HORMONE REPLACEMENT THERAPY WITH PROGESTERONE CREAM

该项目的目的是进一步开发一种新的黄体酮制剂，该制剂可有效用于激素替代疗法-保护冠状动脉免受过度反应。这种高反应性是由于正常衰老过程中绝经后卵巢功能停止后黄体酮缺乏所致。预期的新产品将在导管实验室的猴子和人类压力测试心电图和回声心脏病学协议中进一步研究。这些研究将确定黄体酮在延长跑步机应激试验持续时间、超声心动图心壁运动和冠状动脉功能脂质生化指标方面的有效性。我们还将探讨血脂变化与血小板功能的可能关系。新配方旨在为绝经后妇女充分接受，以鼓励那些开始激素替代疗法的人遵守-在许多情况下持续数十年。黄体酮对心血管系统的保护可以显著降低衰老过程中心血管疾病的发病率，并改善绝经后妇女的生活质量。这种护肤霜的配方被女性广泛接受，对于每天一次的治疗来说，它具有最佳的药代动力学，并且被认为可以降低心血管疾病的风险，包括冠状动脉疾病。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只有一小部分人会受益。绝经后妇女对这种主要的死亡风险和减少这种风险的现有措施既不了解也不容易接受。这种配方有可能显著改善这种情况，提高绝经后妇女的生活质量。建议的商业应用：经皮黄体酮制剂将产生一个血液水平，以减少心血管疾病的风险，因此可能在激素替代治疗中得到广泛应用。该产品的潜在消费者包括所有绝经后妇女，这一数字正在迅速增长，目前已超过2000万。

The objective of this project is to further develop a new progesterone formulation that is effective for hormone replacement therapy-protecting the coronary arteries against hyperreactivity. Such hyperreactivity results from the deficiency of progesterone after the cessation of ovarian function after menopause during the normal aging process. The anticipated new product will be further studied in monkeys in the catheterization laboratory and in human stress test electrocardiogram and echo cardiology protocols. These studies will determine the effectiveness of progesterone in extending treadmill stress test duration, echocardiographic cardiac wall motion, and lipid biochemical measures of coronary function. We will also explore the possible relationship of changes in blood lipids and platelet function. The new formulation is designed to be accepted sufficiently well by post- menopausal women to encourage compliance among those who initiate hormone replacement therapy-for a duration of decades in many cases. Protection of the cardiovascular system by progesterone can be expected to provide for a significant decrease in the incidence of cardiovascular disease during aging, and improved quality of life in post-menopausal women. The skin cream formulation is well accepted by women, has optimal pharmacokinetics for a once a day treatment, and is hypothesized to reduce cardiovascular risks, including coronary artery disease. Even though the risk of death due to cardiovascular causes is nearly 50% for post-menopausal women, and is far greater than any other risk, the presently available forms of hormone replacement therapy are used by only a fraction of those who would benefit. This leading risk of death and' available measures to minimize that risk are neither well understood nor readily accepted by post-menopausal women. This formulation has the potential to significantly improve that situation and enhance quality of life in post-menopausal women. PROPOSED COMMERCIAL APPLICATIONS: The percutaneous formulation of progesterone will produce a blood level to minimize the risk of cardiovascular disease, and thus may find widespread application in hormone replacement therapy. The number of people who would be potential consumers for the product consists of all postmenopausal women, a rapidly growing number which already exceeds 20 million.