Dysmenorrhea Medication
- Author: Karim Anton Calis, PharmD, MPH, FASHP, FCCP; Chief Editor: Michel E Rivlin, MD more...
Medication Summary
Treatment of primary dysmenorrhea is directed at providing relief from the cramping pelvic pain and associated symptoms (eg, headache, nausea, vomiting, flushing, diarrhea) that typically accompany or immediately precede the onset of menstrual flow. The pelvic pain can be distressing and occasionally radiates to the back and thighs, often necessitating prompt intervention. To date, pharmacotherapy has been the most reliable and effective treatment for relieving dysmenorrhea. Because the pain results from uterine vasoconstriction, anoxia, and contractions mediated by prostaglandins, symptomatic relief can often be obtained from use of agents that inhibit prostaglandin synthesis and have anti-inflammatory and analgesic properties.
NSAIDs and combination OCs are the most commonly used therapeutic modalities for the management of primary dysmenorrhea. These agents have different mechanisms of action and can be used adjunctively in refractory cases. The lack of response to NSAIDs and OCs (or the combination) may increase the likelihood of a secondary cause for dysmenorrhea.
Other therapies for dysmenorrhea have been proposed, but most are not well studied. These include thiamine, vitamin E, omega-3 fatty acids, magnesium, acupuncture,[42] acupressure, various herbal medicines, transdermal nitroglycerin, calcium-channel blockers, beta-adrenergic agonists, antileukotrienes, and transcutaneous electrical nerve stimulation (TENS) units. Use of topical, continuous, low-level heat may be beneficial for some patients.[43, 44]
Treatment of secondary dysmenorrhea involves correction of the underlying organic cause. Specific measures (medical or surgical) may be required to treat pelvic pathology (eg, endometriosis) and to ameliorate the associated dysmenorrhea. Periodic use of analgesic agents as adjunctive therapy may be beneficial.
Nonsteroidal anti-inflammatory drugs
Class Summary
NSAIDs are the most commonly used treatments for dysmenorrhea. NSAIDs decrease menstrual pain by decreasing intrauterine pressure and lowering PGF2alpha levels in menstrual fluid.[45, 46, 47] Because they are used for short periods in otherwise healthy young women, they are generally well tolerated and free of serious toxicity. Gastrointestinal (GI) upset is the most common adverse effect associated with NSAIDs, and patients receiving these medications should be monitored for more serious adverse effects, including GI bleeding and renal dysfunction.
Patients should also be monitored for potential pharmacokinetic and pharmacodynamic drug interactions and possible effects on platelet aggregation. NSAIDs are contraindicated in patients with renal insufficiency, peptic ulcer disease, gastritis, bleeding diatheses, and aspirin hypersensitivity. These agents must be used on a regular basis (as-needed use is not adequate in most patients) for several days. To avoid inadvertent exposure to these agents during early pregnancy, NSAIDs should be started at the onset of menstrual bleeding.
While some NSAIDs have been touted as being particularly effective for dysmenorrhea (especially the fenamates), scientific data to support such claims are sparse and generally weak.[48] Moreover, well-designed prospective comparative studies have not been performed. Diclofenac, ibuprofen, ketoprofen, meclofenamate, mefenamic acid, and naproxen are the NSAIDs specifically approved by the US Food and Drug Administration (FDA) for treatment of dysmenorrhea. Aspirin may not be as effective as other NSAIDs, and acetaminophen may be a useful adjunct for alleviating only mild menstrual cramping pain.[49, 48]
NSAIDs that achieve peak serum concentrations within 30-60 minutes and have a faster onset of action (eg, ibuprofen, naproxen, meclofenamate) may be preferred. However, individual patient response varies, and patients may need a trial of several agents before finding one that works. Some NSAIDs (eg, indomethacin) should be avoided because they have a higher incidence of adverse effects.
