Dysmenorrhea - GLOWM

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This chapter should be cited as follows:

Dawood, Y, Glob. libr. women's med.,
(ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10009
This chapter was last updated:

June 2008
Dysmenorrhea
Yusoff M. Dawood, MB ChB, MMed, MD
Department of Obstetrics and Gynecology, Baystate Medical Center, Tufts University School of Medicine, Springfield,
Massachusetts, USA
INTRODUCTION
INCIDENCE
PRIMARY DYSMENORRHEA
SECONDARY DYSMENORRHEA
REFERENCES
INTRODUCTION
Dysmenorrhea, one of the most frequently encountered gynecologic disorders, refers to painful menstruation.
Dysmenorrhea is classified as primary or secondary dysmenorrhea.1, 2, 3, 4, 5, 6 Primary dysmenorrhea is defined
as painful menstrual cramps in the absence of any visible pelvic pathology that could account for it. In secondary
dysmenorrhea, the painful menstruation is accompanied by visible pelvic pathology that accounts for the pain.
Such a classification allows practical differentiation in the management approach, which is based on the causal
mechanism.
INCIDENCE
More than 50% of postpubescent menstruating women are affected by dysmenorrhea, with 10–12% of them
having severe dysmenorrhea with incapacitation for 1–3 days each month.6, 7, 8 Because young women
constitute a significant percentage of the adult work force in the United States, about 600 million working hours
or 2 billion dollars are lost annually because of incapacitating dysmenorrhea if adequate relief is not provided.
Women who continue to work or to attend classes have been shown to have lower work output or scores during
their dysmenorrhea.9, 10
Dysmenorrhea is most common in women between the ages of 20 and 24 years, with most of the severe episodes
occurring before 25 years of age.11 Primary dysmenorrhea also occurs more frequently in unmarried women than
in married women (61% vs. 51%), decreases with age, and does not appear to be related to the type of occupation
or physical condition of the woman. Pregnancy and vaginal delivery do not necessarily relieve primary
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dysmenorrhea. Exercise does not appear to have any significant effect on the incidence of dysmenorrhea.
Associated factors that increase the risk duration and severity of dysmenorrhea include early menarche, long
menstrual periods, overweight, and smoking.12
PRIMARY DYSMENORRHEA
Usually appearing within 6–12 months after the menarche, primary dysmenorrhea occurs almost invariably in
ovulatory cycles. About 88% of adolescents with dysmenorrhea experience their first painful menstruation
within the first 2 years after menarche.13 Dysmenorrhea occurring more than 2 years after the menarche is more
likely to be secondary dysmenorrhea, and the underlying cause should be vigorously sought. Primary
dysmenorrhea usually begins a few hours before or just after the onset of menstruation. The cramps are most
severe on the first or second day of menstruation. Characteristically, the pains are spasmodic in nature and
strongest over the lower abdomen, but they may also radiate to the back and the inner aspects of the thigh, and
they are often described as labor-like pains. The cramp is commonly accompanied by one or more systemic
symptoms, including nausea and vomiting (89%), fatigue (85%), diarrhea (60%), lower backache (60%), and
headache (45%). Nervousness, dizziness, and in some severe cases, syncope and collapse can be associated with
primary dysmenorrhea. Lasting a few hours to 1 day, the symptoms seldom persist for more than 2–3 days.
Primary dysmenorrhea should be diagnosed by its positive clinical features and not through exclusion of other
causes of dysmenorrhea. The hallmarks of primary dysmenorrhea are:
1. Initial onset of primary dysmenorrhea. The condition should have begun within a few months and at the
very most within 2 years of menarche. Despite such fairly rigid criteria, a diagnosis of endometriosis can
be extremely difficult to exclude because endometriosis-related dysmenorrhea has a remarkable
resemblance to primary dysmenorrhea. Typically, the dysmenorrhea of endometriosis in adolescents
begins at 2.9 years after menarche.14
2. Duration of the cramps. The cramps seldom last more than 48–72 hours. Usually the pain lasts only 24
hours or less. The pain also starts a few hours before, or more frequently, only after the onset of the
menstrual flow. Dysmenorrhea, which starts before the onset of menstrual flow and extends into several
days throughout the flow, is less likely to be primary dysmenorrhea.
3. Character of the pain. This is described as cramping or labor-like pain.
4. Pelvic examination. No abnormal findings that could account for the primary dysmenorrhea should be
found during the examination (including rectovaginal).
Etiology
Behavioral and psychologic factors, uterine ischemia, cervical stenosis or narrowing, increased vasopressin
release, increased uterine activity, and increased uterine prostanoid production and release have been implicated
in the cause of primary dysmenorrhea. Evidence suggests that most women with primary dysmenorrhea have
increased or abnormal uterine prostanoid production and release, giving rise to abnormal uterine activity and
therefore to pain.15, 16, 17, 18, 19, 20
Although psychologic factors have not been demonstrated convincingly to be the cause of primary
dysmenorrhea, their contribution should be considered in patients who have not responded to medical therapy
and in the absence of any visible pelvic pathology to account for the pain. Whereas many psychoanalytic
formulations have been advanced to explain the basis of dysmenorrhea, none of these reports studied the
patients before the development of the dysmenorrhea.7 Such observations may be an accompaniment or the
result of the dysmenorrhea but do not generate primary dysmenorrhea.7 Psychologic factors can certainly
influence the reactive component of pain and therefore the perception of apparent increased intensity of pain.
Anticipation of severe dysmenorrhea each month can itself be expected to engender quite a bit of stress.
Dysmenorrhea is more common in working women and in women who scored higher on the Hassle scale, which
is a measure of the stresses or difficulties experienced.7 Such a stressful event as dysmenorrhea has been
demonstrated to reduce the immune response of the woman on day 26 and days 1 and 2 of the cycle.21 Primary
dysmenorrhea itself is not a psychologic disorder, but in its management, the health care provider can enhance
the overall efficacy of pharmacotherapy with appropriate handling of the reactive component of pain.
Traditionally, cervical dilatation has been performed to relieve primary dysmenorrhea on the basis that the
cervical canal is widened. However, there are no objective data to support the suggestion that women in primary
dysmenorrhea have a relative stenosis or narrowing of the cervical canal. In a small number of women who do
have true cervical stenosis associated with menstrual cramps, the condition is secondary dysmenorrhea.
Primary dysmenorrhea occurs only in ovulatory cycles.15, 17 Dysmenorrhea occurring in anovulatory cycles is of
the secondary type. Primary dysmenorrhea can be readily relieved with administration of oral contraceptive pills,
which inhibit ovulation. Some preliminary studies suggest that there may be an increase in circulating
vasopressin levels in women with dysmenorrhea during their menstruation.22 However, serial levels before and
during menstruation have not been studied adequately. An increase in vasopressin levels, without an
accompanying increase in oxytocin levels, can produce dysrhythmic uterine contractions that are more likely to
produce uterine hypoxia and ischemia. Using these observations, a preliminary study indicates that the
vasopressin antagonist is able to inhibit abnormal uterine contractions and relieve primary dysmenorrhea.23
There is ample evidence to indicate that increased or abnormal production and release of endometrial
prostanoids and eicosanoids in many women with primary dysmenorrhea give rise to abnormal uterine activity
and result in uterine hypoxia and ischemia.15, 16, 17, 18, 19, 20 First, there is a striking similarity between the
clinical manifestations of primary dysmenorrhea and the symptoms induced when exogenous prostaglandins E2
or F2α are administered. In both situations, uterine contractions occur, and diarrhea, vomiting, and nausea are
common. Second, measurements of prostaglandin levels from luteal-phase endometrial biopsies, endometrial jet
washings, and menstrual fluids have shown that there is a significantly higher than normal concentration of
prostaglandins in women with painful primary dysmenorrhea. Secretory endometrium, under the influence of
progesterone, has higher concentrations of prostaglandins than proliferative endometrium and with no increase
in endometrial prostaglandin concentrations reported from endometrium of anovulatory cycles. Many
nonsteroidal antiinflammatory drugs that are prostaglandin synthetase inhibitors have been shown to be
effective in the treatment of primary dysmenorrhea. With some of these prostaglandin synthetase inhibitors,
there are also objective data showing that the relief of primary dysmenorrhea is caused by and accompanied by a
concomitant reduction in uterine prostaglandins released during menstruation.
In normal women with no dysmenorrhea, there are fluctuations in uterine activity during different phases of the
menstrual cycle. These changes in the resting tone, active pressure, and frequency of contractions are caused by
changes in ovarian steroid hormone levels that affect the sensitivity of the myometrium to uterotonic substances,
changing concentrations of prostaglandins in the endometrium, and other uterotonic substances that may still be
undefined. During menstruation in the nondysmenorrheic woman, the uterine resting tone is lowest (<10
mmHg), the active pressure is maximum (120 mmHg), and the number of contractions (3–4 per 10 minutes) is
least, compared with the rest of the cycle.4, 5, 11, 15, 16 In dysmenorrheic women, the increased release of uterine
prostaglandins produces a significant degree of myometrial hyperactivity that results in uterine hypoxia and
ischemia. Four different types of abnormalities of uterine contraction have been observed in women with
primary dysmenorrhea, including increased uterine resting tone, increased active pressure, increased number of
contractions, and incoordinate or dysrhythmic uterine activity. Most patients with primary dysmenorrhea appear
to have increased uterine resting tone. When more than one of these uterine contraction abnormalities are
present, they tend to potentiate each other, and pain occurs with a much smaller change in the abnormality than
when only one is present. When the uterine activity is abnormal and increased, uterine blood flow has been
shown to be reduced. With suppression of the abnormal activity, the uterine blood flow is enhanced and
symptoms disappear. One mechanism contributing to the pain of primary dysmenorrhea is uterine ischemia or
uterine hypoxia.
For a better understanding of the pathophysiology of primary dysmenorrhea and the mechanism of action of the
nonsteroidal antiinflammatory drugs in the relief of this condition, it is essential to examine the biosynthesis of
eicosanoids. Prostaglandins are C20 hydrocarbons with a cyclopentene ring and are present in most mammalian
tissues, where they are produced locally under the control of microsomal enzymes collectively called
prostaglandin synthetase. The pathway for the biosynthesis of prostaglandins, including prostacyclin and
thromboxanes, is shown in Figure 1. Synthesized from free and unsaturated fatty acids, such as arachidonic acid
and eicosatrienoic acid, which are often derived from conversion of phospholipids, triglycerides, and cholesterol
esters by the enzyme acyl hydrolase, prostaglandins are produced under the influence of cyclooxygenase (COX),
isomerase, and reductase, which are collectively referred to as prostaglandin synthetase.17 There are two
isoforms of COX, COX-1 and COX-2, which are encoded by distinct genes.24, 25 The gene for COX-1, which is
constitutive and is a housekeeping enzyme, is located on chromosome 9.25 COX-2, which is inducible, is
responsible for changes in prostaglandin production and is encoded by a gene on chromosome 1.25 Availability
of arachidonic acid, endometrial cellular trauma, and availability and inducibility of COX, are important factors
that stimulate prostaglandin production. In uterine tissues, arachidonic acid is usually produced from
phospholipids through hydrolysis by the lysosomal enzyme phospholipase A2. Because this enzyme regulates the
hydrolysis of phospholipids, phospholipase A2, rather than arachidonic acid availability, may be the more
important rate-limiting factor in the biosynthesis of prostaglandins.
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/001f.gif) Fig. 1. Schematic representation of

