Premenstrual Syndrome

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

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II. Epidemiology

  1. Age: Teens may have a higher Prevalence of premenstrual symptoms
  2. Prevalence
    1. Reproductive age women with at least one premenstrual symptom: 90%
    2. Women who have classic premenstrual symptoms: 30%
    3. Moderate symptoms (Premenstrual Syndrome): 5-10%
    4. Women who have Premenstrual Dysphoric Disorder: 2-3%
      1. Severe symptoms interfere with work or activities

III. Pathophysiology

  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 (Luteal Phase)
    2. Symptoms subside with onset of Menses (or within the week following Menses onset)
  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. Depressed mood 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. Disturbed Sleep (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
    1. Record which symptoms are most distressing
  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 (at least the last 2 Menstrual Cycles at the time of diagnosis)
  4. Symptoms onset during the Luteal Phase, after Ovulation (present for at least the 5 days before Menses)
  5. Symptoms resolve within the first week 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 may meet criteria for PMDD (see below)

VII. Diagnosis: Premenstrual Dysphoric Disorder (PMDD, 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 Disorder)
  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: Non-Pharmacologic Strategies (Lifestyle)

  1. Get adequate sleep per night (see Sleep Hygiene)
  2. Moderate regular Exercise
    1. Measures
      1. Aerobic Exercise
      2. Strength Training
      3. Yoga or pilates
    2. Efficacy
      1. May decrease anxiety, anger, pain, Constipation and Breast sensitivity
      2. Pearce (2020) BJGP Open 4(3) +PMID: 32522750 [PubMed]
  3. Dietary changes (limited evidence)
    1. Measures
      1. Low Fat Diet
      2. Low salt diet (may decrease bloating)
      3. Decrease simple Carbohydrate intake
      4. Avoid Caffeine
      5. Avoid Alcohol
    2. Efficacy
      1. No strong evidence that dietary interventions significantly modify PMS/PMDD
      2. However, some studies show up to a 50% response, and none of the recommended strategies are harmful
      3. Siminiuc (2023) Front Nutr +PMID: 36819682 [PubMed]
  4. Supplements with benefit in some studies
    1. Calcium Carbonate 1200 mg per day throughout cycle
      1. May improve mood, water retention and pain (limited evidence)
      2. Shobeiri (2017) Obstet Gynecol Sci 60(1):100-5 +PMID: 28217679 [PubMed]
      3. Thys-Jacobs (1998) Am J Obstet Gynecol 179:444-52 [PubMed]
      4. 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. Chasteberry (Vitex agnus-castus)
      1. May improve irritability, mood swings, Breast tenderness, Constipation
      2. Csupor (2019) Complement Ther Med 47:102190 +PMID: 31780016 [PubMed]
  5. Supplements 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. Magnesium 360 mg/day (variable evidence)
  6. 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