Despite some preliminary data suggesting efficacy in patients with primary dysmenorrhea, the newer cyclooxygenase-2 (COX-2) inhibitors have not been demonstrably superior to conventional NSAIDs.[50] However, these agents may be used in patients who cannot tolerate other NSAIDS or in whom these agents are contraindicated. COX-2–derived prostanoids nonetheless appear to be involved in the pathophysiology of primary dysmenorrhea.[51]
NSAIDs that inhibit type I prostaglandin synthetase and suppress the production of cyclic endoperoxides (eg, fenamates, COX-2–selective agents, propionic acids, indole acetic acids) alleviate dysmenorrhea symptoms by decreasing endometrial and menstrual fluid prostaglandin concentrations.
Naproxen (Naprosyn, Aleve, Anaprox)
Available in both prescription and nonprescription doses. Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis.
Ibuprofen (Advil, Motrin, Nuprin)
Available in both prescription and nonprescription doses. Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis.
Diclofenac (Cataflam, Voltaren)
Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis.
Ketoprofen (Orudis, Actron, Oruvail)
Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in the decrease of prostaglandin synthesis. Smaller initial dosages are particularly indicated in the elderly and in those with renal or liver dysfunction. Doses greater than 75 mg do not improve therapeutic response and may be associated with a higher incidence of adverse effects.
Meclofenamate
Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis. Higher incidence of diarrhea compared with other NSAIDS.
Mefenamic acid (Ponstel)
Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis. Higher incidence of diarrhea compared to other NSAIDS.
Contraceptives
Class Summary
Dysmenorrhea can be prevented altogether in some patients by use of OCs, although these agents are not approved by the FDA for this indication. OCs may be an appropriate treatment choice in patients who do not wish to conceive. The combination OCs suppress the hypothalamic-pituitary-ovarian axis and thereby inhibit ovulation and prevent prostaglandin production in the late luteal phase. This generally significantly reduces the amount of menstrual flow and effectively alleviates primary dysmenorrhea in most patients. Use of OCs in a manner that reduces the number of menstrual cycles (by extending the use of active pills and avoiding the pill-free week or with extended-cycle formulations) may be beneficial for some patients.[52, 53]
Combination OCs, the levonorgestrel intrauterine device, and depot medroxyprogesterone acetate provide effective pain relief and are associated with a reduced menstrual flow. The use of NSAIDs in combination with an OC may be necessary, especially during the first few cycles after initiation of the OC. The dose of ethinyl estradiol should generally be less than 50 mcg. A monophasic OC containing 30 mcg of ethinyl estradiol is a reasonable choice. To date, studies comparing the efficacy of various OC formulations in the management of dysmenorrhea have not been performed.
Medroxyprogesterone (DMPA; DepoProvera)
Inhibits secretion of gonadotropins, thereby inhibiting ovulation and decreasing thickness of endometrium.
Levonorgestrel-releasing intrauterine device (Mirena)
Inhibits secretion of gonadotropins, thereby inhibiting ovulation and decreasing thickness of endometrium.
Ethinyl estradiol and gonane progestin (norgestimate, norgestrel, levonorgestrel, or desogestrel) (Ortho-Cyclen, Ovral, Lo-Ovral, Alesse, Levlen, Levlite, Nordette, Desogen, Ortho-Cept)
Reduces secretion of LH and FSH from pituitary by decreasing amount of gonadotropin-releasing hormones.
Ethinyl estradiol and estrane progestin (norethindrone or ethynodiol acetate) (Ortho-Novum, Ovcon 50, Ortho-Novum 7/7/7, Brevicon, LoEstrin, Modicon, Tri-Norinyl, Demulen, Zovia)
Reduces secretion of LH and FSH from pituitary by decreasing amount of gonadotropin-releasing hormones.
Ethinyl estradiol and drospirenone (Yasmin, YAZ)
Reduces secretion of LH and FSH from pituitary by decreasing amount of gonadotropin-releasing hormones.
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