the pathway for the biosynthesis of prostaglandins and related compounds by means of the arachidonic acid
cascade from phospholipids. (Dawood MY: Hormones, prostaglandins, and dysmenorrhea. In Dawood MY
[ed]: Dysmenorrhea, p 21. Baltimore: Williams & Wilkins, 1981)
Progesterone exerts an important control on the stability of lysosomes; a high level of progesterone tends to
stabilize lysosomes, and a declining level of progesterone labilizes it. At the end of the luteal phase of the
menstrual cycle, if pregnancy does not occur, the corpus luteum undergoes regression leading to a decline in
progesterone level and therefore lysosomal instability. Labilization of the lysosome is then accompanied by
menstrual flow, and phospholipase A2 is released, causing hydrolysis of phospholipids from the cell membrane
and generation of arachidonic acid. This continuing availability of increased arachidonic acid together with the
intracellular destruction and trauma accompanying the onset of menstruation stimulates production of
prostaglandins.
In women with primary dysmenorrhea, the endometrial tissues are capable of increased production and the
release of prostaglandins during menstruation. Pickles and his colleagues26 were the first to quantitate
prostaglandins in menstrual fluid and demonstrate that dysmenorrheic women produce 8–13 times more
prostaglandin F than do nondysmenorrheic women. Significantly high quantities of prostaglandins are released
per menstruation in women with primary dysmenorrhea (Fig. 2). Most of the production and release of
prostaglandins occurs during the first 48 hours of menstrual flow, accounting for the intense pain experienced
during the first or second day of menstruation in primary dysmenorrhea. The results of correlation between the
amount of prostaglandins released in the menstrual fluid per hour and the clinical symptoms of the
dysmenorrhea during the first 48 hours of the menstruation are shown in Figure 3. There is excellent correlation
between the amount of prostaglandins released and the intensity of the pain for that duration. Luteal-phase
human endometrium from dysmenorrheic women has been shown in vitro to produce seven times more
prostaglandin F2α than luteal phase endometrium of normal women.27
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/002f.gif) Fig. 2. Menstrual fluid

prostaglandins (PG) in normal subjects, dysmenorrheic women, and dysmenorrheic women treated with oral
contraceptives (OC). (Chan WY, Dawood MY: Prostaglandin levels in menstrual fluid of nondysmenorrheic
and dysmenorrheic subjects with and without oral contraceptive or ibuprofen therapy. Adv Prostaglandin
Thromboxane Leukotriene Res 8:1443, 1980)
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/003f.gif) Fig. 3. Relationship between the

clinical symptoms of primary dysmenorrhea (dysmenorrhea score) and the amound of menstruation in a
dysmenorrheic woman. When the rate of prostaglandin release increased, the clinical symptoms
(dysmenorrhea) increased as well. There is a direct relationship between the clinical symptoms and the
amount of prostaglandin released over the same period of time. (Dawood MY: Hormones, prostaglandins, and
dysmenorrhea. In Dawood MY [ed]: Dysmenorrhea, p 21. Baltimore: Williams & Wilkins, 1981)
Arachidonic acid or eicosatrienoic acid can also be converted through the 5-lipoxygenase pathway (Fig. 1) to 5-
hydroxyperoxyeicosatetraenoic acid (5-HPETE) and leukotrienes (A4, B4, C4, D4). Leukotrienes and 5-HPETE
stimulate uterine contraction. The factors regulating the 5-lipoxygenase pathway in the nonpregnant human
uterus are unknown.
The postulated mechanisms for the generation of pain from pelvic structures in primary dysmenorrhea are
summarized in Figure 4. The increased uterine production and release of prostaglandins at menstruation give
rise to increased abnormal uterine activity, which then causes uterine hypoxia and pain. Increased uterine
activity and uterine ischemia or hypoxia are two major factors in the causation of the pain. Prostaglandins, such
as prostaglandin E2, and cyclic endoperoxides hypersensitize pain fibers in the pelvis and uterus to the action of
pain-inducing substances or factors. This understanding of the pathophysiology of primary dysmenorrhea has
enabled the rational use of nonsteroidal antiinflammatory drugs for the relief of primary dysmenorrhea rather
than pharmacotherapy, which merely inhibits uterine contractions, such as with betamimetic agents.
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/004f.gif) Fig. 4. Mechanism of pain

generation from the pelvic structure in primary dysmenorrhea. (Dawood MY: Hormones, prostaglandins, and
dysmenorrhea. In Dawood MY [ed]: Dysmenorrhea, p 21. Baltimore: Williams & Wilkins, 1981)
The roles of prostanoids, such as thromboxane A2 and prostacyclin, and leukotrienes in primary dysmenorrhea
are not well understood. Preliminary evidence suggests that prostacyclin is involved in the pathophysiology of
primary dysmenorrhea.28 Increased uterine leukotriene may be responsible for some forms of primary
dysmenorrhea29 that do not respond to therapy with NSAIDs, because leukotrienes are produced through the 5-
lipoxygenase enzyme pathway rather than the cyclooxygenase pathway (Fig. 1). Prostacyclin is a potent
vasodilator that relaxes uterine muscle in vitro. A reduction of prostacyclin may potentiate enhancement of
uterine activity and vasoconstriction, which gives rise to hypoxia, ischemia, and pain. In some women with
primary dysmenorrhea, an imbalance in the concentrations of different prostaglandins, rather than absolute
increases or decreases, may be responsible for the pain.
Differential Diagnosis
The differential diagnoses of primary dysmenorrhea include all the causes of secondary dysmenorrhea, such as
endometriosis, presence of an intrauterine device, pelvic inflammatory disease and infections, adenomyosis,
uterine myomas, polyps and adhesions, congenital malformation of the Müllerian system (e.g. bicornuate and
septate uterus, transverse vaginal septum, rudimentary blind uterine horn), cervical strictures or stenosis,
ovarian cysts, pelvic congestion syndrome, and defects in the broad ligament (Allen–Masters syndrome).
Endometriosis must be especially considered as it can mimic primary dysmenorrhea very closely and can begin
with the onset of menarche or shortly thereafter. Pelvic pain and dysmenorrhea due to endometriosis in teenage
women have been shown to occur approximately 2.9 years after the menarche.14 Contrary to conventional
thinking, endometriosis can occur in these teenagers and in black women, as shown with the increasingly
frequent use of laparoscopy. In patients with strong indications for endometriosis, such as those with a familial
history of endometriosis in their sisters or mothers (8% risk), laparoscopy should be undertaken fairly early
during management after medical therapy has failed.
There are no special diagnostic tests to confirm the diagnosis of primary dysmenorrhea. Most of the
investigations that are used are for confirming the presence of lesions responsible for secondary dysmenorrhea.
Management
The overall approach to management should include skillful manipulation of the psychologic and behavioral
factors and the specific pharmacotherapy.1, 2, 3, 4, 16 Careful assessment of the proportion contributed by the
psychologic or reactive component of the pain in dysmenorrhea in each of the patients is essential to appropriate
therapy or a combination of therapies. The efficacy of pharmacotherapy and other forms of therapy can be
greatly enhanced by the simple psychotherapy that accompanies the doctor–patient dialogue, explanation, and
reassurance given by the physician. Various modalities of treatment have been used in the treatment of primary
dysmenorrhea and are summarized in Table 1. The most effective medications are oral contraceptives and the
NSAIDs, which are prostaglandin synthetase inhibitors. The drug of choice for the relief of primary
dysmenorrhea is an effective NSAID. However, the choice of medication depends on whether the woman prefers
an oral contraceptive for her birth control needs and whether there is any contraindication to the use of the
combined oral contraceptive or the NSAID. The choice of medication and the medical management of primary
dysmenorrhea is outlined in the algorithm in Figure 5.
Table1. Modalities available for the treatment of primary dysmenorrhea
Approach Specific methods
General measures Psychotherapy, reassurance
Surgery Dilatation and curettage, presacral neurectomy
Endocrine therapy Oral contraceptive pills, inhibition of ovulation
Tocolysis Alcohol, β-receptor stimulators
Analgesics Nonnarcotics, narcotics
Nerve block or stimulation Alcohol or local anesthetic injection of uterosacral ligaments, transcutaneous
electrical nerve stimulation
Approach Specific methods
Prostaglandin synthetase Cyclooxygenase blockers (indomethacin, ibuprofen, sodium naproxen,

inhibitor flufenamic acid)
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/005f.gif) Fig. 5. Algorithm for the

management of primary dysmenorrhea. The (+ ) symbol indicates the subject wishes to have or has the
condition, a response is positive or favorable, or the condition is present. The (–) symbol indicates the subject
does not wish to have or does not have the condition, the response is negative or poor, or the condition is
absent.
ORAL CONTRACEPTIVES (OCPs)
If the patient desires contraception with the combined oral contraceptive pill, this is the method of choice
because she can also get relief from her primary dysmenorrhea. A Cochrane analysis in 2001 concluded
from four randomized controlled trials that combined oral OCPs with medium-dose estrogen and first/second
generation progestogens are more effective than placebo for relief of primary dysmenorrhea.30 The menstrual
fluid prostaglandin levels are reduced to below normal levels in women who use OCPs.19 This reduction in
menstrual fluid prostaglandins is brought about through two mechanisms. First, OCPs reduce menstrual fluid
volume through suppression of endometrial tissue growth, giving rise to reduced prostaglandin levels. Second,
inhibition of ovulation with OCP retards endometrial development and produces an anovulatory cycle with an
endocrine milieu that is essentially similar to the early proliferative phase of the menstrual cycle when
endometrial prostaglandin levels are low. The absence of luteal-phase progesterone levels that are necessary for
increased endometrial prostaglandin biosynthesis also contributes to the anovulatory mechanism of reducing
menstrual fluid prostaglandins. OCPS may also reduce elevation of plasma vasopressin levels found in
dysmenorrheic women and lead to attenuation of uterine hypercontractility.31 With OCPs, more than 90% of
dysmenorrheic women can be satisfactorily relieved of their primary dysmenorrhea. A trial of oral contraceptives
for 3–4 months is useful. Analyses of extended-use OCPs found that few studies actually reported menstrual pain
but the regimen fared slightly better than cyclic use.32 Women who respond well to oral contraceptives can be
maintained on this regimen. However, if dysmenorrhea is not adequately relieved, an appropriate NSAID can be
added. The response to the NSAIDs can then be monitored as in the patient who is placed on such an agent
initially.
NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDs)
Women with primary dysmenorrhea can be given nonsteroidal antiinflammatory drugs if they do not have any
gastroduodenal ulcers or are hypersensitive to NSAIDs. Such therapy can be allowed for 3–6 months, with
adjustment in the doses and the type of NSAIDs. If there is no relief, laparoscopy is indicated. If such measures
are followed and a proper diagnosis of primary dysmenorrhea is made, 80–85% of patients obtain relief. Level 1
evidence indicates that NSAIDs are significantly better than or 7.9 times more effective for pain relief than
placebo.33 Nevertheless, there is insufficient to detect between individual NSAIDs since most comparisons are
based a few trials which are unsuitable for meta-analysis. Therefore, there is not enough evidence to determine
which (if any) individual NSAID is the most effective and safe for treatment of dysmenorrhea. My personal
preference is to select an effective NSAID that has been around for a long time, currently available as a generic
and is therefore relatively inexpensive, has many randomized clinical trials with data on time to onset of relief
with the first dose. Such NSAIDs include ibuprofen, sodium naprozen and ketoprofen. Other NSAIDs shown to
be effective include mefenamic acid and nimesulide. Naproxen 400 mg provides greater pain relief than placebo
and acetaminophen within 30 minutes and maintained at 6 hours after administration.34 In a multicenter,
randomized, double-blind, crossover study, we found 12.5 and 25 mg ketoprofen and 200 mg ibuprofen are
significantly better than placebo, with similar sums of pain intensity differences and total pain relief scores at 4
hours for both medications.35 Although cyclooxygenase (COX) II inhibitors such as rofecoxib,36 valdecoxib,37,
38 and lumiracoxib39 are effective for treating dysmenorrhea and specific inhibitors of the inducible form of
COX, cost considerations, lack of superiority over the COX I inhibitors such as ibuprofen and sodium naproxen
and concerns about the adverse effects of COX II inhibitors do not support their use as a first line choice in the
treatment of primary dysmenorrhea.
Laparoscopy is necessary only in a small percentage of patients with dysmenorrhea in whom medical therapy has
failed. In the event that pelvic disease is discovered at laparoscopy, the appropriate therapy directed to the
underlying pathology is instituted, thereby alleviating the dysmenorrhea.
If no pelvic pathology is found, one of the newer methods of management, which is less established than using
nonsteroidal antiinflammatory drugs, can be employed and becomes one of trial and error, because it is unclear
whether any specific pharmacotherapy could be of help. A preliminary study40 found that a calcium channel
blocker, such as nifedipine, provided some relief. In the investigator's clinical experience, calcium channel
blockers were helpful in difficult cases of primary dysmenorrhea. Other agents that could be resorted to include
the betamimetic drugs, but they are less effective than nonsteroidal antiinflammatory drugs and often carry side
effects.1, 2 These agents probably should not be used on a routine basis, and such attempts are best left to
medical centers carrying out systematic studies of them. A noninvasive method of blocking the propagation of
pain impulses from the pelvis using transcutaneous electrical nerve stimulation (TENS) has been employed.41
Psychiatric help in the management of these patients who have been relieved with nonsteroidal
antiinflammatory drugs and who have no disease in the pelvis might also be appropriate. It should not be
construed that dysmenorrhea is wholly psychosomatic, but in the absence of understanding of the basic
pathophysiologic mechanisms of the dysmenorrhea, symptomatic treatment with analgesics and psychotherapy
to modulate the psychologic factors that may be playing a significant or contributing role to the pain could
ameliorate the dysmenorrhea to some extent. Few patients with primary dysmenorrhea fall into this category if a
correct diagnosis has been made and appropriate steps in the management of the patient have been taken.
Unlike oral contraceptives, nonsteroidal antiinflammatory drugs are taken for the first 2–3 days of the menstrual
flow, there is no significant suppression of the pituitary-ovarian axis, and there are none of the metabolic effects
seen with oral contraceptives, which have to be taken for a minimum of 3 of every 4 weeks. Choosing the most
suitable nonsteroidal antiinflammatory drug should be based on its proven clinical efficacy; rapid absorption to
produce a quick onset of relief; wide margin of safety with a low ulcerogenecity index; minimal, tolerable, and
inconsequential side effects; and long-term safety. The nonsteroidal antiinflammatory drugs should be given as
soon as menstruation begins and should be taken on a continuing basis for the first 2 or 3 days and not on an as-
needed basis. The latter method clearly aims at suppressing pain, whereas the former approach, which is more
likely to be effective in most patients, acts by correction of the derangement in prostaglandin production.
Nonsteroidal antiinflammatory drugs appear to relieve primary dysmenorrhea through suppression of menstrual
fluid prostaglandins, as has been demonstrated in several studies (Fig. 6). These compounds also have direct
analgesic properties.
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/006f.gif) Fig. 6. The effect of ibuprofen, a

nonsteroidal antiinflammatory drug, on primary dysmenorrhea is compared with the control (no treatment),
and treatment is compared with placebo. Only the prostaglandin level (not menstrual fluid volume) is
significantly reduced by the nonsteroidal antiinflammatory drug. (Dawood MY: Overall approach to the
management of dysmenorrhea. In Dawood MY [ed]: Dysmenorrhea, p 261. Baltimore: Williams and Wilkins,
981)
Table 2 provides a summary of the clinical efficacy of NSAIDs grouped according to the structural derivation. In
contrast to oral contraceptives, which inhibit endometrial development and thereby reduce menstrual fluid
prostaglandins (Fig. 6), NSAIDs do not affect endometrial development; instead, they suppress menstrual fluid
prostaglandin through enzymatic inhibition of prostaglandin production.
Table 2. Prostaglandin synthetase inhibitors grouped by their structural derivatives and their clinical efficacy in
dysmenorrhea
Prostaglandin synthetase
inhibitor group Drug Dose Clinical relief
Benzoic acid derivatives Aspirin 500–600 mg No difference from placebo

4×/day except in one study
Buterophenones Phenylbutazone No information

available
Oxyphenbutazone No information
available
Indole acetic acid Indomethacin 25 mg 3–6×/day 73–90% relief
Fenamates Flutenamic acid 100–200 mg 77–82% relief

3×/day
Mefenamic acid 250–500 mg 93% relief

4×/day
Tolfenamic acid 133 mg 3×/day 88% relief
Aryloproponic acid Ibuprofen 400 mg 4×/day 66–100% relief
Naproxen sodium 275 mg 4×/day 78–90% relief
Ketoprofen 50 mg 3×/day 90% relief
Miscellaneous Suprofen 200 mg 4×/day 60–80% relief
Piroxicam Once/day Effective
From Dawood MY: Nonsteroidal antiinflammatory drugs and changing attitudes toward dysmenorrhea. Am J
Med 84 (Suppl 5A):23, 1988.
Contraindications to the use of NSAIDs include gastroduodenal ulcers, previous gastric bleeding, and a previous
history of bronchospasmatic type of reaction after the ingestion of aspirin or aspirin-like drugs. Side effects
of NSAIDs are relatively mild during therapy for primary dysmenorrhea, and are usually well tolerated. The
known side effects of NSAIDs are listed in Table 3.
Table 3. Side effects of prostaglandin synthetase inhibitors
Gastrointestinal symptoms
Indigestion
Heartburn
Nausea
Abdominal pain
Constipation
Vomiting
Anorexia
Diarrhea
Melena
CNS symptoms
Headache
Dizziness
Vertigo
Visual disturbances
Hearing disturbances
Irritability
Depression
Drowsiness
Sleepiness
Other symptoms
Allergic reactions
Rash
Edema
Bronchospasm
Hematologic abnormalities
Effects on the eyes
Fluid retention
Effects on liver and kidney
From Dawood MY: Overall approach to the management of dysmenorrhea. In Dawood MY (ed): Dysmenorrhea,
p 261. Baltimore: Williams & Wilkins, 1981
OTHER FORMS OF TREATMENT.
Although cervical dilatation as a primary method of treatment for primary dysmenorrhea is not warranted,
dilatation of the cervix should be undertaken when laparoscopies are performed. This surgical manipulation does
relieve primary dysmenorrhea temporarily, although with a progressive return of the symptoms. Relief may be
caused by destruction of the paracervical nerve fibers and plexus with consequent neuropraxia or partial
denervation of the cervix and a temporary increase in the diameter of the cervical canal, culminating in enhanced
menstrual fluid flow with shorter contact time between the uterine wall and menstrual fluid containing the
prostaglandins.
Among the betamimetic agents, only terbutaline has been found to be more effective than a placebo.1, 2 The high
incidence of side effects confirmed that this is not usually a practical approach. Alcohol, a tocolytic agent,
diminishes dysmenorrhea, but to obtain complete relief, amounts must be taken that also produce inebriation
and incapacitation. The progesterone-medicated intrauterine device (Progestasert) reduces menstrual fluid
prostaglandin and relieves primary dysmenorrhea.42 It is not exactly prudent to recommend use of an
intrauterine device, which itself gives rise to dysmenorrhea, as a method for treatment of women with primary
dysmenorrhea.
Presacral neurectomy is rarely indicated for treatment of most forms of primary dysmenorrhea. Use of this
procedure should be extremely limited and reserved for patients with chronic pelvic pain when other methods of
pain relief have failed, for patients with pelvic malignancy, and for patients with pelvic pathologies, such as
endometriosis, when there is impingement or involvement of the presacral plexus. Presacral neurectomy
provided relief of dysmenorrhea in 53–72% of patients with different stages of endometriosis,43 much less than
obtained with hormonal treatment.
For cases that have not responded to medical therapy and in which laparoscopic findings are negative, alcohol or
local anesthetics can be injected into the uterosacral ligament to denervate the nerve supply to the paracervical
region temporarily. Transection of the uterosacral ligaments through which these nerves pass has also been
undertaken. With the advent of laser laparoscopy, this is being enthusiastically recommended by some without
carefully considering the potential problems of this procedure, especially in young women with severe primary
dysmenorrhea. Regardless of the methods used to denervate the uterosacral ligament surgically, the healing
process may induce adhesions of the ovary and fallopian tube in this region and compromise the future
reproductive potential of these women. Uterine prolapse has been reported in nulliparous women after
uterosacral transection.
TENS has been studied for the relief of primary dysmenorrhea. It is a noninvasive and effective method for relief
of primary dysmenorrhea and empowers the woman to control her treatment because she can regulate the
intensity and duration of TENS applied. A recent Cochrane review analyzed seven randomized controlled trials
of TENS compared with placebo or no treatment.44 Overall high frequency TENS is more effective for pain relief
in primary dysmenorrhea than placebo TENS.41, 44, 45, 46, 47, 48, 49, 50, 51 Low frequency TENS is no more
effective than placebo TENS. In a placebo-controlled TENS study, we found that in 30% of cycles of women with
severe primary dysmenorrhea TENS provided good relief without the need for any kind of backup pain
medication.41 In the other women, the amount of pain medication required was significantly lower at all time
intervals examined during the first 48 hours of menstruation. TENS appears to be a suitable method of relieving
primary dysmenorrhea in women who may not wish to take medication, have medical contraindications to the
use of NSAIDs or OCPs, have side effects from the use of NSAIDs, or are unable to obtain total relief with
maximum doses of NSAIDs. TENS relieves primary dysmenorrhea through two likely mechanisms. First, with
continuing transcutaneous electrical nerve stimulation, the preganglionic fibers are bombarded with impulses,
which saturate the nerve cells of the dorsal horn and therefore block the propagation of pain impulses along
these fibers (gate control theory). By lowering the "gate", signal reception from the uterine hypoxia and
hypercontractility is blocked.52, 53 Second, TENS induces release of endorphin from these nerve cells that
contributes to the relief of pain.
Other less well established methods of treating primary dysmenorrhea include glyceryl trinitrate, calcium
antagonists, vitamin B6, fish oil, acupuncture, acupressure and even spinal manipulation as summarized
elsewhere.54 Glyceryl trinitrate as a source of nitric oxide can be expected to relax the exaggerated myometrial
contractions in primary dysmenorrhea. Nitoglycerin significantly reduces the pain in primary dysmenorrhea.55,
56, 57. However, there is low tolerability for glyceryl trinitrate because of headache. Magnesium is more effective
than placebo for relief of primary dysmenorrhea.58 There is a suggestion of reduced menstrual fluid PGF2α with
magnesium. However, it is not clear what the dose preparation and regimen to use for magnesium when treating
primary dysmenorrhea. Calcium channel blockers such as nifedipine inhibit myometrial contractility and may
relieve primary dysmenorrhea.59, 60, 61 Vitamin E may relieve primary dysmenorrhea through alteration of
prostaglandin biosynthesis and therefore affect uterine contractions.62, 63, 64, 65 Fish oil (omega-3 fatty acids)
was more effective than placebo.66 There is less compelling evidence for efficacy of acupuncture and acupressure
in relieving primary dysmenorrhea and more well-designed, controlled larger and more definitive studies are
needed.54 Spinal manipulation was found not to be effective for treatment of primary dysmenorrhea in a
Cochrane analysis.67
SECONDARY DYSMENORRHEA
Etiology
The causes of secondary dysmenorrhea include endometriosis, presence of an intrauterine device, pelvic
inflammatory disease and infection, adenomyosis, uterine myomas, polyps and adhesions, congenital
malformation of the müllerian system, cervical stricture or stenosis, ovarian cyst, pelvic congestion syndrome,
and Allen–Masters syndrome. The appearance of painful menstrual cramps years after the menarche may be a
sign of secondary dysmenorrhea, frequently caused by endometriosis. In women with anovulatory cycles, the
menstrual pain is likely to be secondary dysmenorrhea.
Differential Diagnosis
Differential diagnoses in a patient suspected of having secondary dysmenorrhea should include all the above
causes. Although the age at onset of dysmenorrhea is often a useful index for distinguishing primary from
secondary dysmenorrhea, endometriosis can occur with or soon after the onset of menarche. A history of a
current pelvic inflammatory disease, irregular menstrual cycles (especially associated with anovulation),
menorrhagia, use of an intrauterine device, and infertility problems suggest secondary dysmenorrhea. It should
be differentiated from primary dysmenorrhea and from chronic pelvic pain. In chronic pelvic pain, there is no
time relationship between the pain and the phase of the menstrual cycle, but in dysmenorrhea, the pain is
confined only to the menstrual phase or shortly before it. Physical examination, especially careful pelvic and
rectovaginal examination, is likely to reveal causes of secondary dysmenorrhea, such as uterine malformations or
myomas, presence of an intrauterine device, pelvic inflammatory disease, and in some cases, endometriosis.
Adenomyosis should be considered as a cause of dysmenorrhea, particularly when it is present in women older
than 35 years of age. However, the final diagnosis of adenomyosis can be made only on the basis of a uterine
specimen evaluation.
Investigations that may be useful in identifying or confirming the cause of secondary dysmenorrhea include a
complete blood count, erythrocyte sedimentation rate, pelvic ultrasonography, hysterosalpingography, and
genital cultures for pathogens. However, the final diagnosis often requires diagnostic laparoscopy, hysteroscopy,
or dilatation and curettage. By far, laparoscopy is probably the most single useful procedure in the evaluation of
secondary dysmenorrhea, and in primary dysmenorrhea after a trial of medical therapy has not been successful.
Role of Prostaglandins
The pathogenesis of intrauterine device-associated secondary dysmenorrhea is largely similar to that in primary
dysmenorrhea. Studies in animals and women have indicated that the presence of an intrauterine device induces
an endometrial inflammatory response around the vicinity of the device with leukocyte infiltration.68, 69
Prostaglandin levels, particularly prostaglandin F2α, are significantly elevated in the endometrium immediately
around the vicinity of the intrauterine device.68 This elevated production and the release of prostaglandin
induced by the intrauterine device bring about the cascade of events leading to the generation of pain from the
uterus as in the case of primary dysmenorrhea discussed earlier. The intrauterine device also causes
menorrhagia. Treatment with nonsteroidal antiinflammatory drugs can relieve the dysmenorrhea and correct
menorrhagia in women wearing an intrauterine device.70 The increased prostaglandin production because of the
presence of an intrauterine device probably contributes significantly to the menorrhagia. Some prostaglandins
induce smooth muscle contraction and therefore vasoconstriction, and they promote platelet aggregation and
clotting. Other prostaglandins do the opposite. For example, thromboxane A2 stimulates uterine contraction,
induces vasoconstriction, and promotes platelet aggregation, while prostacyclin relaxes the uterus, vasodilates,
and is antiaggregatory for platelets. Elevation and imbalances between the different prostaglandins can bring
about dysmenorrhea and menorrhagia. Because most nonsteroidal antiinflammatory drugs block the action of
cyclooxygenase and therefore inhibit not only prostaglandin F2α and E2, but also prostacyclin and thromboxane,
dysmenorrhea and menorrhagia are alleviated.
Although prostaglandins have been implicated, in some limited studies, as the cause of dysmenorrhea in patients
with endometriosis, the evidence is inconclusive. The dysmenorrhea and pelvic pain from endometriosis are
more likely to be contributed by many different mechanisms depending on the anatomic location, extent, and
activity of the endometriosis within the pelvis. Treatment with nonsteroidal antiinflammatory drugs again is less
likely to be effective than other more specific hormonal or surgical therapies. Elevated endometrial
prostaglandins also have been found in a few women with uterine myomas, but suppression with nonsteroidal
antiinflammatory drugs cannot be used for long-term effective therapy of this condition, except as a short-term
relief while waiting for surgery.
Treatment
As indicated earlier, women wearing the intrauterine device should be treated with nonsteroidal
antiinflammatory drugs for their intrauterine device-induced dysmenorrhea and menorrhagia. In contrast to the
treatment regimen for primary dysmenorrhea, the medication should be given continuously throughout the
duration of the menstrual flow for patients having secondary dysmenorrhea and menorrhagia due to an
intrauterine device.
Therapy for most of the other causes of secondary dysmenorrhea should be directed to the specific underlying
condition. Surgery has a greater role to play in the treatment of most forms of secondary dysmenorrhea and is
usually more definitive. Nonsteroidal antiinflammatory drugs may be given only as a temporary measure to
obtain some relief while waiting for surgery. In endometriosis patients, specific hormonal therapy (i.e. danazol,
gonadotropin releasing hormone agonist, progestins, and oral contraceptives) could also be employed to obtain
adequate relief.
REFERENCES
1 Dawood MY: Overall approach to the management of

dysmenorrhea. In Dawood MY (ed): Dysmenorrhea, p
261. Baltimore: Williams & Wilkins, 1981
2 Dawood MY: Overall approach to the management of

dysmenorrhea. In Dawood MY, McGuire JL, Demers LM
(eds): Premenstrual Syndrome and Dysmenorrhea, p 177.
Baltimore: Urban & Schwarzenberg, 1985
3 Dawood MY: Choosing the correct therapy for

dysmenorrhea. Contemp Obstet Gynecol 19: 235, 1982
4 Dawood MY: Etiology and treatment of dysmenorrhea.

Semin Reprod Endocrinol 3: 283, 1985
5 Dawood MY: Dysmenorrhea. Clin Obstet Gynecol 26: 719,

1983
6 Dawood MY: Dysmenorrhea. J Reprod Med 30: 154, 1985
7 Dawood MY: Nonsteroidal anti-inflammatory drugs and
changing attitudes toward dysmenorrhea. Am J Med 84
(Suppl 5A): 23, 1988
8 Dawood MY: Dysmenorrhea and ibuprofen. Am J Med 77:

87, 1984
9 Bergsjo P: Socioeconomic implications of dysmenorrhea.

Acta Obstet Gynecol Scand 87 (Suppl 1): 67, 1979
10 Frisk M, Widholm O, Horthing H: Dysmenorrhea— PubMed

(http://www.ncbi.nlm.nih.gov/sites/entrez/5834182)
Psyche and soma in teenagers. Acta Obstet Gynecol Scand
44: 329, 1965
11 Dawood MY: Dysmenorrhea and prostaglandins. In Gold

JJ, Josimovich JB (eds): Gynecologic Endocrinology, p
405. 4th edn. New York: Plenum Press, 1987
12 Harlow SD, Park M: A longitudinal study of risk factors PubMed

for the occurrence, duration and severity of menstrual
cramps in a cohort of college women. Br J Obstet
Gynaecol 103: 1134, 1996
13 Widholm O: Epidemiology of premenstrual tension

syndrome and primary dysmenorrhea. In Dawood MY,
McGuire JL, Demers LM (eds): Premenstrual Syndrome
and Dysmenorrhea, p 3. Baltimore: Urban &
Schwarzenberg, 1985
14 Goldstein DP, Cholkony C, Emans JS: Adolescent

endometriosis. J Adolesc Health Care 1: 37, 1980
15 Yilkorkala O, Dawood MY: New concepts in

dysmenorrhea. Am J Obstet Gynecol 130: 833, 1978
16 Dawood MY: Dysmenorrhea and prostaglandins:

Pharmacological and therapeutic considerations. Drugs
122: 42, 1981
17 Dawood MY: Hormones, prostaglandins, and

dysmenorrhea. In Dawood MY (ed): Dysmenorrhea, p 21.
Baltimore: Williams & Wilkins, 1981
18 Chan WY, Dawood MY, Fuchs F: Relief of dysmenorrhea

with the prostaglandin synthetase inhibitor ibuprofen:
Effect on prostaglandin levels in menstrual fluid. Am J
Obstet Gynecol 135: 102, 1979
19 Chan WY, Dawood MY: Prostaglandin levels in menstrual

fluid of nondysmenorrheic and of dysmenorrheic subjects
with and without oral contraceptive or ibuprofen therapy.
Adv Prostaglandin Tromboxane Leukot Res 8: 1443, 1980
20 Chan WY, Dawood MY, Fuchs F: Prostaglandin in
primary dysmenorrhea comparison of prophylactic and
non-prophylactic treatment with ibuprofen and use of
oral contraceptive. Am J Med 70: 535, 1981
21 Marchini M, Manfredi B, Tozzi I et al: Mitogen-induced PubMed

lymphocyte proliferation and peripheral mononuclear cell
beta-endorphin concentrations in primary dysmenorrhea.
Hum Reprod 10: 815, 1995
22 Akerlund M, Stromberg P, Forsling MD: Primary

dysmenorrhea and vasopressin. Br J Obstet Gynaecol 86:
484, 1979
23 Melin P, Akerlund M, Vilhardt H: Antagonism of the

