Dysmenorrhea

LINDA FRENCH, M.D., Michigan State University College of Human Medicine, East Lansing, Michigan

Dysmenorrhea is the leading cause of recurrent short-term school absence in adolescent girls and a common problem
in women of reproductive age. Risk factors for dysmenorrhea include nulliparity, heavy menstrual flow, smoking,
and depression. Empiric therapy can be initiated based on a typical history of painful menses and a negative physical
examination. Nonsteroidal anti-inflammatory drugs are the initial therapy of choice in patients with presumptive
primary dysmenorrhea. Oral contraceptives and depo-medroxyprogesterone acetate also may be considered. If pain
relief is insufficient, prolonged-cycle oral contraceptives or intravaginal use of oral contraceptive pills can be consid-
ered. In women who do not desire hormonal contraception, there is
some evidence of benefit with the use of topical heat; the Japanese
herbal remedy toki-shakuyaku-san; thiamine, vitamin E, and fish oil
supplements; a low-fat vegetarian diet; and acupressure. If dysmen-
orrhea remains uncontrolled with any of these approaches, pelvic
ultrasonography should be performed and referral for laparoscopy
should be considered to rule out secondary causes of dysmenorrhea.
In patients with severe refractory primary dysmenorrhea, additional
safe alternatives for women who want to conceive include transcuta-
neous electric nerve stimulation, acupuncture, nifedipine, and terbu-

ILLUSTRATION BY JOAN BECK

taline. Otherwise, the use of danazol or leuprolide may be considered
and, rarely, hysterectomy. The effectiveness of surgical interruption
of the pelvic nerve pathways has not been established. (Am Fam Phy-
sician 2005;71:285-91, 292. Copyright© 2005 American Academy of
Family Physicians.)

P
See page 225 for rimary dysmenorrhea, which is the-counter medicines, and few consult a
definitions of strength-of-
defined as painful menses in women physician about dysmenorrhea.1-3
recommendation labels.
with normal pelvic anatomy, usu-
Patient information: Pathogenesis
▲

ally begins during adolescence. It is

A handout on dysmen-
orrhea, written by the characterized by crampy pelvic pain begin- Dysmenorrhea is thought to be caused by the
author of this article, is ning shortly before or at the onset of menses release of prostaglandins in the menstrual
provided on page 292. and lasting one to three days. Dysmenor- fluid, which causes uterine contractions and
rhea also may be secondary to pelvic organ pain. Vasopressin also may play a role by
EB C M E
pathology. increasing uterine contractility and causing
This clinical content con- The prevalence of dysmenorrhea is highest ischemic pain as a result of vasoconstriction.
forms to AAFP criteria for
evidence-based continuing in adolescent women, with estimates rang- Elevated vasopressin levels have been reported
medical education (EB ing from 20 to 90 percent, depending on in women with primary dysmenorrhea.
CME). EB CME is clinical the measurement method used.1-3 About 15 The relationship between endometriosis
content presented with
percent of adolescent girls report severe dys- and dysmenorrhea is not clear. Endometrio-
practice recommendations
supported by evidence menorrhea,1,4 and it is the leading cause of sis may be asymptomatic, or it may be asso-
that has been system- recurrent short-term school absenteeism in ciated with pelvic pain that is not limited to
atically reviewed by an adolescent girls in the United States.2,5 A lon- the menstrual period and the low anterior
AAFP-approved source.
gitudinal study6 of a representative cohort of pelvis. In one study7 of women undergo-
Swedish women found a prevalence of dys- ing elective sterilization, no difference was
menorrhea of 90 percent in women 19 years found in the prevalence of dysmenorrhea in
of age and 67 percent in women 24 years of women with and women without an inci-
age. Ten percent of the 24-year-olds reported dental finding of endometriosis. However,
pain that interfered with daily function. an observational study8 of women undergo-
Most adolescents self-medicate with over- ing laparoscopy for infertility supported a

