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

BASICS

  • PMS: Complex of physical/emotional symptoms occurring cyclically during the luteal phase; severe enough to interfere with life.
  • PMDD: Severe, recurrent depressive and anxiety symptoms, with premenstrual onset and remission after menses. Fulfills DSM-5 criteria.
  • System(s) affected: Endocrine/metabolic, nervous, reproductive.

EPIDEMIOLOGY

  • PMS prevalence: 20–30% of menstruating women.
  • PMDD prevalence: 1.2–6.4% (DSM-5 criteria), up to 18% partial criteria.
  • Most common age: Late 20s to mid-30s.

ETIOLOGY & PATHOPHYSIOLOGY

  • Allopregnanolone (progesterone metabolite) interacts with serotonin and GABA receptors, decreasing GABA-mediated inhibition and serotonin.
  • Decreased serotonin system function (especially transporter): Modulated by sex hormones, lowers serotonin.
  • Genetics: Twin studies suggest genetic component. Implicated: 5HT1A and ESR1 gene variants.

RISK FACTORS

  • Age (late 20s–mid-30s)
  • History of mood, anxiety, personality, or substance use disorder
  • Family history
  • Low parity
  • Smoking/nicotine use
  • Psychosocial stress, trauma
  • High BMI (>27.5)

COMMONLY ASSOCIATED CONDITIONS

  • High comorbidity with mood and/or anxiety disorders

DIAGNOSIS

History

  • PMS (ISPMD criteria):
  • Physical or emotional symptoms
  • Luteal phase onset, resolution after menses, symptom-free week
  • Significant impairment during luteal phase
  • PMDD (DSM-5):
  • ≥5 symptoms in week before menses, improving after onset, minimal/absent in week after menses
  • One must be among: depressed mood, anxiety/tension, affective lability, irritability/anger
  • Other symptoms: loss of interest, lethargy, appetite/sleep change, overwhelmed, poor concentration, physical symptoms (bloating, breast tenderness, headache, weight gain, joint/muscle pain)
  • Symptoms severe enough to impair functioning
  • Exclude exacerbation of another condition
  • Confirm by prospective daily symptom record for ≥2 cycles

Physical Exam

  • Not required unless indicated by symptoms (consider thyroid/pelvic exam)

Differential Diagnosis

  • Psychiatric disorders (esp. bipolar, depression, anxiety)
  • Thyroid dysfunction
  • Perimenopause
  • Premenstrual migraine, chronic fatigue, IBS, endometriosis, anemia
  • Seizures, drug/alcohol abuse

Diagnostic Tests

  • Labs not required with classic history.
  • Consider Hgb (anemia), TSH (thyroid), pelvic US (pain/dysmenorrhea).

TREATMENT

General Measures

  • Exercise: Increases β-endorphins (unclear benefit).
  • Daily symptom diary is essential for diagnosis and monitoring.

Medication

First Line

  • SSRIs (luteal phase or continuous dosing equally effective, low to moderate dose):
  • Fluoxetine: 20 mg/day daily or luteal phase, or 90 mg once weekly x2 during luteal phase
  • Sertraline: 50–150 mg/day daily or luteal phase
  • Citalopram: 10–30 mg/day daily or luteal phase
  • Side effects: Nausea, asthenia, somnolence, fatigue, decreased libido, sweating
  • Precautions: Suicidality in youth, bipolar, seizure disorder, QTc (with citalopram), hepatic/renal issues

Second Line

  • Spironolactone: 50–100 mg/day during luteal phase (fluid retention). Monitor K+
  • Oral contraceptives (OCPs): Extended or shortened placebo intervals may help. Drospirenone-containing OCPs may improve symptoms, but with higher VTE risk.
  • Anxiolytics: Alprazolam 0.25 mg TID-QID during luteal phase (addictive potential), buspirone 10–30 mg/day divided in luteal phase
  • Ovulation inhibition:
  • GnRH agonists (leuprolide depot) limited by menopause-like side effects, max 6 months
  • Danazol (androgenic/antiestrogenic side effects)
  • Transdermal estrogen (100–200 µg, needs progesterone add-back)
  • Progesterone: Insufficient evidence
  • Surgery: Bilateral oophorectomy with/without hysterectomy for rare, severe refractory PMDD

CBT (Cognitive-Behavioral Therapy)

  • May be helpful, though direct evidence is limited.

Complementary & Alternative Medicine

  • Effective/Safe: Acupuncture (some evidence), calcium 600 mg BID, vitamin B6 50–100 mg/day, chasteberry, omega-3 fatty acids 2g/day
  • Less evidence: Magnesium, vitamin D/E, manganese, St. John's wort, soy, ginkgo, saffron
  • Not effective: Evening primrose oil, black currant/cohosh, wild yam, dong quai, kava, light therapy

ONGOING CARE

  • Monitor for suicidality, especially in adolescents/youths on SSRIs
  • Lifestyle: Balanced diet (calcium, vitamin D, omega-3), low saturated fat/caffeine, quit tobacco, small frequent meals with complex carbs, reduce salt/sugar/alcohol

PROGNOSIS

  • Most can achieve symptom control
  • PMS resolves at menopause; can persist post-hysterectomy if ovaries remain

ICD-10 CODE

  • N94.3 Premenstrual tension syndrome

CLINICAL PEARLS

  • Daily symptom log for diagnosis: Symptoms in week before menses, resolving before end of menses, severe enough to impair function for at least 2 cycles
  • Luteal-phase only SSRI treatment is as effective as continuous, but with fewer side effects.
  • Patient education: PMDD is real and physiologic; not “crazy”—successful treatment is often possible.