TRT Benefits Outweigh Risks, AACE Tells FDA

The potential benefits of testosterone replacement therapy (TRT) to treat low testosterone (low T) in both men and women substantially outweigh any risks.

That statement was put forth by an expert panel convened at the 2015 American Association of Clinical Endocrinologists Annual Scientific and Clinical Congress, held May 13-17, 2015, in Nashville, Tenn.

The panel’s comment is in repsonse to a March 2015 FDA safety alert that warns that the benefits and safety of testosterone medications prescribed for age-related low T levels have not been established. The FDA called at that time for manufacturers to revise labeling to indicate a possible increased risk of heart attacks and stroke among millions of older men for whom testosterone is prescribed.

The FDA recommendation may have overreached the mark, says the AACE.

In a press release from the AACE, endocrinologist Sandeep Dhindsa, MD, assistant professor of internal medicine at Texas Tech University Health Science Center in Odessa, pointed out a number of gaps in the FDA statement and in the information it is based on:   

     ♦ FDA provided no meaningful definition of aging, so it is unclear whether age restrictions on TRT should also apply to middle-aged men.

     ♦ Recommendation does not address the role of declining testosterone itself in common comorbidities, eg, obesity, type 2 diabetes; medications also may lower testosterone levels.

     ♦ Under new FDA recommendations, men in these populations may not be considered candidates for TRT-even if levels of the hormone are very low.

A soon-to-be-published AACE Reproductive Endocrinology position statement on the association of testosterone and cardiovascular risk notes:

     ♦ “There is no compelling evidence that TRT either increases or decreases cardiovascular risks.”

     ♦ “. . . testosterone therapy favorably changes many cardiovascular risk factors by decreasing fat mass, increasing muscle mass, and decreasing insulin resistance."

Dr Dhindsa points out the benefits of TRT in aging men and notes that age is not the only cause of declining testosterone levels.

     ♦ Benefits: improved libido, improved energy and mood, increased lean body mass, and improved bone mineral density.

     ♦ Causes: low T may be caused by congenital abnormalities, eg, hemochromatosis and defects in androgen synthesis or action, and can be acquired as a result of age, obesity, or type 2 diabetes.

Dhindsa in the AACE press release notes that signs and symptoms consistent with hypogonadism plus an “unequivocally low morning serum testosterone concentration” qualify men for TRT.

     ♦ “Any patient being considered for testosterone replacement therapy should undergo a thorough diagnostic workup.”

     ♦ “The decision to replace testosterone therapy should be guided by the signs, symptoms, and testosterone concentrations rather than the underlying cause.” 

     ♦ Still missing, says Dhindsa, are diagnostic thresholds to more accurately identify men who would benefit from TRT and data on long-term outcomes associated with testosterone therapy.

Don’t limit treatment of hypogonadism, Dhindsa says, based on the cause alone. There is no debate about TRT in men with very low testosterone levels, but ongoing controversy about the efficacy in older men.

     ♦ Normal total testosterone range is 300 ng/dL to 1000 ng/dL.

     ♦ For elderly men the range is ≈ 280 to 450 ng/dL.

     ♦ Treating men with testosterone levels lower than 200 ng/dL is warranted, regardless of the cause or age.

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