PMS occurs in approximately 13 to 18% of women of reproductive age in the United States; approximately 2 to 6% have a severe form of PMS called premenstrual dysphoric disorder (PMDD) (1). Globally, estimates vary from 1 to 50% of women for PMS and up to 18% for PMDD (2).
References
1. Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR). American Psychiatric Association Publishing, Washington, DC, 2022, pp 367-370.
2. Carlini SV, Lanza di Scalea T, McNally ST, Lester J, Deligiannidis KM. Management of Premenstrual Dysphoric Disorder: A Scoping Review. Int J Womens Health. 2022;14:1783-1801. Published 2022 Dec 21. doi:10.2147/IJWH.S297062
Etiology of PMS
The cause of PMS is unclear. Pathophysiology is complex, involving neurotransmitters, neurosteroids, and ovarian hormones (1).
Possible causes or contributing factors include:
Multiple endocrine factors (eg, hypoglycemia, other changes in carbohydrate metabolism, hyperprolactinemia, fluctuations in levels of circulating estrogen and progesterone, abnormal responses to estrogen and progesterone, excess aldosterone or antidiuretic hormone [ADH])
Neurotransmitter-related symptoms (eg, involving GABAergic and serotonergic systems)
Genetic predisposition
Possibly changes in gut microbiota (2)
Possibly magnesium and calcium deficiencies
Estrogen and progesterone can cause transitory fluid retention, as can excess aldosterone or ADH. Allopregnanolone, a metabolite from progesterone, is being studied (3).
Serotonin deficiency is thought to contribute because women who are most affected by PMS have lower serotonin levels and because selective serotonin reuptake inhibitors (SSRIs), which increase serotonin, sometimes relieve symptoms of PMS.
The GABA neurotransmitter has inhibitory effects on the central nervous system.
An exaggerated immune-inflammatory response is being investigated (4).
Etiology references
1. Rapkin AJ, Akopians AL. Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder. Menopause Int. 2012;18(2):52-59. doi:10.1258/mi.2012.012014
2. Takeda T, Yoshimi K, Kai S, Ozawa G, Yamada K, Hiramatsu K. Characteristics of the gut microbiota in women with premenstrual symptoms: A cross-sectional study. PLoS One. 2022;17(5):e0268466. Published 2022 May 27. doi:10.1371/journal.pone.0268466
3. Modzelewski S, Oracz A, Żukow X, Iłendo K, Śledzikowka Z, Waszkiewicz N. Premenstrual syndrome: new insights into etiology and review of treatment methods. Front Psychiatry. 2024;15:1363875. Published 2024 Apr 23. doi:10.3389/fpsyt.2024.1363875
4. Tiranini L, Nappi RE. Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome. Fac Rev. 2022;11:11. Published 2022 Apr 28. doi:10.12703/r/11-11
Symptoms and Signs of PMS
Type and intensity of PMS symptoms vary across patients and from cycle to cycle. Symptoms typically start during the 5 days before menses and ending within a few hours of when menses begins. Symptoms may become more severe during stress or perimenopause. In perimenopausal women, symptoms may persist until after menses.
The most common PMS symptoms are irritability, anxiety, agitation, anger, insomnia, difficulty concentrating, headache, lethargy, depression, and severe fatigue. Fluid retention causes edema, transient weight gain, and breast fullness and pain. Pelvic heaviness or pressure and backache may occur. Some women, particularly younger ones, have dysmenorrhea when menses begins.
Other nonspecific symptoms may include, vertigo, paresthesias of the extremities, syncope, palpitations, constipation, nausea, vomiting, and changes in appetite. Acne and neurodermatitis may also occur.
Preexisting disorders may worsen while PMS symptoms are occurring. They include the following:
Skin disorders (eg, acne, pruritus vulvae, hyperpigmentation, papular eruptions, and exacerbations of atopic dermatitis)
Seizure disorders (increased seizure frequency)
Connective tissue disorders (eg, systemic lupus erythematosus [SLE, or lupus], rheumatoid arthritis, with flare-ups)
Respiratory disorders (eg, allergies, infections)
Migraines
Mood disorders (eg, depression, anxiety)
Sleep disorders (eg, insomnia, hypersomnia)
Premenstrual dysphoric disorder (PMDD)
Some women have premenstrual dysphoric disorder (PMDD—see also Premenstrual dysphoric disorder under Symptoms and Signs of Depressive Disorders), a severe form of PMS. In PMDD, symptoms occur regularly and only during the 2nd half of the menstrual cycle; symptoms end with menses or shortly after. Mood is markedly depressed, and anxiety, irritability, and emotional lability are pronounced. Suicidal thoughts may be present. Interest in daily activities is greatly decreased.
In contrast to PMS, PMDD causes symptoms that are severe enough to interfere with routine daily activities or overall functioning. PMDD is severely distressing, disabling, and often underdiagnosed.
