PROGESTOGENS VS PHYTOESTROGENS-- AN ADJUNCT TO ERT

描述：(改编自申请者的摘要)现在达成了共识 绝经后雌激素替代疗法(ERT)可降低发病率和 冠心病(CHD)死亡率。然而，还有一种持续的 担心同时使用孕激素(HRT)来保护 子宫内膜可能会减少ERT对心血管的益处。这刺激了 对开发心血管安全(心血管安全)孕激素和/或 雌激素期间保护子宫内膜和乳房的替代方法 替代疗法。黄体酮不会减少对心血管的益处 急诊室。然而，它很少或没有提供额外的有益影响 心血管风险，与持续的月经周期有关，不具有保护性 用来丰胸。大豆植物雌激素(SPE)可能是一种有效的替代品 孕激素治疗的方法。我们已经证明SPE有雌激素激动剂。 对心血管系统的影响，但拮抗ERT对 乳腺和子宫内膜组织。此外，SPE与ERT相结合，以拥有 对心血管系统的附加有益作用和对保存 骨密度。因此，我们假设，由于他们的雌激素 激动剂/拮抗剂特性，SPE可以消除对孕激素的需求 绝经后女性子宫内膜异位移植的治疗。 为此，我们的具体目标是：1)评估 增加SPE对推定有益的心血管(血浆)的剂量 脂蛋白浓度，碳水化合物代谢，血管反应性， ERT的血液动力学)和骨(骨代谢的血浆标志物)效应 绝经后受试者的治疗；2)确定SPE的剂量 保护乳腺和子宫内膜组织免受ERT诱导的细胞增殖 3)确定和比较潜在的有益添加剂 SPEs联合孕激素治疗(甲孕酮或孕酮)的疗效观察 接受ERT的绝经后受试者的心血管和骨骼终点；以及 4)测量和比较SPE和MPA的治疗效果 黄体酮对绝经后乳腺和子宫内膜增生症的影响 接受ERT的受试者。

DESCRIPTION: (Adapted from the applicant's abstract) There is now a consensus that postmenopausal estrogen replacement therapy (ERT) reduces morbidity and mortality from coronary heart disease (CHD). However, there is a continuing concern that the concurrent use of a progestogen (HRT) to protect the endometrium may reduce the cardiovascular benefits of ERT. This has stimulated interest in developing cardiovascular-safe (CV-safe) progestogens and/or alternative approaches to protect the endometrium and breast during estrogen replacement therapy. Progesterone does not diminish the cardiovascular benefits of ERT. However, it provides little or no additional beneficial effects on CV-risk, is associated with continued menstrual cycles and is not protective for the breast. Soy phytoestrogens (SPEs) may be an effective alternative approach to progestogen therapy. We have shown that SPEs have estrogen agonist effects on the cardiovascular system, but antagonizes the effects of ERT on mammary and endometrial tissue. Furthermore, SPEs combine with ERT to have additive beneficial effects on the cardiovascular system and on preservation of bone density. Thus, we hypothesize that, because of their estrogen agonist/antagonist properties, SPEs can obviate the need for progestogen therapy during ERT of postmenopausal females. To this end, our specific aims are: 1) To assess the potential contribution of increasing doses of SPEs to the putative beneficial cardiovascular (plasma lipoprotein concentrations, carbohydrate metabolism, vascular reactivity, hemodynamics) and bone (plasma markers of bone metabolism) effects of ERT treatment in postmenopausal subjects; 2) To identify the dose of SPEs that protects the mammary and endometrial tissue from ERT-induced cell proliferation and hyperplasia; 3) To identify and compare the potential additive beneficial effects of SPEs with those of progestogen treatment (MPA or progesterone) on cardiovascular and bone endpoints in postmenopausal subjects receiving ERT; and 4) To measure and compare the effects of SPE administration with those of MPA and progesterone, on mammary and endometrial hyperplasia in postmenopausal subjects receiving ERT.