January 15, 2005 ◆ Volume 71, Number 2 www.aafp.org/afp American Family Physician 285
Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2005 American Academy of Family Physicians. For the private, noncommercial
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 relationship between dysmenorrhea and the
severity of endometriosis. TABLE 1
Risk Factors for Dysmenorrhea
Risk Factors
Young age and nulliparity are associated with Age < 20 years
dysmenorrhea.4,9 However, one longitudinal Attempts to lose weight
study6 found that age was not a risk factor Depression/anxiety
after controlling for parity and other fac- Disruption of social networks
tors, and that dysmenorrhea improved after Heavy menses
childbirth. Heavy menstrual flow is associ- Nulliparity
ated with dysmenorrhea.4,5,9 Table 1 lists risk Smoking
factors for dysmenorrhea.
Behavioral risk factors are of interest
because of the potential to intervene. Sev- Diagnosis
eral observational studies6,10,11 have found In most patients who present with menstrual
an association between smoking and dys- pain, empiric therapy may be prescribed
menorrhea. In women 14 to 20 years of age, with the presumptive diagnosis of primary
attempts to lose weight are associated with dysmenorrhea, based on a typical history
increased menstrual pain independent of of low anterior pelvic pain beginning in
body mass index.12 However, the evidence adolescence and associated specifically with
of an association between overweight and menstrual periods. A history that is incon-
dysmenorrhea is inconsistent.4,6,10 Other sistent and/or physical findings of a pelvic
behaviors such as physical activity and alco- mass, abnormal vaginal discharge, or pelvic
hol consumption have not been associated tenderness that is not limited to the time of
consistently with dysmenorrhea.10,11 the menstrual period suggest a diagnosis of
Mental health problems are another poten- secondary dysmenorrhea. It is appropriate
tially modifiable risk factor. Depression, to perform only an abdominal examination
anxiety, and disruption of social support net- in young adolescents with a typical history
works have been associated with menstrual who have never been sexually active. A pelvic
pain.13 An association between poor self- examination should be performed in females
rated overall health and dysmenorrhea has who have been sexually active to screen for
been noted,9 but socioeconomic status is not sexually transmitted diseases such as chla-
associated consistently with dysmenorrhea.5,9 mydial infection.
Although there has been concern that tubal When the history and physical exami-
sterilization may be a risk factor for dysmen- nation suggest other pelvic pathology, the
orrhea, a cross-sectional study14 found no evaluation should follow accordingly, usually
difference in menstrual pain in women with with pelvic ultrasonography as the initial
and women without tubal sterilization. diagnostic test to rule out anatomic abnor-
malities such as mass lesions. In patients with
severe dysmenorrhea that is unresponsive to
The Author initial treatment, ultrasonography is useful
LINDA FRENCH, M.D., is associate professor and associate chair for clinical ser- to detect ovarian cysts and endometriomas.15
vices in the Department of Family Practice at Michigan State University College It also has reasonably good ability to detect
of Human Medicine, East Lansing. Dr. French received her medical degree from
advanced stage 3 or 4 endometriosis; its
Austral University Faculty of Medicine in Valdivia, Chile, and completed a family
medicine residency at Oakwood Hospital and Medical Center in Dearborn, Mich. concordance with surgical staging is 84 per-
She also completed primary care faculty development and research training fel- cent.16 Sonovaginography (i.e., transvaginal
lowships at Michigan State University. ultrasonography with saline infusion of the
uterus) appears to be better than transvagi-
Address correspondence to Linda French, M.D., Department of Family Practice,
College of Human Medicine, Michigan State University, B101 Clinical Center, East
nal sonography alone in diagnosing recto-
Lansing, MI 48824 (e-mail: Linda.French@hi.msu.edu). Reprints are not available vaginal endometriosis.17 Magnetic resonance
from the author. imaging is limited in its ability to diagnose

286 American Family Physician www.aafp.org/afp Volume 71, Number 2 ◆ January 15, 2005
 Dysmenorrhea
TABLE 2
Treatments for Dysmenorrhea

