The etiology of PMS and PMDD is still largely unknown. The current consensus seems to be that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target issues.

Increasing evidence suggests that serotonine (a hormone of the central nervous system) may be important to the pathogenesis of PMDD. The serotonergic system is in close connection with gonadal hormones. Women with PMDD may be behaviourally or biochemically sub-sensitive to biological changes of the serotonergic system.