Pearls & Pitfalls
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Diagnosis of PMS
For PMS, patient’s report of symptoms
Sometimes a depression inventory
For PMDD, clinical criteria
PMS is diagnosed based on physical symptoms (eg, bloating, weight gain, breast tenderness, swelling of hands and feet). Women may be asked to record their symptoms daily. Physical examination and laboratory testing are not helpful.
If PMDD is suspected, women are asked to rate their symptoms daily for ≥ 2 cycles to determine whether severe symptoms occur regularly.
For PMDD to be diagnosed, women must have ≥ 5 of the following symptoms for most of the week before menses, and symptoms must become minimal or absent during the week after menstruation. Symptoms must include ≥ 1 of the following:
Marked mood swings (eg, sudden sadness)
Marked irritability or anger or increased interpersonal conflicts
Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts
Marked anxiety, tension, or an on-edge feeling
In addition, ≥ 1 of the following must be present:
Decreased interest in usual activities, possibly causing withdrawal
Difficulty concentrating
Low energy or fatigue
Marked changes in appetite, overeating, or specific food cravings
Insomnia or hyperinsomnia
Feelings of being overwhelmed or out of control
Physical symptoms associated with PMS (eg, breast tenderness, edema)
Also, the symptom pattern must have occurred for most of the previous 12 months, and symptoms must be severe enough to interfere with daily activities and function.
Patients with symptoms of depression are evaluated using a depression inventory or are referred to a mental health care professional for formal evaluation.
Treatment of PMS
Sleep hygiene, exercise, and healthy diet
Sometimes selective serotonin reuptake inhibitors (SSRIs) or hormonal medications
PMS can be difficult to treat. No single treatment has proven efficacy for all women, and few woman have complete relief with any single type of treatment. Treatment can thus require trial and error, as well as patience.
General measures
Treatment of PMS is symptomatic, beginning with adequate rest and sleep, regular exercise, and activities that are relaxing. Regular exercise may help alleviate bloating as well as irritability, anxiety, and insomnia. Yoga helps some women.
Dietary changes—increasing protein, decreasing sugar, consuming complex carbohydrates, and eating smaller meals more frequently—may help, as may counseling, avoiding stressful activities, relaxation training, light therapy, sleep adjustments, and cognitive-behavioral therapy. Other possible strategies include avoiding certain foods and drinks (eg, cola, coffee, hot dogs, potato chips, canned goods) and eating more of others (eg, fruits, vegetables, milk, high-fiber foods, low-fat meats, foods high in calcium and vitamin D). Calcium supplements (600 mg twice a day) may lessen negative mood and somatic symptoms.
Some dietary supplements are mildly efficacious for reducing symptoms; they include chasteberry extract from the agnus castus fruit (which appears to lessen physical symptoms), vitamin B6 (no more than 100 mg a day), and vitamin E. Some dietary supplements are mildly efficacious for reducing symptoms; they include chasteberry extract from the agnus castus fruit (which appears to lessen physical symptoms), vitamin B6 (no more than 100 mg a day), and vitamin E.
Cognitive-behavioral therapy may help if mood issues are a major concern, including in women with PMDD. Biofeedback and guided imagery may also help. Psychotherapy can help a woman learn to better cope with the symptoms; stress reduction and relaxation techniques and meditation can help relieve tension and strain (1).
Medications
Nonsteroidal anti-inflammatory drugs (NSAIDs) can help relieve aches, pains, and dysmenorrhea.
Selective serotonin release inhibitors (SSRIs) have been shown in randomized trials to improve mood and lessen physical symptoms such as breast tenderness and changes in appetite in both PMS and PMDD (2). SSRIs are the medications of choice for relief of anxiety, irritability, and other psychological symptoms, particularly if stress cannot be avoided. No specific SSRI appears to be more effective than another. SSRIs can be prescribed continuously or only during the 14-day luteal phase (second half) of the menstrual cycle or with a dose increase during the latter 14-day luteal phase. Their effect on severe PMS and PMDD is rapid (1, 3).
Clomipramine, given for the full cycle or a half-cycle, effectively relieves emotional symptoms, as does nefazodone and venlafaxine, a serotonin-Clomipramine, given for the full cycle or a half-cycle, effectively relieves emotional symptoms, as does nefazodone and venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI).
Anxiolytics may help but are usually less desirable because dependence or addiction is possible. Buspirone, which may be given throughout the cycle or during the late luteal phase, helps relieve symptoms of PMS and PMDD. Adverse effects include nausea, headache, anxiety, and dizziness.Anxiolytics may help but are usually less desirable because dependence or addiction is possible. Buspirone, which may be given throughout the cycle or during the late luteal phase, helps relieve symptoms of PMS and PMDD. Adverse effects include nausea, headache, anxiety, and dizziness.
