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Home , Dysmenorrhea, Endometriosis, Pelvic pain, Vaginal discharge

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 relief is insufficient, prolonged-cycle oral contraceptives or intravaginal use of oral contraceptive pills can be consid- ered. In women who do not desire , there is some evidence of benefit with the use of topical heat; the Japanese herbal remedy toki-shakuyaku-san; thiamine, , and supplements; a low-fat vegetarian diet; and . If dysmen- orrhea remains uncontrolled with any of these approaches, pelvic ultrasonography should be performed and referral for 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, , nifedipine, and terbu- taline. Otherwise, the use of or leuprolide may be considered

and, rarely, . The effectiveness of surgical interruption JOAN BECK 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.) ILLUSTRATION BY

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: ally begins during . It is Pathogenesis A handout on dysmen- P characterized by crampy begin- Dysmenorrhea is thought to be caused by the orrhea, written by the author of this article, is ning shortly before or at the onset of menses release of 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 CME 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 content presented with percent of adolescent girls report severe dys- and dysmenorrhea is not clear. Endometrio- practice recommendations 1,4 supported by evidence menorrhea, 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 . 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 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 use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. 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 , 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 .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 ) 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- 17 Lansing, MI 48824 (e-mail: [email protected]). Reprints are not available vaginal endometriosis. 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 18 ficity, 75 percent). The reference standard Effective test for diagnosis and staging of endometrio- NSAIDs19 A sis is laparoscopy or laparotomy with . 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 Therapy Leuprolide acetate (Lupron)* B 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, intrauterine system (Mirena)25 B harm, and cost. Table 3 provides dosing and Low-fat vegetarian diet26 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-inflammatory 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 effect through inhibition of Uncertain effectiveness 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-analyses33,34 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., [Motrin], Spinal manipulation31,32 B [Naprosyn], [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 Small studies22,23 of cyclooxygenase-2 practice, opinion, or case series. See page 225 for more information. inhibitors have shown efficacy similar to NOTE: At the time of publication new information had appeared regarding the safety of COX-2 inhibitors. Because they appear to increase the risk of , 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 - 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 . Consistent obser- received . 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 and 150 mg (153 to 257) of levonorgestrel daily); an RCT27 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 (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 that induce uterine *—Estimated cost to the pharmacist for one month’s therapy based on average relaxation have been proposed for treat- 41 wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 2004. Cost to ment of dysmenorrhea. In one RCT, 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 . 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 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-medroxyprogesterone acetate (Depo-Provera) are amenorrheic within LIFESTYLE MODIFICATION 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 data39 from users Smoking cessation has not been studied as of the levonorgestrel 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 (LUNA) and and effectiveness may vary among formula- presacral also have been used in tions. It does not appear to suppress fertility refractory cases. Observational data47 show or . 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 , 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 In women who do not desire hormonal women with dysmenorrhea. Am J Obstet Gynecol 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. 48,49 out secondary causes of dysmenorrhea. 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 want to conceive are (in order of clinical for the occurrence, duration and severity of menstrual 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 future: (1) a vasopressin-receptor antagonist 2001;20:411-6. 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. 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 is being used in the management of primary of sonographic appearance in determining extension of disease and modulating surgical approach. J Am Assoc 54 and secondary dysmenorrhea. 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 rently available IUDs. 2003;79:1023-7. The author indicates that she does not have any conflicts 18. Stratton P, Winkel C, Premkumar A, Chow C, Wilson of interest. Sources of funding: none reported. J, Hearns-Stokes R, et al. Diagnostic accuracy of lapa- roscopy, magnetic resonance imaging, and histopatho- logic examination for the detection of endometriosis. Fertil Steril 2003;79:1078-85. REFERENCES 19. Proctor M, Farquhar C. Dysmenorrhoea. Clin Evid 1. Davis AR, Westhoff CL. Primary dysmenorrhea in ado- 2002;(7):1639-53. lescent girls and treatment with oral contraceptives. J 20. Helms JM. Acupuncture for the management of pri- Pediatr Adolesc Gynecol 2001;14:3-8. mary dysmenorrhea. Obstet Gynecol 1987;69:51-6. 2. Banikarim C, Chacko MR, Kelder SH. Prevalence and 21. Pouresmail Z, Ibrahimzadeh R. Effects of acupressure impact of dysmenorrhea on Hispanic female adoles- and ibuprofen on the severity of primary dysmenor- cents. Arch Pediatr Adolesc Med 2000;154:1226-9. rhea. J Tradit Chin Med 2002;22:205-10.

