Department of Psychology, University of Regina, Regina, Saskatchewan, Canada.
Department of Psychiatry, University of North Carolina at Chapel Hill.
JAMA Psychiatry. 2018 Feb 1;75(2):149-157. doi: 10.1001/jamapsychiatry.2017.3998.
The menopause transition and early postmenopausal period are associated with a 2- to 4-fold increased risk for clinically significant depressive symptoms. Although a few studies suggest that hormone therapy can effectively manage existing depression during this time, to our knowledge, there have been no studies testing whether hormone therapy can prevent the onset of perimenopausal and early postmenopausal depressive symptoms.
To examine the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) in preventing depressive symptom onset among initially euthymic perimenopausal and early postmenopausal women. A secondary aim was to identify baseline characteristics predicting TE+IMP's beneficial mood effects.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled randomized trial at the University of North Carolina at Chapel Hill from October 2010 to February 2016. Participants included euthymic perimenopausal and early postmenopausal women from the community, aged 45 to 60 years.
Transdermal estradiol (0.1 mg/d) or transdermal placebo for 12 months. Oral micronized progesterone (200 mg/d for 12 days) was also given every 3 months to women receiving active TE, and identical placebo pills were given to women receiving placebo.
Scores on the Center for Epidemiological Studies-Depression Scale (CES-D), assessed at baseline and months 1, 2, 4, 6, 8, 10, and 12 after randomization, and the incidence of clinically significant depressive symptoms, defined as a CES-D score of at least 16.
Of 172 participants, 130 were white (76%), and 70 were African American (19%), with a mean household income of $50 000 to $79 999. The mean age was 51 years, and 43 developed clinically significant depressive symptoms. Women assigned to placebo were more likely than those assigned to TE+IMP to score at least 16 on the CES-D at least once during the intervention phase (32.3% vs 17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = .03) and had a higher mean CES-D score across the intervention period (P = .03). Baseline reproductive stage moderated the effect of treatment (β, -1.97; SEM, 0.80; P for the interaction = .03) such that mood benefits of TE+IMP vs placebo were evident among women in the early menopause transition (β, -4.2; SEM, 1.2; P < .001) but not the late menopause transition (β, -0.9; SEM, 0.3; P = .23) or among postmenopausal women (β, -0.3; SEM, 1.1; P = .92). Stressful life events in the 6 months preceding enrollment also moderated the effect of treatment on mean CES-D score such that the mood benefits of TE+IMP increased with a greater number of events (β, 1.22; SEM, 0.40; P = .003). Baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not moderate treatment effects.
Twelve months of TE+IMP were more effective than placebo in preventing the development of clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women.
clinicaltrials.gov Identifier: NCT01308814.
绝经过渡和早期绝经后时期与临床显著抑郁症状的 2-4 倍风险增加相关。尽管一些研究表明激素治疗在此期间可以有效地治疗现有的抑郁症，但据我们所知，还没有研究测试激素治疗是否可以预防绝经前和早期绝经后抑郁症状的发生。
检查经皮雌二醇加间歇性米诺孕醇（TE+IMP）在预防最初情绪稳定的绝经前和早期绝经后妇女抑郁症状发作中的疗效。次要目的是确定预测 TE+IMP 有益情绪影响的基线特征。
设计、地点和参与者：北卡罗来纳大学教堂山分校 2010 年 10 月至 2016 年 2 月进行的双盲、安慰剂对照随机试验。参与者包括来自社区的情绪稳定的绝经前和早期绝经后妇女，年龄在 45 至 60 岁之间。
经皮雌二醇（0.1 毫克/天）或经皮安慰剂治疗 12 个月。口服米诺孕醇（200 毫克/天，持续 12 天）每 3 个月给予接受活性 TE 的妇女，而给予安慰剂的妇女给予相同的安慰剂丸。
在随机分组后 1、2、4、6、8、10 和 12 个月时使用流行病学研究中心抑郁量表（CES-D）评估的分数，以及临床上显著抑郁症状的发生率，定义为 CES-D 评分至少为 16。
在 172 名参与者中，130 名是白人（76%），70 名是非洲裔美国人（19%），家庭平均收入为 50000 至 79999 美元。平均年龄为 51 岁，43 人发展为临床上显著的抑郁症状。与安慰剂组相比，接受 TE+IMP 治疗的妇女在干预阶段至少有一次 CES-D 评分至少为 16 的可能性更高（32.3% vs 17.3%；比值比[OR]，2.5；95%CI，1.1-5.7；P =.03），并且在整个干预期间 CES-D 评分更高（P =.03）。基线生殖阶段调节了治疗的效果（β，-1.97；SEM，0.80；P 交互效应 = .03），因此，TE+IMP 与安慰剂相比，在早期绝经过渡的妇女中具有改善情绪的作用（β，-4.2；SEM，1.2；P < .001），但在晚期绝经过渡（β，-0.9；SEM，0.3；P = .23）或绝经后妇女（β，-0.3；SEM，1.1；P = .92）中则没有。在入组前 6 个月发生的应激性生活事件也调节了治疗对平均 CES-D 评分的影响，使得 TE+IMP 的情绪益处随着事件数量的增加而增加（β，1.22；SEM，0.40；P =.003）。基线雌二醇水平、基线血管舒缩症状、抑郁史和虐待史并未调节治疗效果。
在最初情绪稳定的绝经前和早期绝经后妇女中，TE+IMP 治疗 12 个月比安慰剂更有效预防临床上显著抑郁症状的发生。
clinicaltrials.gov 标识符：NCT01308814。