myometrial response to oxytocin and vasopressin
synthetic analgesics. Dan Med Bull 26: 126, 1979
24 Funk CD, Funk LB, Kennedy ME et al: Human PubMed

platelet/erythroleukemia cell prostaglandin G/H
synthase: cDNA cloning, expression of gene chromosomal
assignment. FASEB J 5: 2304-12, 1991
25 Kosaka T, Miyata A, Ihara H et al: Characterization of PubMed

human gene (PTGS2) encoding prostaglandin
endoperoxide synthase 2. Eur J Biochem 221: 889-97,
1994
26 Pickles VR, Hall WJ, Best FA et al: Prostaglandins in

endometrium and menstrual fluid from normal and
dysmenorrheic subjects. J Obstet Gynaecol Br Commonw
72: 185, 1965
27 Walker SM: In vitro synthesis of prostaglandin F2a by

human endometrium. Abstracts of the Twenty-First
British Congress of Obstetrics and Gynecology, p 37.
Sheffield, 1977
28 Wiqvist N, Lindblom B, Wilhelmsson L: The

pathophysiology of primary dysmenorrhea. Res Clin
Forums 1: 47, 1979
29 Demers LM, Hahn DW, McGuire JL: Newer concepts in

dysmenorrhea research: Leukotrienes and calcium
channel blockers. In Dawood MY, McGuire JL, Demers
LM (eds): Premenstrual Syndrome and Dysmenorrhea, p
205. Baltimore: Urban & Schwarzenberg, 1985
30 Proctor ML, Roberts H, Farquhar CM. Combined oral PubMed

contraceptive pill (OCP) as treatment for primary
dysmenorrhea (Cochrane Review). In: The Cochrane
Library, Issue 4, 2001. Oxford: Update Software
31 Ekstrom P, Akerlund M, Forsling M, Kindahl H, PubMed
Laudanski T, Mrugacz G. Stimulation of vasopressin in (http://www.ncbi.nlm.nih.gov/sites/entrez/1390475)
women with primary dysmenorrhea and after oral
contraceptive treatment: effect on uterine contractility. Br
J Obstet Gynaecol 1992; 99:680-4
32 Edelman AB, Gallo MF, Jensen JT, Nichols MD, Schulz PubMed
KF, Grimes DA. Continuous or extended cycle vs cyclic
use of combined oral contraceptives for contraception
(Cochrane Review). In: The Cochrane Library, Issue 3,
2005. Oxford: Update Software
33 Marjoribanks J, Proctor ML, Farquhar C. Nonsteroidal PubMed

anti-inflammatory drus for primary dysmenorrhea
2003. Oxford: Update Software.
34 Milsom I, Minic M, Dawood MY, Akin MD, Spann J,

Niland NF, et al. Comparison of the efficacy and safety of
nonprescription doses of naproxen and naproxen sodium
with ibuprofen, acetaminophen, and placebo in the
treatment of primary dysmenorrhea: a pooled analysis of
five studies. Clin Ther 2002; 24: 1384-400
35 Dawood MY. Multicenter, randomized double-blind,

cross-over study comparing ketoprofen 12.5 mg and 25
mg, ibuprofen 200 mg and placebo in the treatment of
primary dysmenorrhea. Miles Medical research Report
No. 1245, 1994
36 Morrison BW, Daniels SE, Kotey P, Cantu N, Seidenberg

B. Rofecoxib, a specific cyclooxygenase-2 inhibitor in
primary dysmenorrhea: a randomized controlled trial.
Obstet Gynecol 1999; 94: 504-8
37 Daniels SE, Talwalker S, Torri S, Snabes MC, Recker DP,

Verburg KM. Valdecoxib, a cyclooxygenase-2-specific
inhibitor, is effective in treating primary dysmenorrhea.
Obstet Gynecol 2002; 100: 350-8
38 Daniels SE, Torri S, Desjardins PJ. Valdecoxib for

treatment of primary dysmenorrhea: a randomized
double-blind comparison with placebo and naproxen. J
Gen Intern Med 2005; 20: 62-7
39 Bitner M, Kattenhorn J, Hatfield C, Gao J, Kellstein D.

Efficacy and tolerability of lumiracoxib in the treatment
of primary dysmenorrhea. Int J Clin Pract 2004; 58: 340-
5
40 Sandahl B, Weinstein U, Andersson K-E. Trial of calcium
antagonist nifedipinein the treatment of of
dysmenorrhea. Arch Gynecol 227:147, 1979
41 Dawood MY, Ramos J: Transcutaneous electrical nerve

stimulation (TENS) for treatment of primary
dysmenorrhea: A randomized, cross-over comparison
with placebo TENS and ibuprofen. Obstet Gynecol 75:
656, 1990
42 Trobough G, Guderian AM, Erickson RR et al: The effect

of exogenous intrauterine progesterine on the amount
and prostaglandin F2a content of menstrual blood in
dysmenorrheic women. J Reprod Med 21: 153, 1978
43 Nezhat CH, Seidman DS, Nezhat FR, Nezhat CR: Long- PubMed
term outcome of laparoscopic presacral neurectomy for
the treatment of central pelvic pain attributed to
endometriosis. Obstet Gynecol 91: 701, 1998
44 Proctor MI, Smith CA, Farquhar CM, Stones RW.

Transcutaneous electrical nerve stimulation and
acupuncture for primary dysmenorrhea (Cochrane
Review). In: The Cochrane Library, Issue 1, 2002. Oxford:
Update Software.
45 Lewers D, Clelland JA, Jackson JR, Varner RE, Bergman

J. Transcutaneous electrical nerve stimulation in the
relief of primary dysmenorrhea. Phys Ther 1989; 69: 3-9
46 Lundeberg T, Bondesson L, Lundstrom V. relief of

primary dysmenorrhea by transcutaneous electrical nerve
stimulation. Acta Obstet Gynecol Scand 1985; 64: 491-7
47 Mannheimer JS, Whalen EC. The efficacy of

trancutaneous electrical nerve stimulation in
dysmenorrhea. Clin J Pain 1985; 1: 75-83
48 Milsom I, Hedner N, Mannheimer C. A comparative study

of the effect of high-intensity transcutaneous nerve
stimulation and oral naproxen on intrauterine pressure
and menstrual pain in patients with primary
dysmenorrhea. Am J Obstet Gynecol 1994; 170: 123-9
49 Neighbours LE, Clelland J, Jackson JR, Bergman J, Orr J.

Transcutaneous electrical nerve stimulation for pain relief
in primary dysmenorrhea. Clin J Pain 1987; 3: 17-22
50 Santiesteban AJ, Burnham TL, George KL, Kita PJ,

Mehring EA. Primary spasmodic dysmenorrhea: the use
of TENS on acupuncture points. Am J Acupunct 1985; 13:
35-42
51 Walker JB, Katz RI. Peripheral nerve stimulation in the
management of dysmenorrhea. Pain 1981; 11: 355-61
52 Golding JF, AShton H, Marsh R, Thompson JW.

Transcutaneous electrical nerve stimulation produces
variable changes in somatosensory evoked potentials,
sensory perception and apin threshold: clinical
implications for pain relief. J Neurol Neursurg Psychiatry
1986: 49: 1397-406
53 Melzack R, Wall PD. Pain mechanisms: a new theory.

