Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
Premenstrual syndrome (PMS) is defined as a symptom complex of physical and emotional symptoms severe enough to interfere with everyday life and occurring cyclically during the luteal phase of menses.
- Premenstrual dysphoric disorder (PMDD) is a severe form of PMS characterized by severe recurrent depressive and anxiety symptoms with premenstrual (luteal phase) onset that remit a few days after the start of menses.
- The American Psychiatric Association’s DSM-IV revised diagnosis is premenstrual dysphoric disorder when the dominant symptoms are emotional and severe enough to disrupt social and occupational functioning.
- System(s) affected: Endocrine/Metabolic; Nervous; Reproductive
- Almost all women have some physical and psychic symptoms before menses (this is not premenstrual syndrome).
- Approximately 30% of menstruating women suffer from PMS.
- Approximately 5% of menstruating women have PMDD.
- Age: Usually present in late 20s–mid-30s
- History of mood disorder (major depression, bipolar disorder), anxiety disorder, personality disorder, or substance abuse
- Family history
- Low parity
- Tobacco use
- Psychosocial stressors
- High body mass index (BMI)
- Role of genetic predisposition is controversial; however, twin studies do suggest a genetic component.
- Involvement of gene coding for the serotonergic 5HT1A receptor and allelic variants of the estrogen receptor alpha gene (ESR1) is suggested.
- Results from interaction of cyclic changes in ovarian steroids (estrogen, progesterone, allopregnanolone) with central neurotransmitters (serotonin, γ-endorphin, γ-aminobutyric acid [GABA]) and the autonomic nervous system
- Circadian rhythm alterations affecting secretion of melatonin, cortisol, thyroid-stimulating hormone (TSH), and prolactin reported
- Inconclusive evidence regarding low levels of vitamin D, magnesium, and calcium in women with PMDD
- Determine regularity of the menstrual cycle using prospective patient record of symptoms for 2 months, the Daily Record of Severity of Problems (available online at http://www.pmdd.factsforhealth.org/drsp/drsp_month.pdf), or similar inventory.
- DSM-IV criteria:
- Symptoms occur 1 week before menses and resolve in the 1st few days after menses begin (over most menstrual cycles during the past year).
- ≥5 of the following (1 must be among the 1st 4):
- Markedly depressed mood with feelings of hopelessness
- Marked anxiety or tension
- Marked affective lability
- Irritability and anger
- Decreased interest in usual activities and social withdrawal
- Lack of energy
- Appetite change
- Change in sleeping pattern
- Feeling out of control or overwhelmed
- Difficulty concentrating
- Somatic symptoms such as abdominal bloating, breast tenderness, headaches, and joint pain
- For PMDD, emotional symptoms must be severe enough to interfere with work, school, or usual activities.
- Symptoms may be superimposed on an underlying psychiatric disorder but may not be an exacerbation of another condition.
- Criteria must be confirmed by prospective daily charting for a minimum of 2 consecutive symptomatic menstrual cycles.
- Physiologic symptoms:
- Food cravings
- Weight gain
- Sleep disturbance
- Tension/muscle aches
- Mastalgia/breast swelling
- Abdominal bloating/pain
- Emotional symptoms:
- Irritability/mood lability
- Internal tension
- Depressed mood
Diagnostic Tests & Interpretation
- The repetitive nature of symptoms precludes need for labs if a classic history is present.
- Hemoglobin may be helpful to rule out anemia.
- 25-OH vitamin D level to exclude deficiency, although precise relationship of deficiency with the disorder is unclear.
- Serum TSH to rule out hypothyroidism
Imaging to diagnose causes of pelvic pain and dysmenorrhea may be appropriate.
- Premenstrual exacerbation of underlying psychiatric disorder
- Psychiatric disorders (especially bipolar disorder, major depression, anxiety)
- Thyroid disorders
- Premenstrual migraine
- Chronic fatigue syndrome
- Irritable bowel syndrome (painful symptoms)
- Endometriosis (painful symptoms)
- Drug or alcohol abuse
- Selective serotonin reuptake inhibitors (SSRIs) (fluoxetine and sertraline most studied) are highly effective in the treatment of physical and behavioral symptoms of PMDD (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.31–0.51) (1,2,3,4)[A].
