Causes

Researchers are still uncertain about the causes of premenstrual syndrome. Increasingly, however, evidence indicates that fluctuations in important hormones and brain chemicals may be important in PMS.

Activity in the Hypothalamic-Pituitary-Adrenal (HPA) System

The hypothalamic-pituitary-adrenal (HPA) system controls reproduction, appetite, and feelings of well-being. The HPA also is involved in regulating the stress response. A number of reproductive hormones and neurotransmitters (chemical messengers in the brain) play important and complicated interrelated roles in the activity of the HPA system. Disruptions in these chemicals may be important in PMS and premenstrual dysphoric disorder (PMDD).

• Reproductive hormones. The two important female hormones, progesterone and estrogen, are at their highest levels during the premenstrual period. Evidence is increasing that an abnormal response to progesterone, rather than estrogen, is the primary factor in PMS.
• Neurotransmitters. Each hormone is involved in the regulation of two neurotransmitters, serotonin and gamma-aminobutyric acid (GABA). These brain chemicals have properties that protect against PMS symptoms.
• Stress hormones.

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The exact roles and relationships of any of these substances in PMS or premenstrual dysphoric disorder (PMDD) are still unclear. Evidence increasingly suggests that fluctuations in some of these hormones--not whether they are high or low--may be the important factors in premenstrual problems.

Progesterone and GABA. Changes in progesterone and a potent progesterone derivative called allopregnanolone (ALLO) are proving to play important roles in PMS. ALLO in turn regulates gamma-aminobutyric acid (GABA). Imbalances in these hormones that reduce GABA levels have been associated with depression, anxiety, and agitation. GABA is an amino acid that acts as a neurotransmitter to inhibit transmission of impulses from one nerve cell to another. It plays a very important role in the stress response. An important 2002 study reported lower levels of GABA during menstruation in women with premenstrual dysphoric disorder (PMDD). In fact, GABA may become an important target for drugs aimed at relieving PMDD.