Strength of
endometriosis (sensitivity, 69 percent; speci- Intervention recommendation
ficity, 75 percent).18 The reference standard Effective
test for diagnosis and staging of endometrio- NSAIDs19 A
sis is laparoscopy or laparotomy with biopsy.
Probably effective
It should be considered when first-line thera-
Danazol (Danocrine)* B
pies are ineffective and dysmenorrhea causes
Extended-cycle oral contraceptives* B
functional impairment.
Hysterectomy* B
Leuprolide acetate (Lupron)* B
Therapy
Depo-medroxyprogesterone acetate (Depo-Provera)* B
Table 219-32 lists therapies for dysmenorrhea
and the strength of evidence to support their Possibly effective
efficacy. Many of the standard treatments Acupuncture/acupressure20,21 B
have not been well studied. The recommen- COX-2 inhibitors22,23 B
dations reflect a balance between the avail- Fish oil supplements24 B
able evidence and an assessment of benefit, Levonorgestrel intrauterine system (Mirena)25 B
harm, and cost. Table 3 provides dosing and Low-fat vegetarian diet 26 B
cost information for prescription drugs used Oral contraceptives (intravaginal administration)27 B
in the treatment of dysmenorrhea. Oral contraceptives (oral administration)† B
Thiamine supplementation19 B
NSAIDS Toki-shakuyaku-san (Japanese herb)19 B
Nonsteroidal anti-inf lammatory drugs Topical heat19 B
(NSAIDs) are the best-established initial Transcutaneous electric nerve stimulation19 B
therapy for dysmenorrhea.19 They have a Vitamin E supplementation19 B
direct analgesic effect through inhibition of Uncertain effectiveness
prostaglandin synthesis, and they decrease Behavioral interventions including exercise19 C
the volume of menstrual flow. These effects Glyceryl trinitrate C
probably are common to all NSAIDs. Two Nifedipine (Procardia)28 C
meta-analyses 33,34 of randomized con- Surgical interruption of pelvic nerve pathways29 C
trolled trials (RCTs) of NSAIDs and acet- Terbutaline (Bricanyl) 30 C
aminophen found that all of the NSAIDs Ineffective
studied (i.e., ibuprofen [Motrin], naproxen Spinal manipulation31,32 B
[Naprosyn], mefenamic acid [Ponstel], and
aspirin) were effective in treating women NSAIDs = nonsteroidal anti-inflammatory drugs; COX-2 = cyclooxygenase-2.
with dysmenorrhea, and all of the NSAIDs A = consistent, good-quality, patient-oriented evidence; B = inconsistent or limited-
were more effective than acetaminophen.19 quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual
practice, opinion, or case series. See page 225 for more information.
Small studies22,23 of cyclooxygenase-2
At the time of publication new information had appeared regarding the safety
NOTE :
inhibitors have shown efficacy similar to of COX-2 inhibitors. Because they appear to increase the risk of myocardial infarction,
that of NSAIDs in the treatment of dys- the decision to use these agents should only be made after a discussion of risks and
menorrhea. NSAIDs may be most effective benefits with the patient.
when therapy is started before the onset of *—Mechanism: suppression of menses.
menstrual pain and flow, although therapy †—Based on consistent observational data.
need not be continued after the end of the Information from references 19 through 32.
flow.

ORAL CONTRACEPTIVE PILLS from oral contraceptives in the treatment

Treatment of dysmenorrhea is a well- of dysmenorrhea, and in one exploratory
accepted off-label use for oral contracep- RCT35 of women who took desogestrel-
tive pills (OCPs). The proposed mechanism containing OCPs, these women had less
of action is reduced prostaglandin release pain during menses than women who
during menstruation. Consistent obser- received placebo. An observational study36
vational data support a beneficial effect of dysmenorrhea severity in women who

