HORMONE REPLACEMENT THERAPY WITH ESTRIOL SKIN CREAM

该项目的目的是开发新的雌三醇配方，作为激素替代疗法有效-保护冠状动脉免受高反应性和缓解卵巢类固醇缺乏症的心血管更年期症状。这种冠状动脉高反应性至少部分是由于卵巢功能停止后雌激素缺乏造成的。该项目还将进一步开发绝经后妇女卵巢功能丧失导致心血管风险的灵长类细胞模型。预期的新商业产品将是一种配方，旨在用一种天然雌激素代谢物取代雌激素成分，这种代谢物通常在怀孕期间浓度很高，但对雌激素受体的刺激程度较低。雌三醇似乎不会增加患乳腺癌或子宫癌的风险；相反，据报道，它可以降低患癌症的风险。雌三醇护肤霜的设计是提供保护，防止心血管事件作为一个愉快的，化妆品般的配方，可以提高那些开始激素替代疗法的依从性。由于雌激素对心血管系统的保护在雌三醇治疗结束后仅能持续2-4周，雌三醇应以具有长期依从性的形式提供。护肤霜配方被女性所接受，并提供皮肤储存和缓慢释放，适合于日常治疗，我们假设可能会减少心血管事件的可能性。尽管绝经后妇女因心血管原因死亡的风险接近50%，远远高于任何其他风险，但目前可用的激素替代疗法既不被充分理解，也不容易被接受。雌三醇护肤霜将提供一种令人愉快的保护形式和提高生活质量。拟议的商业应用：商业应用将是经皮雌三醇配方，其配方将产生足够的血液水平，以最大限度地降低心血管疾病的风险。该产品有望在激素替代疗法中得到广泛应用，从而提高绝经后妇女的接受度，从而形成一个巨大且不断增长的市场。

The objective of this project is to develop new estriol formulation(s) that are effective as hormone replacement therapy-protecting the coronary arteries against hyperreactivity and relieving cardiovascular menopausal symptoms of ovarian steroid deficiency. Such coronary hyperreactivity results at least in part from the deficiency of estrogens after the cessation of ovarian function. This project will also further develop the primate cellular model of cardiovascular risk due to loss of ovarian function in post-menopausal women. The anticipated new commercial product will be a formulation designed to replace the estrogenic component with a natural estrogen metabolite that is normally found in high concentrations during pregnancy, but less intensely stimulates estrogen receptors. Estriol does not appear to increase the risk of breast or uterine carcinoma; instead, it is reported to decrease the risk of cancer. The estriol skin cream is designed to provide protection against cardiovascular events as a pleasant, cosmetic- like formulation that can achieve improved compliance among those who initiate hormone replacement therapies. Because protection for the cardiovascular system provided by estrogens can be expected to persist for only 2-4 weeks after estriol treatment ends, estriol should be offered in a form attractive for long-term compliance. Skin cream formulations are well accepted by women, and provide skin storage and slow release that are suitable for a daily treatments that we hypothesize may reduce the probability of cardiovascular events. Although the risk of death due to cardiovascular causes is nearly 50% for post-menopausal women, and is far greater than any other risk, presently available forms of hormone replacement therapy are neither well understood nor readily accepted. Estriol skin cream will offer a pleasant form of protection and improved quality of life. PROPOSED COMMERCIAL APPLICATIONS: The commercial application will be a percutaneous formulation of estriol in a formulation that will produce blood levels sufficient to minimize the risk of cardiovascular disease. The product is expected to find widespread application in hormone replacement therapy, resulting in improved acceptance among post-menopausal women, and thus a large and growing market.