基线焦虑敏感性对雌二醇波动预测围绝经期妇女经皮雌二醇治疗的焦虑症状反应-一项随机临床试验。
Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women - A randomized clinical trial.
机构信息
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Psychology, University of Zurich, 8052 Zurich, Switzerland.
Department of Psychology, University of Regina, Regina, Saskatchewan, S4S 0A2 Canada.
出版信息
Psychoneuroendocrinology. 2022 Sep;143:105851. doi: 10.1016/j.psyneuen.2022.105851. Epub 2022 Jul 2.
BACKGROUND
The menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia phenotypes. Greater estradiol (E2) variability predicts the development of perimenopausal depression, especially within the context of stressful life events (SLEs). While transdermal E2 (TE2) reduces perimenopausal depressive symptoms, the mechanisms underlying TE2 efficacy and predictors of TE2 treatment response remain unknown. This study aimed at determining relationships between E2 fluctuations, mood symptoms, and physiologic stress-reactivity (cortisol and interleukin-6) and whether differences in mood-sensitivity to E2 fluctuations predict mood responses to TE2 treatment.
METHODS
This randomized, double-blind, placebo-controlled trial investigated medically healthy women (46-60 years) in the early or late menopause transition. Baseline E2-sensitivity strength was calculated from eight weekly individual correlations between week-to-week E2 change and index week anxiety (State-Trait Anxiety Inventory) and anhedonia (Snaith-Hamilton Pleasure Scale). Women then received eight weeks of TE2 or transdermal placebo.
RESULTS
Analyses included 73 women (active TE2 n = 35). Greater baseline E2 fluctuations predicted greater anhedonia (p = .002), particularly in women with more SLEs. Greater E2 fluctuations also predicted higher cortisol (p = .012) and blunted interleukin-6 (p = .02) stress-responses. Controlling for baseline symptoms, TE2 was associated with lower post-treatment anxiety (p < .001) and anhedonia (p < .001) versus placebo. However, the efficacy of TE2 for anxiety (p = .007) and also for somatic complaints (p = .05) was strongest in women with greater baseline E2 sensitivity strength.
CONCLUSIONS
TE2 treatment reduced perimenopausal anxiety and anhedonia. The ability of baseline mood-sensitivity to E2 fluctuations to predict greater TE2 efficacy has implications for individualized treatment of perimenopausal anxiety disorders.
背景
绝经期（围绝经期）与重度抑郁症的风险增加有关，其特征为焦虑和快感缺失的表现。更大的雌二醇（E2）变异性预测围绝经期抑郁的发展，尤其是在应激性生活事件（SLEs）的背景下。虽然经皮 E2（TE2）可减轻围绝经期抑郁症状，但 TE2 疗效的机制和 TE2 治疗反应的预测因素仍不清楚。本研究旨在确定 E2 波动、情绪症状和生理应激反应（皮质醇和白细胞介素-6）之间的关系，以及情绪对 E2 波动的敏感性差异是否预测对 TE2 治疗的情绪反应。
方法
这项随机、双盲、安慰剂对照试验纳入了处于绝经早期或晚期过渡的医学健康女性（46-60 岁）。从每周 E2 变化与焦虑指数周（状态-特质焦虑量表）和快感缺失（Snaith-Hamilton 快感量表）的每周个体相关性的 8 个每周个体相关性中计算出 E2 敏感性强度的基线。然后，女性接受了 8 周的 TE2 或经皮安慰剂治疗。
结果
分析包括 73 名女性（活性 TE2 n=35）。更大的基线 E2 波动预测了更大的快感缺失（p=0.002），特别是在 SLE 更多的女性中。更大的 E2 波动也预测了更高的皮质醇（p=0.012）和减弱的白细胞介素-6（p=0.02）应激反应。在控制基线症状后，TE2 与治疗后焦虑（p<0.001）和快感缺失（p<0.001）与安慰剂相比降低。然而，TE2 治疗焦虑（p=0.007）和躯体症状（p=0.05）的疗效在基线时 E2 敏感性强度更大的女性中最强。
结论
TE2 治疗可减轻围绝经期焦虑和快感缺失。情绪对 E2 波动的敏感性基线预测 TE2 疗效更大的能力，对围绝经期焦虑障碍的个体化治疗具有意义。
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