THERAPY IN PRACTICE

Pediatr Drugs 2008; 10 (1): 1-7 1174-5878/08/0001-0001/$48.00/0 2008 Adis Data Information BV. All rights reserved.

Dysmenorrhea in Adolescents
Diagnosis and Treatment
Linda French
Department of Family Medicine, University of Toledo, College of Medicine, Toledo, Ohio, USA

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. Primary Dysmenorrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1 Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.2 Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2. Causes of Secondary Dysmenorrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3. Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3.1 General Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3.2 Diagnostic Imaging and Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4.1 NSAIDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4.2 Standard Use of Oral Contraceptives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4.3 Other Hormonal Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 4.4 Other Pharmacologic Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 5. Complementary and Alternative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5.1 Lifestyle Modification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5.2 Supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5.3 Physical Modalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5.4 Surgical Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Abstract

Dysmenorrhea occurs in the majority of adolescent girls and is the leading cause of recurrent short-term school absence in this group. In the vast majority of cases, a presumptive diagnosis of primary dysmenorrhea can be made based on a typical history of low anterior pelvic pain coinciding with the onset of menses and lasting 13 days with a negative physical examination. Risk factors for primary dysmenorrhea include nulliparity, heavy menstrual flow, and smoking. Poor mental health and social supports are other associations. Empiric therapy for primary dysmenorrhea can be initiated without diagnostic testing. Effective therapies include NSAIDs, oral contraceptives, and pharmacologic suppression of menstrual cycles. In atypical, severe, or refractory cases, imaging and/or laparoscopy should be performed to investigate secondary causes of dysmenorrhea. The most common cause of secondary dysmenorrhea is endometriosis, the treatment of which may include medical and surgical approaches. Pharmacologic treatment of young women with pain related to endometriosis is similar to treatment of primary dysmenorrhea but may infrequently include gonadotropin-releasing hormone agonists in severe refractory cases.

Painful menses or dysmenorrhea is a common complaint among adolescent girls, for which they may or may not seek medical attention. Primary dysmenorrhea is defined as painful

menses with normal pelvic anatomy. It usually begins when cycles become ovulatory and is characterized by crampy low anterior pelvic pain beginning shortly before or at the onset of menses and

French

lasting 13 days. Associated peri-menstrual symptoms are generally related to the decreases in circulating estrogen and/or progesterone levels and may include headache, diarrhea, and nausea. In a minority of cases dysmenorrhea is secondary to pelvic organ pathology. The prevalence of dysmenorrhea is highest among adolescents, with estimates ranging from 20% to 90% depending on the method of assessment.[1-3] About 15% of adolescent girls report severe dysmenorrhea,[1,4] and this is the leading cause of short-term absenteeism, including school absence, in adolescent girls in the US, with estimates of prevalence rates for dysmenorrhea-associated absenteeism ranging from 20% to 30%.[2,5] A longitudinal study of a representative cohort of Swedish women showed a prevalence of dysmenorrhea of 90% at 19 years of age and 67% at age 24 years, with 10% of 24-year-olds reporting pain that interfered with daily function.[5] Most adolescents self-medicate with over-the-counter medications, and a minority consult healthcare providers.[1-3] 1. Primary Dysmenorrhea
1.1 Pathogenesis

