Premenstrual dysphoric syndrome - role of progesterone and serotonin

Premenstrual dysphoric disorder (PMDD) is a common mood disorder, characterized by distressing affective, behavioural and somatic symptoms in the late luteal phase of the menstrual cycle. Emerging data suggest that PMDD is characterized by progesterone-influenced dysfunctional emotional processing.

Serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMDD, and their efficacy is extraordinarily high and rapid  compared to when used in patients with depression.The purpose of the proposed two randomized, placebo-controlled studies is to explore efficacy of a selective progesterone receptor modulator (SPRM) and SSRI in PMDD.

The methods comprise neuroimaging of emotion processing, functional and structural brain connectivity at rest, psychological tasks, hormone measurements and genetic analyses.

The study will address the following questions: What are the independent predictors of premenstrual depression and irritability? Is SPRM treatment efficacious?

Are there any treatment-related alternations in brain structure or function from SPRM and SSRI treatment, and are there any neural differences in the treatment responses between these two treatment modalities?Clinically, the study will provide insights into the molecular mechanisms behind PMDD and promote mechanism-based treatments.

Additionally, if efficacious for PMDD, findings will be of relevance also for women with other psychiatric disorders who report a luteal phase worsening of underlying symptoms.