Xu Zhiwei, Chung Hsin-Fang, Dobson Annette J, Wilson Louise F, Hickey Martha, Mishra Gita D
The University of Queensland, School of Public Health, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CRE WaND), Brisbane, Australia.
The University of Queensland, School of Public Health, Brisbane, Australia.
Hum Reprod. 2022 Aug 25;37(9):2175-2185. doi: 10.1093/humrep/deac137.
What is the association between menopausal hormone therapy (MHT) and cause-specific mortality?
Self-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes.
Evidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality.
STUDY DESIGN, SIZE, DURATION: Cohort study (the UK Biobank), 178 379 women, recruited in 2006-2010.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality.
Among the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74).
LIMITATIONS, REASONS FOR CAUTION: Self-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT.
The current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation.
STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests.
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绝经激素治疗（MHT）与特定病因死亡率之间有何关联？
在自然绝经早期、手术绝经或绝经前子宫切除术后自我报告使用MHT，与乳腺癌死亡率较低风险相关，且与心血管疾病或其他病因的死亡率风险无一致关联。
来自女性健康倡议随机对照试验的证据表明，单独使用雌激素与心血管疾病死亡率风险无关，且与乳腺癌死亡率较低风险相关，但来自百万女性研究的证据表明，单独使用雌激素与乳腺癌死亡率较高风险相关。
研究设计、规模、持续时间：队列研究（英国生物银行），2006 - 2010年招募了178379名女性。
参与者/材料、设置、方法：报告了绝经年龄（自然或手术）或子宫切除术，以及MHT和特定病因死亡率信息的绝经后女性。自然绝经年龄、手术绝经年龄、子宫切除年龄和MHT是感兴趣的暴露因素。自然绝经定义为月经自然停止12个月，且此前未行子宫切除术或卵巢切除术。手术绝经定义为在自然绝经前切除双侧卵巢。子宫切除术定义为在自然绝经前切除子宫且未行双侧卵巢切除术。研究结局为特定病因死亡率。
在纳入的178379名女性中，136790名自然绝经，17569名手术绝经，24020名仅行子宫切除术。与50 - 52岁自然绝经的女性相比，40岁前自然绝经的女性（风险比（HR）：2.38，95%置信区间：1.64，3.45）或40岁前子宫切除的女性（HR：1.60，95%置信区间：1.23，2.07）心血管疾病死亡率风险更高，但癌症死亡率风险无差异。在45岁前手术绝经后（HR：0.17，95%置信区间：0.08，0.36）、45 - 49岁（HR：0.15，95%置信区间：0.07，0.35）或≥50岁（HR：0.28，95%置信区间：0.13，0.63）使用MHT与乳腺癌死亡率较低风险相关，且MHT使用与乳腺癌死亡率风险之间的关联不因MHT使用时长（<6年或6 - 20年）而不同。在45岁前自然绝经后（HR：0.59，95%置信区间：0.36，0.95）或45岁前子宫切除后（HR：0.49，95%置信区间：0.32，0.74）使用MHT也与乳腺癌死亡率较低风险相关。
局限性、需谨慎的原因：自然绝经年龄、手术绝经年龄、子宫切除年龄和MHT的自我报告数据。
当前国际指南建议绝经早期女性使用MHT直至绝经平均年龄。我们的研究结果支持这一建议。
研究资金/利益冲突：本项目由澳大利亚国家卫生与医学研究委员会（NHMRC）资助（资助编号APP1027196和APP1153420）。G.D.M. 得到NHMRC首席研究奖学金（APP1121844）支持，M.H. 得到NHMRC研究员资助（APP1193838）支持。不存在利益冲突。
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