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22. Barnard ND, Scialli AR, Hurlock D, Bertron P. Diet and 39. Baldaszti E, Wimmer-Puchinger B, Loschke K. Accept- sex-hormone binding globulin, dysmenorrhea, and pre- ability of the long-term contraceptive levonorgestrel- menstrual symptoms. Obstet Gynecol 2000;95:245-50. releasing intrauterine system (Mirena): a 3-year follow- 23. Daniels SE, Talwalker S, Torri S, Snabes MC, Recker DP, up study. Contraception 2003;67:87-91. Verburg KM. , a cyclooxygenase-2-specific 40. Audet MC, Moreau M, Koltun WD, Waldbaum AS, inhibitor, is effective in treating primary dysmenorrhea. Shangold G, Fisher AC, et al. Evaluation of contracep- Obstet Gynecol 2002;100:350-8. tive efficacy and cycle control of a transdermal contra- 24. Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL. Supple- ceptive patch vs an oral contraceptive: a randomized mentation with omega-3 polyunsaturated fatty acids in controlled trial. JAMA 2001;285:2347-54. the management of dysmenorrhea in adolescents. Am 41. Facchinetti F, Sgarbi L, Piccinini F, Volpe A. A compari- J Obstet Gynecol 1996;174:1335-8. son of glyceryl trinitrate with diclofenac for the treat- 25. Jensen JT. Noncontraceptive applications of the levo- ment of primary dysmenorrhea: an open, randomized, norgestrel intrauterine system. Curr Womens Health cross-over trial. Gynecol Endocrino 2002;16:39-43. Rep 2002;2:417-22. 42. Deutch B. Menstrual pain in Danish women correlated 26. Malmstrom K, Kotey P, Cichanowitz N, Daniels S, Des- with low n-3 polyunsaturated fatty acid intake. Eur J jardins PJ. Analgesic efficacy of etoricoxib in primary Clin Nutr 1995;49:508-16. dysmenorrhea: results of a randomized, controlled trial. 43. Taylor D, Miaskowski C, Kohn J. A randomized clini- Gynecol Obstet Invest 2003;56:65-9. cal trial of the effectiveness of an acupressure device 27. Ziaei S, Rajaei L, Faghihzadeh S, Lamyian M. Compara- (Relief Brief) for managing symptoms of dysmenorrhea. tive study and evaluation of side effects of low-dose J Altern Complement Med 2002;8:357-70. contraceptive pills administered by the oral and vaginal 44. Dawood MY, Ramos J. Transcutaneous electrical nerve route. Contraception 2002;65:329-31. stimulation (TENS) for the treatment of primary dysmen- 28. Andersson KE, Ulmsten U. Effects of nifedipine on myo- orrhea: a randomized crossover comparison with placebo metrial activity and lower in women TENS and ibuprofen. Obstet Gynecol 1990;75:656-60. with primary dysmenorrhoea. Br J Obstet Gynaecol 45. Proctor ML, Smith CA, Farquhar CM, Stones RW. Trans- 1978;85:142-8. cutaneous electrical nerve stimulation and acupuncture 29. Proctor ML, Farquhar CM, Sinclair OJ, Johnson NP. Sur- for primary dysmenorrhoea. Cochrane Database Syst gical interruption of pelvic nerve pathways for primary Rev 2002;(3):CD002123. and secondary dysmenorrhoea. Cochrane Database 46. Akin MD, Weingand KW, Hengehold DA, Goodale MB, Syst Rev 2004(3):CD001896. Hinkle RT, Smith RP. Continuous low-level topical heat 