Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Division of Anesthesiology, Addiction Medicine, and Pain Medicine, Office of Neuroscience, Food and Drug Administration, Silver Spring, MD, USA.
J Clin Endocrinol Metab. 2021 Sep 27;106(10):3007-3018. doi: 10.1210/clinem/dgab407.
Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD.
We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test.
Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing.
No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women.
Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.
下丘脑-垂体-肾上腺(HPA)轴的异常是抑郁症的常见伴随症状,研究已经证明了压力和生活应激事件在围绝经期抑郁症(PMD)发病机制中的作用。由于女性的 HPA 轴功能还受到衰老和卵巢类固醇的进一步调节,因此,功能失调的 HPA 轴可能会增加 PMD 的风险。
我们使用联合地塞米松-促皮质素释放激素(Dex/CRH)试验检查了伴或不伴抑郁的围绝经期女性的 HPA 轴功能。
对 20 名患有 PMD 的女性和 20 名同样处于围绝经期但目前或过去没有抑郁的女性(对照组女性)进行了 Dex/CRH 试验。主要观察指标是皮质醇和促肾上腺皮质激素(ACTH)的血浆水平以及 24 小时尿游离皮质醇(UFC)。有 5 名女性服用了慢性稳定药物,其余女性均身体健康,两组在生殖阶段和年龄方面具有可比性。在进行 Dex/CRH 检测之前,每位女性都接受了标准化的症状评定量表评估。
在基线或刺激后的 ACTH 和皮质醇分泌方面,两组之间均无差异。PMD 和对照组女性的基础血浆雌二醇、孕酮和 24 小时 UFC 水平也没有差异。
尽管有报道称 PMD 患者的应激反应能力增加,但与无抑郁的女性相比,我们并未观察到与 PMD 相关的 HPA 轴活性异常。这些发现表明,PMD 并非普遍与 HPA 失调相关,可能反映了与非生殖相关抑郁的女性不同的潜在病理生理过程。