Neuroactive steroid levels are elevated in the follicular phase and predict premenstrual depression and anxiety symptom severity in women with menstrually related mood disorder

• Published in: Archives of women's mental health Vol. 28; no. 4; pp. 771 - 780
• Main Authors: Kimball, Allison, Bourassa, Jenna, Chicote, Mark L., Gerweck, Anu V., Dichtel, Laura E., Miller, Karen K.
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.08.2025; Springer Nature B.V
• Subjects: Adult; Anxiety - blood; Anxiety - psychology; Anxiety disorders; Case-Control Studies; Clinical significance; Depression - blood; Emotional disorders; Female; Follicular Phase - blood; Follicular Phase - psychology; Humans; Likert scale; Luteal Phase - blood; Mass spectrometry; Mass spectroscopy; Medicine; Medicine & Public Health; Menstrual cycle; Menstruation; Mental depression; Mental disorders; Metabolites; Mood; Mood disorders; Mood Disorders - blood; Mood Disorders - psychology; Neurosteroids; Original Article; Ovulation; Post traumatic stress disorder; Pregnanolone; Pregnanolone - blood; Premenstrual Dysphoric Disorder - blood; Premenstrual Dysphoric Disorder - diagnosis; Premenstrual Dysphoric Disorder - psychology; Premenstrual Syndrome - blood; Premenstrual Syndrome - psychology; Progesterone; Progesterone - blood; Psychiatric Status Rating Scales; Psychiatry; Psychotherapy; Scientific imaging; Severity of Illness Index; Steroid hormones; Steroids; Urine; Womens health; Young Adult; Depression; Anxiety; Neuroactive steroid; Menstrually related mood disorder; Allopregnanolone
• ISSN: 1434-1816; 1435-1102; 1435-1102
• DOI: 10.1007/s00737-024-01532-3

Purpose 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. Methods 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. Results 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. Conclusion 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. Highlights Absolute neuroactive steroid levels are high in the follicular phase in women with menstrually related mood disorder (MRMD) compared to healthy women. Higher neuroactive steroid levels in the follicular phase are associated with more severe depression and anxiety in the luteal phase. Relative neuroactive steroid deficiency is unlikely to play a role in the pathophysiology of MRMD.