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Neuroactive steroid hormone trajectories across the menstrual cycle in premenstrual dysphoric disorder (PMDD): the PHASE study

Molecular Psychiatry (2024)Cite this article

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Abstract

It is presently not known whether endogenous neuroactive steroid hormone trajectories across the menstrual cycle are distinguishable in women with premenstrual dysphoric disorder (PMDD). To improve the rigor in this area of research, we implemented a validated study methodology, involving blood sample collection at 8 key menstrual cycle timepoints, following which the study data is realigned so that all women are compared at the same biological window (i.e., menstrual cycle subphase). Using liquid chromatography-mass spectrometry (LC-MS), we analyzed serum levels of nine steroid hormones previously implicated in the etiology of PMDD, including allopregnanolone. Other than progesterone (p ≤ 0.001), none of the steroid hormones displayed significant changes across menstrual cycle subphases when comparing participants with PMDD to the healthy controls. A thorough investigation of the progesterone trajectory showed that its left shift in the luteal phase (e.g., earlier rise in progesterone) exposes women with PMDD to a higher periovulatory progesterone and a more acute withdrawal in the late luteal subphase. Results of the present study indicate that the largely overlooked brief periovulatory subphase should be thoroughly examined in PMDD and agree with prior conclusions that rapid progesterone withdrawal associates with the development of negative affect.

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Fig. 1: Premenstrual increases in affective symptomatology and functional impairment according to study group.
Fig. 2: Progesterone trajectory according to group across the menstrual cycle on days 2 (early follicular), 7 (mid-follicular), 12 (periovulatory 1), 13 (periovulatory 2), 14 (periovulatory 3), 18 (early luteal), 22 (mid-luteal), and 27 (late luteal).
Fig. 3: Trajectories of study neuroactive steroid hormones (ng/mL) according to group across menstrual cycle days.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the subjects who provided the data for this research study and Mass Spectrometry Core at the University of Illinois at Chicago.

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Authors and Affiliations

  1. College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA

    Ajna Hamidovic

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Sunni Mumford & Enrique Schisterman

  3. College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    John Davis & Fatimata Soumare

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  1. Ajna Hamidovic
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Contributions

AH conceptualized and designed the study. AH acquired the funding. FS acquired the data. FS performed data cleaning. AH and SM conducted the statistical analyses. AH, SM, and ES contributed to data interpretation. AH drafted the manuscript. AH, SM and JD edited and manuscript. AH finalized the manuscript.

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Correspondence to Ajna Hamidovic.

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Hamidovic, A., Mumford, S., Schisterman, E. et al. Neuroactive steroid hormone trajectories across the menstrual cycle in premenstrual dysphoric disorder (PMDD): the PHASE study. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02566-w

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