title: Studies of the components of an oral contraceptive agent in albino rats. II. Progestogenic component and comparison of effects of the components and the combined agent.
abstract: Albino rats were fed norethindrone acetate in the diet for 2 yr at dosage levels (0.3--0.4 mg/kg) of about 10 and 100 times the recommended human dose as used in a combination estrogen-progestogen oral contraceptive. The treated rats had dose-related growth retardation and alopecia, but an enhanced survival rate. Dose-related changes in the male rats included testicular and accessory gonadal atrophy, and in the females, uterine changes. In animals of both sexes at the high dose level, there was liver enlargement with increased foci of cell alterations and cystic mastopathy. Females had increased adrenal gland weights, decreased ovarian weights, and ovarian atrophy. Females at both dose levels had an increased incidence of uterine polyps, and rats of either sex in the high-dose group had an increased incidence of liver neoplastic nodules. However, there were no significant differences with respect to tumor incidence, probability of tumor development, or number of tumors developing in treated compared to untreated rats. In fact, in the females there was a delayed onset of tumor formation.
mesh_terms: D000505:Alopecia / Q000139:chemically induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005835:Genitalia / Q000187:drug effects*; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced; D008136:Longevity / Q000187:drug effects; D008297:Male; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D009640:Norethindrone / Q000009:adverse effects*; D051381:Rats
chemical_list: D009640:Norethindrone