Creasy G W, Kafrissen M E, Upmalis D
Gynecology and Reproductive Research Department, R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
Obstet Gynecol Surv. 1992 Sep;47(9):654-78. doi: 10.1097/00006254-199209000-00026.
Several controversial areas have been reviewed. It would seem from the evidence at hand that progression from endometrial hyperplasia to endometrial carcinoma does occur in a significant percentage of women and that endometrial hyperplasia, particularly adenomatous hyperplasia and atypical hyperplasia, must be regarded as premalignant changes. Gambrell believes that all stages of hyperplasia should be regarded as premalignant. Previous and retrospective studies provide evidence implicating estrogens in the causation of both endometrial hyperplasia and endometrial carcinoma. Although some of these studies may have design flaws, the amount of data is substantial. Prospective studies have demonstrated an increased risk of hyperplasia in women treated with estrogens. An increased risk of endometrial carcinoma in estrogen users compared with nonusers has been suggested even more recently. Reviewed as a whole, the cumulative evidence provided by these studies clearly supports this association, and it would appear the only issue left to resolve may be the magnitude of the association. Cyclic administration of estrogens may decrease the risk of development of endometrial carcinoma. It would seem, however, that such administration does not totally eliminate risk under any circumstances, and in fact, a dose-related relationship appears to persist. It seems well established that progestogens do decrease the risk of both endometrial hyperplasia and endometrial carcinoma associated with the administration of estrogen to peri- and postmenopausal women. Such reduction in risk is significant and lower relative risks in estrogen/progestogen treated women have been reported compared to untreated women. This reduction in risk has been reported in a variety of studies. Whitehead and co-workers have provided a clear biochemical mechanism for progestogen protection of the endometrium in the antagonism of estrogen at the endometrial cellular level. The evidence at hand in the literature would suggest that progestogens should be administered for at least 10 days per cycle. In summary, there is good evidence that the addition of a progestin to estrogen therapy prescribed for the symptoms of menopause provides protection from endometrial hyperplasia and related carcinoma. The protection conferred is greater than that afforded by cyclical estrogen-alone therapy, and allows for continuous therapy, hereby providing greater symptomatic relief. There is little evidence for adverse effects caused by the added progestins, but further studies of women on combined therapy will undoubtedly be warranted.
本文回顾了几个存在争议的领域。从现有证据来看，相当比例的女性确实会从子宫内膜增生发展为子宫内膜癌，子宫内膜增生，尤其是腺瘤样增生和非典型增生，必须被视为癌前病变。甘布尔认为增生的所有阶段都应被视为癌前病变。既往的回顾性研究提供了证据，表明雌激素与子宫内膜增生和子宫内膜癌的病因有关。尽管其中一些研究可能存在设计缺陷，但数据量很大。前瞻性研究表明，接受雌激素治疗的女性患增生的风险增加。最近甚至有人提出，与未使用雌激素的女性相比，使用雌激素的女性患子宫内膜癌的风险增加。总体来看，这些研究提供的累积证据明确支持这种关联，似乎唯一有待解决的问题可能是这种关联的程度。周期性服用雌激素可能会降低患子宫内膜癌的风险。然而，似乎这种服用方式在任何情况下都不能完全消除风险，事实上，剂量相关关系似乎仍然存在。孕激素确实能降低围绝经期和绝经后女性因服用雌激素而患子宫内膜增生和子宫内膜癌的风险，这一点似乎已经得到充分证实。这种风险降低是显著的，与未接受治疗的女性相比，接受雌激素/孕激素治疗的女性的相对风险更低。在各种研究中都报告了这种风险降低的情况。怀特黑德及其同事在子宫内膜细胞水平上为孕激素保护子宫内膜对抗雌激素提供了明确的生化机制。文献中的现有证据表明，孕激素每个周期至少应服用10天。总之，有充分证据表明，为缓解更年期症状而开的雌激素治疗方案中添加孕激素可预防子宫内膜增生及相关癌症。所提供的保护作用大于单纯周期性雌激素治疗，并且允许持续治疗，从而能更好地缓解症状。几乎没有证据表明添加的孕激素会产生不良影响，但无疑有必要对接受联合治疗的女性进行进一步研究。
