Importance  Sexual dysfunction, an important determinant of women’s health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition.

Objective  To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women.

Design, Setting, and Participants  Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS), a 4-year prospective, randomized, double-blinded, placebo-controlled trial of menopausal hormone therapy in healthy, recently menopausal women. Of 727 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017.

Interventions  Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 µg/d transdermal 17β-estradiol (t-E₂), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E₂) or placebo (if randomized to placebo estrogens) for 12 days each month.

Main Outcomes and Measures  Aspects of sexual function and experience (desire, arousal, lubrication, orgasm, satisfaction, and pain) were assessed using the Female Sexual Function Inventory (FSFI; range, 0-36 points; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated.

Results  The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E₂ treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, −0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E₂ and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E₂ treatment was associated with a significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95% CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E₂ treatment compared with placebo (67%; 95% CI, 55%-77% vs 76%; 95% CI, 67%-83%; P = .04). For o-CEE there was no significant reduction in the odds of LSF.

Conclusions and Relevance  Treatment with t-E₂ modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known.

Trial Registration  clinicaltrials.gov Identifier: NCT00154180

重要性  性功能障碍是决定妇女健康和生活质量的重要因素，通常与绝经期前后雌激素水平下降有关。

目的  探讨口服或经皮雌激素治疗与安慰剂相比对绝经后妇女性功能的影响。

设计，背景和参与者  Kronos早期雌激素预防研究（KEEPS）的辅助研究，这是一项针对健康，更年期女性的更年期激素治疗的为期4年的前瞻性，随机，双盲，安慰剂对照试验。在KEEPS的727名参与者中，有670名同意参加这项多中心辅助研究。从上一次月经开始的36个月内，女性年龄在42至58岁之间。收集了2005年7月至2008年6月的数据，并分析了2010年7月至2017年6月的数据。

干预措施  女性被随机分为口服0.45 mg / d的共轭马雌激素（o-CEE），50μg/ d的经皮17β-雌二醇（tE ₂）或安慰剂。参与者还每月接受200 mg口服微粉化孕酮（如果随机分配给o-CEE或tE ₂）或安慰剂（如果随机分配给安慰剂雌激素），每月12天。

主要结果和量度  使用女性性功能量表（FSFI；范围：0-36分；评分越高，表示性功能越好），评估性功能和经历的各个方面（欲望，唤醒，润滑，性高潮，满意度和疼痛）。低性功能（LSF）定义为FSFI总体得分低于26.55。未评估与低FSFI评分（诊断为性功能障碍所需）有关的困扰。

结果  670名参与者的平均（SD）年龄为52.7（2.6）岁。与安慰剂相比，tE ₂治疗与所有时间点的FSFI总评分显着但适度的改善相关（平均疗效，2.6； 95％CI，1.11-4.10；调整后P  = 0.002）。与安慰剂相比，使用o-CEE治疗的FSFI总评分没有显着差异（平均功效为1.4； 95％CI为-0.1至2.8；校正后的P  = 0.13）。tE ₂组和o-CEE组之间的FSFI总体评分在48个月内没有平均差异（调整后的P  = 0.22）。在性功能的各个方面，tE ₂ 与安慰剂相比，治疗与平均润滑显着增加（0.61; 95％CI，0.25-0.97; P  = .001）和疼痛减轻（0.67; 95％CI，0.25-1.09; P = .002）相关。总体而言，tE ₂治疗后患有LSF的女性比例明显低于安慰剂（67％； 95％CI，55％-77％vs 76％； 95％CI，67％-83％；P  = .04） 。对于o-CEE，LSF的几率没有显着降低。

结论和相关性  用tE ₂治疗可以使绝经后早期妇女的性功能得到一定程度的改善，但尚不清楚其是否可以缓解困扰的症状。

试验注册  临床试验.gov标识符：NCT00154180