The Lundquist Institute, Torrance, CA.
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA.
J Clin Oncol. 2024 Oct 20;42(30):3537-3549. doi: 10.1200/JCO.23.01918. Epub 2024 Aug 22.
Menopausal hormone therapy's influence on ovarian and endometrial cancers remains unsettled. Therefore, we assessed the long-term influence of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) and CEE-alone on ovarian and endometrial cancer incidence and mortality in the Women's Health Initiative randomized, placebo-controlled clinical trials.
Postmenopausal women, age 50-79 years, were entered on two randomized clinical trials evaluating different menopausal hormone therapy regimens. In 16,608 women with a uterus, 8,506 were randomly assigned to once daily 0.625 mg of CEE plus 2.5 mg once daily of MPA and 8,102 placebo. In 10,739 women with previous hysterectomy, 5,310 were randomly assigned to once daily 0.625 mg of CEE-alone and 5,429 placebo. Intervention was stopped for cause before planned 8.5-year intervention after 5.6 years (CEE plus MPA) and after 7.2 years (CEE-alone). Outcomes include incidence and mortality from ovarian and endometrial cancers and deaths after these cancers.
After 20-year follow-up, CEE-alone, versus placebo, significantly increased ovarian cancer incidence (35 cases [0.041%] 17 [0.020%]; hazard ratio [HR], 2.04 [95% CI, 1.14 to 3.65]; = .014) and ovarian cancer mortality ( = .006). By contrast, CEE plus MPA, versus placebo, did not increase ovarian cancer incidence (75 cases [0.051%] 63 [0.045%]; HR, 1.14 [95% CI, 0.82 to 1.59]; = .44) or ovarian cancer mortality but did significantly lower endometrial cancer incidence (106 cases [0.073%] 140 [0.10%]; HR, 0.72 [95% CI, 0.56 to 0.92]; = .01).
In randomized clinical trials, CEE-alone increased ovarian cancer incidence and ovarian cancer mortality, while CEE plus MPA did not. By contrast, CEE plus MPA significantly reduced endometrial cancer incidence.
绝经激素治疗对卵巢癌和子宫内膜癌的影响仍未确定。因此，我们评估了共轭马雌激素（CEE）加醋酸甲羟孕酮（MPA）和 CEE 单药对两项妇女健康倡议随机、安慰剂对照临床试验中卵巢和子宫内膜癌发生率和死亡率的长期影响。
绝经后 50-79 岁的女性参加了两项评估不同绝经激素治疗方案的随机临床试验。在 16608 名有子宫的女性中，8506 名被随机分配至每日一次 0.625mg 的 CEE 加每日一次 2.5mg 的 MPA 和 8102 名安慰剂。在 10739 名有子宫切除术史的女性中，5310 名被随机分配至每日一次 0.625mg 的 CEE 单药和 5429 名安慰剂。干预在计划的 8.5 年干预后 5.6 年（CEE 加 MPA）和 7.2 年后（CEE 单药）因原因停止。结果包括卵巢和子宫内膜癌的发病率和死亡率以及这些癌症后的死亡率。
经过 20 年的随访，CEE 单药治疗与安慰剂相比，卵巢癌发病率显著升高（35 例[0.041%] 17 例[0.020%]；风险比[HR]，2.04[95%CI，1.14 至 3.65]；.014）和卵巢癌死亡率（.006）。相比之下，CEE 加 MPA 与安慰剂相比，并未增加卵巢癌的发病率（75 例[0.051%] 63 例[0.045%]；HR，1.14[95%CI，0.82 至 1.59]；.44）或卵巢癌死亡率，但显著降低了子宫内膜癌的发病率（106 例[0.073%] 140 例[0.10%]；HR，0.72[95%CI，0.56 至 0.92]；.01）。
在随机临床试验中，CEE 单药治疗增加了卵巢癌的发病率和死亡率，而 CEE 加 MPA 则没有。相比之下，CEE 加 MPA 显著降低了子宫内膜癌的发病率。
