Additional effects of medroxyprogesterone acetate on mammary tumors in oophorectomized, estrogenized, DMBA-treated rats
Sakamoto, S.; Kudo, H.; Suzuki, S.; Mitamura, T.; Sassa, S.; Kuwa, K.; Chun, Z.; Yoshimura, S.; Maemura, M.; Nakayama, T.; Shinoda, H.
Anticancer Research 17(6d): 4583-4587
1997
ISSN/ISBN: 0250-7005 PMID: 9494572 Document Number: 475093
Although hormone replacement therapy not only relieves vasomotor symptoms but also reduces cardiovascular disease and osteoporosis, long-term estrogen therapy increases the risk of endometrial and/or mammary cancer. We investigated the effects of conjugated estrogens with or without medroxyprogesterone acetate in oophorectomized, 7,12-dimethylbenz(a)anthracene-treated rats. Chemically induced mammary carcinogenesis was completely suppressed by the simultaneous oophorectomy, but conjugated estrogens replacement with or without medroxyprogesterone acetate markedly stimulated mammary carcinogenesis in the ovariectomized rats. The chronic administration of conjugated estrogens and medroxyprogesterone acetate markedly reduced the activities of thymidylate synthetase and thymidine kinase and bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors. These results indicate that the treatment using conjugated estrogens with or without medroxyprogesterone acetate may promote the mammary carcinogenesis in postmenopausal women but the chronic administration of medroxyprogesterone acetate may alter the development of established mammary cancer.