aged 1420 years.[14] Other behavioral characteristics such as physical activity and alcohol consumption have not been found to be associated with dysmenorrhea.[12,13] Another potentially modifiable risk factor is poor mental health. Depression, anxiety, and disruption of social support networks have been inconsistently associated with menstrual pain.[14,15] While poor self-rated overall health is associated with dysmenorrhea,[9] there have been conflicting reports regarding an association with socioeconomic status.[4,9,14] 2. Causes of Secondary Dysmenorrhea In the vast majority of cases, dysmenorrhea in adolescence has no underlying organic pathology. However, sexually transmitted infections (STIs), endometriosis, and congenital anomalies are possible secondary causes of menstrual pain.[16-18] Endometriosis is the presence of endometrial-like tissue outside the uterus, typically in the peritoneal cavity. Its biologic activity is estrogen dependent. The tissue generally originates in the uterus and is transported through the fallopian tubes with the menses. Endometriosis is the most important differential diagnosis because it is the most common and the most likely condition to present in a way that mimics primary dysmenorrhea. The typical presentation of endometriosis is pelvic pain that occurs during menses but which is not limited to the menstrual period and the low anterior pelvis. The pain associated with endometriosis ranges from absent to chronic unrelenting pelvic pain. Endometriosis may also be discovered during investigation of infertility, but even advanced disease in that context may not have associated pain. Less common etiologies for secondary dysmenorrhea are congenital malformations and dermoid tumors. Infectious etiologies including STIs should be considered in cases of dysmenorrhea of recent onset, especially when abnormal vaginal discharge and/or pelvic tenderness are present. Both chlamydial and gonococcal infections may also be asymptomatic. 3. Management
3.1 General Considerations

The current concept of the pathogenesis of primary dysmenorrhea is that it is primarily related to release of prostaglandins in the menstrual fluid. Prostaglandins are involved in the regulation of ovulation and in endometrial physiology, including proliferation of endometrial glands and menstruation.[6] High levels of prostaglandins are associated with uterine contractions and pain. Vasopressin may also play a role by increasing uterine contractility and by causing ischemic pain as a result of vasoconstriction.[7] Elevated vasopressin levels are also observed in women with primary dysmenorrhea.
1.2 Risk Factors

Risk factors for primary dysmenorrhea include young age and nulliparity.[8-10] However, one longitudinal study found that age was not a risk factor after controlling for parity and other factors, and that dysmenorrhea improved after childbirth.[5] Heavy menstrual flow is consistently associated with dysmenorrhea.[4,8,9] A family history of endometriosis is a risk factor for endometriosis, which is a secondary cause of dysmenorrhea (see section 2). Behavioral risk factors are of interest because of the potential for intervention. Observational studies have consistently found an association between smoking and dysmenorrhea.[5,10-12] Any association between being overweight and dysmenorrhea is inconsistent,[5,9,12,13] and attempts to lose weight are associated with increased menstrual pain independent of body mass index in women
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A management approach for adolescents with dysmenorrhea is presented in figure 1. In the vast majority of cases, empiric therapy (see section 4) may be initiated with a presumptive diagnosis of primary dysmenorrhea based on a typical history of low anterior pelvic pain starting in adolescence and associated specifically with menstrual periods and a normal physical examination. It is appropriate to limit the physical examination in young adolescents with a typical history who have never been sexually active to an abdominal
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Dysmenorrhea in Adolescents

examination. However, many clinicians prefer to perform a pelvic examination of sexually active teens. Screening for Chlamydia trachomatis and Neisseria gonorrheae is recommended by the US Preventive Services Task Force[19] in asymptomatic sexually active adolescent women, and a sample of urine or vaginal fluid should be obtained for that purpose. A history that is inconsistent with primary dysmenorrhea or physical findings of pelvic tenderness outside the menstrual period, a pelvic mass, or abnormal vaginal discharge suggests a diagnosis of secondary dysmenorrhea. In such cases, further diagnostic evaluation is indicated (see section 3.2) and the work-up should follow accordingly.
Painful menses Low anterior pelvic pain for 13 days around start of menses?

3.2 Diagnostic Imaging and Procedures

Yes
Presumptive diagnosis of primary dysmenorrhea

No

Treat with NSAID and/or OCs (optional suppression of menses with depo-medroxyprogesterone or extended-cycle OCs)

Dysmenorrhea controlled?

Yes
Continue therapy

No

Suspect secondary dysmenorrhea

Signs or symptoms of STI?

