Menstrual Cramps Research:
2002-2006
     
J Midwifery Womens Health. 2006 Nov-Dec;51(6):402-9.
The use of herbs and dietary supplements in gynecology: an evidence-based review.
Dennehy CE.
Department of Clinical Pharmacy, University of California San Francisco, 521 Parnassus Avenue, Suite C-152, Box 0622, San Francisco, CA 94143, USA. dennehyc@pharmacy.ucsf.edu <dennehyc@pharmacy.ucsf.edu>

Consumers frequently use herbs and dietary supplements to treat chronic conditions that are poorly responsive to prescription drugs or when prescription drugs carry a high side effect burden. Women may use herbs and supplements for chronic gynecologic conditions, such as menopause, premenstrual syndrome, dysmenorrhea, cyclic mastalgia, and infertility. This review is an evidence-based evaluation of herbs and supplements for these conditions. Therapies that carry a higher level of support from randomized controlled trial evidence include black cohosh for menopause; vitamins B(1) and E for dysmenorrhea; calcium, vitamin B(6), and chasteberry for premenstrual syndrome; and chasteberry for cyclic mastalgia. There were too few trials involving herbs and supplements in infertility to warrant a solid recommendation, but chasteberry, antioxidants, and Fertility Blend have some preliminary support. Midwives may want to consider these alternatives in addition to more traditional treatment options when meeting with patients.

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Contraception. 2006 Nov;74(5):359-66. Epub 2006 Sep 15.
Menstrual-cycle-related symptoms: a review of the rationale for continuous use of oral contraceptives.
Archer DF.
Contraceptive Research and Development Program, Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA, 23507, USA.

As many as 80% of reproductive-aged women experience physical changes associated with menstruation, and 20% to 40% experience menstrual-cycle-related symptoms. Decades of research in women with menstrual disorders, such as dysmenorrhea and menorrhagia, have shown that continuous use of oral contraceptives (OCs), without the hormone-free interval, is a safe and effective method to relieve these symptoms and ultimately induce amenorrhea in many women. If given the opportunity, a majority of women would opt for extended-cycle or continuous regimens, and numerous clinical trials have shown that continuous OC regimens induce amenorrhea in 80% to 100% of women by 10 to 12 months of use. For women who do not wish to become pregnant, a continuous OC regimen should be an available option.

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Obstet Gynecol. 2006 Oct;108(4):915-23.
Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a randomized controlled trial.
Abbott JA, Jarvis SK, Lyons SD, Thomson A, Vancaille TG.
University of New South Wales, Sydney Australia. jason.abbott@sesiahs.health.nsw.gov.au

OBJECTIVE: To estimate whether botulinum toxin type A is more effective than placebo at reducing pain and pelvic floor pressure in women with chronic pelvic pain and pelvic floor muscle spasm. METHODS: This study was a double-blinded, randomized, placebo-controlled trial. All participants presented with chronic pelvic pain of more than 2 years duration and evidence of pelvic floor muscle spasm. Thirty women had 80 units of botulinum toxin type A injected into the pelvic floor muscles, and 30 women received saline. Dysmenorrhea, dyspareunia, dyschezia, and nonmenstrual pelvic pain were assessed by visual analog scale (VAS) at baseline and then monthly for 6 months. Pelvic floor pressures were measured by vaginal manometry. RESULTS: There was significant change from baseline in the botulinum toxin type A group for dyspareunia (VAS score 66 versus 12; chi2 = 25.78, P < .001) and nonmenstrual pelvic pain (VAS score 51 versus 22; chi2 = 16.98, P = .009). In the placebo group only dyspareunia was significantly reduced from baseline (64 versus 27; chi2 = 2.98, P = .043). There was a significant reduction in pelvic floor pressure (centimeters of H2O) in the botulinum toxin type A group from baseline (49 versus 32; chi2 = 39.53, P < .001), with the placebo group also having lower pelvic floor muscle pressures (44 versus 39; chi2 = 19.85, P = .003). CONCLUSION: Objective reduction of pelvic floor spasm reduces some types of pelvic pain. Botulinum toxin type A reduces pressure in the pelvic floor muscles more than placebo. Botulinum toxin type A may be a useful agent in women with pelvic floor muscle spasm and chronic pelvic pain who do not respond to conservative physical therapy. Clinical Trial Registration: Australian Clinical Trials Registry, http://www.actr.org.au.

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Obstet Gynecol. 2006 Aug;108(2):428-41.
Primary dysmenorrhea: advances in pathogenesis and management.
Dawood MY.
Departments of Obstetrics and Gynecology and Physiology, West Virginia University School of Medicine, Morgantown, West Virginia.

Primary dysmenorrhea is painful menstrual cramps without any evident pathology to account for them, and it occurs in up to 50% of menstruating females and causes significant disruption in quality of life and absenteeism. Current understanding implicates an excessive or imbalanced amount of prostanoids and possibly eicosanoids released from the endometrium during menstruation. The uterus is induced to contract frequently and dysrhythmically, with increased basal tone and increased active pressure. Uterine hypercontractility, reduced uterine blood flow, and increased peripheral nerve hypersensitivity induce pain. Diagnosis rests on a good history with negative pelvic evaluation findings. Evidence-based data support the efficacy of cyclooxygenase inhibitors, such as ibuprofen, naproxen sodium, and ketoprofen, and estrogen-progestin oral contraceptive pills (OCPs). Cyclooxygenase inhibitors reduce the amount of menstrual prostanoids released, with concomitant reduction in uterine hypercontractility, while OCPs inhibit endometrial development and decrease menstrual prostanoids. An algorithm is provided for a simple approach to the management of primary dysmenorrhea.

