Abstract
Cimetidine has been associated with gynecomastia as a side effect. Because other antiandrogens have been linked to the development of breast enlargement in men, the suggestion by earlier workers that cimetidine possessed antiandrogenic properties prompted us to study the endocrine effects of cimetidine in rats. Cimetidine directly antagonized the effects of exogenously administered testosterone on androgen target tissues. Ventral prostate and seminal vesicle weights were less in cimetidine-treated castrate adult male rats androgenized with testosterone-filled subcutaneous silastic capsules than in vehicle-injected controls. Cimetidine possessed no intrinsic androgen-like bioactivity in prepubertal male rats when given in doses of 50 mg/kg/day for 1 wk. Cimetidine competitively inhibited DHT binding to its cytoplasmic receptor and decreased specific nuclear uptake of [3H]dihydrotestosterone in rat ventral prostate slices. No effects on plasma gonadotropin or testosterone concentrations were observed. We conclude that cimetidine is a nonsteroidal-antiandrogen and that this property may contribute to the production of gynecomastia in cimetidine-treated men.
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