Mechanisms of Hormone Action

Chronic Administration of Anabolic Steroids Disrupts Pubertal Onset and Estrous Cyclicity in Rats

Abstract

Use of anabolic-androgenic steroids (AAS) is becoming increasingly popular among adolescent girls, yet the effects of AAS on female physiology and development are not well understood. The present study compared the effects of chronic exposure to three individual AAS: stanozolol (0.05-5 mg/kg), 17-methyltestosterone (0.5-5 mg/kg), and methandrostenolone (0.5-5 mg/kg), on the onset of puberty and estrous cyclicity in the rat. Female rats received daily injections of AAS for thirty days (Postnatal Day [PN] 21-51). Rats receiving the highest dose of each of the AAS (5 mg/kg) displayed vaginal opening at a younger age than rats receiving the oil vehicle. The day of first vaginal estrus was delayed in rats receiving stanozolol (5 mg/kg) or 17-methyltestosterone (0.5-5 mg/kg), but not in rats receiving methandrostenolone. At the highest dose (5 mg/kg), each of the AAS reduced the incidence of regular estrous cyclicity during the treatment period. Concurrent administration (on PN21-51) of the androgen receptor antagonist, flutamide, (10 mg/kg, twice daily) reversed the effects of 17-methyltestosterone (5 mg/kg) on vaginal opening. Flutamide administration also eliminated the effects of stanozolol (5 mg/kg) and 17-methyltestosterone (5 mg/kg) on the day of first vaginal estrus. In contrast, rats receiving flutamide and methandrostenolone (5 mg/kg) exhibited first vaginal estrus earlier than controls. The present results indicate that chronic exposure to AAS during development has deleterious effects on the female neuroendocrine axis and that these effects appear be mediated via multiple mechanisms.