Premenstrual Syndrome

Aka: Premenstrual Syndrome, PMS, PMDD, Premenstrual Dysphoric Disorder, Late Luteal Phase Dysphoric Disorder

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II. Epidemiology

  1. Women who have classic premenstrual symptoms: 30-40%
  2. Moderate symptoms (Premenstrual Syndrome): 5-10%
  3. Women who have Premenstrual Dysphoric Disorder: 2-3%
    1. Severe symptoms interfere with work or activities

III. Etiology

  1. Idiopathic
  2. Possible mechanisms
    1. Relative Progesterone deficiency in Luteal Phase
    2. Prostaglandin excess
    3. Cyclic decreases in CNS Dopamine and Serotonin
    4. Premenstrual Estrogen causes Vitamin B6 deficiency
      1. Vitamin B6 is coenzyme for Dopamine and Serotonin
    5. Estrogen-mediated Sodium retention with Fluid Shifts
    6. Increased luteal-phase Insulin to oral Carbohydrates

IV. Symptoms

  1. Timing
    1. Symptom onset 2-12 days before Menses
    2. Symptoms subside with onset of Menses
  2. Somatic or Physical Symptoms
    1. Abdominal Bloating
    2. Breast Pain, tenderness or swelling
    3. Headache
    4. Arthralgias or myalgias
    5. Edema
    6. Weight gain
  3. Affective or Psychological Symptoms
    1. Anxiety
    2. Irritability
    3. Aggression (e.g. angry outbursts)
    4. Depression with Wide mood swings
    5. Social withdrawal
    6. Other symptoms included in DSM5 Criteria (see below)
      1. Increased appetite
      2. Lethargy or Fatigue
      3. Forgetfulness or Reduced concentration
      4. Sleep Disorders (Insomnia or Hypersomnia)

V. History

  1. Consider office Psychiatric Exam during Follicular Phase
  2. Complete medical history
  3. Assess nutritional status
  4. Comorbid factors
    1. Alcohol Abuse
    2. Drug Abuse
    3. Domestic Abuse
  5. Assess functional Impairment

VI. Diagnosis: Premenstrual Syndrome (ACOG)

  1. Consider keeping Daily Symptom Diary for 3 cycles
  2. At least one symptom from the affective and somatic symptoms (see above)
    1. Abdominal Bloating, Breast Pain, Headache, Arthralgias, myalgias, edema or weight gain
    2. Anxiety, irritability, aggression, depression or social withdrawal
  3. Symptoms present in each Menstrual Cycle (record which symptom is most distressing)
  4. Symptoms onset after day 13 of the cycle (at or after Ovulation)
  5. Symptoms resolve within 4 days of Menses onset
  6. Symptoms not due to to other causes (medications, hormonal therapy, drug or alchohol use)
  7. Impaired performance socially, academically or in the work place

VII. Diagnosis: Premenstrual Dysphoric Disorder (DSM 5)

  1. Timing
    1. At least 5 symptoms present in the final week before Menses onset
    2. Symptoms start to improve within days of Menses onset and are minimal or absent by day 7 of cycle
    3. Symptom pattern persists for most of the Menstrual Cycles occurring in the prior year
    4. Symptom pattern should be confirmed on daily symptom diary kept for at least 2 months
  2. Major symptoms (at least one must be present)
    1. Marked mood lability or mood swings
    2. Marked irritability or anger
    3. Marked depressed mood, hopelessness or self deprication
    4. Marked anxiety or tension
  3. Minor symptoms (must total at least 5 symptoms present when added to major symptoms)
    1. Decreased interest in usual activities
    2. Diminished concentration
    3. Lethargy or Fatigue
    4. Appetite change, over-eating or food cravings
    5. Insomnia or Hypersomnia
    6. Overwhelmed or out of control Sensation
    7. Physical symptoms (e.g. Breast tenderness, Arthralgias, myalgias, bloating, weight gain)
  4. Severity
    1. Significant distress or impaired relationships or performance socially, academically or in the work place
  5. Not due to other condition
    1. Not due to Major Depression, Panic Disorder, Dysthymia or Personality Disorder (conditions may however overlap)
    2. Not due to substance use (hormonal agents or other medications, Alcohol or Drugs of Abuse)
    3. Not due to medical condition (e.g. Hypothyroidism, Anemia, Migraine Headache, Endometriosis)
  6. References
    1. (2013) DSM 5, APA, Washington, DC, p. 171-2

VIII. Differential Diagnosis

  1. Mood Disorder (Major Depression, Anxiety)
  2. Eating Disorder (Anorexia Nervosa, Bulimia)
  3. Substance Abuse
  4. Anemia
  5. Migraine Headache
  6. Hypothyroidism
  7. Endometriosis
  8. Perimenopause
  9. Oral Contraceptive adverse effects

