Beral Valerie, Bull Diana, Green Jane, Reeves Gillian
Million Women Study Coordinating Centre, Cancer Research UK Epidemiology Unit, Richard Doll Building, Roosevelt Drive, Oxford, OX3 7LF, UK.
Lancet. 2007 May 19;369(9574):1703-10. doi: 10.1016/S0140-6736(07)60534-0.
Ovarian cancer is the fourth most common cancer in women in the UK, with about 6700 developing the malignancy and 4600 dying from it every year. However, there is limited information about the risk of ovarian cancer associated with the use of hormone replacement therapy (HRT).
948,576 postmenopausal women from the UK Million Women Study who did not have previous cancer or bilateral oophorectomy were followed-up for an average of 5.3 years for incident ovarian cancer and 6.9 years for death. Information on HRT use was obtained at recruitment and updated where possible. Relative risks for ovarian cancer were calculated, stratified by age and hysterectomy status, and adjusted by area of residence, socioeconomic group, time since menopause, parity, body-mass index, alcohol consumption, and use of oral contraceptives.
When they last reported HRT use, 287,143 women (30%) were current users and 186 751 (20%) were past users. During follow-up, 2273 incident ovarian cancers and 1591 deaths from the malignancy were recorded. Current users were significantly more likely to develop and die from ovarian cancer than never users (relative risk 1.20 [95% CI 1.09-1.32; p=0.0002] for incident disease and 1.23 [1.09-1.38; p=0.0006] for death). For current users of HRT, incidence of ovarian cancer increased with increasing duration of use, but did not differ significantly by type of preparation used, its constituents, or mode of administration. Risks associated with HRT varied significantly according to tumour histology (p<0.0001), and in women with epithelial tumours the relative risk for current versus never use of HRT was greater for serous than for mucinous, endometroid, or clear cell tumours (1.53 [1.31-1.79], 0.72 [0.52-1.00], 1.05 [0.77-1.43], or 0.77 [0.48-1.23], respectively). Past users of HRT were not at an increased risk of ovarian cancer (0.98 [0.88-1.11] and 0.97 [0.84-1.11], respectively, for incident and fatal disease). Over 5 years, the standardised incidence rates for ovarian cancer in current and never users of HRT were 2.6 (2.4-2.9) and 2.2 (2.1-2.3) per 1000, respectively-ie, one extra ovarian cancer in roughly 2500 users; death rates were 1.6 (1.4-1.8) and 1.3 (1.2-1.4) per 1000, respectively-ie, one extra ovarian cancer death in roughly 3300 users.
Women who use HRT are at an increased risk of both incident and fatal ovarian cancer. Since 1991, use of HRT has resulted in some 1300 additional ovarian cancers and 1000 additional deaths from the malignancy in the UK.
卵巢癌是英国女性中第四大常见癌症，每年约有6700人患此恶性肿瘤，4600人因此死亡。然而，关于激素替代疗法（HRT）与卵巢癌风险相关的信息有限。
来自英国百万女性研究的948576名绝经后女性，她们既往无癌症或双侧卵巢切除术史，随访其卵巢癌发病平均5.3年，死亡平均6.9年。在招募时获取HRT使用信息，并尽可能进行更新。计算卵巢癌的相对风险，按年龄和子宫切除术状态分层，并根据居住地区、社会经济群体、绝经后时间、产次、体重指数、饮酒情况和口服避孕药使用情况进行调整。
在她们最后一次报告HRT使用情况时，287143名女性（30%）为当前使用者，186751名女性（20%）为过去使用者。随访期间，记录到2273例卵巢癌发病和1591例因该恶性肿瘤死亡。当前使用者患卵巢癌并死于该病的可能性显著高于从未使用者（发病疾病的相对风险为1.20[95%CI 1.09 - 1.32；p = 0.0002]，死亡的相对风险为1.23[1.09 - 1.38；p = 0.0006]）。对于HRT当前使用者，卵巢癌发病率随使用时间延长而增加，但根据所用制剂类型、成分或给药方式无显著差异。与HRT相关的风险因肿瘤组织学显著不同（p<0.0001），在上皮性肿瘤女性中，当前使用与从未使用HRT相比，浆液性肿瘤的相对风险高于黏液性、子宫内膜样或透明细胞肿瘤（分别为1.53[1.31 - 1.79]、0.72[0.52 - 1.00]、1.05[0.77 - 1.43]或0.77[0.48 - 1.23]）。HRT过去使用者患卵巢癌的风险未增加（发病和致命疾病的相对风险分别为0.98[0.88 - 1.11]和0.97[0.84 - 1.11]）。5年期间，HRT当前使用者和从未使用者的卵巢癌标准化发病率分别为每1000人2.6（2.4 - 2.9）和2.2（2.1 - 2.3）——即大约每2500名使用者中多1例卵巢癌；死亡率分别为每1000人1.6（1.4 - 1.8）和1.3（1.2 - 1.4）——即大约每3300名使用者中多1例卵巢癌死亡。
使用HRT的女性患卵巢癌发病和死亡的风险均增加。自1991年以来，在英国，HRT的使用已导致约1300例额外的卵巢癌以及1000例额外的该恶性肿瘤死亡。
