Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder

Menopause Int. 2012 Jun;18(2):52-9. doi: 10.1258/mi.2012.012014.


Premenstrual syndrome (PMS) and premenstrual dysphoric disorder are triggered by hormonal events ensuing after ovulation. The symptoms can begin in the early, mid or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormone. Although evidence for a hormonal abnormality has not been established, the symptoms of the premenstrual disorders are related to the production of progesterone by the ovary. The two best-studied and relevant neurotransmitter systems implicated in the genesis of the symptoms are the GABArgic and the serotonergic systems. Metabolites of progesterone formed by the corpus luteum of the ovary and in the brain bind to a neurosteroid-binding site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its configuration, rendering it resistant to further activation and finally decreasing central GABA-mediated inhibition. By a similar mechanism, the progestogens in some hormonal contraceptives are also thought to adversely affect the GABAergic system. The lowering of serotonin can give rise to PMS-like symptoms and serotonergic functioning seems to be deficient by some methods of estimating serotonergic activity in the brain; agents that augment serotonin are efficacious and are as effective even if administered only in the luteal phase. However, similar to the affective disorders, PMS is ultimately not likely to be related to the dysregulation of individual neurotransmitters. Brain imaging studies have begun to shed light on the complex brain circuitry underlying affect and behaviour and may help to explicate the intricate neurophysiological foundation of the syndrome.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Calcium Compounds / therapeutic use
  • Contraceptives, Oral, Hormonal / administration & dosage
  • Contraceptives, Oral, Hormonal / adverse effects
  • Contraceptives, Oral, Hormonal / chemistry
  • Estradiol / therapeutic use
  • Estrogen Antagonists / therapeutic use
  • Estrogens / therapeutic use
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Hysterectomy
  • Menstrual Cycle / physiology
  • Ovariectomy
  • Ovulation Inhibition
  • Premenstrual Syndrome / drug therapy
  • Premenstrual Syndrome / metabolism
  • Premenstrual Syndrome / physiopathology*
  • Progesterone / metabolism
  • Progesterone Congeners / administration & dosage
  • Progesterone Congeners / adverse effects
  • Receptors, GABA / metabolism
  • Salpingectomy
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin / metabolism


  • Calcium Compounds
  • Contraceptives, Oral, Hormonal
  • Estrogen Antagonists
  • Estrogens
  • Progesterone Congeners
  • Receptors, GABA
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Gonadotropin-Releasing Hormone
  • Progesterone
  • Estradiol