IX. Management Algorithm

  1. Step 0
    1. Confirm diagnosis
    2. Daily symptom diary
  2. Step 1: Lifestyle modification (50% response - although no evidence to support benefit)
    1. Dietary changes
      1. Low Fat Diet
      2. Low salt diet (may decrease bloating)
      3. Decrease simple Carbohydrate intake
      4. Avoid Caffeine
      5. Avoid Alcohol
    2. Aerobic Exercise regularly
    3. Bright Light Therapy (10k Lx cool-white fluorescent)
    4. Get adequate sleep per night (see Sleep Hygiene)
    5. Other measures
      1. Relaxation Techniques
      2. Anger Management
      3. Individual and family therapy
      4. Self-help support group
  3. Step 2: Antidepressant Trial (SSRI or SNRI)
    1. Typically used as continuous daily dosing
      1. However, may consider Luteal Phase dosing only
        1. Days 17-28 or 14 days before anticipated Menses
        2. Base starting dose timing on symptom diary
    2. Citalopram (Celexa) or Escitalopram (Levapro)
    3. Fluoxetine (Prozac)
      1. Daily: 20-40 mg qAM OR
      2. Cyclic: 20 mg qd for last 12 days of cycle
    4. Sertraline (Zoloft) 50-100 mg qd
    5. Paroxetine (Paxil) 10-20 mg qd
      1. Avoid without adequate Contraception
    6. References
      1. Dimmock (2000) Lancet 356:1131-6 [PubMed]
      2. Halbreich (2002) Obstet Gynecol 100:1219-29 [PubMed]
  4. Step 3: Oral Contraceptive pill (OCP) trial
    1. Consider Seasonal Contraception
    2. Not uniformly effective in all women
    3. Benefit appears to be due to Estrogen component with adjunctive benefit from Drosperinone (Spironolactone analogue)
      1. Monophasic pills may be most appropriate
      2. Yasmin improves mood and physical symptoms
  5. Step 4: Dietary Supplementation trial for 3 months
    1. Calcium Carbonate 1200 mg per day throughout cycle
      1. Thys-Jacobs (1998) Am J Obstet Gynecol 179:444-52 [PubMed]
      2. Ghanbari (2009) Taiwan J Obstet Gynecol 48(2): 124-9 [PubMed]
    2. Vitamin B6 (Pyridoxine) 100 mg daily throughout cycle
      1. Needs confirmation with larger studies
      2. Kashanian (2007) Int J Gynaecol Obstet 96(1): 43-4 [PubMed]
      3. Wyatt (1999) BMJ 318:1375-81 [PubMed]
    3. Other agents with insufficient or variable evidence
      1. Vitamin E 400 to 600 IU daily throughout cycle
        1. May decrease PMS symptoms (esp. Breast tenderness)
      2. Vitamin D Supplementation
        1. Variable evidence
        2. Bertone-Johnson (2014) BMC Womens Health 14:56 [PubMed]
      3. Chasteberry
        1. May improve irritability, mood swings, Breast tenderness, Constipation
      4. Magnesium 360 mg/day (variable evidence)
    4. Avoid supplements found not to be efficacious
      1. Black Cohosh
      2. Dong Quai
      3. Evening Primrose Oil
      4. Progesterone
      5. Red Clover
      6. Vitamin A
      7. Soy products
  6. Step 5: Counseling
    1. Cognitive Behavioral Therapy
      1. Lustyk (2009) Arch Womens Ment Health 12(2): 85-96 [PubMed]
  7. Step 6: Consider Symptom directed medication
    1. Dysphoria with bloating
      1. Spironolactone 25-100 mg/day during Luteal Phase
      2. Thiazide Diuretics have not shown benefit
    2. Breast Tenderness
      1. See Mastalgia
      2. Oral Contraceptives
      3. Danazol 100 mg bid up to 6 cycles
        1. Risk of masculinization, abnormal LFTs and Lipids
    3. Dysmenorrhea or Menorrhagia: NSAIDS
      1. Mefenamic Acid (Ponstel)
      2. NaproxenSodium (Anaprox)
    4. Headaches and Premenstrual Migraines
      1. NSAIDS
      2. Estradiol patch 0.5 - 0.1 mid-cycle to Menses
  8. Step 7: Anxiolytic trial
    1. Second-line agents for failed SSRI trial
    2. Buspirone
      1. Daily: 5-20 mg qd throughout cycle OR
      2. Cyclic: 5-20 mg qd for last 12 days of cycle
    3. Benzodiazepines
      1. Addictive potential (use only for refractory cases)
      2. Not recommended
      3. Clonazepam 0.5 mg qhs to tid on premenstrual days
  9. Step 8: Pharmacologic Ovarian Suppression
    1. GnRH Agonist (very expensive: $500 per month)
      1. Leuprolide (Depo Lupron) 3.75 mg IM monthly or
      2. Leuprolide (Depo Lupron) 11.25 mg IM q3 months or
      3. Goserelin (Zoladex) 3.6 mg SQ qMonth or
      4. Goserelin (Zoladex) 10.8 mg SQ q3 months or
      5. Nafarelin (Synarel) 200 to 400 mcg intranasal bid
    2. Concurrently add back Estrogen Replacement
      1. Indicated if GnRH Agonist used for >6 months
      2. Estrogen (Premarin) 6.25 mg qd and
      3. Provera 2.5 mg PO qd if intact Uterus
  10. Step 9: Consider Oophorectomy

X. Resources

  1. PMS Access
    1. Phone: (800) 222-4PMS

XI. References

  1. Ransom (1998) Physician and Sportsmed 26(4):35-43
  2. Rapkin (1999) Fam Pract Recert 21(1):42-73
  3. (2000) Obstet Gynecol 95:1-9 [PubMed]
  4. Bhatia (2002) Am Fam Physician 66:1239-54 [PubMed]
  5. Biggs (2011) Am Fam Physician 84(8): 918-24 [PubMed]
  6. Daugherty (1998) Am Fam Physician 58(1):183-92 [PubMed]
  7. Dickerson (2003) Am Fam Physician 67(8):1743-52 [PubMed]
  8. Hofmeister (2016) Am Fam Physician 94(3): 236-40 [PubMed]

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