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Cochrane Database Syst Rev. 2006 Jul 19;3:CD002119.
Spinal manipulation for primary and secondary dysmenorrhoea.
Proctor M, Hing W, Johnson T, Murphy P.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. One possible treatment is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in certain vertebrae causes decreases spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynaecological pain as it can present as cyclic pain altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1980 to April 2006), CINAHL (1982 to March 2006), AMED (1985 to April 2006), Biological Abstracts (1969 to March 2006), PsycINFO (1806 to April 2006), and SPORTDiscus (1830 to April 2006). Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative interventions (for example chiropractic, osteopathy, or manipulative physiotherapy) versus each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an intrauterine device (IUD). DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude manipulation (HVLA), and one of the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two review authors. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. AUTHORS' CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.

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Fertil Steril. 2006 Jun 16; [Epub ahead of print]
Randomized controlled trial assessing a traditional Chinese medicine remedy in the treatment of primary dysmenorrhea.
Kennedy S, Jin X, Yu H, Zhong S, Magill P, van Vliet T, Kistemaker C, Voors C, Pasman W.
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, Oxfordshire, United Kingdom.

A proof-of-concept study to assess the safety and efficacy of a traditional Chinese medicine formula as treatment for primary dysmenorrhea showed no statistically significant benefit over placebo. However, some efficacy parameters suggested possible superiority of the active treatment and so a larger study needs to be performed to determine whether this remedy has a role in the treatment of dysmenorrhea.

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Eur J Obstet Gynecol Reprod Biol. 2006 May 1; [Epub ahead of print]
The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea.
Letzel H, Megard Y, Lamarca R, Raber A, Fortea J.
Humanwissenschaftliches Zentrum der Ludwig-Maximilians-Universitat Munchen, 80336 Munchen, Germany.

OBJECTIVE: To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100mg and compare that with placebo and naproxen 500mg in women with primary dysmenorrhoea. STUDY DESIGN: In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100mg, naproxen 500mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events. RESULTS: Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p=0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated. CONCLUSIONS: Aceclofenac (100mg) and naproxen (500mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria.

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Int J Gynaecol Obstet. 2006 Mar;92(3):221-227. Epub 2006 Jan 20.
Impact of pregnancy on primary dysmenorrhea.
Juang CM, Yen MS, Twu NF, Horng HC, Yu HC, Chen CY.
Division of General Gynecology, Department of Obstetrics and Gynecology, Veterans General Hospital, Taipei, Taiwan; Institute of Epidemiology, College of Public Health, National Yang-Ming University, Taipei, Taiwan; Kin-Man County Hospital, Kin-Man, Taiwan.

Objective: Because it has been observed that dysmenorrhea can improve after childbirth, this investigation was intended to quantify the impact of both gestational length and mode of delivery on primary dysmenorrhea. Methods: This is an 8-year prospective observational study. Patients with a history of dysmenorrhea who later gave birth were evaluated for improvement on the severity of dysmenorrhea, with use of visual analogue scale (VAS), and Likert-type scale. Result: Final analysis involved 3694 patients. Women who had spontaneous delivery would have significantly more improvement than women with cesarean delivery per VAS (term delivery, 51 vs. 33, P<0.001; preterm delivery, 17 vs. 10, P<0.001). For first delivery, patients in the spontaneous delivery subgroup were the most likely to have improvement in severity of dysmenorrhea. For second delivery, only patients in the spontaneous delivery subgroup had statistically significant improvement. Conclusion: Both length of gestation and mode of delivery have an impact on primary dysmenorrhea. The most significant improvement occurred after the first delivery.

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J Obstet Gynaecol Can. 2005 Dec;27(12):1117-30.
Primary dysmenorrhea consensus guideline.
[Article in English, French]
Lefebvre G, Pinsonneault O, Antao V, Black A, Burnett M, Feldman K, Lea R, Robert M.
Ottawa ON.

