Postpartum depression: neurosteroid pathogenesis and pathogenesis-based treatment with micronized progesterone

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2026.83.29-40

Keywords:

postpartum depression, allopregnanolone, neurosteroids, micronized progesterone, pathogenetic treatment

Abstract

Background. Postpartum depression (PPD) affects 17.22% of women globally, representing a critical public health challenge with serious consequences for mother and child. Recent advances in neurosteroid research have demonstrated that the pathogenesis of postpartum depression is fundamentally associated with the abrupt postpartum decline in estrogen, progesterone, and its metabolite allopregnanolone levels.

Objective of the review: to analyze the neurobiological mechanisms of PPD, evaluate current diagnostic approaches, and investigate the evidence base regarding the use of micronized progesterone as a pathogenetically grounded therapeutic option, particularly in resource-limited settings.

Materials and methods. A literature search was conducted in the PubMed/MEDLINE, Cochrane Library, Embase, and Google Scholar databases for the period from 2014 to 2026. The search was performed using the keywords. Inclusion criteria comprised randomized controlled trials, systematic reviews, meta-analyses, clinical guidelines, as well as original studies investigating neurosteroid function and clinical trials of progesterone therapy for PPD. Epidemiological data regarding the prevalence of postpartum depression and diagnostic instruments, including the EPDS, PHQ-9, DSM-5, and the ICD-11, were also included in the analysis. A comparative analysis of treatment protocols was conducted taking into account international standards and the specific features of the Ukrainian healthcare system.

Literature analysis. Allopregnanolone, a potent modulator of GABA-A receptors, plays a central role in the etiology of PPD. Although rapidly acting neurosteroid medications, including brexanolone and zuranolone, demonstrate high efficacy, their limited accessibility due to cost necessitates alternative therapeutic approaches. Micronized bioidentical progesterone, as a substrate for endogenous allopregnanolone synthesis, demonstrates a significant reduction in symptoms, with the prevalence of depression decreasing from 86.7% to 23.3% (p < 0.05), while maintaining safety during lactation when administered vaginally.

Conclusions. Micronized progesterone represents a pathogenetically grounded, safe, and economically accessible treatment option for PPD, particularly relevant within the Ukrainian healthcare context. Improvement of PPD treatment outcomes requires the implementation of universal screening programs and the development of clear patient referral protocols.

Author Biographies

O.V. Furman, National Pirogov Memorial Medical University, Vinnytsіa

PhD, associate professor, Department of Obstetrics and Gynecology No. 2

O.V. Bulavenko, National Pirogov Memorial Medical University, Vinnytsіa

DSc, professor, head of the Department of Obstetrics and Gynecology No. 2

B.O. Markevich, National Pirogov Memorial Medical University, Vinnytsіa

PhD, assistant, Department of Obstetrics and Gynecology No. 1

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Published

2026-05-14

How to Cite

Furman, O., Bulavenko, O., & Markevich, B. (2026). Postpartum depression: neurosteroid pathogenesis and pathogenesis-based treatment with micronized progesterone : Literature review. REPRODUCTIVE ENDOCRINOLOGY, (83), 29–40. https://doi.org/10.18370/2309-4117.2026.83.29-40

Issue

No. 83 (2026)

Section

Interdisciplinary problems

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