30. Akerlund M, Andersson KE, Ingemarsson I. Effects of in the treatment of dysmenorrhea. Obstet Gynecol terbutaline on myometrial activity, uterine blood flow, 2001;97:343-9. and lower abdominal pain in women with primary dys- 47. Chen FP, Chang SD, Chu KK, Soong YK. Comparison menorrhoea. Br J Obstet Gynaecol 1976;83:673-8. of laparoscopic presacral neurectomy and laparoscopic 31. Hondras MA, Long CR, Brennan PC. Spinal manipula- uterine nerve ablation for primary dysmenorrhea. J tive therapy versus a low force mimic maneuver for Reprod Med 1996;41:463-6. women with primary dysmenorrhea: a randomized, 48. Eskenazi B, Warner M, Bonsignore L, Olive D, Samuels observer-blinded, clinical trial. Pain 1999;81:105-14. S, Vercellini P. Validation study of nonsurgical diagnosis 32. Proctor M, Hing W, Johnson T, Murphy P. Spinal manip- of endometriosis. Fertil Steril 2001;76:929-35. ulation for primary and secondary dysmenorrhoea. 49. Frackiewicz EJ. Endometriosis: an overview of the Cochrane Database Syst Rev 2004(3):CD002119. disease and its treatment. J Am Pharm Assoc (Wash) 33. Zhang WY, Li Wan Po A. Efficacy of minor 2000;40:645-57. in primary dysmenorrhoea: a systematic review. Br J 50. Akerlund M. Can primary dysmenorrhea be alleviated Obstet Gynaecol 1998;105:780-9. by a vasopressin antagonist? Results of a pilot study. 34. Weaver AL. : clinical pharmacology and clini- Acta Obstet Gynecol Scand 1987;66:459-61. cal experience. Clin Ther 2001;23:1323-38. 51. Brouard R, Bossmar T, Fournie-Lloret D, Chassard D, 35. Hendrix SL, Alexander NJ. Primary dysmenorrhea treat- Akerlund M. Effect of SR49059, and orally active V1a ment with a desogestrel-containing low-dose oral vasopressin receptor antagonist, in the prevention of contraceptive. Contraception 2002;66:393-9. dysmenorrhoea. BJOG 2000;107:614-9. 36. Milsom I, Sundell G, Andersch B. The influence of differ- 52. Paranjape SB, Thibonnier M. Development and thera- ent combined oral contraceptives on the prevalence and peutic indications of orally-active non-peptide vaso- severity of dysmenorrhea. Contraception 1990;42:497- pressin receptor antagonists. Expert Opin Investig 506. Drugs 2001;10:825-34. 37. Proctor ML, Roberts H, Farquhar CM. Combined oral 53. Valentin L, Sladkevicius P, Kindahl H, Broeders A, Marsal K, contraceptive pill (OCP) as treatment for primary dys- Melin P. Effects of a vasopressin antagonist on women with menorrhoea. Cochrane Database Syst Rev 2001(3): dysmenorrhea. Gynecol Obstet Invest 2000;50:170-7. CD002120. 54. Wildemeersch D, Schacht E, Wildemeersch P. Treatment 38. Sulak PJ, Kuehl TJ, Ortiz M, Shull BL. Acceptance of alter- of primary and secondary dysmenorrhea with a novel ing the standard 21-day/7-day oral contraceptive regi- ‘frameless’ intrauterine levonorgestrel-releasing drug men to delay menses and reduce hormone withdrawal delivery system: a pilot study. Eur J Contracept Reprod symptoms. Am J Obstet Gynecol 2002;186:1142-9. Health Care 2001;6:192-8.

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