Chlormadinone and mammary nodules.

Abstract

A study was conducted to determine whether high dose levels of the natural hormone progesterone would produce fibroadenomatous nodules in the mammary glands of beagle bitches similar to those appearing after high dosages of chlormadinone acetate and medroxyprogesterone acetate both derivatives of 17alpha-hydroxyprogesterone. In this investigation natural progesterone was administered by subcutaneous injection in an oily vehicle at 3 different dose levels (7.5 mg/kg daily for 24 weeks following an initial period of 12 weeks at 975 mg/kg daily and then 22.5 mg/kg daily for 38 weeks) for a 74 week period to beagle bitches. Microscopic postmortem examinations of the mammary glands revealed marked lobular hyperplasia in most cases with secretory activity generally proportional to the progesterone dosage received. 2 of the 5 high dose animals also exhibited some bizarre but well circumscribed fibroadenomatous nodules with some cell atypia and mitotic activity possible early stages of a benign complex tumor. The authors believe that the occurrence of such fibroadenomatous nodules in animals after exposure to the natural hormone gives reason to doubt the relevance to the human female of the development of similar nodules in the animals after high doses of 17alpha-hydroxyprogesterone.