For many women, the days before menstruation involve more than mild discomfort. Irritability, sleep problems, anxiety and deep sadness can become so severe that everyday life is difficult to manage. Women experiencing such symptoms may be suffering from PMDD – premenstrual dysphoric disorder. Up to eight percent of women worldwide are affected. Researchers from Leipzig have now found new clues about possible biological mechanisms behind the condition.
Every morning after waking up, levels of the stress hormone cortisol rise briefly and sharply. This so-called cortisol awakening response helps the body prepare for the day and cope with stress. In women with PMDD, however, this morning rise around ovulation appears to be reduced. The finding comes from a study published in the British Journal of Psychiatry.
The study was conducted by a team led by Prof. Julia Sacher and Kim Carina Hoffmann from the Max Planck Institute for Human Cognitive and Brain Sciences and Leipzig University Hospital, together with colleagues from Leipzig and Jena.
Serotonin as part of the puzzle
For the study, the researchers examined 30 women with PMDD and 29 healthy participants during two phases of the menstrual cycle. The participants provided saliva samples, underwent MRI and PET scans, and completed questionnaires. PET is an imaging technique that allows researchers to visualize metabolic processes in the brain.
The team also analysed the interaction between cortisol and the neurotransmitter serotonin, which plays an important role in regulating mood. The results showed that lower cortisol peaks shortly before menstruation were associated with stronger depressive symptoms and increased binding of serotonin transporters in the midbrain.
A major burden for those affected
“Although the symptoms of these patients occur only a few days each month, their severity is comparable to that of a major depressive episode,” explains Prof. Julia Sacher. “Over the course of a woman’s reproductive life, the cumulative burden can amount to the equivalent of around six years of clinically relevant depressive symptoms.”
The study provides important clues about how stress hormones and serotonin may interact during the menstrual cycle. However, because the study included only 59 participants, further research will be needed to confirm the findings. The researchers also emphasize that the results show associations, not a direct cause of the disorder. In the long term, such insights could help scientists better understand PMDD and develop more targeted treatments.
Original publication:
Hoffmann, K. C.; Zsido, R. G.; Villringer, A.; Hesse, S.; Sabri, O.; Engert, V.; Sacher, J.: Exploring the cortisol awakening response in premenstrual dysphoric disorder and in healthy females across the menstrual cycle. British Journal of Psychiatry (2025)
