ArticlePsychoneuroendocrinology2024
GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder.
Article in Psychoneuroendocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02777372 (Psychophysiology, Neurosteroids, and Stress in Premenstrual Dysphoric Disorder), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Psychophysiology, Neurosteroids, and Stress in Premenstrual Dysphoric Disorder
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Effectiveness of digital healthcare in managing menstrual symptoms: a systematic review.Women's health nursing (Seoul, Korea) · 2025Pooled it
- Short-termJournal of the International Society of Sports Nutrition · 2026Trial
- Exploring the Effect of Genetic Testing on Personalised Treatment Plans for Depression.Actas espanolas de psiquiatria · 2026Article
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Efficacy of open-label placebos for premenstrual syndrome: a randomised controlled trial.BMJ evidence-based medicine · 2025Article
- Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation.Psychoneuroendocrinology · 2024Article
- The link between childhood traumatic events and the continuum of premenstrual disorders.Frontiers in psychiatry · 2024Article
- Premenstrual syndrome: new insights into etiology and review of treatment methods.Frontiers in psychiatry · 2024Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
rationalePremenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD's pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD.
aimsThe aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms.
methodsParticipants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3α,5α-THP; 3α5β-THP; pregnenolone; 3α,5α-androsterone; 3α,5β-androsterone; 3α,5α-A-diol; 3α5β-A-diol; 3α,5α-THDOC; 3α5β-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50 mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment.
resultsParticipants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (p > 0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3α,5α-androsterone.
conclusionsThis was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.