PROGESTOGEN EFFECT ON BONE AND COGNITION IN MENOPAUSE

临床医生已经认识到更年期孕激素的使用 服用雌激素替代疗法的妇女可预防子宫内膜增生症 和癌症。然而，孕激素的添加可能会有 对骨骼新陈代谢有重大影响。最新的体外和体内实验 数据表明，孕激素是有效的骨细胞有丝分裂原，并可能 促进骨形成，而雌激素可能只起抑制骨骼的作用 再吸收。出于这些原因，我们建议研究新陈代谢 孕激素对骨矿物质含量、骨组织形态计量学的影响 以及雌激素-黄体酮的情绪认知功能 缺乏绝经的早更年期人口。我们将比较三种类型的 孕激素；微粉化黄体酮、去甲肾上腺素(净)和 醋酸甲羟孕酮(MPA)。你的假设将在这里得到检验 建议是：1)孕激素诱导抑郁情绪的改变和减少 独立于雌激素的认知功能。我们建议进行一项 6组绝经后妇女的纵向、双盲研究 年龄在45-60岁之间的妇女(n=44/组)将被随机分组 接受安慰剂，微粒化黄体酮(400毫克/天)，净(2.5 毫克/天)、甲孕酮(20毫克/天)、微粉化雌二醇(1毫克/天)和微粉化 雌二醇(1毫克)Mpa(10毫克/天)在两年的研究期间。 每组都将接受调整后的钙摄入量(每天1500毫克)和 维生素D(400IU/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含量的变化 双能x射线骨密度仪测定：2)骨 骨活检组织形态计量学；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)促钙激素的变化(血清甲状旁腺激素 激素、降钙素、维生素D代谢物)；以及5)心理测量， 耐受性、血脂谱和协变量，如种族、体格 活动量和钙的摄入量也将进行评估。这些研究将 为性行为的作用机制提供重要的新信息 类固醇对骨代谢的影响，将指导临床医生的选择 治疗和预防绝经后黄体生成素 骨质疏松。

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.