No

Yes
Confirm and treat

In cases of severe dysmenorrhea, especially if unresponsive to initial empiric therapy, further diagnostic evaluation is indicated. The gold standard for diagnosis and staging of endometriosis is laparoscopy or laparotomy with biopsy. The macroscopic appearance of endometriosis is variable and includes clear vesicles, red lesions, dark pigmented lesions with hemosiderin, and white scarred lesions. Cystic masses of endometriosis are called endometriomas. Endometriosis disease severity has been defined by the American Society for Reproductive Medicine in four stages, ranging from minimal to severe.[16] Scoring is based on the location and size of lesions, together with the presence of adhesions. Ultrasound is useful for detecting ovarian cysts, endometriomas, and some congenital malformations.[20] It also has reasonably good ability to detect advanced, stage 3 or 4 endometriosis, with a concordance with surgical staging of 84%.[21] As ultrasound is noninvasive, it is usually the investigation that is ordered first. Sonovaginography (transvaginal ultrasonography with saline infusion of the uterus) appears to be superior to transvaginal sonography alone for diagnosing rectovaginal endometriosis.[22] Magnetic resonance imaging has been studied and found to be rather limited in its ability to diagnose endometriosis (sensitivity 69%, specificity 75%),[23] but may be useful for detection of obstructive anomalies. In severe cases of dysmenorrhea, early laparoscopy may be considered in the evaluation of the patient for endometriosis for two reasons: (i) pain may be reduced by debulking the ectopic tissue;[24] and (ii) severe pain at a young age may predict a progressive course that includes compromised fertility, a possibility that the patient may wish to be aware for eventual family planning.[24,25] However, as noted in section 2, there is no close relationship between pain and infertility in patients with endometriosis. 4. Drug Therapy Table I provides a list of commonly used therapies for dysmenorrhea.
4.1 NSAIDs

Pelvic ultrasound Consider laparoscopy

Endometriosis?

No
Normal anatomy?

Yes
Consider suppression of menses with depomedroxyprogesterone or extended-cycle OCs

No
Surgery if indicated

Yes
Unexplained dysmenorrhea

Fig. 1. Management approach to the adolescent with dysmenorrhea. OC = oral contraceptive; STI = sexually transmitted infection.
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The most established initial therapy for dysmenorrhea is NSAIDs.[26] At least two possible mechanisms of action of NSAIDs exist: they have a direct analgesic effect through inhibition of prostaglandin synthesis, and they decrease the volume of menstrual flow. These are probably both class effects of the NSAIDs. The cyclo-oxygenase (COX)-2 inhibitor celecoxib is approved for treatment of dysmenorrhea, but is not superior to NSAIDs. Head-to-head comparisons of different formulations are largely lacking, and when new drugs have been compared with
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Table I. Treatments for dysmenorrhea Effective First-line therapy NSAIDs in standard dosage range Oral contraceptives Suppression of menses Depo-medroxyprogesterone acetate 150 mg every 3 mo Extended-cycle oral contraceptives: 12 wk on hormonal pills followed by 1 wk off Levonorgestrel intrauterine system Probably effective Physical modalities Topical heat Acupuncture/acupressure Topical magnetic device Transcutaneous electric nerve stimulation (TENS) Herbs and supplements Thiamine supplementation 100 mg/day Tocopherol (vitamin E) 400 IU/day Fish oil 2 g/day

low in adolescents, this is not considered to be a contraindication by most clinicians.

4.3 Other Hormonal Approaches

older drugs they have been found to be equivalent. Selection of a particular drug should be made on the basis of attributes such as cost and convenience. Two meta-analyses of randomized controlled trials (RCTs) of NSAIDs and acetaminophen (paracetamol) found that all NSAIDs studied (ibuprofen, naproxen, mefenamic acid, and aspirin [acetylsalicylic acid]) were effective, and all were more effective than acetaminophen.[26] NSAIDs may be most effective when started prior to the onset of menstrual pain and flow.
4.2 Standard Use of Oral Contraceptives

Treatment of dysmenorrhea with oral contraceptives (OCs) is a well accepted off-label practice. The proposed mechanism of action is reduced prostaglandin release during menstruation. Use of OCs is associated with low levels of COX-2 and endometrial proliferation markers.[27] A few RCTs and a large body of consistent observational data provide evidence for the effectiveness of OCs in the treatment of dysmenorrhea.[28,29] One observational study of dysmenorrhea severity among users of different forms of contraception suggested that monophasic formulations were more effective than triphasics.[30] OCs are contraindicated in patients with procoagulable conditions. Cigarette smoking increases the risk of venous thromboembolism even in young women, but as the absolute risk is still very
2008 Adis Data Information BV. All rights reserved.