For some women, hormonal medications are effective. Options include:
Estrogen-progestin oral contraceptives, which block the ovulatory surge of sex steroids; most effective is a combination of drospirenone and ethinyl estradiol and a regimen with a shorter hormone-free interval (4 rather than 7 days) (Estrogen-progestin oral contraceptives, which block the ovulatory surge of sex steroids; most effective is a combination of drospirenone and ethinyl estradiol and a regimen with a shorter hormone-free interval (4 rather than 7 days) (4)
Progesterone by vaginal suppository (200 to 400 mg once a day)Progesterone by vaginal suppository (200 to 400 mg once a day)
An oral progestogen (eg, micronized progesterone 100 mg at bedtime) for 10 to 12 days before mensesAn oral progestogen (eg, micronized progesterone 100 mg at bedtime) for 10 to 12 days before menses
A long-acting progestin (eg, medroxyprogesterone 200 mg IM every 2 to 3 months) A long-acting progestin (eg, medroxyprogesterone 200 mg IM every 2 to 3 months)
Treatments that are under investigation include ulipristal acetate, a selective Treatments that are under investigation include ulipristal acetate, a selectiveprogesterone receptor modulator, and dutasteride, which may modulate the balance of receptor modulator, and dutasteride, which may modulate the balance ofprogesterone, and allopregnanolone (1).
Women who choose to use an oral contraceptive for contraception can take drospirenone plus ethinyl estradiol. However, risk of venous thromboembolism may be increased with third generation progestins, such as drospirenone.Women who choose to use an oral contraceptive for contraception can take drospirenone plus ethinyl estradiol. However, risk of venous thromboembolism may be increased with third generation progestins, such as drospirenone.
Rarely, for very severe or refractory symptoms, a gonadotropin-releasing hormone (GnRH) agonist (eg, leuprolide 3.75 mg IM, goserelin 3.6 mg subcutaneously every month) with low-dose estrogen/progestin (eg, oral estradiol 0.5 mg once a day plus micronized progesterone 100 mg at bedtime) is given to minimize cyclic fluctuations. Rarely, for very severe or refractory symptoms, a gonadotropin-releasing hormone (GnRH) agonist (eg, leuprolide 3.75 mg IM, goserelin 3.6 mg subcutaneously every month) with low-dose estrogen/progestin (eg, oral estradiol 0.5 mg once a day plus micronized progesterone 100 mg at bedtime) is given to minimize cyclic fluctuations.
Fluid retention may be relieved by reducing sodium intake and taking a diuretic (eg, spironolactone 100 mg orally once a day) just before symptoms are expected. However, minimizing fluid retention and taking a diuretic do not relieve all symptoms and may have no effect.Fluid retention may be relieved by reducing sodium intake and taking a diuretic (eg, spironolactone 100 mg orally once a day) just before symptoms are expected. However, minimizing fluid retention and taking a diuretic do not relieve all symptoms and may have no effect.
Surgery
In women with severe PMDD symptoms refractory to other interventions, bilateral oophorectomy may alleviate symptoms because it eliminates menstrual cycles (5). Menopausal hormone therapy is then indicated until about age 51 (the average for menopause).
Treatment references
1. Tiranini L, Nappi RE. Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome. Fac Rev. 2022;11:11. Published 2022 Apr 28. doi:10.12703/r/11-11
2. Shah NR, Jones JB, Aperi J, Shemtov R, Karne A, Borenstein J. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis. Obstet Gynecol. 2008;111(5):1175-1182. doi:10.1097/AOG.0b013e31816fd73b
3. Marjoribanks J, Brown J, O'Brien PM, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. 2013;2013(6):CD001396. Published 2013 Jun 7. doi:10.1002/14651858.CD001396.pub3
4. Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2012;(2):CD006586. Published 2012 Feb 15. doi:10.1002/14651858.CD006586.pub4
5. Reid RL. When should surgical treatment be considered for premenstrual dysphoric disorder?. Menopause Int. 2012;18(2):77-81. doi:10.1258/mi.2012.012009
Guidelines for Premenstrual Syndrome
The following is a list of professional medical society or government clinical practice guidelines regarding this medical issue (this is not a comprehensive list):
American College of Obstetricians and Gynecologists (ACOG) Clinical Practice Guideline. Management of Premenstrual Disorders. 2023.
Key Points
Symptoms of premenstrual syndrome (PMS) can be nonspecific and vary across patients.
Diagnose PMS based on symptoms alone.
If symptoms seem severe and disabling, consider premenstrual dysphoric disorder (PMDD), which is often underdiagnosed, and ask patients to record symptoms for ≥ 2 cycles; for a diagnosis of PMDD, clinical criteria must be met.
Usually, treatment is a matter of trying various strategies to identify what helps a particular patient; start with lifestyle modifications, then SSRIs, oral contraceptives, or sometimes cognitive-behavioral therapy.
GnRH agonists and oophorectomy are reserved for severe cases.
Drugs Mentioned In This Article
