While the exact causes of premenstrual syndrome (PMS) are unknown, it is believed to be associated with central nervous system sensitivity, hormonal imbalances in the body, and brain chemicals. In women sensitive to the normal cyclical hormonal changes associated with the menstrual cycle, these changes trigger PMS-related biochemical events in the central nervous system and other target tissues.

Serotonin plays a major role in the processes leading to the manifestation of premenstrual symptoms in the central nervous system. Fluctuations in serotonin, a brain chemical crucial for mood regulation, can trigger PMS symptoms. Studies of women with PMS have shown several differences in the serotonergic system compared to normal women.

Progesterone, primarily produced in the ovaries, itself produces anxiety, while its products are anxiolytic. Progesterone increases serotonin reuptake, leading to an increase in serotonin cycling.