Kimball Allison, Bourassa Jenna, Chicote Mark L, Gerweck Anu V, Dichtel Laura E, Miller Karen K
Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, USA.
Arch Womens Ment Health. 2025 Aug;28(4):771-780. doi: 10.1007/s00737-024-01532-3. Epub 2024 Nov 27.
Menstrually related mood disorder (MRMD) is marked by severe affective symptoms in the late luteal phase of the menstrual cycle. We hypothesized that women with MRMD experience relative neuroactive steroid deficiency, specifically low allopregnanolone levels due to reduced conversion of progesterone, in association with the onset of affective symptoms in the late luteal phase.
Nine subjects with MRMD and 14 healthy controls were studied. Daily Record of Severity of Problems was used to diagnose MRMD by DSM-5 criteria for premenstrual dysphoric disorder. Depression and anxiety symptom severity (16-Item Quick Inventory of Depressive Symptomatology Self Report, Generalized Anxiety Disorder 7-Item Scale) and levels of plasma neuroactive steroids by mass spectrometry were assessed at the mid-follicular, mid-luteal, and late luteal phases.
Depression severity was greater in women with MRMD than healthy controls in the late luteal phase only, as expected. In the mid-follicular phase, the mean allopregnanolone level and allopregnanolone/progesterone ratio were higher in women with MRMD than healthy controls. There were no differences between groups in luteal phase allopregnanolone levels. Higher follicular phase allopregnanolone sulfate and allopregnanolone levels were associated with greater depression severity in the mid-luteal and late luteal phases and greater anxiety severity in the late luteal phase.
Levels of allopregnanolone, which have antidepressant effects, were higher in the mid-follicular phase in women with MRMD compared to healthy controls. In MRMD, increased conversion of progesterone to allopregnanolone in the mid-follicular phase may be a compensatory response to luteal phase depression and anxiety, or increased allopregnanolone levels could paradoxically trigger depression and anxiety.
月经相关情绪障碍（MRMD）的特征是在月经周期的黄体晚期出现严重的情感症状。我们假设，患有MRMD的女性会出现相对的神经活性类固醇缺乏，特别是由于孕酮转化减少导致别孕烯醇酮水平较低，这与黄体晚期情感症状的发作有关。
对9名患有MRMD的受试者和14名健康对照者进行了研究。使用《问题严重程度每日记录》，根据DSM-5经前烦躁障碍标准诊断MRMD。在卵泡中期、黄体中期和黄体晚期评估抑郁和焦虑症状的严重程度（16项抑郁症状快速自评量表、广泛性焦虑障碍7项量表）以及通过质谱法测定的血浆神经活性类固醇水平。
正如预期的那样，只有在黄体晚期，患有MRMD的女性的抑郁严重程度高于健康对照者。在卵泡中期，患有MRMD的女性的平均别孕烯醇酮水平和别孕烯醇酮/孕酮比值高于健康对照者。两组在黄体期别孕烯醇酮水平上没有差异。卵泡期较高的硫酸别孕烯醇酮和别孕烯醇酮水平与黄体中期和晚期更严重的抑郁以及黄体晚期更严重的焦虑相关。
与健康对照者相比，患有MRMD的女性在卵泡中期具有抗抑郁作用的别孕烯醇酮水平较高。在MRMD中，卵泡中期孕酮向别孕烯醇酮转化的增加可能是对黄体期抑郁和焦虑的一种代偿反应，或者别孕烯醇酮水平的升高可能反常地引发抑郁和焦虑。
