Nonsteroidal antiandrogen drugs

Hirsutism is a bothersome hyperandrogenic manifestation of PCOS that may require at least six months of treatment before improvement begins. According to a 2015 Cochrane review, the most effective first-line therapy for mild hirsutism is oral contraceptives. 32 Spironolactone, 100 mg daily, and flutamide, 250 mg twice daily, are safe for patient use, but the evidence for their effectiveness is minimal. 32 Other therapies include eflornithine (Vaniqa), electrolysis, or light-based therapies such as lasers and intense pulsed light. Any of these can be used as monotherapy in mild cases or as adjunctive therapy in more severe cases. 33

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.

Administration of NILANDRON to beagle dogs resulted in drug-related deaths at dose levels that produce AUC exposures in dogs much lower than the AUC exposures of men receiving the therapeutic doses of 150 and 300 mg/day. Nilutamide-induced toxicity in dogs was cumulative with progressively lower doses producing death when given for longer durations. Nilutamide given to dogs at 60 mg/kg/day (1-2 times human AUC exposure) for 1 month produced 100% mortality. Administration of 20 and 30 mg/kg/day nilutamide (½-1 times human AUC exposure) for 6 months resulted in 20% and 70% mortality in treated dogs. Administration to dogs of 3, 6, and 12 mg/kg/day nilutamide (1/10-½ human AUC exposure) for 1 year resulted in 8%, 33%, and 50% mortality, respectively. A “no-effect level” for nilutamide-induced mortality in dogs was not identified. Pathology data from the one-year oral toxicity study suggest that the deaths in dogs were secondary to liver toxicity. Marked-to-massive hepatocellular swelling and vacuolization were observed in affected dogs. Liver toxicity in dogs was not consistently associated with elevations of liver enzymes.

Nonsteroidal antiandrogen drugs

nonsteroidal antiandrogen drugs


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