"Exposome, Heredity, Cancer and Health" Team, Centre for Epidemiology and Population Health (CESP UMR 1018), Université Paris-Saclay, Inserm, Institut Gustave Roussy, Villejuif, France.
Department of Statistics, Computer Science and Applications "G. Parenti", University of Florence, Florence, Italy.
J Natl Cancer Inst. 2023 Jun 8;115(6):671-679. doi: 10.1093/jnci/djad035.
Epidemiological studies have found that menopausal hormone therapy (MHT) use is associated with an increased ovarian cancer risk. However, whether different MHT types confer the same level of risk is unclear. We estimated the associations between different MHT types and the risk of ovarian cancer in a prospective cohort.
The study population included 75 606 postmenopausal women from the E3N cohort. Exposure to MHT was identified from self-reports in biennial questionnaires between 1992 and 2004 and from drug claim data matched to the cohort between 2004 and 2014. Hazard ratios and 95% confidence intervals (CIs) of ovarian cancer were estimated using multivariable Cox proportional hazards models with MHT as a time-varying exposure. Tests of statistical significance were 2-sided.
Over an average 15.3 years follow-up, 416 ovarian cancers were diagnosed. Hazard ratios of ovarian cancer associated with ever use of estrogens combined with progesterone or dydrogesterone and ever use of estrogens combined with other progestagen were equal to 1.28 (95% CI = 1.04 to 1.57) and 0.81 (95% CI = 0.65 to 1.00), respectively (Phomogeneity = .003), compared with never use. The hazard ratio for unopposed estrogen use was 1.09 (95% CI = 0.82 to 1.46). We found no trend according to duration of use or time since last use except for estrogens combined with progesterone or dydrogesterone, which showed decreasing risk with increasing time since last use.
Different MHT types may impact ovarian cancer risk differentially. The possibility that MHT containing progestagens other than progesterone or dydrogesterone may confer some protection should be evaluated in other epidemiological studies.
流行病学研究发现，激素替代疗法（MHT）的使用与卵巢癌风险增加有关。然而，不同类型的 MHT 是否具有相同的风险水平尚不清楚。我们在一项前瞻性队列研究中估计了不同类型的 MHT 与卵巢癌风险之间的关联。
该研究人群包括来自 E3N 队列的 75606 名绝经后妇女。MHT 的暴露情况通过 1992 年至 2004 年期间的两年一次的问卷和 2004 年至 2014 年期间与队列相匹配的药物索赔数据来确定。使用多变量 Cox 比例风险模型，以 MHT 作为时变暴露，估计卵巢癌的风险比和 95%置信区间（CI）。统计显著性检验为双侧。
在平均 15.3 年的随访中，诊断出 416 例卵巢癌。与从未使用过 MHT 相比，曾经使用过雌激素与孕激素或地屈孕酮联合使用以及曾经使用过雌激素与其他孕激素联合使用的卵巢癌发病风险比分别为 1.28（95%CI=1.04 至 1.57）和 0.81（95%CI=0.65 至 1.00）（P 同质性=0.003）。单独使用雌激素的风险比为 1.09（95%CI=0.82 至 1.46）。我们没有发现与使用时间或末次使用时间间隔相关的趋势，除了雌激素与孕激素或地屈孕酮联合使用，随着末次使用时间的延长，风险呈下降趋势。
不同类型的 MHT 可能会对卵巢癌风险产生不同的影响。其他流行病学研究应评估含有除孕激素或地屈孕酮以外的孕激素的 MHT 是否可能带来一些保护作用。
