Gynecomastia induced in normal males by spironolactone.

Abstract

The short‐term (1 week) and long‐term (10 month) effects of spironolactone have been determined in normal males. There were no adverse effects or changes in plasma testosterone, luteinizing hormone, or progesterone levels during one week of treatment with spironolactone (200 mg/day) in 6 normal men. A continuous 4‐hr sampling technique to provide an integrated plasma sample resulted in plasma hormone concentrations similar to the mean values for intermittent sampling. There was considerable intraindividual variability in the levels of each hormone. To evaluate the long‐term effects of spironolactone, 30 normal males were randomly divided into three groups: placebo, 100 mg spironolactone per day (low dose), and 100 mg spironolactone per day increased at two months to 200 mg spironolactone per day (high dose). The study was double blind and lasted 10 months. The presence of gynecomastia was determined clinically and confirmed by thermography. Two metabolic clearance studies with either 3H‐testosterone or 3H‐androstenedione were obtained (1) just before spironolactone treatment and (2) again with the same steroid either the last day of the 10‐month treatment period or with the development of gynecomastia. The concentrations of testosterone, estradiol, estriol, luteinizing hormone, follicle stimulating hormone, progesterone, and prolactin were also determined before treatment and at two‐month intervals during treatment. Eighteen individuals received spironolactone (10 in the low‐dose group and 8 in the high‐dose group); of these, 8 developed gynecomastia. There were none in the placebo group. The incidence of gynecomastia was 30% in the low‐dose group and 62% in the high‐dose group. In addition, one individual in the high‐dose group discontinued taking the drug early because of decreased libido, bringing the incidence of adverse effects in this high‐dose group to 75%. Spironolactone induced no significant changes in the metabolic clearance of androstenedione or testosterone. Plasma concentrations of the various hormones did not change as a result of either spironolactone or the development of gynecomastia. Inhibition of testosterone synthesis or alteration in its metabolic clearance by spironolactone does not appear to be the cause of spironolactone‐induced gynecomastia in man.