BACKGROUND Premature menopause is associated with depression in postmenopausal women. However, current evidence ignores the differences between premature natural and surgical menopause, and there is a lack of exploration of the mechanisms underlying the association between premature menopause and depression. OBJECTIVE To examine the association of premature natural and surgical menopause with incidence of depression requiring hospitalization, and to evaluate whether frailty and menopausal hormone therapy (MHT) are significant factors contributing to a higher incidence of depression requiring hospitalization associated with premature natural and surgical menopause, in comparison to women who experience menopause at age 40 and older. STUDY DESIGN This cohort included 139691 postmenopausal women from the UK Biobank, 44734 of whom participated the 7-y online mental health survey. Reproductive histories were obtained at enrollment. Depression requiring hospitalization was identified based on electronic health records and the Patient Health Questionnaire (PHQ) - 9. Cox proportional hazard models and Poisson regression models were fitted. RESULTS During a median (IQR) follow-up of 12.53 (11.71-13.25) years, 7563 participants (5.41%) developed depression requiring hospitalization. In the fully adjusted model, compared with women who experienced menopause≥ 40, the HRs (95% CIs) of those with premature natural and surgical menopause for depression requiring hospitalization were 1.27 (1.17-1.38) and 1.76 (1.43-2.16), respectively. Similar findings were observed in the association of premature natural (RR = 1.17, 95% CI: 1.00-1.39) and surgical menopause (RR = 1.62, 95% CI: 1.05-2.51) with depression as measured by the PHQ-9 score. An inverse dose-response relationship was observed in the analysis of alternate age thresholds and depression requiring hospitalization. When premature natural menopause was compared with women who experienced menopause≥ 40, the proportion of the mediating effect of frailty and MHT on depression requiring hospitalization was 27.43% (9.53%-229.00%) and 65.15% (45.57%-136.00%), respectively. When premature surgical menopause was compared with women who experienced menopause≥ 40, the proportion of the mediating effect of frailty and MHT on depression requiring hospitalization was 8.30% (2.59%-34.00%), 42.90% (27.96%-81.00%), respectively. CONCLUSION Premature menopause, especially surgical premature menopause, is significantly associated with depression requiring hospitalization in women. Frailty and adjustment of hormone therapy strategies during menopause may be potential targets for intervention.

中文翻译：

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过早自然绝经和手术绝经与需要住院治疗的抑郁症发生率的关联：一项前瞻性队列研究。


背景 过早绝经与绝经后妇女的抑郁症有关。然而，目前的证据忽略了过早自然绝经和手术绝经之间的差异，并且缺乏对过早绝经与抑郁症之间关联的机制的探索。目的 探讨过早自然绝经和手术绝经与需要住院治疗的抑郁症发生率的相关性，并评估虚弱和更年期激素治疗 （MHT） 是否是导致与过早自然和手术绝经相关的需要住院治疗的抑郁症发生率较高的重要因素，与在 40 岁及以上经历绝经的女性相比。研究设计 该队列包括来自英国生物银行的 139691 名绝经后妇女，其中 44734 名参加了 7 年在线心理健康调查。在入组时获得生育史。根据电子健康记录和患者健康问卷 （PHQ） - 9 确定需要住院治疗的抑郁症。拟合 Cox 比例风险模型和 Poisson 回归模型。结果 在 12.53 （11.71-13.25） 年的中位 （IQR） 随访期间，7563 名参与者 （5.41%） 患上需要住院治疗的抑郁症。在完全调整的模型中，与经历过绝经的女性相比≥40，因需要住院治疗的抑郁症而过早自然绝经和手术绝经患者的 HR （95% CI） 分别为 1.27 （1.17-1.38） 和 1.76 （1.43-2.16）。通过 PHQ-9 评分衡量，在自然过早 （RR = 1.17,95% CI： 1.00-1.39） 和手术绝经 （RR = 1.62， 95% CI： 1.05-2.51） 与抑郁症的相关性中观察到类似的发现。 在交替年龄阈值和需要住院治疗的抑郁症的分析中观察到负剂量-反应关系。将过早自然绝经与绝经女性进行比较≥40 时，虚弱和 MHT 对需要住院治疗的抑郁症的中介作用比例分别为 27.43% （9.53%-229.00%） 和 65.15% （45.57%-136.00%）。将手术过早绝经与绝经女性进行比较≥40 时，虚弱和 MHT 对需要住院治疗的抑郁症的中介作用比例分别为 8.30% （2.59%-34.00%） 和 42.90% （27.96%-81.00%）。结论 过早绝经，尤其是手术过早绝经，与女性需要住院治疗的抑郁症显著相关。更年期虚弱和激素治疗策略的调整可能是干预的潜在目标。