Premenstrual Syndrome: Tailoring Treatment

Premenstrual syndrome, commonly referred to as PMS, is a cyclic, multisymptom disorder that is characterized by various physical, behavioral, and emotional symptoms, including irritability, anxiety, depression, breast pain, edema, fatigue, abdominal distention, and headaches.^1-3

The severity of and types of symptoms associated with PMS vary. The majority of the female population reports experiencing some degree of discomfort during their menstrual cycles and at least 1 PMS symptom, but some females experience severe symptoms that negatively interfere with their overall quality of life.^1,2

PMS occurs during the luteal phase of a female’s menstrual cycle, followed by a resolution of symptoms within the first few days after the onset of menstrual bleeding.^1,2 The exact cause of PMS is unknown; however, normal ovarian function and fluctuations in estrogen and progesterone levels are thought to be potential triggers of symptoms commonly associated with PMS.^1,2,4 Factors that have been identified as contributors to PMS symptoms include genetics, stress, prior traumatic events, and sociocultural factors.^1-8 Results from various clinical studies suggest that chemical changes in the brain may be involved, as well.^1-7,9 Other theories suggest that PMS may be caused by multiple endocrine factors, including hypoglycemia, changes in carbohydrate metabolism, hyperprolactinemia, fluctuations in levels of circulating estrogen and progesterone, abnormal responses to estrogen and progesterone, and excessive aldosterone.^9,10

An estimated 60% to 80% of women report their PMS symptoms as mild and not interfering with their lives, 20% to 25% describe their symptoms as clinically significant, and 3% to 8% perceive their symptoms as having a considerable negative impact on their overall quality of life, including work, relationships, and daily routine.^1,6,11,12 Premenstrual dysphoric disorder (PMDD) is a severe form of PMS experienced by an estimated 2% to 8% of females.^1-5 Patients exhibiting severe PMS or PMDD symptoms should be encouraged to seek further medical evaluation and treatment. PMS symptoms may change as a woman approaches menopause, but studies show that women who experience PMS symptoms are at greater risk for menopausal symptoms.^13,14

Symptoms

PMS symptoms vary from female to female, but they are typically consistent for an individual patient each month (Online Table 1^1-11).^1,7,11 In general, the majority of females experience mild physical symptoms, food cravings, or mood changes, which are considered to be normal signs of the ovulatory cycle. PMS, however, is defined as having at least 1 mood or physical symptom during the 5 days prior to menses.^1-7 The number of and severity of symptoms, as well as the impact on overall well-being, can assist health care providers in ascertaining whether a patient has typical PMS symptoms or PMDD.¹

Table 1: Common PMS Symptoms

• Headache or backache

• Bloating/weight gain

• Abdominal pain, diarrhea, constipation

• Joint or muscle pain

• Breast tenderness

• Swelling of the ankles, feet, and hands

• Fatigue

• Acne

• Mood swings/irritability

• Appetite changes or cravings

• Difficulty/trouble concentrating or memory issues

• Depression/anxiety

• Insomnia

^{Adapted from references 1-11.}

The symptoms commonly associated with PMS manifest about 7 days before onset of menses, peak 2 days before menses, and usually cease upon initiation of menses or shortly thereafter.^1-7 Common physical PMS symptoms include bloating/ weight gain/swelling and breast tenderness. ^1-7,9 Symptoms such as fatigue, anxiety, insomnia, and irritability are also common.^1-11 Depressive and anxiety disorders are the most common conditions that overlap with PMS.¹¹ According to the American College of Obstetricians and Gynecologists, while the symptoms of depression and anxiety are comparable to the emotional symptoms of PMS, depression and anxiety symptoms are present all month.¹¹ An estimated 50% of females seeking treatment for PMS have one of these disorders.¹¹

Treatment

Women with mild to moderate PMS symptoms typically do not require pharmacologic treatment.¹ However, results from a survey show that an estimated 80% of women use some type of nonprescription product for symptomatic relief, including mineral supplements, vitamins, analgesics, and herbs.¹ Treatment should be tailored to meet the specific needs of each patient, which may entail a combination of therapies since a singleentity agent is unlikely to address all the symptoms.¹

Many experts recommend the implementation of nonpharmacologic measures as first-line therapy, including lifestyle and dietary modifications, regular exercise, and stress-reduction techniques.^1-3,10,11 During the premenstrual phase of a cycle, decreasing or eliminating intake of caffeine, salt, and alcoholic beverages, along with eating foods rich in complex carbohydrates and low in protein, may also decrease the incidence of symptoms.^1,2,4,10,11 Results from clinical studies show that females who exercise regularly may experience PMS symptoms less often and that are milder compared with females who do not exercise.^1,2,4,10,11

