Lacey James V, Brinton Louise A, Leitzmann Michael F, Mouw Traci, Hollenbeck Albert, Schatzkin Arthur, Hartge Patricia
Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, National Institutes of Health, Rockville, MDUSA.
J Natl Cancer Inst. 2006 Oct 4;98(19):1397-405. doi: 10.1093/jnci/djj375.
Recent studies offer conflicting data on risks of ovarian cancer in users of menopausal hormone therapy. Some findings of increased risks associated with unopposed estrogen use are based on older studies of women with intact uteri, and small sample size and incomplete exposure information have limited the data on estrogen plus progestin associations.
The National Institutes of Health-AARP Diet and Health Study Cohort included 97,638 women aged 50-71 years at baseline who completed two questionnaires (1995-1996 and 1996-1997). We identified 214 incident ovarian cancers among these women through the year 2000 using data from state cancer registries and mortality indexes. We estimated relative risks (RRs) of ovarian cancer for detailed hormone therapy exposures using multivariable proportional hazards regression models. All statistical tests were two-sided.
Use of unopposed estrogen for fewer than 10 years was not associated with ovarian cancer. Compared with use of no hormone therapy, use of unopposed estrogen for 10 or more years was statistically significantly associated with ovarian cancer among all women (RR = 1.89, 95% confidence interval [CI] = 1.22 to 2.95; P = .004; 56 versus 72 ovarian cancers per 100,000 person-years, respectively) and, albeit not statistically significantly, among women with hysterectomy (n = 19,359, RR = 1.70, 95% CI = 0.87 to 3.31; P = .06). Among the 73,483 women with intact uteri, 51,698 had used no hormone therapy or only estrogen plus progestin. Compared with no hormone therapy use, 5 or more years of use of sequential (progestin for < 15 days per cycle; RR = 3.09, 95% CI = 1.68 to 5.68; P < .001; 49 versus 108 per 100,000 person-years) or continuous (progestin for > or = 15 days per cycle; RR = 1.82, 95% CI = 1.03 to 3.23; P = .02; 49 versus 66 per 100,000 person-years) estrogen plus progestin regimens were statistically significantly associated with ovarian cancer.
Long durations of use of unopposed estrogen and of estrogen plus progestin, especially sequential regimens, are associated with increased ovarian cancer risk. These data expand the range of possible risks associated with menopausal hormone therapy.
近期研究关于绝经激素治疗使用者患卵巢癌风险的数据相互矛盾。一些与单纯使用雌激素相关的风险增加的研究结果基于对子宫完整女性的较早研究，且样本量小和暴露信息不完整限制了关于雌激素加孕激素关联的数据。
美国国立卫生研究院-美国退休人员协会饮食与健康研究队列包括97638名基线年龄为50 - 71岁的女性，她们完成了两份问卷（1995 - 1996年和1996 - 1997年）。我们利用州癌症登记处和死亡率指数的数据，在这些女性中确定了截至2000年的214例卵巢癌新发病例。我们使用多变量比例风险回归模型估计详细激素治疗暴露情况下卵巢癌的相对风险（RRs）。所有统计检验均为双侧检验。
使用单纯雌激素少于10年与卵巢癌无关。与未使用激素治疗相比，在所有女性中，使用单纯雌激素10年或更长时间与卵巢癌在统计学上显著相关（RR = 1.89，95%置信区间[CI] = 1.22至2.95；P = 0.004；每100000人年分别为56例和72例卵巢癌），在子宫切除的女性中（n = 19359，RR = 1.70，95%CI = 0.87至3.31；P = 0.06）虽无统计学显著性。在73483名子宫完整的女性中，51698名未使用激素治疗或仅使用雌激素加孕激素。与未使用激素治疗相比，序贯（孕激素每周期<15天；RR = 3.09，95%CI = 1.68至5.68；P < 0.001；每100000人年分别为49例和108例）或连续（孕激素每周期≥15天；RR = 1.82，95%CI = 1.03至3.23；P = 0.02；每100000人年分别为49例和66例）雌激素加孕激素方案与卵巢癌在统计学上显著相关。
长期使用单纯雌激素以及雌激素加孕激素，尤其是序贯方案，与卵巢癌风险增加相关。这些数据扩展了与绝经激素治疗相关的可能风险范围。