January 15, 2005 ◆ Volume 71, Number 2 www.aafp.org/afp American Family Physician 287
 (Mirena) showed a decrease in prevalence
TABLE 3 of dysmenorrhea from 60 percent before
Agents Used in the Treatment of Dysmenorrhea use of the device to 29 percent after 36
months of use.
Cost A novel treatment approach is intravagi-
Agent Dosage (generic)* nal administration of standard OCPs (i.e.,
Danazol (Danocrine) 100 or 200 mg twice daily $172 to 286 30 mcg of ethinyl estradiol and 150 mg
(153 to 257) of levonorgestrel daily); an RCT 27 of 150
Leuprolide acetate 3.75 mg IM monthly 473 women found fewer systemic side effects
(Lupron) and less dysmenorrhea with the intravagi-
NSAIDs† nal approach (21 percent with intravaginal
Diclofenac (Voltaren) 50 mg three times daily 22 (12 to 16) use versus 44 percent with standard oral
Ibuprofen (Motrin) 800 mg three times daily 6 (3 to 5) administration; number needed to treat,
Mefenamic acid Initial dose: 500 mg, followed 23 4; P < .001). Contraceptive patches appear
(Ponstel) by 250 mg four times daily to be less effective than OCPs taken orally
Naproxen (Naprosyn) 500 to 550 mg twice daily 13 (9 to 10) in treating women with dysmenorrhea.40
Oral contraceptives 1 tablet daily 22 to 36
OTHER PHARMACOLOGIC TREATMENTS
IM = intramuscularly; NSAIDs = nonsteroidal anti-inflammatory drugs; COX-2 =
cyclooxygenase-2. Several medications that induce uterine
*—Estimated cost to the pharmacist for one month’s therapy based on average
relaxation have been proposed for treat-
wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 2004. Cost to ment of dysmenorrhea. In one RCT,41 it was
the patient will be higher, depending on prescription filling fee. found that glyceryl trinitrate is less effective
†—Cost for NSAIDs assumes four days of therapy per month.
than diclofenac and is associated with a high
incidence of headache. Early uncontrolled
pilot studies28,30 of oral nifedipine and intra-
used different forms of contraception venous terbutaline showed promise, but fur-
showed lower mean scores in users of ther study on these drugs is needed.
monophasic formulations compared with Treatment to suppress the menstrual cycle
triphasics. However, a Cochrane review37 with danazol (Danocrine) or leuprolide ace-
found insufficient evidence from RCTs to tate (Lupron) may be considered, rarely, in
draw conclusions about the effectiveness refractory cases. These are expensive thera-
of OCPs in treating dysmenorrhea. pies with significant side effects; they usu-
ally are reserved for treatment of conditions
OTHER HORMONAL METHODS other than primary dysmenorrhea, such as
Several other off-label methods exist for endometriosis and chronic pelvic pain that
treating dysmenorrhea with hormonal is not limited to the time of the menstrual
contraceptives. Most women who receive period.
depo-medrox y progesterone acetate
LIFESTYLE MODIFICATION
(Depo-Provera) are amenorrheic within
the first year of use. Simi- Few studies have examined the effect of life-
larly, extended-cycle use of style-modification interventions in the man-
An intravaginal contracep- OCPs (i.e., usually taking agement of dysmenorrhea. One cross-over
tive is more effective and OCPs for 12 weeks followed study26 of a low-fat vegetarian diet versus
associated with fewer by one week off) leads to less- placebo pill showed decreased duration and
side effects than the same frequent menstrual periods. intensity of dysmenorrhea in women in the
agent in an oral form. In a retrospective review, 38 21 intervention group. Although some studies
percent of women who chose have reported a benefit with exercise, the
extended-cycle regimens did effect is questionable because participants
so primarily for treatment of dysmen- were not blinded to the study hypothesis.19
orrhea. Observational data 39 from users Smoking cessation has not been studied as
of the levonorgestrel intrauterine device an intervention to manage dysmenorrhea.