Several other off-label approaches for treatment of dysmenorrhea using hormonal contraceptive products exist. Some approaches involve hormonal suppression of menses. Most women receiving depo-medroxyprogesterone acetate are amenorrheic within the first year of use. Similarly, extended-cycle use of OCs, usually 12 weeks on OCs followed by 1 week off, result in less frequent menstrual periods. A Cochrane review[31] of extended-cycle OCs versus 28-day cycle OCs identified six RCTs that met inclusion criteria. Bleeding patterns were equivalent or reduced in the extended-cycle groups. Not all studies reported menstrual pain, but those that did found less pain with extendedcycle regimens. There was no difference in adherence or safety profiles. A retrospective study reported that 21% of women who chose extended-cycle regimens did so primarily for treatment of dysmenorrhea.[32] Observational data from users of the levonorgestrel intrauterine device (L-IUD) showed a decrease in prevalence of dysmenorrhea from 60% before use to 29% after 36 months with L-IUD.[33] Many clinicians prefer not to use this form of contraception in nulliparous patients or minors because of concerns about complications related to the presence of a foreign body in women at increased risk for STIs. However, nulliparity, per se, is not a contraindication for use of this method. A small study of adolescents using the transdermal contraceptive patch for at least 6 months found that 39% reported a decrease in menstrual pain, although 11% reported increased pain.[34] A novel approach of intravaginal administration of standard OCs (ethinylestradiol 30 g and levonorgestrel 150 mg/day) in 150 women in an RCT showed fewer systemic adverse effects with the intravaginal approach and less dysmenorrhea (21% with intravaginal use vs 44% with standard oral administration; number needed to treat = 4, p < 0.001).[35] On the other hand, contraceptive patches appeared to be less effective than OCs in another study.[36]
4.4 Other Pharmacologic Treatments

Several medications with a mechanism of action of uterine relaxation have been proposed for treatment of dysmenorrhea. Glyceryl trinitrate was less effective than diclofenac, and there was a high withdrawal rate due to headache with the former.[37] Early uncontrolled pilot studies of oral nifedipine and intravenous terbutaline showed promise, but these agents have not been fully studied.[38,39]
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Dysmenorrhea in Adolescents

A 6-month course of a gonadotropin-releasing-hormone (GnRH) analog, leuprolide (leuprorelin) or goserelin, may be considered in severe refractory cases of endometriosis to induce a hypoestrogenic state.[24] However, these are expensive therapies with significant adverse effects and they do not prevent recurrence over the long term. They are not indicated for severe endometriosis in women <18 years old or for >6 months duration. The gonadotropin inhibitor danazol has also been used and is effective, but its androgenic adverse effects, including acne, fatigue, and weight gain, make it an unlikely choice.[40] The aromatase inhibitors anastrozole and letrozole inhibit estrogen production, including local aromatization of androgens that may persist with the use of GnRH agonists/antagonists. Preliminary studies show promise for these agents in the medical treatment of endometriosis. Aromatase inhibitors reduce endometrial cell proliferation in vitro,[41] and small case series have shown reductions in dysmenorrhea.[42-44] One small RCT showed the combination of goserelin and anastrozole to be superior to goserelin alone for reduction of pain and symptom recurrence after surgery for severe endometriosis.[45] Other experimental treatments for dysmenorrhea include selective progesterone receptor modulators, tumor necrosis factor- inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, and estrogen receptor agonists.[46,47] 5. Complementary and Alternative Medicine
5.1 Lifestyle Modification

