Suppr超能文献

新型孕激素:对围绝经期和绝经后女性影响的综述

New progestogens: a review of their effects in perimenopausal and postmenopausal women.

作者信息

Sitruk-Ware Régine

机构信息

Rockefeller University and Population Council, New York, New York, USA.

出版信息

Drugs Aging. 2004;21(13):865-83. doi: 10.2165/00002512-200421130-00004.

Abstract

The progestins have different pharmacological properties depending upon the parent molecule, usually testosterone or progesterone, from which they are derived. Very small structural changes in the parent molecule may induce considerable differences in the activity of the derivative. In postmenopausal women with an intact uterus, progestins are used in combination with estrogen as hormone-replacement therapy (HRT). The development of new generations of progestins with improved selectivity profiles has been a great challenge. Steroidal and nonsteroidal progesterone-receptor (PR) agonists have been synthesised as well, although the latter are still in a very early stage of development. Several new progestins, which have been synthesised in the last 2 decades, may be considered fourth-generation progestins. These include dienogest, drospirenone, Nestorone (Population Council, New York, NY, USA), nomegestrol acetate and trimegestone. The fourth-generation progestins have been designed to have no androgenic or estrogenic actions and to be closer in activity to the physiological hormone progesterone. Drospirenone differs from the classic progestins as it is derived from spirolactone. It is essentially an antimineralocorticoid steroid with no androgenic effect but a partial antiandrogenic effect. The antiovulatory potency of the different progestins varies. Trimegestone and Nestorone are the most potent progestins synthesised to date, followed by two of the older progestins, 3-keto-desogestrel and levonorgestrel. The new molecules trimegestone, drospirenone and dienogest also have antiandrogenic activity. Following the publication of the results of the Women's Health Initiative study, the role of progestins in HRT became controversial. Unfortunately, this concern has been directed towards progestins as a class, although striking differences exist among the progestins. Natural progesterone and some of its derivatives, such as the 19-norprogesterone molecules, and the new molecules drospirenone and dienogest are not androgenic and, therefore, have no negative effect on the lipid profile. The effects of progestins on breast tissue remain controversial as well. However, depending on the progestin and the duration of application, breast cell differentiation and apoptosis may predominate over proliferation. It is still unclear if the currently available progestins are able to bind specifically to the PR isoforms PR-A or PR-B and whether this is of clinical relevance to breast cell proliferation is also unclear. Although it is likely that the new progestins may have neutral effects on the risk of coronary heart disease or breast cancer in younger postmenopausal women, this hypothesis must be confirmed in large randomised, well controlled clinical trials.

摘要

孕激素因其母体分子(通常是睾酮或孕酮)不同而具有不同的药理特性。母体分子中非常微小的结构变化可能会导致衍生物的活性产生显著差异。在子宫完整的绝经后女性中,孕激素与雌激素联合使用作为激素替代疗法(HRT)。开发具有改善选择性特征的新一代孕激素一直是一项巨大的挑战。甾体和非甾体孕酮受体(PR)激动剂也已合成,不过后者仍处于非常早期的开发阶段。在过去20年中合成的几种新孕激素可被视为第四代孕激素。这些包括地诺孕素、屈螺酮、奈斯孕酮(美国纽约人口理事会)、醋酸诺美孕酮和孕三烯酮。第四代孕激素被设计为无雄激素或雌激素作用,且活性更接近生理激素孕酮。屈螺酮与经典孕激素不同,它源自螺内酯。它本质上是一种抗盐皮质激素甾体,无雄激素作用但有部分抗雄激素作用。不同孕激素的抗排卵效力各不相同。孕三烯酮和奈斯孕酮是迄今为止合成的效力最强的孕激素,其次是两种较老的孕激素,3-酮去氧孕烯和左炔诺孕酮。新分子孕三烯酮、屈螺酮和地诺孕素也具有抗雄激素活性。在妇女健康倡议研究结果公布后,孕激素在HRT中的作用变得具有争议性。不幸的是,这种担忧针对的是整个孕激素类别,尽管不同孕激素之间存在显著差异。天然孕酮及其一些衍生物,如19-去甲孕酮分子,以及新分子屈螺酮和地诺孕素无雄激素作用,因此对血脂没有负面影响。孕激素对乳腺组织的影响也存在争议。然而,根据孕激素和应用持续时间的不同,乳腺细胞分化和凋亡可能比增殖更为显著。目前尚不清楚现有的孕激素是否能够特异性结合PR异构体PR-A或PR-B,以及这是否与乳腺细胞增殖具有临床相关性也不清楚。尽管新孕激素可能对年轻绝经后女性患冠心病或乳腺癌的风险具有中性影响,但这一假设必须在大型随机、严格对照的临床试验中得到证实。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验