288 American Family Physician www.aafp.org/afp Volume 71, Number 2 ◆ January 15, 2005
 Dysmenorrhea

Complementary and Alternative A single small study44 of transcutaneous

Medicines electric nerve stimulation (TENS) suggested
SUPPLEMENTS that TENS is more effective in treating dys-
Thiamine at a dosage of 100 mg daily was menorrhea than a sham procedure, with
found to be effective in treating dysmenor- 42 percent of women reporting
rhea in a double-blind RCT of more than 500 good to excellent pain relief Nonsteroidal anti-inflam-
East Indian women aged 12 to 21 years with with TENS compared with 3
matory drugs are the initial
moderate to severe symptoms.19 It is unclear percent of control patients.
therapy of choice in patients
whether thiamine would be effective in U.S. However, a systematic review45
with primary dysmenorrhea.
women, whose diet may be quite different found insufficient evidence to
from that of Indian women. A single RCT determine if TENS is effective.
of vitamin E found that 2,500 IU taken daily In a study46 of a topical heated patch com-
for five days starting two days before men- pared with low-dose ibuprofen (i.e., 400 mg
struation was more effective than placebo in three times daily) and placebo, the heated
treating dysmenorrhea.19 A small RCT24 of patch was as effective as ibuprofen.
omega-3 polyunsaturated fatty acids found A well-designed study31 of spinal manip-
that 2 g daily of a fish oil supplement sig- ulative therapy versus a sham procedure
nificantly reduced pain compared with pla- showed similar pain relief in both groups.
cebo. High intake of fish n-3 fatty acid also In addition, a systematic review32 of spinal
was associated with less average symptom manipulation in the treatment of dysmenor-
severity in an observational study of Danish rhea concluded that there is no evidence to
women.42 suggest effectiveness.

HERBAL REMEDIES Surgical Therapies

The Japanese herbal remedy toki-shakuyaku- In rare instances, a surgical approach may be
san (TSS) has been shown in an RCT to considered for women with severe, refractory
be better than placebo in the treatment of dysmenorrhea. Refractory dysmenorrhea is
women with dysmenorrhea.19 Because this an accepted indication for hysterectomy. Lap-
product is not regulated, the ingredients aroscopic uterine nerve ablation (LUNA) and
and effectiveness may vary among formula- presacral neurectomy also have been used in
tions. It does not appear to suppress fertility refractory cases. Observational data47 show
or ovulation. There are insufficient data to that at one year after the procedure, pain
evaluate other herbal products.19 relief persisted in 82 percent of women having
presacral neurectomy and in only 51 percent
PHYSICAL TREATMENTS having LUNA. Information about long-term
Limited evidence from RCTs suggests that outcomes is relatively lacking. A Cochrane
acupuncture and acupressure are effective in meta-analysis29 of surgical interruption of
treating dysmenorrhea. In a study20 of acu- pelvic nerve pathways as a treatment for
puncture versus sham acupuncture, 91 per- dysmenorrhea concluded that evidence was
cent of patients in the treatment group had insufficient to recommend the procedure,
pain relief compared with 36 percent of con- regardless of the cause of the dysmenorrhea.
trol patients. Patients in the treatment group
had a 41 percent reduction in use of pain Approach to the Patient
medication, while no difference was noted in NSAIDs are the initial therapy of choice
control patients.20 A study21 of acupressure at in patients with presumptive primary dys-
a point on the hand found pain relief similar menorrhea. Because all NSAIDs are equal
to that in patients who took ibuprofen and in efficacy, agent selection should be guided
better than that in patients who received by cost, convenience, and patient prefer-
sham acupressure. A study43 of acupressure ence, with ibuprofen or naproxen being a
underwear was inconclusive because of lack good choice for most patients. If hormonal
of blinding. contraception is desired, monophasic OCPs