found to be effective.[50] It is unclear whether thiamine would be effective in women from the US whose diet may be quite different. A Bandolier review has reported on tocopherol (vitamin E) treatment of young women with dysmenorrhea.[51] The review identified three RCTs that were consistent in reporting a benefit. In the most recent of these, 88% of women responded by the third to fourth cycle with a clinically important reduction in dysmenorrhea versus 11% of women receiving placebo.[52] The active treatment consisted of tocopherol 200 IU twice daily taken for 5 days a month starting 2 days prior to expected menses. While a metaanalysis[53] of the use of antioxidant vitamins in older adults to prevent cardiovascular disease showed an increase of 4/1000 per year in all-cause mortality with high-dose tocopherol used continuously, this moderate dose in young women who use it intermittently is unlikely to pose significant risk. In a small RCT, daily supplementation with omega-3 polyunsaturated fatty acids in the form of a fish oil supplement of approximately 2 g/day showed a statistically significant reduction in pain in adolescents with dysmenorrhea compared with placebo.[54] High intake of fish n-3 fatty acid was also associated with less dysmenorrhea in an observational study of Danish women.[55]
5.3 Physical Modalities

Lifestyle modification interventions for management of dysmenorrhea have been the subject of little study. One elegant crossover study of a low-fat vegetarian diet versus placebo pill showed decreased duration and intensity of dysmenorrhea with the diet.[48] However, another study, in Japanese women aged 1924 years, found no association between dysmenorrhea and a low-fat diet.[49] Instead, they found a small but significant inverse association between high fiber intake and dysmenorrhea. Although some studies have reported benefit from exercise, the beneficial effect is open to question because participants were not blinded to the study hypothesis.[26] Smoking cessation as an intervention to manage dysmenorrhea has not been studied.
5.2 Supplements

Thiamine supplementation at a dosage of 100 mg/day has been studied in a double-blinded RCT of more than 500 Indian women aged 1221years with moderate to severe dysmenorrhea and was
1

A small RCT of a 2700 gauss magnetic device (LadyCare)1 has shown positive results in women with dysmenorrhea.[56] The device is secured to the underwear by magnetic force between two parts placed inside and outside of the underwear over the pelvic area. A low-powered, 140 gauss magnetic device identical in appearance served as a control in this study. The mean reduction in pain was 53% with the active treatment device versus 15% with the placebo, which was statistically significant (p < 0.02). Limited evidence from RCTs suggests that acupuncture and acupressure are effective. In a study of acupuncture versus sham acupuncture, 91% had pain relief with acupuncture versus 36% with sham acupuncture, and there was a corresponding 41% reduction in the use of pain medication versus no reduction.[57] A study of acupressure at a point located in the hand found pain relief to be similar to that achieved with ibuprofen and superior to that for sham acupressure.[58] A study using an acupressure panty was inconclusive because of a lack of blinding.[59] A single small study of transcutaneous electrical nerve stimulation (TENS) suggested that TENS is more effective than placebo TENS for dysmenorrhea, with 42% of women obtaining good to excellent pain relief with TENS compared with 3% with placebo.[60] However, a systematic review found insufficient evidence to determine that TENS is effective for primary dysmenorrhea.[61]

The use of trade names is for product identification purposes only and does not imply endorsement.
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2008 Adis Data Information BV. All rights reserved.

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In a study of a topical heated patch versus low-dose ibuprofen (400 mg three times daily) or placebo, the patch was equivalent to ibuprofen in the treatment of dysmenorrhea.[62] A well designed study of spinal manipulative therapy versus sham therapy showed similar pain relief in both groups, suggesting that manipulation is not effective.[63] In addition, a systematic review of spinal manipulation to treat dysmenorrhea concluded that there is no evidence to suggest effectiveness.[64]
5.4 Surgical Therapies

In rare instances, a surgical approach may be considered for severe and refractory pelvic pain, but usually not for dysmenorrhea alone. However, pelvic nerve ablation surgeries are of uncertain benefit and hysterectomy is unlikely to be considered in adolescent girls.[65] 6. Conclusion The initial therapy of choice for patients with presumptive primary dysmenorrhea is NSAIDs. If hormonal contraception is desired, OCs and depo-medroxyprogesterone acetate may also be considered. If relief is insufficient, extended-cycle OC use or intravaginal use of OCs should be considered. For women not desiring hormonal contraception, thiamine supplementation, topical heat, magnet therapy, and a diet rich in fiber and fish or fish oil supplements are relatively simple and inexpensive alternatives that can be used alone or in combination. If dysmenorrhea is not controlled with any of these approaches, pelvic ultrasound should be performed and/or laparoscopy considered to rule out secondary causes of dysmenorrhea. Acknowledgments
No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.