- Intermittent luteal phase dosing (OR 0.55, 95% CI 0.45–0.68) is less effective than full-cycle dosing (OR 0.28, 95% CI 0.18–0.42) but has fewer adverse effects (4)[A].
- Higher doses are not correlated with increased response (1,4)[A].
- Other nonselective serotonergic agents (e.g., venlafaxine, clomipramine) also may be effective (3)[C].
- Alternative therapies should be considered if no response to SSRIs: Alprazolam, buspirone, gonadotropin-releasing hormone (GnRH) agonists, danazol, bromocriptine, spironolactone, oral contraceptives, meclofenamate, progesterone (2,3)[C]
- Oral contraceptive pills (OCPs) may improve physical symptoms but not mood (2,3)[C].
- OCPs can cause adverse effects similar to PMDD symptoms; monophasic preparations should be used continuously (daily without interruption) for PMDD (3)[C].
- OCPs containing the progestin drospirenone (structurally similar to spironolactone) may improve physical symptoms and mood changes associated with PMDD (2,5)[A].
- Vitamin D supplementation, 2,000 IU/d, with no risk of toxicity (3)[C]
- Calcium carbonate 600 mg b.i.d. effectively reduces physical and emotional premenstrual symptoms (6,7)[B].
- Vitamin B6 may reduce the severity of premenstrual symptoms (6)[B].
- Chasteberry (Vitex agnus-castus) may reduce physical premenstrual symptoms (6)[C].
- Cognitive-behavioral therapy (CBT) is as effective as drug therapy, but there is no additional benefit of combining CBT and drug therapy (2)[B].
- Fluoxetine (Prozac, Sarafem) 20 mg/day every day, or 20 mg/day only during luteal phase, or 90 mg once a week × 2 weeks in luteal phase
- Sertraline (Zoloft) 50–150 mg/day every day or 50–150 mg/day only during luteal phase
- Citalopram (Celexa) 10–30 mg/day every day or 10–30 mg/day only during luteal phase
- Adverse effects:
- GI upset
- Sexual dysfunction
- Contraindications: Patients taking monoamine oxidase inhibitors (MAOIs)
- Increased risk of suicidal thinking and behavior in children and adolescents with depressive disorders; uncertain if this risk applies to those taking SSRIs for PMDD
- Bipolar disorder
- Seizure disorder
- Hepatic dysfunction
- Renal dysfunction
- Possible interactions:
- MAOIs (e.g., phenelzine, isocarbazine, tranylcypromine, linezolid)
- Spironolactone (Aldactone) 50–100 mg/day × 7–10 days during luteal phase; helpful for fluid retention; adverse reactions: lethargy, headache, irregular menses, hyperkalemia
- Oral contraceptives: Ethinyl estradiol/drospirenone (Yasmin/Yaz): 1 tablet/day; although unstudied, other OCPs also may be effective.
- Alprazolam (Xanax) 0.25 mg t.i.d.–q.i.d. only during luteal phase; taper at onset of menses (other benzodiazepines not studied for PMDD). Caution: Addictive potential
- GnRH agonists:
- Leuprolide (Lupron) depot 3.75 mg/month IM
- Precautions: Menopause-like side effects (e.g., osteoporosis, hot flashes, headaches, muscle aches, vaginal dryness, irritability) limit treatment to 6 months; if extended treatment is needed, supplement with estrogen and progesterone “add-back” therapy, minimizing frequency and dose of progestational agent.
- Danazol (Danocrine), 300–400 mg b.i.d.; adverse reactions: androgenic and antiestrogenic effects (e.g., amenorrhea, weight gain, acne, fluid retention, hirsutism, hot flashes, vaginal dryness, emotional lability)
Issues for Referral
Referral to psychiatrist may be indicated for mood or anxiety disorder if patient has no symptom-free period.
