Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD)



  • Premenstrual syndrome (PMS), a complex of physical and emotional symptoms sufficiently severe to interfere with everyday life, occurs cyclically during the luteal phase of menses.
  • Premenstrual dysphoric disorder (PMDD) is a severe form of PMS characterized by severe recurrent depressive and anxiety symptoms, with premenstrual (luteal phase) onset, that remits a few days after the start of menses as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).
  • System(s) affected: endocrine/metabolic, nervous, reproductive



  • Many women have some physical and psychological symptoms before menses that can encompass a spectrum from mild molimina to severe and disabling symptoms.
  • The prevalence of PMS is reported anywhere between 20% and 30% of menstruating women. 1.2% to 6.4% of women have PMDD based on DSM-5 criteria (1) with upward of 18% of menstruating women meeting partial DSM criteria (2).

Etiology and Pathophysiology

Although not yet fully understood, there are two main views on the pathophysiology (1):

  • Changing levels of the progesterone metabolite allopregnanolone interacts with serotonin and γ-aminobutyric acid (GABA) receptors, provoking downstream effects of decreased GABA-mediated inhibition and decreased serotonin levels.
  • Decreased function of the serotonin system (in particular the serotonin transporter) serves as the primary abnormality and thus when modulated by sex hormones leads to decreased serotonin levels in patients with PMS/PMDD.


  • The role of genetic predisposition is controversial; however, twin studies do suggest a genetic component.
  • Involvement of gene coding for the serotonergic 5HT1A receptor and allelic variants of the estrogen receptor-α gene (ESR1) is suggested.

Risk Factors

  • Age: usually presents in the late 20s to mid-30s
  • History of mood disorder (major depression, bipolar disorder), anxiety disorder, personality disorder, or substance abuse
  • Family history
  • Low parity
  • Cigarette smoking and other nicotine-containing products
  • Psychosocial stressors/history of trauma
  • High BMI (>27.5)

Commonly Associated Conditions

There is a high prevalence of comorbid mood disorders and/or anxiety disorders in patients with PMS/PMDD.

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