METHODS: Members of this consensus group were selected based on individual expertise to represent a range of practical and academic experience both in terms of location in Canada and type of practice, as well as subspecialty expertise along with general gynaecology backgrounds. The consensus group reviewed all available evidence through the English and French medical literature and available data from a survey of Canadian women. Recommendations were established as consensus statements. The final document was reviewed and approved by the Executive and Council of the SOGC. RESULTS: This document provides a summary of up-to-date evidence regarding the diagnosis, investigations, and medical and surgical management of dysmenorrhea. The resulting recommendations may be adapted by individual health care workers when serving women who suffer from this condition. CONCLUSIONS: Dysmenorrhea is an extremely common and sometimes debilitating condition for women of reproductive age. A multidisciplinary approach involving a combination of lifestyle, medications, and allied health services should be used to limit the impact of this condition on activities of daily living. In some circumstances, surgery is required to offer the desired relief. OUTCOMES: This guideline discusses the various options in managing dysmenorrhea. Patient information materials may be derived from these guidelines in order to educate women in terms of their options and possible risks and benefits of various treatment strategies. Women who find an acceptable management strategy for this condition may benefit from an improved quality of life. EVIDENCE: MEDLINE and Cochrane databases were searched for articles in English and French on subjects related to primary dysmenorrhea, menstrual pain and pelvic pain from January 1990 to December 2004 in order to prepare a Canadian consensus guideline on the management of primary dysmenorrhea. VALUES: The quality of evidence is rated using the criteria described in the Report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice are ranked according to this method. SPONSORS: The development of this consensus guideline was supported by unrestricted educational grants from Pfizer Canada Inc., Janssen-Ortho, Wyeth, Organon Canada Ltd., and Berlex Canada Inc. RECOMMENDATIONS: Section 3: Diagnosis / Differential Diagnosis / Investigations 1. In adolescents experiencing dysmenorrhea in the first 6 months from the start of menarche, and when an anovulatory patient complains of dysmenorrhea, the diagnosis of obstructing malformation of the genital tract should be considered. (III-A) 2. The diagnosis of secondary dysmenorrhea should be considered when symptoms appear after many years of painless menses. (III-A) 3. In view of the high prevalence of dysmenorrhea, and evidence that many women do not seek medical attention for this problem, health care providers should include specific questions regarding menstrual pain when obtaining a woman's medical history. (III-B) 4. In an adolescent who has never been sexually active and has a typical history of mild to moderate dysmenorrhea, a pelvic examination is not necessary. (III-D) 5. A pelvic examination is indicated in all patients not responding to conventional therapy of dysmenorrhea or when an organic pathology is suspected. (III-B) Section 4: Non-medicinal Therapeutic Options 1. Unlike low-frequency TENS, high-frequency TENS provides more effective dysmenorrhea pain relief compared with placebo. High-frequency TENS may be considered as a supplementary treatment in women unable to tolerate medication. (II-B) 2. Women who inquire about alternatives to relieve dysmenorrhea, may be instructed that, at the present time, there is limited evidence that acupuncture may be of benefit (II-B), there is no evidence to support spinal manipulation as an effective treatment (II-D), and there is limited evidence to support topical heat therapy (II-B). Section 5: Medicinal Therapeutic Options 1. Women suffering from primary dysmenorrhea should be offered NSAIDs as a first-line treatment for the relief of pain and improved daily activity unless they have a contraindication to the use of NSAIDs. (I-A) 2. Oral contraceptives may be recommended for the treatment of primary dysmenorrhea. The added contraceptive advantage may make oral contraceptives a first-line therapy for some women. (1-A) 3. Consideration may be given to continuous use of oral contraceptive pills for withdrawal bleeding and the associated dysmenorrhea. (1-A) 4. Depot medroxyprogesterone acetate and levonorgestrel intrauterine system have been shown to be effective in the treatment of dysmenorrhea and therefore can be considered as treatment options in the management of primary dysmenorrhea. (II-B) Section 6: Surgical Options 1. Surgery constitutes the final diagnostic and therapeutic option in the management of dysmenorrhea. Laparoscopy should be considered in women who have persistent dysmenorrhea despite medical therapy of NSAIDs and/or oral contraceptives. (III-C) 2. Hysterectomy may be considered for the management of dysmenorrhea when medical alternatives have been refused or failed and fertility is no longer possible or desired. (II-B) 3. As there is limited evidence for use of presacral neurectomy in the management of primary dysmenorrhea, the risks must be carefully weighed against the expected benefits. (III-C) 4. Laparoscopic uterosacral ligament resection has not been shown to reduce dysmenorrhea and therefore should not be advocated as a mainstream treatment option. (III-C) Section 7: Complementary and Alternative Medicine (CAM) 1. The following CAM has limited support and may be considered in the treatment of primary dysmenorrhea, though further study is required: *Vitamin B1 (I-B) 2. The following CAMs showed an initial positive response for the treatment of primary dysmenorrhea and merit further study: *Vitamin E (I-C) *Fish oil / Vitamin B12 combination (I-C) *Magnesium (II-1 C) *Vitamin B6; (II-1 C) *Toki-shakuyaku-san (II-1 C) *Fish oil (II-3 C) *Neptune krill oil (II-3 C) 3. The following CAMs have not been shown to have any benefit in the treatment of primary dysmenorrhea and may need further study: *Vitamin B6 / Magnesium combination (II-1) *Vitamin E (daily) in addition to Ibuprofen (during menses) (II-3) *Fennel (II-3).

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Eur J Contracept Reprod Health Care. 2005;10 Suppl 1:12-8.
Belara--a reliable oral contraceptive with additional benefits for health and efficacy in dysmenorrhoea.
Zahradnik HP.
Department of Obstetrics & Gynaecology, Clinic for Endocrinology and Reproductive Healthcare, Universitats-Frauenklinik, Hugstetter Strasse 55, 79106 Freiburg, Germany.

Although modern oral contraceptives are safe and have few side-effects, compliance towards them is sometimes less than ideal for various reasons. Compliance, however, can only be achieved when the contraceptive method is accepted by the users, that is, when it is adapted to their individual needs. Consisting of a combination of 2 mg chlormadinone acetate and 0.03 mg ethinylestradiol, Belara is a modern oral hormonal contraceptive with an unadjusted Pearl index of 0.44 (95% CI, 0.2-0.8) and an adjusted one of 0.04 (95% CI, 0.002-0.2). Its compliance rate in clinical use has been shown to be above 90%. This good acceptance is a consequence of the low rate of intermenstrual bleeding (about 8% up to the 3(rd) cycle and below 2% from the 12(th) cycle); its high cycle stability (in approximately 98% from the 6(th) cycle); the good weight stability (weight is unchanged in about 84% from the 12(th) cycle); and finally the very low rate of side-effects (below 2% after 12 cycles). In addition, a number of other benefits of using Belara also contribute to this good compliance rate. These include almost 70% improvement or complete remission of increased seborrhoea after 12 months, almost 90% improvement or cure of acne after 12 months, and improvement or remission of dysmenorrhoea after 12 months in 79% of cases. After 4 months, improvement or remission of dysmenorrhoea associated with the use of another ovulation inhibitor was seen in more than 90% of cases after switching to Belara. In conclusion, besides being an effective, modern oral hormonal contraceptive Belara offers a considerable range of additional benefits for a range of symptoms, including primary dysmenorrhea and acne.

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Eur J Contracept Reprod Health Care. 2005;10 Suppl 1:19-25.
Belara—proven benefits in daily practice.
Bitzer J.
Department of Gynaecological Public Health and Psychosomatics, Universitats-Frauenklinik, Schanzenstrasse 46, CH-4031 Basel, Switzerland.

Today, a contraceptive method is available to suit nearly every type of woman, every age and all preferences and expectations. All that seems to remain for users is to look for the right product to satisfy their personal requirements. The physician takes on the role of the adviser, responsible mainly for errors of judgement and undesirable effects. The choice of the suitable contraceptive depends on three factors: the patient profile, the profile of the method used and the user's life situation. In selecting the method of contraception, statistical measures such as the Pearl Index, rate of adverse events, risks and health benefits as well as the pharmacological profile, resulting intake modality and potential interactions should be considered. The patient profile includes both subjective wishes and standards of value relevant for world view, family planning and psychological well-being, as well as objective parameters such as age, BMI, medical history and the woman's sexual behaviour. Evaluation of these parameters by the physician is a major component of successful contraceptive counselling. Belara is a new oral contraceptive on the European market based on a monophasic combination of 2 mg chlormadinone acetate and 0.03 mg ethinylestradiol. As well as high contraceptive efficacy and a low rate of side effects, Belara features an outstanding safety profile due to its almost complete absence of mineralocorticoid and glucocorticoid action and its absent impact on hepatic metabolism. In daily practice, Belara exhibits mild antiandrogenic activity which also makes it suitable for users with antiandrogen-induced seborrhoea and moderate acne. Symptoms of PMS or unspecific dysmenorrhea and menstrual irregularities can also be alleviated or completely eliminated by taking Belara. Belara use has not been associated with any significant weight gain. In daily practice, Belara is suitable for every woman of every age without specific risk factors requiring safe contraception. Belara also has considerable additional health benefits that should also be considered when choosing a suitable contraceptive.

