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Cohort study, 2025

Is the stress hormone cortisol different in women with PMDD?

Yes. Women with PMDD had weaker cortisol peaks in the early cycle phase, and lower cortisol was linked to more depression during the premenstrual phase.

Moderate study design 30 women with PMDD and 29 healthy women

What they did

A longitudinal study of 30 women with PMDD and 29 healthy women. Saliva samples were collected at specific times during two cycle phases to measure cortisol levels. Brain imaging scans measured serotonin levels, and depression was assessed using a standard rating scale.

What they found

Women with PMDD had lower cortisol peaks during the periovulatory phase compared to healthy women. During the premenstrual phase, lower cortisol peaks were associated with lower serotonin in the brain and higher depression symptoms.

What it means for you

This suggests women with PMDD may have different stress responses and disrupted communication between stress and serotonin systems, linked to worsening depression. The study uses objective biological measurements, though the sample is relatively small and from one country.

30

women with PMDD

29

healthy controls

About the study

Original title
Exploring the cortisol awakening response in premenstrual dysphoric disorder and in healthy females across the menstrual cycle
Authors
Hoffmann K, Zsido RG, Villringer A et al.
Journal
The British journal of psychiatry : the journal of mental science
Year
2025
Study design
Cohort study
What was tested
None
Open access
Yes
Original abstract

Background: Research suggests there are alterations in the cortisol awakening response (CAR) in patients with premenstrual dysphoric disorder (PMDD), as demonstrated by delayed cortisol peaks and flatter diurnal cortisol slopes compared to healthy controls. While inconsistent, previous work also demonstrates a relation between alterations in CAR, prefrontal serotonin transporter (5-HTT) binding and severity of depressive symptoms. Aims: This longitudinal study explores CAR in relation to midbrain and prefrontal 5-HTT binding and depressive symptoms in patients with PMDD and in healthy controls across the menstrual cycle. Method: Thirty patients with PMDD and 29 controls each provided 3 saliva samples for assessment of CAR (awakening, +30 min, +60 min) and 5 to assess the diurnal cortisol slope (09.00, 12.00, 15.00, 18.00, 21.00 h) during the periovulatory and premenstrual phases. [ 11 C]DASB positron emission tomography scans were performed to measure 5-HTT non-displaceable binding potential (BP ND ). Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Associations between cortisol measures, 5-HTT BP ND and depressive symptoms were examined using linear mixed-effects models, independent t -tests, mixed analysis of variance (ANOVA) and Spearman rank correlations. Results: A significant interaction effect between group and cycle phase was found for cortisol peak concentrations (estimate = 0.78, p = 0.05, d = 0.62, 95% CI: [0.01, 1.56]; and corrected for awakening cortisol concentration: estimate = 0.90, p = 0.02, d = 0.77, 95% CI: [0.15, 1.66]). Cortisol peak concentrations correlated negatively with both midbrain 5-HTT BP ND ( r = -0.34, p R 2 = 0.12) and depressive symptoms ( r = -0.30, p = 0.02, R 2 = 0.09) during the premenstrual phase. Conclusions: Patients with PMDD showed attenuated cortisol peaks in the periovulatory phase compared with healthy controls, who demonstrated plastic changes across the cycle. Results point towards an interplay between the stress and the serotonergic system, as well as to the severity of depressive symptoms during the premenstrual phase.

Reproduced under CC-BY.

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