When the cycle alters stress hormones:
Findings on depressed mood before menstruation
Depressed mood, quick temper, sleep problems, anxiety, feeling detached and barely able to cope with everyday life – women with premenstrual dysphoric disorder (PMDD), a condition that causes great suffering for those affected, are familiar with all of these symptoms. It is known that the symptoms occur between ovulation and menstruation, but the cause is still largely unclear. Now, in a recent study, researchers led by Julia Sacher and Kim Carina Hoffmann from the Max Planck Institute for Human Cognitive and Brain Sciences and the Department of Cognitive Neurology at the University of Leipzig Medical Center have shown that patients with PMDD have a blunted morning stress hormone response around the time of ovulation, in contrast to healthy women. In collaboration with colleagues at the Clinic and Polyclinic for Nuclear Medicine at University of Leipzig Medical Center and the Institute for Psychosocial Medicine, Psychotherapy, and Psycho-Oncology at Jena University Hospital, they further demonstrated that lower cortisol peaks towards the end of the cycle are associated with more depressive symptoms and increased serotonin transporter binding in the midbrain.
The study’s first author, Kim Carina Hoffmann, explains the approach: "In this study, we examined the link between the stress and serotonin systems. We were particularly interested in the cortisol awakening response, the rise in the stress hormone cortisol within the first hour after awakening. This response prepares the body and brain for upcoming stressors in daily stressors and helps us regulate emotional states. We found that the stress hormone peaks around ovulation are reduced in women with PMDD in the morning after awakening. Our study also showed that not all people always reach their cortisol peaks within the first 30 to 45 minutes after waking up. For example, in healthy women around ovulation, this peak occurs later."
In this comprehensive study, now been published in the British Journal of Psychiatry, the scientists examined 30 patients with PMDD and 29 healthy controls in two cycle phases –around ovulation and shortly before the onset of menstruation. Cycle phases were determined using a combination of a cycle tracking app, urine-based ovulation tests, and ultrasound examinations to accurately determine ovulation. Blood samples were collected during both cycle phases to assess the ovarian hormones progesterone and estrogen. In each cycle phase, participants additionally provided multiple saliva samples, underwent MRI and PET scans, and completed standardized questionnaires. PMDD symptoms were assessed using both a questionnaire and a diagnostic interview.
In addition, for the first time, the researchers investigated the complex interactions between the neurotransmitter serotonin, which regulates mood, the stress hormone cortisol, and the occurrence of depressive symptoms throughout the cycle in patients with PMDD and healthy women. Results show that reduced cortisol peaks in the premenstrual phase were associated with more depressive symptoms and increased serotonin transporter binding potentials. The blunted cortisol peaks highlight the relevance of the cortisol awakening response for mood regulation, while the increased serotonin transporter binding could reflect a compensatory response of the brain to an altered HPA-balance, potentially explaining the depressive mood at this time, e.g., due to the subsequent reduction of serotonin availability in the synaptic cleft.
Prof Julia Sacher, MD, leads the Cognitive Neuroendocrinology research group affiliated with the Day Clinic for Cognitive Neurology at University of Leipzig Medical Center and with the Neurology Department at MPI CBS. She has been studying PMDD intensively for many years. "Up to eight percent of all women worldwide are affected by PMDD. Although the symptoms of these patients occur only a few days each month, their severity is comparable to that of a major depressive episode. Over the course of a woman’s reproductive years, the cumulative burden can amount to the equivalent of six years of clinically relevant depressive symptoms. Our findings provide new insights into the interaction between the stress and serotonin systems in these patients and may eventually lead to more individualized treatment approaches. This line of work also highlights the need to critically reconsider current standards for assessing the cortisol awakening response, particularly with respect to gender differences, cycle phases, and hormonal influences."