References
1. Davis AR, Westhoff CL. Primary dysmenorrhea in adolescent girls and treatment with oral contraceptives. J Pediatr Adolesc Gynecol 2001 Feb; 14 (1): 3-8 2. Banikarim C, Chacko MR, Kelder SH. Prevalence and impact of dysmenorrhea on Hispanic female adolescents. Arch Pediatr Adolesc Med 2000 Dec; 154 (12): 1226-9 3. Strinic T, Bukovic D, Pavelic L, et al. Anthropological and clinical characteristics in adolescent women with dysmenorrhea. Coll Antropol 2003 Dec; 27 (2): 707-11 4. Klein JR, Litt IF. Epidemiology of adolescent dysmenorrhea. Pediatrics 1981 Nov; 68 (5): 661-4 5. Sundell G, Milsom I, Andersch B. Factors influencing the prevalence and severity of dysmenorrhoea in young women. Br J Obstet Gynaecol 1990 Jul; 97 (7): 588-94 6. Jabbour HN, Sales KJ, Smith OP, et al. Prostaglandin receptors are mediators of vascular function in endometrial pathologies. Mol Cell Endocrinol 2006 Jun 27; 252 (1-2): 191-200
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7. Liedman R, Skillern L, James I, et al. Validation of a test model of induced dysmenorrhea. Acta Obstet Gynecol Scand 2006; 85: 451-7 8. Burnett MA, Antao V, Black A, et al. Prevalence of primary dysmenorrhea in Canada. J Obstet Gynaecol Can 2005 Aug; 27 (8): 765-70 9. Teperi J, Rimpela M. Menstrual pain, health, and behaviour in girls. Soc Sci Med 1989; 29 (2): 163-9 10. Andersch B, Milsom I. An epidemiologic study of young women with dysmenorrhea. Am J Obstet Gynecol 1982 Nov 15; 144 (6): 655-60 11. Juang CM, Yen MS, Twu NF, et al. Impact of pregnancy on primary dysmenorrhea. Int J Gynaecol Obstet 2006 Mar; 92 (3): 221-7 12. Harlow SD, Park M. A longitudinal study of risk factors for the occurrence, duration and severity of menstrual cramps in a cohort of college women. Br J Obstet Gynaecol 1996 Nov; 103 (11): 1134-42 13. Parazzini F, Tozzi L, Mezzopane R, et al. Cigarette smoking, alcohol consumption, and risk of primary dysmenorrhea. Epidemiology 1994 Jul; 5 (4): 469-72 14. Rapkin AJ, Tsao JC, Turk N, et al. Relationships among self-rated tanner staging, hormones, and psychosocial factors in healthy female adolescents. J Pediatr Adolesc Gynecol 2006 Jun; 19 (3): 181-7 15. Montero P, Bernis C, Fernandez V, et al. Influence of body mass index and slimming habits on menstrual pain and cycle irregularity. J Biosoc Sci 1996 Jul; 28 (3): 315-23 16. American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67 (5): 817-21 17. Proctor M, Farquhar C. The diagnosis and management of dysmenorrhoea. BMJ 2006; 132: 1134-8 18. Farquhar C. Endometriosis. BMJ 2007; 334: 249-53 19. US Preventive Services Task Force, Agency for Healthcare Research and Quality. Screening for gonorrhea: summary of recommendations [online]. Available from URL: http://www.ahrq.gov/clinic/uspstf/uspsgono.htm [Accessed 2007 Nov 21] 20. Moore J, Copley S, Morris J, et al. A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Ultrasound Obstet Gynecol 2002 Dec; 20 (6): 630-4 21. Exacoustos C, Zupi E, Carusotti C, et al. Staging of pelvic endometriosis: role of sonographic appearance in determining extension of disease and modulating surgical approach. J Am Assoc Gynecol Laparosc 2003 Aug; 10 (3): 378-82 22. Dessole S, Farina M, Rubattu G, et al. Sonovaginography is a new technique for assessing rectovaginal endometriosis. Fertil Steril 2003 Apr; 79 (4): 1023-7 23. Stratton P, Winkel C, Premkumar A, et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril 2003 May; 79 (5): 1078-85 24. Practice Committee of the American Society of Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril 2006 Nov; 86 (5 Suppl.): S18-27 25. Ballweg ML. Impact of endometriosis on womens health: comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol 2004 Apr; 18 (2): 201-18 26. Proctor ML, Farquhar CM. Dysmenorrhoea. In: Group BP, editor. Clinical evidence. London: BMJ Publishing Group, 2003: 2058-78 27. Maia Jr H, Maltez A, Studard E, et al. Effect of the menstrual cycle and oral contraceptives on cyclooxygenase-2 expression in the endometrium. Gynecol Endocrinol 2005 Jul; 21 (1): 57-61 28. Davis AR, Westhoff C, OConnell K, et al. Oral contraceptives for dysmenorrhea in adolescent girls: a randomized trial. Obstet Gynecol 2005 Jul; 106 (1): 97-104 29. Hendrix SL, Alexander NJ. Primary dysmenorrhea treatment with a desogestrelcontaining low-dose oral contraceptive. Contraception 2002 Dec; 66 (6): 393-9 30. Milsom I, Sundell G, Andersch B. The influence of different combined oral contraceptives on the prevalence and severity of dysmenorrhea. Contraception 1990 Nov; 42 (5): 497-506 31. Edelman AB, Gallo MF, Jensen JT, et al. Continuous or extended cycle vs. cyclic use of combined oral contraceptives for contraception. Cochrane Database Syst Rev 2005; (3): CD004695 32. Sulak PJ, Kuehl TJ, Ortiz M, et al. Acceptance of altering the standard 21-day/ 7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am J Obstet Gynecol 2002 Jun; 186 (6): 1142-9
Pediatr Drugs 2008; 10 (1)

