Suppressed testicular and cardiac function secondary to androgen abuse was shown to be effectively fully reversible in 7 to 18 months, apart from reductions in testis volume and serum sex hormone-binding globulin (SHBG) levels, according to the results of a cross-sectional observational study published in The Journal of Clinical Endocrinology & Metabolism.
Originating as a means for performance enhancement in elite athletes, androgen abuse is on the rise among young men in the general public and is a serious but neglected public health issue. Few studies have investigated the rate, extent, and determinants of recovery from the reproductive and cardiac effects of androgen abuse.
A cross-sectional observational study of 93 participants compared current (n=41) and past (n=31) androgen abusers with healthy nonuser control participants (n=21) to estimate the rate and extent of recovery from reproductive and cardiac dysfunction secondary to androgen abuse. All participants were 18 to 55 years of age and exercised at least 3 times per week. Past androgen users were defined as those who had ceased using androgens for at least 3 months. Men with a history of vasectomy were excluded from analyses of sperm output.
During a single visit, participants provided a standardized medical history and blood and semen samples and completed quality of life questionnaires. They also underwent a physical examination, testicular ultrasound, body composition analysis by dual-energy absorptiometry analysis, and cardiac function evaluation based on echocardiography and computed tomography calcium score.
All groups were well matched for mean age (current users, 34±1 years; past users, 33±2 years; nonusers, 32±2 years). Current users and past users had significantly different mean ages at first androgen use (current users, 27±1 years; past users, 23±1 years; P =.014), but similar median durations of androgen abuse (2.4 years for both current and past users), delivery method of drug, and variety of androgens used.
Current users had lower testis volume, sperm output and motility, and levels of serum dehydroepiandrosterone, luteinizing hormone, follicle-stimulating hormone, SHBG, anti-Müllerian hormone, and inhibin B and total inhibin, as well as higher serum testosterone, dihydrotestosterone, estradiol, estrone, and 3α and 3β androstanediols than nonusers. Except for testis volume and serum SHBG, reproductive function measures did not differ between past users and nonusers, indicating full reversibility after cessation of androgen abuse. Neither age nor any anthropometric variables were associated with rate of recovery of sperm or hormonal variables, but total duration of androgen abuse was associated with a slower recovery of sperm variables (output, concentration, motility).
Current users had significantly greater left ventricular interventricular septum thickness (10.7±0.4 mm) and posterior wall thickness (10.6±0.3 mm) compared with control participants (8.7±0.5 and 8.9±0.5 mm, respectively), though all measurements in all groups were within the normal range (≤11 mm). Past users did not differ from nonusers in either variable, indicating full recovery after cessation.
This study suggests that suppression of testicular function resulting from androgen abuse in young men for an average duration of >2 years is fully reversible, apart from residual reduction in testis volume and serum SHBG, within 7 to 18 months of cessation. The duration of prior use delayed sperm recovery but not the recovery of hormonal variables.
The researchers noted that differences in the results of this study from other studies in the literature that have reported sustained testicular function impairment after androgen abuse may be due to differences in net androgen exposure, which is difficult to document retrospectively. A limitation of this study was its observational nature, which was unavoidable given the illicit nature of androgen abuse.
Future studies with larger cohorts, longer lifetime androgen abuse exposure, and older men are warranted. Future studies that examined measurements of sperm function would clarify the rate and extent of recovery of sperm fertility. Moreover, research on the effects of androgen abuse in women is important to gather information on women who take androgens, an understudied population.
Shankara-Narayana N, Yu C, Savkovic S, et al. Rate and extent of recovery from reproductive and cardiac dysfunction due to androgen abuse by men [published online February 7, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz324