US Pharm. 2013;38(9):23-26.
ABSTRACT: Primary dysmenorrhea is the most common menstrual
complaint, and it is frequently self-treated by patients of all ages.
Teenagers are especially prone to experiencing dysmenorrhea symptoms and
selecting OTC therapies without adult supervision. Nonsteroidal
anti-inflammatory drugs and combined oral contraceptives represent
first-line therapy for dysmenorrhea pain, but several dietary and herbal
supplements also show promise. When possible, pharmacists should
educate patients regarding proper drug selection and dosing in order to
optimize patient outcomes.
Dysmenorrhea is the most common menstrual complaint in the United
States, impacting more than 50% of women over the course of their
lifetime.1 Primary dysmenorrhea is specifically defined as recurrent, crampy abdominal pain that occurs in the absence of abnormal pelvic pathology.2,3 Incidence of primary dysmenorrhea is highest during the teenage years, with 60% to 90% of this population reporting symptoms.4-6
It is estimated that 14% of teenagers with symptoms miss school because
of pain, and the percentage increases to 50% if pain is severe.7
Other risk factors for primary dysmenorrhea include heavy or prolonged
menstrual flow, family history of dysmenorrhea, smoking, nulliparity,
and lower socioeconomic status.2,3
Despite reports that upward of 90% of teenagers self-treat primary
dysmenorrhea, studies of United States and Canadian adolescents revealed
that only 14% to 16% sought advice from a physician prior to
self-treatment.5,7-9 In fact, 78% reported no adult
supervision in choosing medication, instead relying on what was
conveniently available in the medicine cabinet at home or on advice from
friends.9 Furthermore, 53% were unsure of correct dosing for the OTC medications used to treat primary dysmenorrhea.6,8
At least 70% took their medications incorrectly with regard to dosage
and/or dosing frequency, with the most frequent errors being ingestion
of single doses that were larger than recommended or dosing intervals
that were less frequent than recommended.6,8 Polypharmacy was
also common, with 31% reporting use of two concurrent OTC medications
and 15% reporting use of three or more medications.8
Because of the high incidence of primary dysmenorrhea in the
adolescent population and the tendency of teenagers to self-treat the
condition without adult supervision, pharmacists are uniquely positioned
to offer care and advice to these patients at the time OTC medications
DIAGNOSIS AND PATHOPHYSIOLOGY
Dysmenorrhea typically presents as crampy pain along the midline of the lower abdomen.3,4 Pain may be accompanied by complaints of diarrhea, nausea, vomiting, fatigue, dizziness, headache, and backache.3,4
Primary dysmenorrhea symptoms first present just after a stable
menstrual cycle has been established; accordingly, any patient
experiencing pain prior to or within the first 6 months of menarche
should be referred for further evaluation. The same is true for patients
presenting with first-time pain after several years of asymptomatic
The patient with primary dysmenorrhea generally experiences reproducible symptoms from cycle to cycle.3 Symptoms typically start several hours before the menstrual flow begins.3,4
Pain severity peaks at the time of maximal menstrual flow (usually
within first 2 days of menses) and quickly dissipates thereafter.3 Therefore, total pain duration usually ranges from 12 to 72 hours.3,4
Assuming that the patient presents with this typical pattern of
symptoms, practice guidelines indicate that formal medical evaluation
and pelvic examination are not needed for diagnosis.3
However, patients should be referred for assessment should symptoms
occur outside this normal pattern or when symptoms do not respond to
first-line OTC therapies.3 In such cases, the physician
should conduct a history and physical examination in order to determine
potential secondary causes of dysmenorrhea, the most common of which is
The pain of primary dysmenorrhea is caused by excessive prostaglandin (PG) production within secretory endometrial cells.2,4,10 This PG release, in turn, causes uterine contractions, uterine muscle ischemia, and increased peripheral nerve sensitivity.2,4,10
The therapeutic objective for treating primary dysmenorrhea is
reduction of pain so that the patient can participate in usual
activities of daily living without limitation. Common nonpharmacologic
strategies include hot baths, heating pads, and exercise.8 Unfortunately, data supporting these methods are lacking, and drug therapy is often necessary.11-13
Drug treatments generally target inhibition of PG synthesis or
reduction in the number of endometrial cells present at the time of
First-line therapies for primary dysmenorrhea generally involve
nonsteroidal anti-inflammatory drugs (NSAIDs) or hormonal contraception.
No studies have directly compared the two methods; thus, no conclusions
may be reached regarding preferential selection between these two
options based on efficacy alone.
NSAIDs: Simple analgesics (specifically NSAIDs)
reduce primary dysmenorrhea pain via inhibition of PG synthesis and have
been the mainstay of therapy for decades. Simple analgesics are most
commonly used as self-treatment by adolescents, with acetaminophen,
aspirin, ibuprofen, and naproxen being reported most often.6,8,9
These drugs may be coadministered with antihistamines or diuretics
(e.g., pyrilamine or pamabrom) because of coformulation within many
available OTC products; however, there are no studies demonstrating that
these added ingredients improve patient response. Unfortunately, some
of these medications are not effective for dysmenorrhea (see discussion
below) or are contraindicated for use in children and adolescents
A systematic review of 73 randomized, controlled trials concluded
that NSAIDs were superior to placebo for treatment of primary
dysmenorrhea pain and reduced the number of days absent from school and
work.14 It should be noted that these effectiveness data did not apply to aspirin or acetaminophen.14
Numerous NSAIDs have been studied for this indication, but no
literature exists to indicate the effectiveness of any one agent over
another.14 Consequently, NSAID choice is best guided by cost
and availability. Most patients will be candidates for NSAID therapy,
unless use is precluded by allergy or pre-existing gastrointestinal (GI)
or renal issues.
Patients should generally be advised to begin NSAID therapy just
prior to the start of menses and to continue dosing on a scheduled basis
for 2 to 3 days following the onset of each cycle.2 Despite
these recommendations, the average time to first dose is 30 minutes
after the onset of pain for most teenagers, with only 16% taking the
medications prophylactically.6 Therefore, education regarding
proper dosing may help improve patient outcomes. Average study dosages
for drugs available in the United States appear in TABLE 1.
Although typical NSAID side effects such as GI upset and drowsiness were
reported more often than placebo in controlled trials, incidence did
not reach statistical significance, which was likely due in part to the
short-term duration of therapy for the primary dysmenorrhea indication.14
Hormonal Contraception: Although NSAIDs provide
pain relief for a large percentage of patients with primary
dysmenorrhea, 20% to 25% will fail this therapy.14 When
NSAIDs fail or are contraindicated, or when contraception is desired,
hormonal contraception is a viable and effective method for treating
primary dysmenorrhea. Hormonal contraceptives treat primary dysmenorrhea
by causing regression of the endometrium, shortening the time of
endometrial proliferation, and limiting the secretory activity of
endometrial glands. The most commonly studied hormonal contraceptive
method for this indication is the combined oral contraceptive (COC)
pill, but other methods, including the contraceptive patch,
contraceptive ring, medroxyprogesterone injection, and
levonorgestrel-releasing intrauterine system, are also endorsed by
practice guidelines because of their similar mechanisms of action.3
A systematic review of 10 randomized, controlled trials concluded
that low- to medium-dose (i.e., 20-35 mcg ethinyl estradiol) COCs are
superior to placebo for treatment of primary dysmenorrhea pain and
reduce the number of days absent from school and work.15 One
study in this review also suggested that third-generation pills
(containing desogestrel, etonogestrel, and norgestimate) may be more
effective than second-generation pills (containing levonorgestrel and
norethindrone) in providing pain relief, but this finding was not
observed in the other studies comparing third-generation pills with
first- and second-generation pills.15 Not surprisingly, COCs
were more likely than placebo to cause nausea, headache, and weight
gain, but withdrawal from therapy did not differ between groups.15
It must be remembered that rare side effects of hormonal contraception
include vascular events such as venous thromboembolism, myocardial
infarction, and stroke; thus, patients must be screened for additive
risk factors before beginning therapy. For information about conditions
that preclude use of hormonal contraception, see the CDC’s report, “U.S.
Medical Eligibility Criteria for Contraceptive Use, 2010”
Traditional dosing strategies for COCs utilize placebo pills to
stimulate a chemical withdrawal bleed. This withdrawal bleed may still
produce PGs and pain, so continuous-dosing contraceptive strategies have
been studied as a way to improve response rates. In a small study of 38
patients, a low-dose monophasic COC was randomly dosed in a traditional
21-day hormone/7-day placebo pattern (usual dosing) or a 28-day hormone
pattern (continuous dosing).16 Reported pain relief was
statistically greater in the continuous-dosing versus usual-dosing group
1 month after starting therapy, but both dosing strategies showed
equivalent reductions in pain after 6 months of therapy.16
This finding may be explained by the fact that several COC cycles are
required to achieve maximal endometrial regression. Thus, continuous
dosing may perhaps be best recommended at the start of therapy, with
long-term continuation if the patient prefers not to experience
withdrawal bleeding. Patients selecting continuous-dosing methods may be
more likely to experience breakthrough spotting than those using more
traditional dosing methods, but the continuous-dosing method is
otherwise safe for long-term use.15
Upon initiation of hormonal contraception, patients should be
cautioned that breakthrough bleeding and spotting might be common during
the first two to three cycles of use. They should also be advised that
maximal dysmenorrhea pain relief might not be experienced for a few
months, although some relief likely will be noted in the first or second
cycle. As with all hormonal contraception, patients should be cautioned
to immediately discontinue use and contact a physician should any signs
or symptoms of vascular events occur. It may be helpful to teach
patients the mnemonic ACHES: abdominal pain, chest pain, headache,
eye/vision changes, and severe leg pain.
Alternative and Emerging Therapies
Many patients may prefer to use more “natural” methods for treating
dysmenorrhea pain, and the literature supports use of several dietary,
herbal, and alternative medicine methods.
Although a wide variety of herbal and dietary supplements have been
purported to help improve dysmenorrhea pain (including vitamin B1, vitamin B6,
vitamin E, magnesium, and fish oil), systematic reviews have concluded
that the only supplements with any reasonable evidence supporting
effectiveness are vitamin B1 (B1 deficiency is
thought to promote muscle cramping), magnesium (supplementation is
thought to reduce PG levels), and Chinese herbal remedies.17,18 Unfortunately, evidence is less clear regarding optimal dosing and preparation for most of these products. Vitamin B1
(thiamine) dosed at 100 mg orally once daily was used in one large,
well-controlled study; thus, this dosage is the most reasonable to
recommend to most patients.17 The Chinese herbal preparations
that have showed efficacy have generally been multi-ingredient products
that are intended to “regulate Qi and blood,” “reinforce Chi and
blood,” “warm the interior,” or “tonify the kidney and liver.”18
Interestingly, some data suggest that such herbal preparations may even
be superior to NSAIDs and COCs for relieving dysmenorrhea pain, but
larger studies are needed to confirm these trends.18 Despite the overall paucity of large, well-designed studies of vitamin B1,
magnesium, and Chinese herbal preparations for dysmenorrhea, the risk
of side effects from each product is small, and so it may be reasonable
to allow patients to try such remedies, if desired.
More recently, vitamin D supplementation has been studied as a
dysmenorrhea treatment based on the observation that higher vitamin D
levels lead to reductions in PG synthesis.19 In a small,
randomized, placebo-controlled study of patients with baseline 25(OH)D
(25-hydroxyvitamin D) levels less than 45 ng/mL, a single dose of
300,000 IU of vitamin D administered 5 days prior to menses
significantly reduced primary dysmenorrhea pain and reduced the
percentage of patients requiring NSAID rescue therapy.19
Although vitamin D may be a promising therapy for dysmenorrhea, the
unknown impact of such supplementation in patients with more normal
baseline 25(OH)D levels and the lack of knowledge regarding duration of
effect after a single dose (if 300,000 IU were given monthly, this would
far exceed the safe limits set by the Institute of Medicine) suggest
that vitamin D should be further studied for this indication.20
Various acupuncture methods have also been studied as a remedy for
primary dysmenorrhea. Acupuncture is known to increase levels of
endorphins, serotonin, and acetylcholine in the central nervous system.
Systematic reviews have suggested that various acupuncture methods may
be more effective than placebo, herbal remedies, and NSAIDs for treating
dysmenorrhea pain.21,22 Thus, patients interested in nonpharmacologic methods of treatment may want to explore this possible treatment.
Primary dysmenorrhea is a common menstrual complaint that is
frequently self-treated by patients of all ages. Teenagers are
especially likely to experience dysmenorrhea symptoms and to select OTC
therapies without adult supervision. Pharmacists should provide
education to patients regarding proper drug selection and dosing, when
possible, in order to optimize patient outcomes.
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19. Lasco A, Catalano A, Benvenga S. Improvement of primary
dysmenorrhea caused by a single oral dose of vitamin D: results of a
randomized, double-blind, placebo-controlled study. Arch Intern Med. 2012;172:366-367.
20. Bertone-Johnson ER, Manson JE. Vitamin D for menstrual and
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dysmenorrhea caused by a single oral dose of vitamin D.” Arch Intern Med. 2012;172:367-369.
21. Chung YC, Chen HH, Yeh ML. Acupoint stimulation intervention for
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