PROGESTOGENS VS PHYTOESTROGENS-- AN ADJUNCT TO ERT

描述：（改编自申请人的摘要）现在有一个共识 绝经后雌激素替代疗法（ERT）可降低发病率， 冠心病（CHD）死亡率。然而，有一个持续的 关注同时使用孕激素（HRT）来保护 子宫内膜可能降低ERT的心血管获益。这刺激 有兴趣开发心血管安全（CV安全）孕激素和/或 雌激素治疗期间保护子宫内膜和乳房的替代方法 替代疗法预后不会减少心血管益处 的ERT。然而，它提供很少或没有额外的有益效果， CV风险，与持续的月经周期相关，并且没有保护作用 对于乳房。大豆植物雌激素（SPEs）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具有雌激素激动剂， 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联合收割机与ERT相结合， 对心血管系统和保护 骨密度因此，我们假设，由于它们的雌激素 由于具有激动剂/拮抗剂特性，SPEs可以抑制对孕激素的需求， 绝经后女性的ERT治疗。 为此，我们的具体目标是：1）评估 增加剂量的SPE对推定的有益心血管（血浆 脂蛋白浓度，碳水化合物代谢，血管反应性， 血流动力学）和骨（骨代谢的血浆标志物）的影响 绝经后受试者的治疗; 2）确定 保护乳腺和子宫内膜组织免受ERT诱导的细胞增殖 3）识别和比较潜在的添加剂有益于 SPEs与孕激素治疗（MPA或孕酮）对 接受ERT的绝经后受试者的心血管和骨终点;以及 4)测量并比较SPE与MPA的给药效果 和孕酮对绝经后乳腺和子宫内膜增生的影响 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.