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Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001896.
Update of: Cochrane Database Syst Rev. 2000;(2):CD001896.
Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea.
Proctor ML, Latthe PM, Farquhar CM, Khan KS, Johnson NP.
Department of Corrections, Psychological Service, PO Box 302 457, North Harbour, Auckland, New Zealand 1310. michelle.proctor@woosh.co.nz

BACKGROUND: Dysmenorrhoea is the occurrence of painful menstrual cramps of uterine origin and is a very common gynaecological complaint with negative effect on a sufferer's quality of life. Medical therapy for dysmenorrhoea includes oral contraceptive pills (OCP) and nonsteroidal anti-inflammatory drugs (NSAIDs) which both act by suppressing prostaglandin levels. While these treatments are very successful there is still a 20 to 25% failure rate and surgery has been an option for such cases. Uterine nerve ablation (UNA) and presacral neurectomy (PSN) are two surgical treatments that have become increasingly utilised in recent years due to advances in laparoscopic procedures. These procedures both interrupt the majority of the cervical sensory pain nerve fibres. Observational studies have supported the use of these procedures for primary dysmenorrhoea. However, both operations only partially interrupt the cervical sensory nerve fibres in the pelvic area and, therefore, this type of surgery may not always benefit women with dysmenorrhoea. OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve pathways as treatment for primary and secondary dysmenorrhoea, and to determine the most effective surgical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 9 June 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to Nov 2003), EMBASE (1980 to Nov 2003), and CINAHL (1982 to Oct 2003). Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of surgical techniques of interruption of the pelvic nerve pathways (using both open and laparoscopic procedures) for the treatment of primary and secondary dysmenorrhoea. The main outcome measures were pain relief and adverse effects. DATA COLLECTION AND ANALYSIS: Eleven randomised controlled trials (RCTs) were identified that initially appeared to fulfil the inclusion criteria for this review. Two trials were subsequently excluded (Garcia Leon 2003; Sutton 1991). Of the remaining nine trials, eight were included in the meta-analysis. The results of one trial were included in the text of the review for discussion because the data were not available in a form that allowed them to be combined in the meta-analysis. Five trials investigated laparoscopic uterine nerve ablation (LUNA), two trials laparoscopic presacral neurectomy (LPSN) and two open presacral neurectomy (PSN). MAIN RESULTS: For the treatment of primary dysmenorrhoea there was some evidence of the effectiveness of laparoscopic uterine nerve ablation (LUNA) when compared to a control or no treatment. The comparison between LUNA and laparoscopic presacral neurectomy (LPSN) for primary dysmenorrhoea showed no significant difference in pain relief in the short term; however, long-term LPSN was shown to be significantly more effective than LUNA. For the treatment of secondary dysmenorrhoea six identified RCTs addressed endometriosis and one included women with uterine myomas. The treatment of LUNA combined with surgical treatment of endometrial implants versus surgical treatment of endometriosis alone showed that the addition of LUNA did not aid pain relief. For PSN combined with endometriosis treatment versus endometriosis treatment alone there was an overall difference in pain relief although the data suggests this may be specific to laparoscopy and for midline abdominal pain only. Adverse events were significantly more common for presacral neurectomy; however, the majority were complications such as constipation, which may spontaneously improve. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea, regardless of cause. Future methodologically sound and sufficiently powered RCTs should be undertaken.

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J Midwifery Womens Health. 2005 Sep-Oct;50(5):e51-7.
Rose tea for relief of primary dysmenorrhea in adolescents: a randomized controlled trial in Taiwan.
Tseng YF, Chen CH, Yang YH.
School of Nursing, Chung Hwa College of Medical Technology, Tainan, Taiwan.

Primary dysmenorrhea occurs in as many as 50% of female adolescents and is associated with significant decreases in academic performance, sports participation, and socialization with peers. Complementary and alternative medicine treatment options are of interest to patients and health care providers. The use of rose tea to alleviate menstrual pain has long been a part of folk knowledge around the world but has not been studied scientifically. To determine the effectiveness of drinking rose tea as an intervention for reducing pain and psychophysiologic distress in adolescents with primary dysmenorrhea, 130 female adolescents were randomly assigned to an experimental (n = 70) and a control (n = 60) group. Preintervention and postintervention data at 1 month, 3 months, and 6 months were gathered on the biopsychosocial outcomes of dysmenorrhea. The results showed that compared with the control group, the experimental group perceived less menstrual pain, distress, and anxiety and showed greater psychophysiologic well-being through time, at 1, 3, and 6 months after the interventions. Findings suggest that drinking rose tea is a safe, readily available, and simple treatment for dysmenorrhea, which female adolescents may take to suit their individual needs.

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J Altern Complement Med. 2005 Aug;11(4):681-7.
A randomized, double-blinded, placebo-controlled pilot study to investigate the effectiveness of a static magnet to relieve dysmenorrhea.
Eccles NK.
The Chiron Clinic, London, England.

Objectives: The aim of this study was to investigate the hypothesis that a specially designed, static magnet of 2700 gauss, attached over the pelvic area, could relieve menstrual pain. Design: This was a randomized, double-blind, placebo-controlled, postal questionnaire study. Setting: The study was conducted in a primary care, single center. Participants: Sixty-five (65) women (mean age 29.1 +/- 1.52 years) were recruited from an advertisement in a London newspaper. The entry criterion was regular dysmenorrhea. The exclusion criterion was known secondary dysmenorrhea. Of the 65 women who were enrolled, 35 completed the study. Interventions: A questionnaire-based assessment was completed by each subject and checked by telephone before and after random allocation to use of either the static magnet device (2700 gauss) or an identical, weaker magnetic placebo device (140 gauss). Assessment was made by telephone before and after a complete menstrual cycle. None of the participants was examined or seen face-to-face. Main outcome measures: The main outcome measures were level of pain, using the McGill Pain and Visual Analogue Scales, and ratings of associated symptoms such as irritability, restriction of usual activities, and painkiller consumption. Results: There was a significant reduction (p < 0.02) in pain in the magnet group compared to the placebo group. Pain score differences (McGill pain score before - pain score after use of device) were -17 (-53, 13) (median and interquartile ranges) in the magnet group and -5.0 (-29, 27) in the placebo group. The 95% Mann-Whitney confidence intervals for the median difference between the magnet and placebo groups (magnet - placebo) were -53.0 to 23.38. A reduction in irritability symptoms in the magnet group approached statistical significance (p = 0.056). Conclusions: Despite the small number of participants, the level of significance reached in the reduction of pain merits reporting. This is a pilot study to a much larger study of the same device as an analgesic in women with primary dysmenorrhea.

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Obstet Gynecol. 2005 Jul;106(1):97-104.
Oral contraceptives for dysmenorrhea in adolescent girls: a randomized trial.
Davis AR, Westhoff C, O'Connell K, Gallagher N.
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, USA.

OBJECTIVE: To assess whether a low-dose oral contraceptive (OC) is more effective than placebo treatment for dysmenorrhea pain in adolescents. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial of 76 healthy adolescents aged 19 years or younger reporting moderate or severe dysmenorrhea. Subjects were randomly allocated to receive either an OC (ethinyl estradiol [E2] 20 microg and levonorgestrel 100 microg) or a matching placebo for 3 months. Participants used their usual pain medications as needed during the trial. The main outcome measure was score on the Moos Menstrual Distress Questionnaire (pain subscale) for the third menstrual cycle on treatment. Secondary outcomes included pain intensity (rated 0 to 10), days of any pain, days of severe pain, hours of pain on worst day, and use of pain medications. RESULTS: The mean Moos Menstrual Distress Questionnaire pain score was lower (less pain) in the OC group than the placebo group (3.1, standard deviation 3.2 compared with 5.8, standard deviation 4.5, P = .004, 95% confidence interval for the difference between means 0.88-4.53). By cycle 3, OC users rated their worst pain as less (mean pain rating 3.7 compared with 5.4, P = .02) and used fewer pain medications than placebo users (mean pain pills used 1.3 compared with 3.7, P = .05). By cycle 3, OC users reported fewer days of any pain, fewer days of severe pain, and fewer hours of pain on the worst pain day than placebo users; however, these differences did not reach statistical significance. CONCLUSIONS: Among adolescents, a low-dose oral contraceptive relieved dysmenorrhea-associated pain more effectively than placebo. LEVEL OF EVIDENCE: I.

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J Midwifery Womens Health. 2005 Sep-Oct;50(5):e51-7.
Rose tea for relief of primary dysmenorrhea in adolescents: a randomized controlled trial in Taiwan.
Tseng YF, Chen CH, Yang YH.
School of Nursing, Chung Hwa College of Medical Technology, Tainan, Taiwan.

Primary dysmenorrhea occurs in as many as 50% of female adolescents and is associated with significant decreases in academic performance, sports participation, and socialization with peers. Complementary and alternative medicine treatment options are of interest to patients and health care providers. The use of rose tea to alleviate menstrual pain has long been a part of folk knowledge around the world but has not been studied scientifically. To determine the effectiveness of drinking rose tea as an intervention for reducing pain and psychophysiologic distress in adolescents with primary dysmenorrhea, 130 female adolescents were randomly assigned to an experimental (n = 70) and a control (n = 60) group. Preintervention and postintervention data at 1 month, 3 months, and 6 months were gathered on the biopsychosocial outcomes of dysmenorrhea. The results showed that compared with the control group, the experimental group perceived less menstrual pain, distress, and anxiety and showed greater psychophysiologic well-being through time, at 1, 3, and 6 months after the interventions. Findings suggest that drinking rose tea is a safe, readily available, and simple treatment for dysmenorrhea, which female adolescents may take to suit their individual needs.

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J Altern Complement Med. 2005 Aug;11(4):681-7.
A randomized, double-blinded, placebo-controlled pilot study to investigate the effectiveness of a static magnet to relieve dysmenorrhea.
Eccles NK.
The Chiron Clinic, London, England.

Objectives: The aim of this study was to investigate the hypothesis that a specially designed, static magnet of 2700 gauss, attached over the pelvic area, could relieve menstrual pain. Design: This was a randomized, double-blind, placebo-controlled, postal questionnaire study. Setting: The study was conducted in a primary care, single center. Participants: Sixty-five (65) women (mean age 29.1 +/- 1.52 years) were recruited from an advertisement in a London newspaper. The entry criterion was regular dysmenorrhea. The exclusion criterion was known secondary dysmenorrhea. Of the 65 women who were enrolled, 35 completed the study. Interventions: A questionnaire-based assessment was completed by each subject and checked by telephone before and after random allocation to use of either the static magnet device (2700 gauss) or an identical, weaker magnetic placebo device (140 gauss). Assessment was made by telephone before and after a complete menstrual cycle. None of the participants was examined or seen face-to-face. Main outcome measures: The main outcome measures were level of pain, using the McGill Pain and Visual Analogue Scales, and ratings of associated symptoms such as irritability, restriction of usual activities, and painkiller consumption. Results: There was a significant reduction (p < 0.02) in pain in the magnet group compared to the placebo group. Pain score differences (McGill pain score before - pain score after use of device) were -17 (-53, 13) (median and interquartile ranges) in the magnet group and -5.0 (-29, 27) in the placebo group. The 95% Mann-Whitney confidence intervals for the median difference between the magnet and placebo groups (magnet - placebo) were -53.0 to 23.38. A reduction in irritability symptoms in the magnet group approached statistical significance (p = 0.056). Conclusions: Despite the small number of participants, the level of significance reached in the reduction of pain merits reporting. This is a pilot study to a much larger study of the same device as an analgesic in women with primary dysmenorrhea.

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Obstet Gynecol. 2005 Jul;106(1):97-104.
Oral contraceptives for dysmenorrhea in adolescent girls: a randomized trial.
Davis AR, Westhoff C, O'Connell K, Gallagher N.
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, USA.

OBJECTIVE: To assess whether a low-dose oral contraceptive (OC) is more effective than placebo treatment for dysmenorrhea pain in adolescents. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial of 76 healthy adolescents aged 19 years or younger reporting moderate or severe dysmenorrhea. Subjects were randomly allocated to receive either an OC (ethinyl estradiol [E2] 20 microg and levonorgestrel 100 microg) or a matching placebo for 3 months. Participants used their usual pain medications as needed during the trial. The main outcome measure was score on the Moos Menstrual Distress Questionnaire (pain subscale) for the third menstrual cycle on treatment. Secondary outcomes included pain intensity (rated 0 to 10), days of any pain, days of severe pain, hours of pain on worst day, and use of pain medications. RESULTS: The mean Moos Menstrual Distress Questionnaire pain score was lower (less pain) in the OC group than the placebo group (3.1, standard deviation 3.2 compared with 5.8, standard deviation 4.5, P = .004, 95% confidence interval for the difference between means 0.88-4.53). By cycle 3, OC users rated their worst pain as less (mean pain rating 3.7 compared with 5.4, P = .02) and used fewer pain medications than placebo users (mean pain pills used 1.3 compared with 3.7, P = .05). By cycle 3, OC users reported fewer days of any pain, fewer days of severe pain, and fewer hours of pain on the worst pain day than placebo users; however, these differences did not reach statistical significance. CONCLUSIONS: Among adolescents, a low-dose oral contraceptive relieved dysmenorrhea-associated pain more effectively than placebo. LEVEL OF EVIDENCE: I.

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Ann Pharmacother. 2005 May;39(5):854-62. Epub 2005 Apr 12.
Etoricoxib: a highly selective COX-2 inhibitor.
Martina SD, Vesta KS, Ripley TL.
College of Pharmacy, University of Oklahoma, Oklahoma City, OK 73190-5040, USA.

OBJECTIVE: To review the available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of etoricoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that is not currently approved for use in the US. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-December 2004), Current Contents (1998-December 2004), and Cochrane Library (4th quarter 2004). References from retrieved articles, information from the manufacturer, and abstracts from the American College of Rheumatology and Annual European Congress of Rheumatology meetings were searched. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English evaluating etoricoxib were included in this review. An abstract was excluded if it presented preliminary data from trials that are now published, analyzed data previously reported in a published clinical trial, or compared etoricoxib with placebo for an indication with published active-comparator controlled trials. DATA SYNTHESIS: Twelve clinical trials evaluating efficacy were reviewed. Efficacy for acute pain has been evaluated in acute gout, primary dysmenorrhea, and dental surgery and for chronic pain in rheumatoid arthritis, osteoarthritis, and chronic lower back pain. For safety, 3 clinical trials and 6 retrospective analyses of gastrointestinal, renovascular, or cardiovascular adverse effects were reviewed. CONCLUSIONS: Available studies demonstrate the efficacy of etoricoxib compared with nonsteroidal antiinflammatory drugs, but no published studies to date have compared etoricoxib with other selective COX-2 inhibitors. While these agents have demonstrated a significant reduction in gastrointestinal adverse effects, the cardiovascular adverse effects of selective COX-2 inhibition are not well defined. Further study is necessary to delineate the benefits and risks of etoricoxib compared with alternative treatment regimens.

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Treat Endocrinol. 2005;4(3):139-45.
Extended-cycle oral contraception: a new option for routine use.
Nelson AL.
Harbor-UCLA Medical Center, Torrance, California 90209-2910, USA. AnitaNelsonWHC@earthlink.net

Extended use of oral contraceptive (OC) pills can successfully suppress endometrial activity and prevent menstruation for several months. Given that missed menses in women not using hormonal contraception may be of medical concern, understanding how hormonal contraceptives eliminate these concerns is important for both patient and healthcare provider acceptance. OC withdrawal bleeding is an artificial, iatrogenic event, which results from the deliberate, periodic interruption of hormonal support of the endometrium. Historically, it was important to provide periodic bleeding to reassure OC efficacy, but today it is recognized that these bleeding episodes are medically unnecessary and cause patient discomfort and out-of-pocket expenses. Decades of experience with prolonged use of OCs have been accumulated for women with specific menstrual-related problems such as endometriosis, dysmenorrhea, and menstrual migraine headaches. Today there is a US FDA-approved product to routinely reduce the number of withdrawal periods. Clinical trials show that there is an initial increase in unscheduled bleeding and spotting days with extended-cycle OC use, but an absolute decrease in total days of bleeding and spotting from the first cycle of use. Over time, unscheduled bleeding and spotting decreases to rates found with the use of conventional-cycle regimens. Every woman who is interested in using OC pills should be offered the opportunity to choose how to use them, to determine if and when she will have withdrawal bleeding.

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BJOG. 2005 Apr;112(4):466-9.
A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea.
Ziaei S, Zakeri M, Kazemnejad A.
Department of Obstetrics and Gynaecology, Faculty of Medical Science, Tarbiat Modarres University, PO Box 14115.111, Tehran, IR, Iran.

