OVARIAN STEROIDS AND CALCIUM HOMEOSTASIS

最近完成的工作绝经后妇女与主要 高甲状旁腺激素显示雌激素治疗不仅能够 阻止骨吸收，但也能够刺激PTH-1，25- （OH）2D轴，提高肠道钙吸收，从而提高钙 平衡和骨密度。 雌激素刺激 肾1，25-（OH）2D合成需要进一步阐明。 此操作 雌激素的增加可能是由于对肾脏的直接影响，也可能是 由继发性甲状旁腺功能亢进介导， 骨吸收，或者另一种可能性是雌激素可能增加 肾对PTH的敏感性 为了解决这些问题， 雌激素对维生素D代谢和肠道功能的影响 将在PTH缺乏的患者中检查吸收 甲状旁腺素治疗前后的甲状旁腺功能减退。 GnRH类似物亮丙瑞林的长期给药已被证明 将促性腺激素和卵巢类固醇抑制到去势水平。 这 一种可逆的“医学卵巢切除术”可能对女性有益 子宫内膜异位症、子宫肌瘤、多毛症或乳腺癌。 然而，雌激素缺乏可能与负钙有关 平衡和骨质流失。 子宫内膜异位症患者的短期研究 或纤维瘤将检查亮丙瑞林诱导的 低雌激素对钙稳态的影响，并测试 醋酸甲羟孕酮、降钙素或吲哚美辛阻滞骨 再吸收和/或改善肠Ca吸收。 在女性研究中 患有多毛症或乳腺癌者，长期服药效果更佳 将评价亮丙瑞林卵巢切除术的变化 钙稳态和骨密度。 口语的潜在能力 避孕药（作为治疗多毛症的辅助剂）和 非甾体类雌激素拮抗剂他莫昔芬（作为抗肿瘤剂， 治疗乳腺癌）以保护骨的作用。

Recently completed work postmenopausal women with primary hyperparathyroidism showed that estrogen therapy was not only able to block bone resorption, but also was able to stimulate the PTH-1,25- (OH)2D axis, raise intestinal Ca absorption and thereby improve Ca balance and bone density. The mechanism by which estrogen stimulates renal 1,25-(OH)2D synthesis requires further elucidation. This action of estrogen may be due to a direct effect on the kidney, or it may be mediated by secondary hyperparathyroidism accompanying the inhibition of bone resorption, or another possibility is that estrogen may increase renal sensitivity to PTH. To approach these questions, the effect of estrogens on vitamin D metabolism and fractional intestinal 47Ca absorption will be examined in patients with PTH-deficient hypoparathyroidism before and after the administration of PTH. Chronic administration of the GnRH analogue leuprolide has been shown to suppress gonadotropins and ovarian steroids to castrate levels. This type of reversible "medical oophorectomy" may be of benefit to women with endometriosis, uterine fibroids, hirsutism or breast cancer. However, estrogen deprivation may be associated witH negative calcium balance and bone loss. Short-term studies in women with endometriosis or fibroids will examine the effect of leuprolide-induced hypoestrogenism on Ca homeostasis, and test the ability of medroxyprogesterone acetate, calcitonin or indomethacin to block bone resorption and/or improve intestinal Ca absorption. In studies in women with hirsutism or breast cancer, the effect of more long-term medical oophorectomy with leuprolide will be evaluated with respect to changes in Ca homeostasis and bone density. The potential ability of oral contraceptives (as an adjunctive agent in treating hirsutism) and the nonsteroidal estrogen antagonist tamoxifen (as an adjunctive agent in treating breast cancer) to protect bone will be evaluated.