EFFECTS OF HORMONE REPLACEMENT THERAPY ON THE MAMMARY-GLAND OF SURGICALLY POSTMENOPAUSAL CYNOMOLGUS MACAQUES

OBJECTIVE: Our purpose was to define the proliferative response and re ceptor status in the mammary glands of surgically postmenopausal macaq ues given hormone replacement therapy, equivalent for monkeys to that given women. STUDY DESIGN: Surgically postmenopausal adult female cyno molgus macaques (Macaca fascicularis) were given either no treatment ( n = 26), conjugated equir:e estrogens (n = 22), or combined therapy wi th conjugated equine estrogens and medroxyprogesterone acetate (n = 21 ). Drugs were administered in the diet, at doses equivalent on a calor ic basis to 0.625 mg per woman per day for conjugated equine estrogens and 2.5 mg per woman per day for medroxyprogesterone acetate, for 30 months. Mammary gland proliferation was assessed subjectively and by m orphometric and stereologic means. Estrogen receptor and progesterone receptor content and proliferation were studied by immunohistochemistr y. RESULTS: In this model combined therapy with conjugated equine estr ogens and medroxyprogesterone acetate induced greater proliferation th an did conjugated equine estrogens alone. The percentage of estrogen r eceptor-positive cells was decreased in the conjugated equine estrogen s plus medroxyprogesterone acetate group. The percentage of progestero ne receptor-positive cells was increased by treatment with conjugated equine estrogens alone. CONCLUSION: These results indicate a prolifera tive response of mammary gland epithelium to therapy with conjugated e quine estrogens plus medroxyprogesterone acetate in postmenopausal mac aques. The clinical implication of this finding may be a greater risk for development of breast neoplasms in women receiving combined hormon e replacement therapy.