OBJECTIVE: To study the effect of vitamin E in the treatment of primary dysmenorrhoea. DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: A secondary school in Tehran, Iran. POPULATION: Two hundred and seventy-eight girls aged 15-17 years who suffered from primary dysmenorrhoea. METHODS: Participants were given 200 units of vitamin E or placebo twice a day, beginning two days before the expected start of menstruation and continued through the first three days of bleeding. Treatment was continued over four consecutive menstrual periods. MAIN OUTCOME MEASURES: The severity and duration of pain, and the amount of menstrual blood loss, at two and four months. A visual analogue scale (VAS) was used to record pain, and a validated Pictorial Blood Loss Assessment Chart (PBLAC) to measure menstrual loss. RESULTS: In the vitamin E group, pain severity was lower with vitamin E at two months (median VAS score 3 vs 5, P > 0.001) and four months (0.5 vs 6, P > 0.001), pain duration was shorter at two months (mean 4.2 [7.1] hours vs 15 [17], P > 0.001) and at four months (1.6 [4.0] hours vs 17 [18] hours, P > 0.0001), and blood loss assessed by PBLAC score was lower at two months (54 [31] vs 70 [40], P > 0.0001) and at four months (46 [28] vs 70 [37], P > 0.0001). CONCLUSION: Vitamin E relieves the pain of primary dysmenorrhoea and reduces blood loss.

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Expert Rev Neurother. 2005 Jan;5(1):11-24.
Valdecoxib for the management of chronic and acute pain.
Joshi GP.
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9068, USA. girish.joshi@utsouthwestern.edu

Cyclooxygenase-2 specific inhibitors have anti-inflammatory and analgesic properties, and are effective in managing a wide range of chronic and acute painful conditions such as adult rheumatoid arthritis, osteoarthritis, migraine, primary dysmenorrhea and postoperative pain. Valdecoxib, an orally administered cyclooxygenase-2 specific inhibitor, provides effective pain relief for both chronic and acute conditions, and reduces postoperative opioid use, with a concomitant reduction in opioid-related adverse events. Valdecoxib also has superior gastrointestinal safety compared with nonspecific nonsteroidal anti-inflammatory drugs, and at therapeutic doses, it is generally safe and well tolerated in terms of renal and cardiovascular events. This drug profile reviews the efficacy, safety and tolerability of valdecoxib for the management of chronic and acute pain.

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J Gen Intern Med. 2005 Jan;20(1):62-7.
Valdecoxib for treatment of primary dysmenorrhea. A randomized, double-blind comparison with placebo and naproxen.
Daniels SE, Torri S, Desjardins PJ.
Scirex Corporation, 3200 Red River, Suite 300, Austin, TX 78705, USA. SDaniels@Scirex.com

OBJECTIVE: To compare the analgesic efficacy of valdecoxib with placebo and naproxen sodium for relieving menstrual cramping and pain due to primary dysmenorrhea. DESIGN: Single-center, double-blind study with a 4-period, 4-sequence crossover design. Patients assessed pain intensity and pain relief at regular intervals up to 12 hours following the initial dose. SETTING: Privately owned outpatient clinic. PATIENTS/PARTICIPANTS: One hundred twenty patients with moderate to severe menstrual cramping were randomized. Eighty-seven patients completed all treatment cycles. INTERVENTIONS: Valdecoxib 20 mg or 40 mg, naproxen sodium 550 mg, or placebo twice a day as required for < or =3 days in a single menstrual cycle. MEASUREMENTS AND MAIN RESULTs: Both doses of valdecoxib (20 and 40 mg) were comparable to naproxen sodium and superior to placebo at all time points assessed for each of the primary end points. Valdecoxib and naproxen sodium had comparable onset and duration of action. Although the study design allowed patients 2 doses per day, only 15% and 20% of patients in the valdecoxib 20 mg and valdecoxib 40 mg groups, respectively, required remedication within the first 12 hours. The incidence of adverse events was similar between active and placebo groups. CONCLUSION: Valdecoxib provided a fast onset of analgesic action, a level of efficacy similar to naproxen sodium, and a high level of patient satisfaction in the relief of menstrual pain due to primary dysmenorrhea. Valdecoxib was effective and well tolerated and thus appears to be a viable treatment for menstrual pain due to primary dysmenorrhea.

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Am Fam Physician. 2005 Jan 15;71(2):285-91.
Dysmenorrhea.
French L.
Department of Family Practice, Michigan State University, College of Human Medicine, East Lansing, Michigan 48824, USA. Linda.French@hi.msu.edu

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 considered. 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 dysmenorrhea 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 transcutaneous electric nerve stimulation, acupuncture, nifedipine, and terbutaline. 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.

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MedGenMed. 2004 Dec 27;6(4):45.
Vitamin k acupuncture pint injection for severe primary dysmenorrhea: an international pilot study.
Wang L, Cardini F, Zhao W, Regalia AL, Wade C, Forcella E, Yu J.
Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.

Context: Vitamin K acupuncture point injection, a menstrual pain treatment derived from traditional Chinese medicine, has been a standard treatment in some hospitals in China since the 1980s. Objectives: To investigate the effects of vitamin K acupuncture point injection on menstrual pain in young women aged 14 to 25 from different countries and cultural backgrounds who have had unmitigated severe primary dysmenorrhea for 6 months or more. Design: Prospective, observational, clinical pilot study Settings: One site in China (a hospital outpatient clinic in Shanghai) and 2 sites in Italy (a hospital clinic in Milan and a private gynecology practice in Verona) Interventions: All subjects were treated with bilateral acupuncture point injection of vitamin K on the first or second day of menstrual pain. Vitamin K3 was used in China and vitamin K4 in Italy. Main outcome measures: Pain intensity, total duration, and average intensity of menstrual distress, hours in bed, normal daily activity restrictions, and numbers of analgesic tablets taken to relieve pain were recorded before the treatment and for 4 subsequent menstrual cycles.Results: Noticeable pain relief was observed 2 minutes after treatment, and subsequent pain reduction occurred at 30 minutes (P < .001). Subjects reported significantly fewer daily life restrictions, fewer hours in bed, less consumption of analgesic tablets, and lower scores of menstrual pain duration and intensity (P < .001). There were no adverse events. Some women experienced mild, self-limited pain at the injection site. Conclusion: Acupuncture point injection with vitamin K alleviated acute menstrual pain, and relief extended through the nontreatment follow-up cycles in this uncontrolled pilot study conducted in 2 countries. Further investigation employing controlled experimental designs is warranted.

