A recent systematic review of the safety and efficacy of testosterone replacement therapy (TRT) largely reinforces the 2010 Endocrine Society Clinical Practice Guidelines for male hypogonadism, but also identifies critical areas to update.
Writing in Mayo Clinic Proceedings, published online ahead of print, Allen D. Seftel, MD, of Rowan University in Camden, NJ, and colleagues reviewed Level 1a evidence on TRT published after 2010. The recent research suggests that severe lower urinary tract symptoms (LUTS) and untreated obstructive sleep apnea may not be absolute contraindications to TRT. In several studies including hypogonadal men on TRT, detrimental effects, such as worse sleepiness or voiding, were not observed.
TRT may provide beneficial effects in men with metabolic syndrome. Recent randomized trials indicated improvements in insulin sensitivity and sexual function. The literature also reinforced evidence showing TRT improves physical functioning in frail men, such as muscle strength and bone health. How TRT affects the risk of fracture in men with osteoporosis requires further study and might alter the current recommendation for periodic bone density scans.
As in the 2010 guidelines, the reviewers found inconsistent effects of TRT on quality of life, wellbeing, and erectile function (even in men refractory to phosphodiesterase type 5 inhibitors).
Importantly, future studies need to investigate the effect of TRT in men treated for prostate cancer. There also remains a lack of high quality prospective trials examining the effects of TRT on cardiovascular risk.
In March 2015, the FDA issued a safety communication about a possible increased risk of heart attack and stroke with prescription testosterone products. The FDA noted that TRT is indicated only for men with disorders of the testicles, pituitary gland, or brain. The warning, however, was based mostly on retrospective research, according to the reviewers. Some recent study findings challenge the assumption. The FDA has requested clinical trials to clearly address the question. “The most pressing need for further high-quality trials remains in the arena of CV morbidity and mortality associated with TRT,” according to the reviewers.
The current review was based on a total of 17 Level 1 trials published from 2010 to March 2, 2015 and did not include retrospective studies, which is a limitation.
- Seftel, AD; Kathrins, M; and Niederberger, C. Mayo Clinic Proceedings; doi: 10.1016/j.mayocp.2015.06.002.
- FDA safety communication, March 2015.