ADDITIONAL EFFECTS OF MEDROXYPROGESTERONE ACETATE ON MAMMARY-TUMORS IN OOPHORECTOMIZED, ESTROGENIZED, DMBA-TREATED RATS

Although hormone replacement therapy not only relieves vasomotor sympt oms but also reduces cardiovascular diseases and osteoporosis, long-te rm estrogen therapy ina eases the risk of endometrial and/or mammary c ancer. We investigated the effects of conjugated estrogens with or wit hout medroxyprogesterone acetate in oophorectomized 7,12-dimethylbenz( a)anthancene-treated rats. Chemically induced mammary carcinogenesis w as completely suppressed by the simultaneous oophorectomy, replacement with or without medroxyprogesterone markedly stimulated mammary carci nogenesis in the ovariectomized rats. The chronic administration of co njugated estrogens and medroxyprogesterone acetate markedly reduced th e activities of thymidylate synthetase and thymidine kinase and bromod eoxyuridine-immunoreactive (S-phase) cells in mammary tumors. These re sults indicate that the treatment using conjugated estrogens with or w ithout medroxyprogesterone acetate may promote the mammary carcinogene sis in postmenopausal women but the chronic administration of medroxyp rogesterone acetate may alter the development of established mammary c ancer.