Various nonprescription products are marketed for females to manage mild to moderate PMS symptoms (Online Table 2). Nonprescription agents include nonsteroidal anti-inflammatory drugs (NSAIDs), diuretics, vitamins, minerals, and herbal products that contain evening primrose oil, chasten berry, or black cohosh.¹ Combination products are also available, including Midol and Pamprin, which contain an analgesic (acetaminophen), a diuretic (pamabrom), and an antihistamine (pyrilamine maleate).¹ During counseling, pharmacists should advise patients of the potential for drowsiness associated with the use of combination products containing antihistamines.¹

Table 2: Examples of Nonprescription Combination Menstrual Products

Brand Name

Active Ingredients

Excedrin Menstrual Complete

Acetaminophen 250 mg

Aspirin 250 mg

Caffeine 65 mg

Midol Maximum Strength Menstrual Complete

Acetaminophen 500 mg

Caffeine 60 mg

Pyrilamine Maleate 15 mg

Menstridol (formerly Midol Extended Relief Menstrual Complete)

Naproxen sodium 220 mg

Midol PM

APAP 500 mg

Diphenhydramine citrate 38 mg

Midol Teen

Acetaminophen 325 mg

Caffeine 60 mg

Pyrilamine maleate 15 mg

Pamprin Multi-symptom Caplets

Acetaminophen 500 mg

Pamabrom 25 mg

Pyrilamine maleate 15 mg

Premsyn PMS Maximum Strength Premenstrual Relief

Acetaminophen 500 mg

Pamabrom 25 mg

Pyrilamine maleate 15 mg

Diurex Max Water Caplets

Pamabrom 50 mg

Diurex Water Caps

Caffeine Anhydrous 200 mg

The FDA has approved 3 nonprescription diuretics for the relief of water retention, bloating, weight gain, and swelling: ammonium chloride, caffeine, and pamabrom.¹ Pamabrom is the diuretic most commonly found in nonprescription menstrual products.¹ Patients with a history of peptic ulcer disease or anxiety/ insomnia disorders should not use products containing caffeine or pamabron.¹ In addition, the use of ammonium chloride is contraindicated in individuals with renal or hepatic impairment due to the possibility of metabolic acidosis.¹ Patients taking monoamine oxidase inhibitors or theophylline should avoid the use of diuretics containing caffeine.¹

NSAIDs

Analgesics, such as NSAIDs, have been shown to provide relief for the physical symptoms of PMS, such as headache, cramps, and/or pain, when taken several days prior to and during the first days of menses.¹ Patients should be advised to only take the recommended dose and be aware of the adverse effects.¹

Magnesium

Theories suggest that a magnesium deficiency may lead to symptoms of irritability associated with PMS.^1,15 Results from 1 clinical study demonstrated that a 360-mg daily dose of magnesium taken during the luteal phase may provide some relief of PMS symptoms.^1,15 It is important to remind patients to take this 360-mg dose daily during the premenstrual phase only, as magnesium may cause diarrhea in some patients.^1,15

Pyridoxine (Vitamin B₆)

Vitamin B₆ has also been used for treating such PMS symptoms as irritability, fatigue, bloating, and depression.^1,4,15 Studies have shown that a dose of 80 mg per day improved mood and anxiety levels in study subjects compared with the placebo group.^1,4,15 Recommended doses should be limited to 100 mg daily to reduce the incidence of neuropathy.¹

Calcium and Vitamin D

Although studies suggest that blood calcium and vitamin D levels are lower in women with PMS and that calcium supplementation may decrease symptom severity, it is unclear whether these nutrients may prevent the initial development of PMS.¹⁶ In 1 study, the effect of a calcium dose of 600 mg twice a day was studied in females with moderate to severe PMS.^1,17 According to the results, emotional and behavioral symptoms (mood swings, food cravings, depression, anger) and physical symptoms (breast tenderness, backaches, abdominal cramping, fluid retention) were all reduced.^1,17 Results from another study showed that high dietary intake of both calcium and vitamin D may prevent the development of PMS symptoms.¹ Patients should be advised to take 1200 mg daily in divided doses, but no more than 500 mg per dose.^1,17 Since calcium may cause gastric upset or constipation, it should be taken with food.¹ Patients should be advised to also take at least 600 IU of vitamin D per day.¹

Conclusion

Prior to recommending any of these products to manage PMS symptoms, pharmacists should screen for possible drug—drug interactions and contraindications. The treatment and management of PMS should be individualized and tailored according to the severity of a patient’s symptoms, medical history, allergy history, and current medication profile, including alternative medications. Patients should avoid the use of unnecessary of medications and only use products to treat their specific symptoms.

