testosterone agents are increasingly used for older men for what the FDA calls “age-related hypogonadism.” Late last year, the FDA discussed this issue and the increasing evidence for increased risk for cardiovascular disease associated with testosterone therapy.

In August 2015, several members of the FDA have penned an article that was published in the New England Journal of Medicine to explain the agency’s requirement for warnings about the possible increased risks for heart attacks and strokes in the labeling of prescription testosterone therapies (Nguyen CP, et al. N Engl J Med. 2015;373:689-691).

The FDA’s perspective underlines the lack of evidence for clear clinical benefits in treating older men with testosterone therapy merely to bring their titers up to the levels of young men rather than to treat classical hypogonadism. The FDA members also noted the “evidence from recent large observational studies that suggests potential cardiovascular risk associated with testosterone use.”

The AUA Position

Despite this, the American Urological Association (AUA) still does not warn physicians against using testosterone to treat age-related hypogonadism. Rather, the AUA’s position statement says that “there is conflicting evidence about the impact of testosterone therapy on cardiovascular risks” and that “testosterone therapy is appropriate treatment for patients with clinically significant hypogonadism, including those with idiopathic clinical hypogonadism that may or may not be age-related, after full discussion of potential adverse effects” (

Christine P. Nguyen, MD, the FDA’s Deputy Director for Safety in the Division of Bone, Reproductive, and Urologic Products, said that she and the coauthors of the editorial cannot speak for the AUA in terms of explaining the urology association’s stance.

FDA versus AUA

“We at FDA independently reviewed data informing the use, risks, and benefits of testosterone replacement therapy in reaching our conclusions,” Dr Nguyen told Urology Practice Management. “We acknowledge that professional medical societies may have different opinions and positions than those of the FDA, for a variety of reasons.”

The FDA announced its decision in March 2015 to require drug manufacturing companies to revise their testosterone drug labels ( The FDA approved the final labeling changes in May 2015.

Age-Related Hypogonadism

In their perspective, Dr Nguyen and colleagues described the recent marked increase in testosterone use for age-related hypogonadism and the conclusion of an Institute of Medicine committee that there is sparse evidence to support this practice.

“To date, there is no definitive evidence that increasing serum testosterone concentrations in these men is beneficial and safe, and the need to replace testosterone in older men who lack a distinct, well-recognized cause of hypogonadism remains debatable,” the investigators noted.

Moreover, men are often prescribed testosterone without any defined cause of hypogonadism and for only short periods of time, suggesting that they do not have classic hypogonadism. The authors expressed strong concern over this phenomenon, particularly in light of evidence of increased risk for cardiovascular events with testosterone.

Cardiovascular Risk

The FDA investigators noted that they reviewed 5 retrospective cohort studies and 2 meta-analyses of controlled trials, and found that testosterone supplementation may indeed be linked to increased risks for heart attack and stroke.

Furthermore, an FDA Advisory Committee concluded that the labeling for testosterone should note the lack of evidence for the safety and efficacy of the drugs in patients with age-related hypogonadism, and that low testosterone levels need to be confirmed before testosterone is prescribed. The committee also called for a controlled clinical trial to definitively examine testosterone’s effects on cardiovascular outcomes.

“Given the widespread use of testosterone for age-related hypogonadism, the lack of substantial evidence to support such use, and the unknown effect of the label changes on prescribing patterns, the cardiovascular safety of testosterone products in older men remains an important public health concern,” concluded Dr Nguyen and colleagues in the article.

“We believe the health of American men will be well served by the presence of accurate drug labels and reliable data to inform clinical decision making.”

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