X. Management Algorithm

  1. Step 1
    1. Confirm diagnosis
    2. Daily symptom diary
    3. Encourage lifestyle modification
      1. See Non-pharmacologic Management as above
  2. Step 2: Antidepressant Trial (SSRI or SNRI)
    1. Background
      1. First-line, effective medical management for PMS and PMDD
      2. SSRI use in teens may be associated with increased Suicidal Ideation and behavior (RR 2)
    2. Timing
      1. Continuous, SSRI daily dosing (preferred)
        1. More effective than intermittent Luteal Phase dosing
      2. Intermittent, Luteal PhaseSSRI dosing only
        1. Days 17-28 or starting 14 days before anticipated Menses (and continue for 3 days after)
        2. Base starting dose timing on symptom diary
        3. Avoids the Antidepressant Withdrawal with longterm SSRI use
          1. Reilly (2023) J Psychopharmacol 37(3):261-7 +PMID: 35686687 [PubMed]
    3. Commonly used SSRI Medications in PMS/PMDD
      1. Citalopram (Celexa) or Escitalopram (Levapro)
      2. Fluoxetine (Prozac)
        1. Daily: 20-40 mg qAM OR
        2. Cyclic: 20 mg qd for last 12 days of cycle
      3. Sertraline (Zoloft) 50-100 mg qd
      4. Paroxetine (Paxil) 10-20 mg qd
        1. Avoid without adequate Contraception
    4. Other agents
      1. SNRIs (e.g. Venlafaxine)
        1. Appear effective, but are associated with higher rates of adverse effects
        2. Consider in comorbid Anxiety Disorder
        3. Sepede (2016) Clin Neuropharmacol 39(5):241-61 +PMID: 27454391 [PubMed]
    5. References
      1. Dimmock (2000) Lancet 356:1131-6 [PubMed]
      2. Halbreich (2002) Obstet Gynecol 100:1219-29 [PubMed]
      3. Jespersen (2024) Cochrane Database Syst Rev 8(8):CD001396 +PMID: 39140320 [PubMed]
  3. Step 3: Oral Contraceptive pill (OCP) trial (second-line management)
    1. OCPs suppress Ovulation and the associated Estrogen and Progesterone fluctuations
      1. Consider Seasonal Contraception
      2. Not uniformly effective in all women with Premenstrual Disorders
    2. Adjunctive benefit to Estrogen with Drosperinone (Spironolactone analogue, e.g. Yasmin)
      1. Monophasic pills are typically used
      2. May improve mood and physical symptoms based on limited evidence
        1. Ma (2023) Cochrane Database Syst Rev 6(6):CD006586 +PMID: 37365881 [PubMed]
  4. Step 5: Mental Health Related Interventions
    1. Cognitive Behavioral Therapy
      1. May improve anxiety, depression, negative behaviors, daily life impact and overall premenstrual symptoms
      2. Lustyk (2009) Arch Womens Ment Health 12(2): 85-96 [PubMed]
      3. Kancheva (2021) Psychol Health Med 26(10):1282-93 +PMID: 32845159. [PubMed]
    2. Other Measures
      1. Bright Light Therapy (10k Lx cool-white fluorescent)
      2. Relaxation Techniques
      3. Anger Management
      4. Individual and family therapy
      5. Self-help support group
  5. 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
    5. General Pain management
      1. NSAIDs as needed (with food or milk)
      2. Acupuncture
    6. Anxiolytics
      1. Second-line agents if anxiety refractory to SSRI or SNRI
      2. Buspirone
        1. Daily: 5-20 mg orally daily throughout cycle OR
        2. Cyclic: 5-20 mg orally daily for last 12 days of cycle
      3. Benzodiazepines (avoid!)
        1. NOT recommended
          1. Addictive potential (use only for refractory cases with significant Impairment)
        2. Dosing listed for historical purposes
          1. Some providers have used Clonazepam 0.5 mg qhs to three times daily on premenstrual days
  6. Step 7: Pharmacologic Ovarian Suppression (third-line medications)
    1. GnRH Agonist (very expensive: $500 per month, and with significant adverse effects)
      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. Option 1: Topical
        1. Estradiol 1.5 mg topical daily
        2. Progesterone 400 mg Luteal Phase vaginally
      3. Option 2: Systemic
        1. Estrogen (Premarin) 6.25 mg orally daily and
        2. Provera 2.5 mg orally daily if intact Uterus
    3. References
      1. Wyatt (2004) BJOG 111(6):585-93 +PMID: 15198787 [PubMed]
  7. Step 8: Consider Oophorectomy
    1. Consider in severe, refractory symptoms despite GnRH Agonists

XI. References

  1. Ransom (1998) Physician and Sportsmed 26(4):35-43
  2. Rapkin (1999) Fam Pract Recert 21(1):42-73
  3. (2023) Obstet Gynecol 142(6):1516-33 +PMID: 37973069 [PubMed]
  4. (2000) Obstet Gynecol 95:1-9 [PubMed]
  5. Bhatia (2002) Am Fam Physician 66:1239-54 [PubMed]
  6. Biggs (2025) Am Fam Physician 111(4): 345-50 [PubMed]
  7. Biggs (2011) Am Fam Physician 84(8): 918-24 [PubMed]
  8. Daugherty (1998) Am Fam Physician 58(1):183-92 [PubMed]
  9. Dickerson (2003) Am Fam Physician 67(8):1743-52 [PubMed]
  10. Hofmeister (2016) Am Fam Physician 94(3): 236-40 [PubMed]

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