不良生活事件与早发性卵巢功能不全：影响机制与临床干预的研究进展

Adverse Life Events and Premature Ovarian Insufficiency: Mechanisms and Clinical Interventions

摘要: 早发性卵巢功能不全(premature ovarian insufficiency, POI)是一种严重影响育龄女性生殖健康及全身健康的内分泌疾病，其病因复杂，且约半数病例病因不明。除外遗传因素与自身免疫异常等传统致病机制，环境及心理社会因素在POI发生发展中的作用逐渐受到重视。其中，不良生活事件作为重要的心理社会应激来源，被认为与POI密切相关。现有研究表明，不良生活事件可通过多条生物学通路对卵巢功能产生负向调控，包括干扰下丘脑–垂体–卵巢轴的调控节律，增强机体氧化应激反应并诱发线粒体功能障碍，激活免疫炎症相关信号通路，以及介导表观遗传修饰改变，从而对卵巢储备造成持续性损害。因此，将心理社会因素纳入POI临床评估与管理，对于实现疾病的早期识别与个体化干预具有重要意义。本文在整合流行病学研究、基础实验及临床证据的基础上，对不良生活事件参与POI发生发展的潜在机制及干预策略进行系统梳理，并探讨应激源类型、疾病亚型及个体差异对“应激–卵巢损伤”轴的调节作用，梳理可用于干预效果监测的潜在生物标志物与基于机制通路的新型干预靶点，以期为疾病的预防、风险评估及综合管理提供理论依据。

Abstract: Premature ovarian insufficiency (POI) is a complex endocrine disorder that profoundly affects the reproductive and overall health of women of reproductive age. Its etiology is multifactorial, and approximately half of the cases remain idiopathic. In addition to established mechanisms such as genetic factors and autoimmune abnormalities, increasing attention has been directed toward the role of environmental and psychosocial factors in the onset and progression of POI. Among these, adverse life events—serving as significant sources of psychosocial stress—are considered to be closely associated with POI. Current evidence suggests that adverse life events may impair ovarian function through multiple biological pathways. These include disruption of the hypothalamic–pituitary–ovarian (HPO) axis, enhancement of oxidative stress leading to mitochondrial dysfunction, activation of immune-inflammatory signaling pathways, and involvement in epigenetic regulatory processes. Collectively, these mechanisms may contribute to sustained damage to ovarian reserve. Based on an integration of epidemiological studies, experimental research, and clinical evidence, this review systematically summarizes the potential mechanisms by which adverse life events contribute to the development and progression of POI, as well as related intervention strategies. In addition, this review discusses how stressor characteristics, POI subtypes, and individual differences modulate the “stress–ovarian damage” axis, and summarizes potential biomarkers for monitoring intervention efficacy as well as novel mechanism-based therapeutic targets. The aim is to provide a theoretical basis for disease prevention, risk assessment, and comprehensive management.