Complementary and Alternative Medicine
- Some data support the use of the following:
- Calcium: 600 mg b.i.d.
- Vitamin D: 2,000 IU/day
- Vitamin B6: 100 mg/day (usually 50 mg b.i.d.)
- Magnesium: 200–400 mg/day
- Vitamin E: 400 IU/day
- Manganese: 1.8 mg/day
- Chasteberry (Vitex agnus-castus): 4 mg/day of extract
- St. John’s wort: 900 mg/day (0.18% hypericin, 23.38% hyperforin)
- Evidence supporting efficacy and/or safety of herbal products is lacking; the following products/interventions have not been found useful for PMS/PMDD, although not all studies are of high quality and able to completely eliminate possibility of benefit:
- Evening primrose oil
- Black current oil
- Black cohosh
- Wild yam root
- Dong quai
- Kava kava
- Light-based therapy
Bilateral oophorectomy, usually with concomitant hysterectomy, is option for rare, refractory cases with severe, disabling symptoms.
Aerobic exercise is helpful in decreasing premenstrual symptoms (8)[C].
Increased risk of suicidal thinking and behavior in children and adolescents with depressive disorders; uncertain if this risk applies to those taking SSRIs for PMDD
- Reduce consumption of salt, sugar, caffeine, dairy products, and alcohol (anecdotal reports).
- Eat small, frequent portions of food high in complex carbohydrates (limited data).
- Counsel patients to eat a balanced diet rich in calcium and omega-3 fatty acids and low in saturated fat and caffeine.
- Advise aerobic exercise.
- Counsel women that they are not “crazy.” PMDD is a real disorder with a physiologic basis.
- Although incompletely understood, successful treatment is usually possible.
- Many patients can have their symptoms adequately controlled. PMS disappears at menopause.
- PMS sometimes continues after hysterectomy.
1. Brown J, O’Brien PM, Marjoribanks J, et al. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. 2009:CD001396.
2. Cunningham J, Yonkers KA, O’Brien S, et al. Update on research and treatment of premenstrual dysphoric disorder. Harv Rev Psychiatry. 2009;17:120–37.
3. Pearlstein T, Steiner M. Premenstrual dysphoric disorder: burden of illness and treatment update. J Psychiatry Neurosci. 2008;33:291–301.
4. Shah NR, Jones JB, Aperi J, et al. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis.Obstet Gynecol. 2008;111:1175–82.
5. Lopez LM, Kaptein A, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2008:CD006586.
6. Whelan AM, Jurgens TM, Naylor H et al. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol.2009;16:e407–29.
7. Thys-Jacobs S, McMahon D, Bilezikian JP. Cyclical changes in calcium metabolism across the menstrual cycle in women with premenstrual dysphoric disorder.J Clin Endocrinol Metab. 2007;92:2952–9.
8. The American College of Obstetricians and Gynecologists. Practice Bulletin. Management of premenstrual syndrome. Clinical Management Guidelines No. 15.April 2000.
Freeman EW et al. Therapeutic management of premenstrual syndrome. Expert opinion on pharmacotherapy. 2010
625.4 Premenstrual tension syndromes
- 82639001 premenstrual tension syndrome (disorder)
- 596004 premenstrual dysphoric disorder (disorder)
- To determine whether the symptoms your patient describes are PMS, have the patient keep a daily log of her symptoms and menses. Symptoms beginning in the week before menses and abating before the end of menses, occurring over at least 2 months, and severe enough to interfere with daily functioning are diagnostic.
- The difference between PMS and PMDD is that PMDD is a severe form of PMS characterized by recurrent depressive and anxiety symptoms with premenstrual (luteal phase) onset, severe enough to disrupt social and occupational functioning. These symptoms remit a few days after the onset of menses.
- PMDD is not the same as more generalized depressive or anxiety disorders. PMDD-associated symptoms of depression and anxiety resolve within the first few days of menses.
- Treatment during the luteal phase only is somewhat less effective than continuous-cycle treatment with SSRIs but has fewer adverse effects.