Dysmenorrhea in Adolescents

33. Baldaszti E, Wimmer-Puchinger B, Loschke K. Acceptability of the long-term contraceptive levonorgestrel-releasing intrauterine system (Mirena): a 3-year follow-up study. Contraception 2003 Feb; 67 (2): 87-91 34. Harel Z, Riggs S, Vaz R, et al. Adolescents experience with the combined estrogen and progestin transdermal contraceptive method Ortho Evra. J Pediatr Adolesc Gynecol 2005 Apr; 18 (2): 85-90 35. Ziaei S, Rajaei L, Faghihzadeh S, et al. Comparative study and evaluation of side effects of low-dose contraceptive pills administered by the oral and vaginal route. Contraception 2002 May; 65 (5): 329-31 36. Audet MC, Moreau M, Koltun WD, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA 2001 May 9; 285 (18): 2347-54 37. Facchinetti F, Sgarbi L, Piccinini F, et al. A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial. Gynecol Endocrinol 2002 Feb; 16 (1): 39-43 38. Akerlund M, Andersson KE. Effects of terbutaline on human myometrial activity and endometrial blood flow. Obstet Gynecol 1976 May; 47 (5): 529-35 39. Andersson KE, Ulmsten U. Effects of nifedipine on myometrial activity and lower abdominal pain in women with primary dysmenorrhoea. Br J Obstet Gynaecol 1978 Feb; 85 (2): 142-8 40. Selak V, Farquhar C, Prentice A, et al. Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 2001; (4): CD000068 41. Meresman GF, Bilotas M, Abello V, et al. Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis. Fertil Steril 2005 Aug; 84 (2): 459-63 42. Hefler LA, Grimm C, van Trotsenburg M, et al. Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril 2005 Oct; 84 (4): 1033-6 43. Amsterdam LL, Gentry W, Jobanputra S, et al. Anastrazole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril 2005 Aug; 84 (2): 300-4 44. Ailawadi RK, Jobanputra S, Kataria M, et al. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 2004 Feb; 81 (2): 290-6 45. Soysal S, Soysal ME, Ozer S, et al. The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 2004 Jan; 19 (1): 160-7 46. Olive DL, Lindheim SR, Pritts EA. New medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol 2004 Apr; 18 (2): 319-28 47. Ferrero S, Abbamonte LH, Anserini P, et al. Future perspectives in the medical treatment of endometriosis. Obstet Gynecol Surv 2005 Dec; 60 (12): 817-26 48. Barnard ND, Scialli AR, Hurlock D, et al. Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. Obstet Gynecol 2000 Feb; 95 (2): 245-50 49. Nagata C, Hirokawa K, Shimizu N, et al. Associations of menstrual pain with intakes of soy, fat and dietary fiber in Japanese women. Eur J Clin Nutr 2005 Jan; 59 (1): 88-92

