Testosterone Therapy and CVD Risk: AACE Physicians Take a Stance

The link between testosterone therapy and cardiovascular risks has been a hot topic of debate, with researchers offering competing evidence and statements supporting or refuting the existence of link between testosterone supplementation and increased cardiovascular risk. Now, physicians from the American Association of Clinical Endocrinologists (AACE) have publicly stated their position on the issue.

In March 2015, the Food and Drug Administration (FDA) announced that manufacturers of testosterone products must change the labels to include increased risks of heart attack and stroke. However, research was presented quickly after saying that there is no evidence linking testosterone therapy and cardiovascular risks. Despite the report, multiple other studies have come out since then bringing attention back to connection and the FDA called for additional clinical trials to be conducted on the testosterone supplements in August 2015. Most recently on the issue, the AACE released a report in Endocrine Practice showing its position that there is no substantial evidence connecting the therapy and heart risks.

The authors noted that out of five meta-analyses (consisting of 27 studies) that looked at the potential relationship between testosterone therapy and increased cardiovascular events, only one found an increase (54% when compared to a placebo). However, the cardiovascular events included conditions other than heart attack and stroke, like hypertension and peripheral edema. The team also pointed out that none of the studies assessing the efficacy of testosterone therapy were conducted with the purpose of examining cardiovascular risks.

“On the contrary, a recent meta-analysis that included 75 randomized, placebo-controlled trials of testosterone treatment and evaluated the incidence of major adverse cardiovascular events did not find any association of testosterone therapy with actual cardiovascular events,” the report said.

Low testosterone is often not a causational factor, but a sign indicating an underlying illness all its own. Therefore, healthcare providers should not hesitate to address those problems and be even more cautious in those patients before prescribing testosterone therapy. The AACE recognizes that physicians should still discuss cardiovascular changes that can result from testosterone therapy and reiterate that contradicting research makes this area unclear.

“Recent reports related testosterone treatment to increased cardiovascular events. However, there is no compelling evidence that testosterone therapy either increases or decreases cardiovascular risk,” the authors wrote. They agree with the FDA that large trials are needed to focus on testosterone therapy and cardiovascular benefits and risks.

Based on the research that is available on the perceived link, the AACE authors provided the following recommendations:

1. We recommend that symptomatic men, who have unequivocally low total and/or free testosterone levels that are assayed on at least two samples drawn before 10 a.m. should be considered for [testosterone replacement therapy] TRT. The decision to replace testosterone therapy 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.

2. Since the risk/benefit ratio of TRT is not well established in aging-associated hypogonadism, we advise the practicing clinician to be extra cautious in the symptomatic elderly with demonstrably low testosterone levels prior to embarking on replacement therapy and to avoid treatment of the frail elderly altogether.

“Physicians should have a detailed discussion with such patients about the above-mentioned reports before embarking on testosterone replacement,” the team advised.