PROGESTOGEN EFFECT ON BONE AND COGNITION IN MENOPAUSE

孕激素对更年期骨骼和认知的影响

• 批准号: 2052311
• 负责人: JAMES H. LIU
• 金额: $ 36.54万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-10 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2052311
• 关键词: biopsy; bone density; bone metabolism; calcium metabolism; chemoprevention; clinical trials; cognition; dietary supplements; estradiol; female; glucose tolerance test; hormone therapy; human subject; human therapy evaluation; lipid metabolism; longitudinal human study; medroxyprogesterone; menopause; norethindrone; nutrition related tag; photon absorptiometry; progesterone; psychometrics; psychomotor function; vitamin D

Clinicians have recognized that the use of a progestogen in menopausal women on estrogen hormone replacement can prevent endometrial hyperplasia and carcinoma. However, the addition of progestational agents may have a significant impact on bone metabolism. Recent in vitro and in vivo data suggest that progestogens are potent bone cell mitogens and may promote bone formation whereas estrogens may act only to inhibit bone resorption. For these reasons, we proposed to examine the metabolic effects of progestogens on bone mineral content, bone histomorphometry, and on emotional-cognitive function in an estrogen-progesterone deficient, early menopausal population. We will compare 3 types of progestogens; micronized progesterone, norethindrone (NET), and medroxyprogesterone acetate (MPA). Thy hypotheses to be tested in this proposal are: 1) progestogen's induce depressive mood changes and reduce cognitive function independent of estrogen. We propose to carry out a longitudinal, double-blinded study in which six groups of menopausal women between the ages of 45-60 years, (n=44/group) will be randomized to receive either placebo, micronized progesterone (400 mg/day), NET (2.5 mg/day), MPA (20 mg/day), micronized estradiol (1 mg/day), and micronized estradiol (1 mg) + MPA (10 mg/day) during a two year study duration. Each group will receive an adjusted calcium intake (1500 mg/day) and vitamin D (400 IU/day) to reduce experimental variance related to diet and vitamin D. Primary variables that will be examined include: 1) changes in bone mineral content at the lumbar spine and proximal femur as determined by dual energy x-ray absorptiometry; 2) bone histomorphometry by bone biopsy; 3) changes in markers of bone metabolism (serum osteocalcin, bone alkaline phosphatase, urinary pyridinium crosslinks); 4) changes in calciotropic hormones (serum parathyroid hormone, calcitonin, vitamin D metabolites); and 5) psychometric, tolerance and lipid profile and covariates such as race, physical activity, and calcium intake also will be evaluated. These studies will provide significant new information on the mechanism of action of sex steroids on bone metabolism and will guide clinicians in the selection and dosing of progestogens for treatment and prevention of postmenopausal osteoporosis.

临床医生已经认识到，在绝经期使用孕激素 女性对雌激素替代可预防子宫内膜增生 和癌。 然而，添加促孕剂可能具有 对骨代谢有显著影响。 最近的体外和体内研究 数据表明，孕激素是有效的骨细胞有丝分裂原，并且可能 促进骨形成，而雌激素可能只起到抑制骨形成的作用。 再吸收 基于这些原因，我们建议检查代谢 孕激素对骨矿物质含量，骨组织形态计量学， 以及雌孕激素对情绪认知功能的影响 有缺陷的绝经早期人群。 我们将比较三种类型的 孕激素;微粉化孕酮，炔诺酮（NET），和 醋酸甲羟孕酮（MPA）。 你的假设将在这个测试 建议是：1）孕激素引起抑郁情绪改变， 认知功能独立于雌激素。 我们建议进行一项 一项纵向、双盲研究，其中6组绝经后妇女 年龄在45-60岁之间的女性（n=44/组）将被随机化 接受安慰剂、微粒化孕酮（400 mg/天）、NET（2.5 Mpa（20 mg/天）、微粉化雌二醇（1 mg/天）和微粉化雌二醇（1 mg/天）。 雌二醇（1 mg）+ MPA（10 mg/天）。 每组将接受调整后的钙摄入量（1500 mg/天）， 维生素D（400 IU/天），以减少与饮食相关的实验差异 和维生素D。 将被检查的主要变量包括：1） 腰椎和股骨近端骨矿物质含量的变化 通过双能X射线吸收测定法测定; 2）骨 通过骨活检进行组织形态学测量; 3）骨代谢标志物的变化 （血清骨钙素、骨碱性磷酸酶、尿吡啶 4）促钙激素（血清甲状旁腺激素）的变化 激素、降钙素、维生素D代谢物）;和5）心理测量， 耐受性和血脂谱和协变量，如种族、体格 活动和钙摄入量也将进行评估。 这些研究将 提供了重要的新信息的作用机制的性别 类固醇对骨代谢的影响，并将指导临床医生的选择 以及用于治疗和预防绝经后妇女的孕激素的给药 骨质疏松