50. Gokhale LB. Curative treatment of primary (spasmodic) dysmenorrhoea. Indian J Med Res 1996 Apr; 103: 227-31 51. Vitamin E for dysmenorrhea. Bandolier, 2005 [online]. Available from URL: http:/ /www.jr2.ox.ac.uk/bandolier/band136/b136-6.html [Accessed 2007 Nov 14] 52. Ziaei S, Zakeri M, Kazemnejad A. A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. BJOG 2005 Apr; 112 (4): 466-9 53. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003 Jun 14; 361 (9374): 2017-23 54. Harel Z, Biro FM, Kottenhahn RK, et al. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol 1996 Apr; 174 (4): 1335-8 55. Deutch B. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Eur J Clin Nutr 1995 Jul; 49 (7): 508-16 56. Eccles NK. A randomized, double-blinded, placebo-controlled pilot study to investigate the effectiveness of a static magnet to relieve dysmenorrhea. J Altern Complement Med 2005 Aug; 11 (4): 681-7 57. Helms JM. Acupuncture for the management of primary dysmenorrhea. Obstet Gynecol 1987 Jan; 69 (1): 51-6 58. Pouresmail Z, Ibrahimzadeh R. Effects of acupressure and ibuprofen on the severity of primary dysmenorrhea. J Tradit Chin Med 2002 Sep; 22 (3): 205-10 59. Taylor D, Miaskowski C, Kohn J. A randomized clinical trial of the effectiveness of an acupressure device (relief brief) for managing symptoms of dysmenorrhea. J Altern Complement Med 2002 Jun; 8 (3): 357-70 60. Dawood MY, Ramos J. Transcutaneous electrical nerve stimulation (TENS) for the treatment of primary dysmenorrhea: a randomized crossover comparison with placebo TENS and ibuprofen. Obstet Gynecol 1990 Apr; 75 (4): 656-60 61. Proctor ML, Smith CA, Farquhar CM, et al. Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhoea. Cochrane Database Syst Rev 2002; (1): CD002123 62. Akin MD, Weingand KW, Hengehold DA, et al. Continuous low-level topical heat in the treatment of dysmenorrhea. Obstet Gynecol 2001 Mar; 97 (3): 343-9 63. Hondras MA, Long CR, Brennan PC. Spinal manipulative therapy versus a low force mimic maneuver for women with primary dysmenorrhea: a randomized, observer-blinded, clinical trial. Pain 1999 May; 81 (1-2): 105-14 64. Proctor ML, Hing W, Johnson TC, et al. Spinal manipulation for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2001; (4): CD002119 65. Wilson ML, Farquhar CM, Sinclair OJ, et al. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2000; (2): CD001896

Correspondence: Professor Linda French, Department of Family Medicine, University of Toledo, College of Medicine, 2240 Dowling Hall, 3000 Arlington Ave, Toledo, OH 43614, USA. E-mail: linda.french@utoledo.edu

2008 Adis Data Information BV. All rights reserved.

Pediatr Drugs 2008; 10 (1)