OVARIAN STEROIDS AND CALCIUM HOMEOSTASIS

卵巢类固醇和钙稳态

• 批准号: 3327078
• 负责人: NEIL A BRESLAU
• 金额: $ 12.17万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3327078
• 关键词: 1,25 dihydroxycholecalciferol; bone density; breast neoplasms; calcification stimulant; calcitonin; calcium metabolism; endometriosis; estrogen inhibitor; estrogens; female; gastrointestinal nutrient absorption; hirsutism; hormone regulation /control mechanism; human subject; hypoparathyroidism; indomethacin; leuprolide; medroxyprogesterone; nutrition related tag; oral contraceptives; tamoxifen; vitamin metabolism

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.

最近完成了绝经后妇女的工作 甲状旁腺功能亢进表明雌激素疗法不仅能够 阻止骨吸收，但也能够刺激PTH-1,25- （OH）2D轴，提高肠道Ca吸收，从而改善CA 平衡和骨密度。 雌激素刺激的机制 肾脏1,25-（OH）2D合成需要进一步阐明。 这个动作 雌激素可能是由于对肾脏的直接影响，或者可能是 伴随于抑制 骨吸收或其他可能性是雌激素可能增加 肾脏对PTH的敏感性。 为了解决这些问题， 维生素D代谢和分数47CA的雌激素 缺乏PTH的患者将检查吸收 PTH给药之前和之后的甲状腺功能低下。 GNRH类似物亮脂的长期给药已显示为 将促性腺激素和卵巢类固醇抑制至castrate水平。 这 可逆的“医疗卵形切除术”可能对女性有益 子宫内膜异位症，子宫肌瘤，多肌或乳腺癌。 但是，雌激素剥夺可能与负钙有关 平衡和骨丢失。 对子宫内膜异位症女性的短期研究 或肌瘤将检查Leuprolide诱导的效果 CA稳态上的低雌激素，并测试 乙酸酯，降钙素或吲哚美辛可阻断骨骼 吸收和/或改善肠道CA的吸收。 在女性研究中 使用毛毛神或乳腺癌，更长期的医学效果 将对变化的卵巢切除术和亮脂剂进行评估 在CA稳态和骨密度中。 口服的潜在能力 避孕药（作为治疗毛毛学的辅助药物）和 非雌激素拮抗剂他莫昔芬（作为辅助剂 将评估治疗乳腺癌的治疗）。

项目成果

An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial.

通过磁共振成像评估促性腺激素释放激素类似物和醋酸甲羟孕酮对子宫肌瘤体积的影响：一项前瞻性、随机、双盲、安慰剂对照、交叉试验。

• DOI: 10.1210/jcem.76.5.8496313
• 发表时间: 1993
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Carr,BR;Marshburn,PB;Weatherall,PT;Bradshaw,KD;Breslau,NA;Byrd,W;Roark,M;Steinkampf,MP
• 通讯作者: Steinkampf,MP

Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study.

口服避孕药、促性腺激素释放激素激动剂或联合使用治疗多毛症：一项临床研究中心研究。

• DOI: 10.1210/jcem.80.4.7714086
• 发表时间: 1995
• 期刊: The Journal of clinical endocrinology and metabolism.
• 作者: Carr,BR;Breslau,NA;Givens,C;Byrd,W;Barnett-Hamm,C;Marshburn,PB
• 通讯作者: Marshburn,PB

Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: a prospective, randomized, double-blind, placebo-controlled, crossover trial.

促性腺激素释放激素激动剂和醋酸甲羟孕酮对钙代谢的影响：一项前瞻性、随机、双盲、安慰剂对照、交叉试验。

• DOI: 10.1016/s0015-0282(03)02166-6
• 发表时间: 2003
• 期刊: Fertility and sterility
• 影响因子: 6.7
• 作者: Carr,BruceR;Breslau,NeilA;Peng,Noel;Adams-Huet,Beverley;Bradshaw,KarenD;Steinkampf,MichaelP
• 通讯作者: Steinkampf,MichaelP

Calcium, estrogen, and progestin in the treatment of osteoporosis.

钙、雌激素和孕激素治疗骨质疏松症。

• 发表时间: 1994
• 期刊: Rheumatic diseases clinics of North America
• 作者: Breslau,NA