The exact cause of PMDD is unknown, but it is believed to be an abnormal response to the natural hormonal fluctuations that occur throughout the menstrual cycle.[1] It is important to note that PMDD is not caused by irregular blood levels of estrogen, progesterone, or progesterone metabolites (like allopregnanolone). The cyclic changes in sex hormones between people with and without PMDD are similar.[2][3]
Rather, in people with PMDD, the brain is highly sensitive to the hormonal shifts in the luteal phase, especially the rise in allopregnanolone, provoking an aberrant neurotransmitter response that negatively affects emotional regulation.[4][5][6] The opioid, GABA, and serotonin systems have all been implicated in the pathology of PMDD, but the serotonin system appears to be the most important (likely underlying the effectiveness of SSRIs for many people with PMDD).