Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal cynomolgus macaques.
OBJECTIVE
Our purpose was to define the proliferative response and receptor status in the mammary glands of surgically postmenopausal macaques given hormone replacement therapy, equivalent for monkeys to that given women.


METHODS
Surgically postmenopausal adult female cynomolgus macaques (Macaca fascicularis) were given either no treatment (n = 26), conjugated equine estrogens (n = 22), or combined therapy with conjugated equine estrogens and medroxyprogesterone acetate (n = 21). Drugs were administered in the diet, at doses equivalent on a caloric 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 morphometric and stereologic means. Estrogen receptor and progesterone receptor content and proliferation were studied by immunohistochemistry.


RESULTS
In this model combined therapy with conjugated equine estrogens and medroxyprogesterone acetate induced greater proliferation than did conjugated equine estrogens alone. The percentage of estrogen receptor-positive cells was decreased in the conjugated equine estrogens plus medroxyprogesterone acetate group. The percentage of progesterone receptor-positive cells was increased by treatment with conjugated equine estrogens alone.


CONCLUSIONS
These results indicate a proliferative response of mammary gland epithelium to therapy with conjugated equine estrogens plus medroxyprogesterone acetate in postmenopausal macaques. The clinical implication of this finding may be a greater risk for development of breast neoplasms in women receiving combined hormone replacement therapy.
Cline
J M
JM
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1040, USA.
Soderqvist
G
G
von Schoultz
E
E
Skoog
L
L
von Schoultz
B
B
D000818:Animals; D002455:Cell Division; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D010052:Ovariectomy; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D004966:Estrogens, Conjugated (USP); D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017258:Medroxyprogesterone Acetate