Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (J.E.M., S.S.B.).
Fred Hutchinson Cancer Research Center, Seattle, Washington (A.K.A., G.L.A., R.L.P.).
Ann Intern Med. 2019 Sep 17;171(6):406-414. doi: 10.7326/M19-0274. Epub 2019 Sep 10.
Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown.
To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups.
Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611).
40 U.S. clinical centers.
9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status.
Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years.
Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a "global index" (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up.
The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age.
The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing.
The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs.
尚不清楚接受双侧输卵管卵巢切除术（BSO）的女性与未接受 BSO 的女性在接受激素治疗的绝经期健康结果上是否存在差异。
按 BSO 状态检查雌激素治疗结局，并按 10 年年龄组进行进一步分层。
随机 Women's Health Initiative Estrogen-Alone 试验的亚组分析。（ClinicalTrials.gov：NCT00000611）。
美国 40 个临床中心。
9939 名年龄在 50 至 79 岁之间、有子宫切除术且已知卵巢切除术状态的女性。
结合马雌激素（CEE）（0.625mg/d）或安慰剂，中位数治疗时间为 7.2 年。
在干预阶段和 18 年的累积随访期间，冠心病和浸润性乳腺癌（试验的 2 个主要终点）、全因死亡率和“全球指数”（这些终点加上中风、肺栓塞、结直肠癌和髋部骨折）的发生情况。
CEE 单独使用的效果与 BSO 状态无显著差异。然而，年龄改变了 CEE 在有 BSO 史的女性中的作用。在干预阶段，在年龄较大的女性（年龄≥70 岁）中，CEE 与净不良影响显著相关（全球指数的危险比，1.42[95%CI，1.09 至 1.86]），但在年轻女性中全球指数并未升高（年龄的 P 趋势=0.016）。在累积随访期间，50 岁至 59 岁有 BSO 的女性因治疗而全因死亡率降低（危险比，0.68[CI，0.48 至 0.96]），而年龄较大的 BSO 女性没有降低（年龄的 P 趋势=0.034）。对于保留卵巢的女性，无论年龄大小，CEE 与结局之间均无显著关联。
CEE 与 BSO 的时间关系存在差异；未调整多次检验进行了几项比较。
在整个队列中，CEE 的效果与 BSO 状态无差异，但某些发现因年龄而异。在有 BSO 史的女性中，年龄在 70 岁或以上的女性在治疗期间出现不良影响，而在 60 岁之前随机分配至 CEE 的女性在长期内似乎有死亡获益。
WHI 计划由美国国立心肺血液研究所、美国国立卫生研究院和美国卫生与公众服务部资助。惠氏公司捐赠了研究药物。
