Gynecomastia and Semen Abnormalities Induced by Spironolactone in Normal Men

Abstract

The clinical and hormonal effects of spironolactone on the pituitary-testicular axis were evaluated in healthy, young men. One group of nine men took 100 mg daily for 4 weeks, none for 4 weeks, then 400 mg daily for 4 weeks. The dialyzable fraction of testosterone increased by 20% (P < 0.01) during both periods of spironolactone administration. The serum concentrations of FSH, LH, testosterone andestradiol, however, did not change during either period, nor did the FSH and LH responses to synthetic gonadotropin-releasing hormone. Another group of 9 men took 400 mg of spironolactone daily for up to 24 weeks. During this time6 developed gynecomastia and 2 noted a decrease in libido. Two men had decreases in sperm density and motility that were apparently drug-related, although the mean sperm density of all 9 men did not change significantly. No change occurred in the mean serum concentrations of FSH, LH, testosterone or estradiol. In vitro incubation of canrenone, the principal circulating metabolite of spironolactone, in concentrations achieved in vivo, with serum from normal men resulted in a small but significant displacement of testosterone from its binding protein and in a smallspurious increase in die serum testosterone concentration. We conclude that spironolactone-induced gynecomastia and occasional semen abnormalities do not appear to be due to changes in the serum concentrations of testosterone or estradiol. We hypothesize that these changes may be related to binding of canrenone to tissue androgen receptors.