FROM ENDOCRINE PRACTICE
Rigorous studies have not linked testosterone replacement therapy to heart attack or stroke, and the decision to prescribe testosterone replacement therapy should be based on a full diagnostic work-up – not the underlying cause of hypogonadism, according to a new position statement from the American Association of Clinical Endocrinologists.
The statement challenges several aspects of a recent Food and Drug Administration safety announcement warning about “possible” increased risks of heart attack and stroke with testosterone replacement therapy (TRT) and approving its use only for testicular, pituitary, or brain disorders that cause low testosterone, not for age-associated hypogonadism.
In fact, AACE rejoined, randomized controlled trials have lacked the power to assess whether TRT increases the chances of cardiovascular events or death. Data linking TRT to cardiovascular problems come from a few retrospective studies , the “major flaws” of which limit their ability to assess risk. “Large-scale prospective randomized controlled trials on testosterone therapy, focusing on cardiovascular benefits and risks, are clearly needed. As with therapeutics in general, common sense, experience, and an individualized approach are recommended” (Endocr Pract. 2015;21:1066-73).
The benefits and risks of TRT in age-associated hypogonadism remain uncertain, according to both the FDA and AACE. Until better studies are available, AACE recommends that clinicians consider TRT for men with signs and symptoms that are consistent with hypogonadism, regardless of cause, and who have at least two “unequivocally low” testosterone levels in samples drawn before 10 a.m.
Clinicians also should educate patients about the possible cardiovascular risks of TRT, should be “extra cautious” when considering TRT for symptomatic elderly men with low testosterone levels, and should avoid TRT entirely in frail elderly men “until better outcome data are available,” AACE also recommended. Furthermore, clinicians should avoid TRT for patients with uncontrolled or poorly controlled heart failure, a history of heart attack or cerebrovascular accident within the past 6 months, an individual or family history of a procoagulant state, or an individual history of thromboembolism, AACE stated.
Although TRT can improve some cardiovascular risk factors by promoting muscle gain and fat loss, decreasing insulin resistance, and potentially reversing metabolic syndrome, it remains unclear whether low testosterone is a marker of cardiovascular illness or a causal factor, AACE noted. Replacement therapy is most likely to benefit men with very low testosterone levels, not those whose levels are just below normal, according to AACE.
The American Urological Association has echoed several recommendations from AACE, emphasizing in its own statement that “testosterone therapy in the absence of hypogonadism is inappropriate” and calling for more federal and industry funding for studies of the indications, benefits, and risks of approved treatments for hypogonadism as well as studies of new potential therapies. “Current evidence does not provide any definitive answers regarding the risks of testosterone therapy on prostate cancer and cardiovascular disease, and patients should be so informed,” noted the statement from the AUA, which was last updated in August 2015.
The AACE Reproductive Endocrinology Scientific Committee listed the following disclosures: first author Dr. Neil Goodman reported serving on the AbbVie speaker bureau for AndroGel and senior author Dr. Glenn Cunningham reported receiving research support from Abbvie, having served on advisory panels for Abbvie, Apricus, Clarus Therapeutics, Endo Pharma, and Lilly and having consulted for Clarus Therapeutics, Endo Pharma, Ferring, Purdue Pharma, and Repros Therapeutics. Two other coauthors declared financial relationships with Abbvie, GlaxoSmithKline, Merck, Sanofi-Aventies, and a number of other pharmaceutical companies. The other two coauthors declared no competing interests.