Beral V, Gaitskell K, Hermon C, Moser K, Reeves G, Peto R
Lancet. 2015 May 9;385(9980):1835-42. doi: 10.1016/S0140-6736(14)61687-1. Epub 2015 Feb 13.
Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk.
Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use.
During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005).
The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.
Medical Research Council, Cancer Research UK.
半数涉及绝经激素治疗与卵巢癌风险信息的流行病学研究仍未发表，一些回顾性研究可能因选择性参与或回忆偏倚而存在偏差。我们旨在以最小的偏倚评估激素治疗对卵巢癌风险的影响。
对来自52项流行病学研究的个体参与者数据集进行集中分析。主要分析涉及前瞻性研究（将最后一次激素治疗使用情况向前外推长达4年）。敏感性分析包括回顾性研究。调整后的泊松回归得出与从未使用者相比的相对风险（RR）。
在前瞻性随访期间，12110名绝经后女性患卵巢癌，其中55%（6601名）曾使用激素治疗。在最后记录为当前使用者的女性中，即使使用时间不足5年，风险也会增加（RR 1.43，95%CI 1.31 - 1.56；p<0.0001）。将当前或近期使用（任何持续时间，但在诊断前<5年停药）合并计算得出RR为1.37（95%CI 1.29 - 1.46；p<0.0001）；在欧洲和美国的前瞻性研究以及仅使用雌激素和雌激素 - 孕激素制剂的研究中，这种风险相似，但在四种主要肿瘤类型中有所不同（异质性p<0.0001），仅在两种最常见类型中明确增加，即浆液性（RR 1.53，95%CI 1.40 - 1.66；p<0.0001）和子宫内膜样（1.42，1.20 - 1.67；p<0.0001）。使用停止时间越久，风险越低，尽管在长期激素治疗使用停止约10年后，浆液性或子宫内膜样肿瘤仍有过剩（RR 1.25，95%CI 1.07 - 1.46，p = 0.005）。
风险增加很可能在很大程度上或完全是因果关系；如果是这样，从50岁左右开始使用激素治疗5年的女性，每1000名使用者中约有1例额外的卵巢癌，如果其预后典型，每1700名使用者中约有1例额外的卵巢癌死亡。
医学研究理事会、英国癌症研究中心。
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