Patients experiencing severe symptoms or not achieving relief from nonprescription treatment should always be referred to their primary health care provider for further evaluation and treatment. In addition, patients with preexisting medical conditions and lactating females should always seek counsel from their primary health care provider before taking any of these products, even natural or herbal medications. During counseling, pharmacists can further assist patients by recommending nonpharmacologic measures that may prevent or decrease PMS symptoms, such as relaxation techniques, avoiding stress, establishing a daily exercise routine, eating a well-balanced diet, getting sufficient rest, and avoiding or limiting their intake of salt, caffeine, or alcohol before their cycle.

Table 3: Resources on Premenstrual Syndrome

• United States Department of Health and Human Services: Office of Women’s Health: http://womenshealth.gov/publications/our-publications/fact-sheet/premenstrual-syndrome.html?from=AtoZ

• American College of Obstetricians and Gynecologists: www.acog.org/Patients/FAQs/Premenstrual-Syndrome-PMS

• The Hormone Foundation website: www.hormone.org/questions-and-answers/2010/premenstrual-syndrome-and-premenstrual-dysphoric-disorder

• Mayo Clinic website: www.mayoclinic.org/diseases-conditions/premenstrual-syndrome/basics/definition/con-20020003

Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia.

References

• Shrimp L. Disorders related to menstruation. In: Krinsky D, Berardi R, Ferreri S, et al, eds. Handbook of Nonprescription Drugs. 18th ed. Washington, DC: American Pharmacists Association; 2015.
• Raines K. Diagnosing premenstrual syndrome. Medscape website. www.medscape.com/viewarticle/718973.
• Alba P. Rodriguez C. Premenstrual syndrome and dysphoric premenstrual syndrome. Vertex. 2014; 25(117):370-376.
• Campagne DM, Campagne G. The premenstrual syndrome revisited. Eur J Obstet Gynecol Reprod Biol. 2007;130(1):4-17.
• Vigod SN, Ross LE, Steiner M. Understanding and premenstrual dysphoric disorder; an update for the women’s health practitioner. Obstet Gynecol Clin North Am. 2009;36(4):907-924. doi: 10.1016/j.ogc.2009.10.010.
• Jarvis CI, Lynch AM, Morin AK. Management strategies for premenstrual syndrome/premenstrual dysphoric disorder. Ann Pharmacother. 2008;42(7):967-978. doi: 10.1345/aph.1K673.
• Johnson SR. Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a clinical primer for practitioners. Obstet Gynecol. 2004;104(4):845-859.
• Premenstrual syndrome fact sheet. Office on Women’s Health website. www.womenshealth.gov/publications/our-publications/fact-sheet/premenstrual-syndrome.html?from=AtoZ. Updated December 23, 2013.
• Premenstrual syndrome. Medline Plus website. www.nlm.nih.gov/medlineplus/ency/article/001505.htm. Updated June 11, 2014.
• Premenstrual syndrome (PMS). Merck Manuals website. www.merckmanuals.com/professional/gynecology_and_obstetrics/menstrual_abnormalities/premenstrual_syndrome_pms.html. Updated October 2013.
• Premenstrual syndrome. The American College of Obstetricians and Gynecologists website. www.acog.org/~/media/For%20Patients/faq057.pdf?dmc=1&ts=20120413T1431137968.
• Rapkin AJ, Mikacich JA. Premenstrual syndrome and premenstrual dysphoric disorder in adolescents. Curr Opin Obstet Gynecol. 2008;20(5):455-463. doi: 10.1097/GCO.0b013e3283094b79.
• Freeman EW, Sammel MD, Rinaudo PJ, Sheng L. Premenstrual syndrome as a predictor of menopausal symptoms. Obstet Gynecol. 2004;103(5 pt 1):960-966.
• Biggs W, Demuth R. Premenstrual syndrome and premenstrual dysphoric disorder.American Family Physician's website. www.aafp.org/afp/2011/1015/p918.html#afp20111015p918-b11.
• Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol. 2009;16(3):e407-429.
• Bertone-Johnson ER, Hankinson SE, Bendich A, Johnson SR, Willett WC, Manson JE. Calcium and vitamin D intake and risk of incident premenstrual syndrome. Arch Intern Med. 2005;165(11):1246-1252.
• Thys-Jacobs S, Starkey P, Bernstein D, Tian J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol. 1998;179(2):444-452.