Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats.
Megestrol acetate (17alpha-acetoxy-6-dehydro-6-methylprogesterone), a synthetic steroid with high progestational activity, is used in oral contraceptives but also in the treatment of prostatic diseases in man. To investigate whether megestrol acetate has any androgenic properties the growth of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles was studied morphologically in castrated rats treated with megestrol acetate and in non-treated castrated rats. The effect of megestrol acetate on the body weight, the levator ani muscle and the adrenals was also studied. Megestrol acetate was administered in daily doses of 0.02 mg, 0.2 mg, 2.0 mg or 20.0 mg for a period of 21 days. Megestrol acetate in the two higher doses retarded growth and gave a low weight for the levator ani muscle at autopsy indicating an anti-anabolic or catabolic action of megestrol acetate in high doses. Megestrol acetate in daily doses of 0.2, 2.0 and 20.0 mg caused an involution of the adrenal glands. After the two higher doses the weight of the adrenals amounted to only about a third of that of the untreated rats. Megestrol acetate in the lower doses had no demonstrable effect on the growth of the accessory reproductive glands. After the two higher doses of megestrol acetate some growth of the dorsal part of the dorsolateral prostate and of the coagulating glands was observed. Only the seminal vesicles exhibited complete morphological criteria of an androgenic stimulation and then only after the largest dose of megestrol acetate. The investigation shows that megesterol acetate has weak androgenic properties which are apparent at a dose per kg body weight approximately 200 times greater than that used in the treatment of prostatic diseases in man.
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology; D000311:Adrenal Glands / Q000033:anatomy & histology / Q000187:drug effects*; D000728:Androgens; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002369:Castration; D003864:Depression, Chemical; D008297:Male; D008535:Megestrol / Q000008:administration & dosage / Q000494:pharmacology*; D009132:Muscles / Q000033:anatomy & histology / Q000187:drug effects; D009929:Organ Size; D010388:Pelvis; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects*; D051381:Rats; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects*; D013737:Testis / Q000502:physiology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects
D000085:Acetates; D000728:Androgens; D008535:Megestrol