Cline J M, Soderqvist G, von Schoultz E, Skoog L, von Schoultz B
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1040, USA.
Am J Obstet Gynecol. 1996 Jan;174(1 Pt 1):93-100. doi: 10.1016/s0002-9378(96)70379-4.
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.
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.
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.
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.
我们的目的是确定接受激素替代疗法的手术绝经后猕猴乳腺的增殖反应和受体状态，该疗法对猴子而言等同于给予女性的疗法。
对手术绝经后的成年雌性食蟹猕猴（猕猴属）进行分组，一组不接受治疗（n = 26），一组给予结合马雌激素（n = 22），另一组给予结合马雌激素与醋酸甲羟孕酮的联合治疗（n = 21）。药物通过饮食给予，按热量计算，结合马雌激素的剂量相当于每位女性每天0.625毫克，醋酸甲羟孕酮的剂量相当于每位女性每天2.5毫克，持续30个月。通过主观评估以及形态学和体视学方法评估乳腺增殖情况。采用免疫组织化学方法研究雌激素受体和孕激素受体的含量及增殖情况。
在该模型中，结合马雌激素与醋酸甲羟孕酮的联合治疗比单独使用结合马雌激素诱导的增殖更明显。结合马雌激素加醋酸甲羟孕酮组中雌激素受体阳性细胞的百分比降低。单独使用结合马雌激素治疗可使孕激素受体阳性细胞的百分比增加。
这些结果表明绝经后猕猴乳腺上皮对结合马雌激素加醋酸甲羟孕酮治疗有增殖反应。这一发现的临床意义可能是接受联合激素替代疗法的女性患乳腺肿瘤的风险更高。
