Premenstrual Syndrome

1. 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
2. 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
3. Diagnosis
   1. Daily Symptom Diary for at least 2 months
      1. Symptoms present in each Menstrual Cycle
         1. Which symptom is most distressing
      2. Symptoms begin at or after Ovulation
      3. Symptoms resolve near Menses
      4. Symptom free period of at least 7 days each cycle
   2. Additional History and Exam
      1. Thorough 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
4. Symptoms
   1. Timing
      1. Symptom onset 2-12 days before Menses
      2. Symptoms subside with onset of Menses
   2. Physical
      1. Abdominal bloating
      2. Constipation
      3. Edema and Weight gain
      4. Hot Flashes
      5. Headache
      6. Breast Pain
      7. Rhinitis
      8. Acne Vulgaris
      9. Palpitations
   3. Psychological
      1. Anxiety and Phobias
      2. Irritability and Aggression (e.g. angry outbursts)
      3. Depression with Wide mood swings
      4. Increased appetite
      5. Lethargy or Fatigue
      6. Forgetfulness or Reduced concentration
      7. Sleep Disorders
5. Differential Diagnosis
   1. Mood Disorder (Major Depression, Anxiety)
   2. Eating Disorder (Anorexia Nervosa, Bulimia)
   3. Substance Abuse
   4. Anemia
   5. Hypothyroidism
   6. Perimenopause
   7. Oral Contraceptive adverse effects
6. 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: Counseling
      1. Cognitive Psychotherapy
   4. Step 3: 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
      2. Vitamin B6 (Pyridoxine) 100 mg qd throughout cycle
         1. Needs confirmation with larger studies
         2. Wyatt (1999) BMJ 318:1375-81
      3. Vitamin E 400 to 600 IU qd throughout cycle
         1. Decreases PMS symptoms (esp. Breast tenderness)
      4. Vitamin D Supplementation
      5. Chasteberry improves irritability, mood swings, Breast tenderness, Constipation
      6. Magnesium 360 mg/day (variable evidence)
      7. 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
   5. Step 4: 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
   6. Step 5: 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. Naproxen sodium (Anaprox)
      4. Headaches and Premenstrual Migraines
         1. NSAIDS
         2. Estradiol patch 0.5 - 0.1 mid-cycle to Menses
   7. Step 6: SSRI trial
      1. Consider as first-line therapy
      2. Typically used as continuous daily dosing
      3. Consider Luteal Phase dosing only
         1. Days 17-28 or 14 days before anticipated Menses
         2. Base starting dose on symptom diary
      4. Citalopram (Celexa) or Escitalopram (Levapro)
      5. Fluoxetine (Prozac)
         1. Daily: 20-40 mg qAM OR
         2. Cyclic: 20 mg qd for last 12 days of cycle
      6. Sertraline (Zoloft) 50-100 mg qd
      7. Paroxetine (Paxil) 10-20 mg qd
         1. Avoid without adequate Contraception
      8. References
         1. Dimmock (2000) Lancet 356:1131-6
         2. Halbreich (2002) Obstet Gynecol 100:1219-29
   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
7. Resources
   1. PMS Access
      1. Phone: (800) 222-4PMS
8. 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
   4. Bhatia (2002) Am Fam Physician 66:1239-54
   5. Daugherty (1998) Am Fam Physician 58(1):183-92
   6. Dickerson (2003) Am Fam Physician 67(8):1743-52
   7. Biggs (2011) Am Fam Physician 84(8): 918-24