January 15, 2005 ◆ Volume 71, Number 2 www.aafp.org/afp American Family Physician 289
 and depo-medroxyprogesterone acetate also 3. Strinic T, Bukovic D, Pavelic L, Fajdic J, Herman I, Stipic
I, et al. Anthropological and clinical characteristics in
may be considered. If relief is insufficient, adolescent women with dysmenorrhea. Coll Antropol
the physician may consider prolonged-cycle 2003;27:707-11.
OCP use or intravaginal use of OCPs. 4. Andersch B, Milsom I. An epidemiologic study of young
women with dysmenorrhea. Am J Obstet Gynecol
In women who do not desire hormonal
1982;144:655-60.
contraception, topical heat; TSS; thiamine, 5. Klein JR, Litt IF. Epidemiology of adolescent dysmenor-
vitamin E, or fish oil supplements; a low-fat rhea. Pediatrics 1981;68:661-4.
vegetarian diet; and acupressure are rela- 6. Sundell G, Milsom I, Andersch B. Factors influencing
tively simple and inexpensive alternatives the prevalence and severity of dysmenorrhoea in young
women. Br J Obstet Gynaecol 1990;97:588-94.
that can be used alone or in combination.
7. Moen MH, Stokstad T. A long-term follow-up study of
If dysmenorrhea is not controlled with any women with asymptomatic endometriosis diagnosed
of these approaches, pelvic ultrasonogra- incidentally at sterilization. Fertil Steril 2002;78:773-6.
phy should be performed and referral for 8. Momoeda M, Taketani Y, Terakawa N, Hoshiai H, Tanaka
K, Tsutsumi O, et al. Is endometriosis really associated with
laparoscopy should be considered to rule pain? Gynecol Obstet Invest 2002;54(suppl 1):18-21.
out secondary causes of dysmenorrhea.48,49 9. Teperi J, Rimpela M. Menstrual pain, health and behav-
In severe refractory primary dysmenorrhea, iour in girls. Soc Sci Med 1989;29:163-9.
additional safe alternatives for women who 10. Harlow SD, Park M. A longitudinal study of risk factors
for the occurrence, duration and severity of menstrual
want to conceive are (in order of clinical
cramps in a cohort of college women [published erra-
preference) TENS, acupuncture, nifedip- tum appears in Br J Obstet Gynaecol 1997;104:386]. Br
ine (Procardia), and terbutaline (Bricanyl). J Obstet Gynaecol 1996;103:1134-42.
Otherwise, danazol or leuprolide may be 11. Parazzini F, Tozzi L, Mezzopane R, Luchini L, Marchini
M, Fedele L. Cigarette smoking, alcohol consump-
considered and, rarely, hysterectomy. tion, and risk of primary dysmenorrhea. Epidemiology
1994;5:469-72.
Therapies on the Horizon 12. Montero P, Bernis C, Fernandez V, Castro S. Influence of
Several of the therapeutic approaches discussed body mass index and slimming habits on menstrual pain
and cycle irregularity. J Biosoc Sci 1996;28:315-23.
in this article deserve further study before we 13. Alonso C, Coe CL. Disruptions of social relationships
can say definitively whether they are effective. accentuate the association between emotional distress
Two options may become available in the near and menstrual pain in young women. Health Psychol
2001;20:411-6.
future: (1) a vasopressin-receptor antagonist
14. Harlow BL, Missmer SA, Cramer DW, Barbieri RL. Does
is being tested. Because vasopressin appears tubal sterilization influence the subsequent risk of men-
to be involved in the pathogenesis of dysmen- orrhagia or dysmenorrhea? Fertil Steril 2002;77:754-60.
orrhea, vasopressin-receptor antagonists are 15. Moore J, Copley S, Morris J, Lindsell D, Golding S, Ken-
theoretically useful. However, studies50-53 to nedy S. A systematic review of the accuracy of ultra-
sound in the diagnosis of endometriosis. Ultrasound
date have not shown consistent evidence of Obstet Gynecol 2002;20:630-4.
efficacy. And (2) a frameless levonorgestrel 16. Exacoustos C, Zupi E, Carusotti C, Rinaldo D, Marconi
IUD has been introduced in Europe, where it D, Lanzi G, et al. Staging of pelvic endometriosis: role
of sonographic appearance in determining extension of
is being used in the management of primary disease and modulating surgical approach. J Am Assoc
and secondary dysmenorrhea.54 The frameless Gynecol Laparosc 2003;10:378-82.
device decreases menstrual flow and provides 17. Dessole S, Farina M, Rubattu G, Cosmi E, Ambrosini
contraceptive efficacy similar to that of cur- G, Nardelli GB. Sonovaginography is a new technique
for assessing rectovaginal endometriosis. Fertil Steril
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18. Stratton P, Winkel C, Premkumar A, Chow C, Wilson
The author indicates that she does not have any conflicts
J, Hearns-Stokes R, et al. Diagnostic accuracy of lapa-
of interest. Sources of funding: none reported.
roscopy, magnetic resonance imaging, and histopatho-
logic examination for the detection of endometriosis.
Fertil Steril 2003;79:1078-85.
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