Reproductive · PANCE / PANRE

Premenstrual Syndrome (PMS) and PMDD

Cyclical physical and mood symptoms in the luteal phase; PMDD is the severe form.

Also known as: PMS, PMDD, premenstrual dysphoric disorder, premenstrual syndrome

Overview

PMS is the cyclical occurrence of one or more bothersome physical, behavioral, or mood symptoms in the luteal phase, resolving within a few days of menses onset, with a symptom-free interval in the follicular phase. PMDD (DSM-5-TR diagnosis) requires >=5 symptoms with at least one being a mood symptom and causing significant impairment.

Epidemiology

Up to 80% of menstruating women report some premenstrual symptoms. PMS affects 20-30% with bothersome symptoms; PMDD affects 3-8%.

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Risk factors

  • Personal or family history of mood disorders (depression, anxiety, PMDD)
  • History of trauma, chronic stress
  • Smoking, obesity, increased caffeine intake (weak associations)
  • Genetic susceptibility (ESR1 gene variants)

Pathophysiology

Symptoms are triggered by normal cyclical changes in ovarian hormones (estradiol and progesterone) in genetically susceptible individuals with altered serotonergic and GABAergic responses. Allopregnanolone, a progesterone metabolite acting on GABA-A receptors, is implicated.

Clinical presentation

Symptoms

  • Mood: irritability, depression, anxiety, mood lability, anger, sense of being overwhelmed, decreased interest, difficulty concentrating
  • Physical: bloating, breast tenderness, headache, fatigue, joint/muscle aches, appetite/sleep changes
  • Symptoms appear in late luteal phase (~1-2 weeks before menses) and resolve within a few days of menses onset

Signs / physical exam

  • Physical exam is typically normal
  • Mental status exam may demonstrate dysphoria during luteal phase

Differential diagnosis

  • Major depressive disorder or anxiety disorder — Persistent symptoms NOT confined to luteal phase; prospective symptom diary distinguishes
  • Bipolar disorder — Mood symptoms not strictly cyclical; manic/hypomanic episodes
  • Thyroid disease — TSH and free T4 abnormal
  • Premenstrual exacerbation (PME) of an underlying disorder — Symptoms present throughout cycle but worsen premenstrually; treat the primary disorder
  • Perimenopause — Irregular cycles, vasomotor symptoms, age usually >40
  • Endometriosis / dysmenorrhea — Pain predominates; dyspareunia, dyschezia; laparoscopy or imaging

Diagnostic workup

Diagnostic criteria

Prospective symptom diary across at least 2 cycles documenting symptom timing and resolution. ACOG PMS criteria: >=1 affective or somatic symptom, in the 5 days before menses, in 3 consecutive cycles, with relief within 4 days of menses, no symptoms days 5-12 of cycle, and impairment. DSM-5-TR PMDD: >=5 symptoms with at least 1 from mood category, prospective documentation across 2 cycles, significant impairment.

Labs

  • Targeted to rule out medical mimics: TSH, CBC if fatigue, prolactin if galactorrhea/amenorrhea

Imaging

  • Not routinely indicated

Diagnostic algorithm

FeaturePMSPMDD
Symptom number>=1 mood or somatic>=5 symptoms (>=1 mood)
ImpairmentMild-moderateMarked, interferes with function
Diagnosis sourceACOG clinical criteriaDSM-5-TR psychiatric criteria
First-line med txSSRI or OC if severe; supplements for mildSSRI (continuous or luteal); drospirenone OC
Comparison of PMS and PMDD.

Treatment

First-line

  • Lifestyle: aerobic exercise, regular sleep, stress reduction, smoking cessation, reduce caffeine/alcohol/sodium in luteal phase
  • Supplements with modest evidence: calcium 1000-1200 mg/day, vitamin B6 (50-100 mg/day; >100 mg/day risks neuropathy), magnesium
  • Cognitive behavioral therapy
  • For PMDD or severe PMS: SSRI (fluoxetine, sertraline, paroxetine, citalopram, escitalopram) — either continuous OR luteal-phase dosing (cycle days 14-28); rapid onset (often within days)
  • Combined oral contraceptive containing drospirenone with a 24/4 regimen (e.g., Yaz) — FDA-approved for PMDD
  • GnRH agonists (leuprolide) with add-back estrogen/progestin for severe refractory cases

Second-line / adjunct

  • Spironolactone 50-100 mg in luteal phase for bloating, mastalgia
  • Targeted symptom therapy: NSAIDs for dysmenorrhea/headache, diuretics for edema
  • Surgical: bilateral oophorectomy (with hysterectomy) — last resort for severe, refractory PMDD

Complications

  • Functional impairment (work, school, relationships)
  • Suicidality and self-harm (PMDD carries elevated risk)
  • Comorbid depression, anxiety, substance use

PANCE pearls

  • PMDD is a DSM-5-TR diagnosis with prospective symptom tracking required across 2 cycles — distinguishes from PME of other mood disorders.
  • SSRIs work rapidly in PMDD (often within days), unlike in major depression — can be used continuously or only during the luteal phase.
  • Drospirenone-containing combined OCs (Yaz) are FDA-approved for PMDD; other COCs less consistently studied.
  • PMS/PMDD do not begin in the postmenopausal period — consider other diagnoses if onset is after menopause.
  • Suicide risk is elevated in PMDD — screen and address active mood/safety concerns even in 'cyclical' presentations.

References

  • ACOG PB 15 — ACOG Premenstrual Syndrome (Obstet Gynecol, multiple updates)
  • DSM-5-TR — DSM-5-TR Diagnostic Criteria for Premenstrual Dysphoric Disorder (APA 2022)
  • ISPMD 2011 — International Society for Premenstrual Disorders consensus on diagnosis

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