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.