Anthony M, Williams J K, Dunn B K
Georgetown University Medical Center, Washington, DC 20007, USA.
Ann N Y Acad Sci. 2001 Dec;949:261-78. doi: 10.1111/j.1749-6632.2001.tb04031.x.
Selective estrogen receptor modulators (SERMs) are drugs that bind to the estrogen receptor (ER); in some tissues they act like estrogen (agonists), while in other tissues they oppose the action of estrogen (antagonists). The SERM tamoxifen acts as an estrogen antagonist in the breast in that it prevents and treats breast cancer, but it acts as an estrogen agonist in the endometrium, where it can induce cancer. Estrogen, and to a lesser extent SERMs, are effective in preventing and treating osteoporosis. Contrary to the prevalent hypothesis that estrogen provides benefit to women with regard to secondary prevention of coronary heart disease (CHD), randomized clinical trials have demonstrated that estrogen is associated with an increased risk of CHD in this population of women. Conflicting results have been reported on the effect of estrogens on cognitive function. The latest and largest randomized clinical trials have demonstrated a beneficial role in short-term memory in nondemented women, in contrast to the absence of such benefit in improving symptoms in women with Alzheimer's disease. Although estrogens have been used successfully to treat some menopausal symptoms such as hot flashes, the SERMs tamoxifen and raloxifene actually induce or increase hot flashes. Data on the beneficial and adverse effects of estrogen and SERMs are reported along with an elaboration of the constellation of properties that would characterize an ideal SERM working through the ER.
选择性雌激素受体调节剂（SERM）是一类能与雌激素受体（ER）结合的药物；在某些组织中它们表现得像雌激素（激动剂），而在其他组织中它们则拮抗雌激素的作用（拮抗剂）。SERM他莫昔芬在乳腺中作为雌激素拮抗剂发挥作用，可预防和治疗乳腺癌，但在子宫内膜中它却作为雌激素激动剂，能诱发癌症。雌激素以及在较小程度上的SERM在预防和治疗骨质疏松症方面是有效的。与普遍认为雌激素对女性冠心病（CHD）二级预防有益的假设相反，随机临床试验表明，雌激素会增加这类女性患CHD的风险。关于雌激素对认知功能的影响，已有相互矛盾的报道。最新且规模最大的随机临床试验表明，雌激素对未患痴呆症的女性短期记忆有有益作用，而在改善阿尔茨海默病女性症状方面则无此益处。尽管雌激素已成功用于治疗一些更年期症状，如潮热，但SERM他莫昔芬和雷洛昔芬实际上会诱发或加重潮热。文中还报告了雌激素和SERM的有益及不良作用，并详细阐述了通过ER发挥作用的理想SERM应具备的一系列特性。