Science 1965: 150: 971-9
54 Dawood MY. Primary Dysmenorrhea. Advances in PubMed

Pathogenesis and Management. Obstet Gynecol 2006;
108: 428-41
55 Morgan PJ, Kung R, Tarshis J, Nitroglycerine as a uterine

relaxant: a systematic review. J Obstet Gynaecol Can
2002; 24: 403-9
56 Transdermal nitroglycerin in the management of pain

associated with primary dysmenorrhea: a multinational
pilot study. The Transdermal
Nitroglycerine/Dysmenorrhea Study Group. J Int Med
Res 1997: 25: 41-4
57 Moya RA, Moisa CF, Morales F, Wynter H, Ali A, PubMed

Narancio E. Transdermal glyceryl trinitrate in the
management of primary dysmenorrhea. Int J Gynaecol
Obstet 2000; 69: 113-18
58 Wilson MI, Murphy PA. Herbal and dietary therapies for

primary and secondary dysmenorrhea (Cochrane
Review). In: The Cochrane Library, Issue, 2001. Oxford:
Update Software.
59 Sandahl B, Weinstein U, Andersson K-E: Trial of calcium

antagonist nifedipine in the treatment of primary
dysmenorrhea. Arch Gynecol 227: 147, 1979
60 Andersson KE, Ulmsten U, Andersson KE. Effects of

nifedipine on myometrial activity and lower abdominal
pain in women with primary dysmenorrhea. Br J Obstet
Gynaecol 1978; 85: 142-8
61 Ulmsten U. Calcium blockade as a rapid pharmacological

test to evaluate primary dysmenorrhea. Gynecol Obstet
Invest 1983; 1985; 20: 78-83
62 Beharka AA, Wu D, SErafini M, Meydani SN. Mechanism PubMed
of Vvtamin E inhibition of cyclooxygenase in (http://www.ncbi.nlm.nih.gov/sites/entrez/11958951)
macrophages from old mice: role of peroxynitrite. Free
Radic Biol Med 2002; 32: 503-11
63 Sakamoto W, Fujie K, Nishihira J, Mino M, Morita I, PubMed

Minota S. Inhibition of PGE2 production in macrophages
from vitamin E-treated rats. Prostaglandins Leukot
Essent Fatty Acids 1991; 44: 89-92
64 Pentland AP, Morrison AR, Jacobs SC, Hruza LI, Herbert PubMed
JS, Packer L. Tocopherol analogs suppress arachidonic
acid metabolism via phospholipase inhibition. J Biol
Chem 1992; 267: 15578-84
65 Ali M, Gudbranson CG, McDonald JW. Inhibition of

human platelet cyclooxygenase by alpha-tocopherol.
Prostaglandins Med 1980; 4: 79-85
66 Wilson MI, Murphy PA. Herbal and dietary therapies for

primary and secondary dysmenorrhea (Cochrane
Review). In: The Cochrane Library, Issue 3, 2001. Oxford:
Update Software.
67 Proctor Ml, Hing W, Johnson TC, Murphy PA. Spinal PubMed

manipulation for primary and secondary dysmenorrhea
2004. Oxford: Update Software
68 Spillman CH, Duby RT: Prostaglandin mediated luteolytic

effect of an intrauterine device in sheep. Prostaglandins 2:
159, 1972
69 Hillier K, Kasonde JM. Prostaglandin E and F

concentrations in human endometrium after intrauterine
contraceptive device. Lancet 1976; 1: 774
70 Anderson ABM, Gillebaud J, Haynes PJ et al. Reduction

of menstrual blood-loss by prostglandin synthetase
inhibitors. Lancet 1976; 1: 774
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This chapter should be cited as follows:

This chapter was last updated:

(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/001f.gif) Fig. 1. Schematic representation of

(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/002f.gif) Fig. 2. Menstrual fluid

(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/003f.gif) Fig. 3. Relationship between the

(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/004f.gif) Fig. 4. Mechanism of pain

Table1. Modalities available for the treatment of primary dysmenorrhea

Approach Specific methods

General measures Psychotherapy, reassurance

Surgery Dilatation and curettage, presacral neurectomy

Endocrine therapy Oral contraceptive pills, inhibition of ovulation

Tocolysis Alcohol, β-receptor stimulators

Analgesics Nonnarcotics, narcotics

Approach Specific methods

Prostaglandin synthetase Cyclooxygenase blockers (indomethacin, ibuprofen, sodium naproxen,

(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/005f.gif) Fig. 5. Algorithm for the

ORAL CONTRACEPTIVES (OCPs)

NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDs)

(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0180/006f.gif) Fig. 6. The effect of ibuprofen, a

Benzoic acid derivatives Aspirin 500–600 mg No difference from placebo

Buterophenones Phenylbutazone No information

Indole acetic acid Indomethacin 25 mg 3–6×/day 73–90% relief

Fenamates Flutenamic acid 100–200 mg 77–82% relief

Mefenamic acid 250–500 mg 93% relief

Tolfenamic acid 133 mg 3×/day 88% relief

Aryloproponic acid Ibuprofen 400 mg 4×/day 66–100% relief

Naproxen sodium 275 mg 4×/day 78–90% relief

Ketoprofen 50 mg 3×/day 90% relief

Miscellaneous Suprofen 200 mg 4×/day 60–80% relief

Piroxicam Once/day Effective

Table 3. Side effects of prostaglandin synthetase inhibitors

1 Dawood MY: Overall approach to the management of

2 Dawood MY: Overall approach to the management of

3 Dawood MY: Choosing the correct therapy for

4 Dawood MY: Etiology and treatment of dysmenorrhea.

5 Dawood MY: Dysmenorrhea. Clin Obstet Gynecol 26: 719,

6 Dawood MY: Dysmenorrhea. J Reprod Med 30: 154, 1985

8 Dawood MY: Dysmenorrhea and ibuprofen. Am J Med 77:

9 Bergsjo P: Socioeconomic implications of dysmenorrhea.

10 Frisk M, Widholm O, Horthing H: Dysmenorrhea— PubMed

11 Dawood MY: Dysmenorrhea and prostaglandins. In Gold

12 Harlow SD, Park M: A longitudinal study of risk factors PubMed

13 Widholm O: Epidemiology of premenstrual tension

14 Goldstein DP, Cholkony C, Emans JS: Adolescent

15 Yilkorkala O, Dawood MY: New concepts in

16 Dawood MY: Dysmenorrhea and prostaglandins:

17 Dawood MY: Hormones, prostaglandins, and

18 Chan WY, Dawood MY, Fuchs F: Relief of dysmenorrhea

19 Chan WY, Dawood MY: Prostaglandin levels in menstrual

21 Marchini M, Manfredi B, Tozzi I et al: Mitogen-induced PubMed

22 Akerlund M, Stromberg P, Forsling MD: Primary

23 Melin P, Akerlund M, Vilhardt H: Antagonism of the

24 Funk CD, Funk LB, Kennedy ME et al: Human PubMed

25 Kosaka T, Miyata A, Ihara H et al: Characterization of PubMed

26 Pickles VR, Hall WJ, Best FA et al: Prostaglandins in

27 Walker SM: In vitro synthesis of prostaglandin F2a by

28 Wiqvist N, Lindblom B, Wilhelmsson L: The

29 Demers LM, Hahn DW, McGuire JL: Newer concepts in

30 Proctor ML, Roberts H, Farquhar CM. Combined oral PubMed

33 Marjoribanks J, Proctor ML, Farquhar C. Nonsteroidal PubMed

34 Milsom I, Minic M, Dawood MY, Akin MD, Spann J,