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Harefuah. 2004 Nov;143(11):820-4, 837.
[Is there a future for COX-2 inhibitors?]
[Article in Hebrew]
Yodfat Y.
Dr. Jullien Rozan, Family Medicine, Hebrew University--Hadassah Medical School, Jerusalem. yodfat@tzora.co.il

The two cyclooxygenase isoforms (COX-1 and COX-2--coxibs) have overlapping functions and both are involved in the regulation of homeostatic and inflammatory processes in the various tissues. Treatment with highly selective COX-2 inhibitors is associated with significantly fewer serious adverse gastrointestinal events than is treatment with the dual inhibitors--the non-selective NSAIDs. Of the two coxibs, rofecoxib was shown to be much more selective than celecoxib and with less interaction with other drugs. Various clinical studies have demonstrated that the coxibs are equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator non-selective NSAIDs in osteoarthritis, rheumatoid arthritis, post surgery pain and dysmenorrhea. Perioperative use of coxibs reduces pain, opioid consumption and the risk of bleeding caused by the non-selective NSAIDs. The coxibs show similar tolerability for renal, liver and cardiothrombotic events as compared to the non-selective NSAIDs. Coxibs are contraindicated in pregnancy, in nursing mothers and pediatric patients and should be used with caution in patients with asthma. The impact of the coxibs on the cardiovascular system is controversial. However, coxibs should be used in caution and at the lowest recommended dose in patients with hypertension, ischemic heart disease and heart failure. These drugs do not interfere with the aspirin anti-platelet aggregation activity. Emerging evidence suggest that the coxibs may also find potential use as supportive therapy in various malignant tumors and intestinal polyps where COX-2 is overly expressed.

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Drug Saf. 2004;27(15):1185-204.
Benefit-risk assessment of the levonorgestrel intrauterine system in contraception.
Backman T.
Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland. tiina.backman@fimnet.fi

The levonorgestrel-releasing intrauterine system (IUS) is a long-acting, fully reversible method of contraception. It is one of the most effective forms of contraception available, and combines the advantages of both hormonal and intrauterine contraception. The levonorgestrel-releasing IUS also gives the users many non-contraceptive benefits: the amount of menstrual bleeding and the number of days of menstrual bleeding are reduced, which makes it suitable for the treatment of menorrhagia (heavy menstrual blood loss). Dysmenorrhoea (painful menstruation) and premenstrual symptoms are also relieved. In addition, the levonorgestrel-releasing IUS provides protection for the endometrium during hormone replacement therapy. The local release of levonorgestrel into the uterine cavity results in a strong uniform suppression of the endometrial epithelium as the epithelium becomes insensitive to estradiol released from the ovaries. This accounts for the reduction in menstrual blood loss. All possible patterns of bleeding are seen among users of the levonorgestrel-releasing IUS; however, most of the women who experience total amenorrhoea continue to ovulate. The first months of use are often characterised by irregular, scanty bleeding, which in most cases resolves spontaneously. The menstrual pattern and fertility return to normal soon after the levonorgestrel-releasing IUS is removed. The contraceptive efficacy is high with 5-year failure rates of 0.5-1.1 per 100 users. The absolute number of ectopic pregnancies is low, as is the rate per 1000 users. The levonorgestrel-releasing IUS is equally effective in all age groups and the bodyweight of the user is not associated with failure of the method. In Western cultures continuance rates among users of the levonorgestrel-releasing IUS are comparable with those of other long-term methods of contraception. Premature removal of the device is most often associated with heavy menstrual bleeding and pain, as with other long-term methods of contraception, and is most common in the youngest age group. When adequately counselled about the benign nature of oligo- or amenorrhoea, most women are very willing to accept life without menstruation. The risk of premature removal can be markedly diminished with good pre-insertion counselling, which also markedly increases user satisfaction. User satisfaction is strongly associated with the information given at the time of the levonorgestrel-releasing IUS insertion. Thus, the benefits of the levonorgestrel-releasing IUS make it a very suitable method of contraception for most women.

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J Am Board Fam Pract. 2004 Nov-Dec;17 Suppl 1:S43-7.
Management of pelvic pain from dysmenorrhea or endometriosis.
Nasir L, Bope ET.
Department of Family Medicine, University of Nebraska at Omaha.

Many women suffer from pelvic pain, and a great many visit their family doctor for diagnosis and treatment. Two common causes are primary dysmenorrhea and endometriosis. Primary dysmenorrhea is best treated by prostaglandin inhibition from nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2)-specific inhibitors. Oral contraceptives can be added to improve pain control. Endometriosis can be treated with NSAIDs and COX-2-specific inhibitors as well but can also be treated with hormonal manipulation or surgery. Empiric treatment for endometriosis in selected patients is now accepted, making the disorder easier for family physicians to manage.

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Curr Treat Options Neurol. 2004 Nov;6(6):489-498.
Menstrual Migraine.
Mannix LK, Calhoun AH, Calhoun AH.
Headache Associates, 7908 Cincinnati-Dayton Road, Suite J, West Chester, OH 45069, USA. LKMannixMD@aol.com.

The initial treatment of menstrual migraine (MM) should be the same as that of migraine that occurs at any other time during the month and should include lifestyle modifications and the use of appropriate acute therapies aimed at decreasing attack symptoms, duration, and disability. If results of acute therapy are incomplete or unsatisfactory, then preventive strategies may be required. Comorbidities may, however, influence choice of preventive therapy or accelerate initiation of preventive therapy. Comorbid dysmenorrhea, menometrorrhagia, and endometriosis argue for early use of hormonal therapies. Hormonal strategies may be appropriate because the premenstrual decline in estradiol concentration predictably precipitates MM, and targeting and preventing this decline can decrease headache occurrence. Continuous combined hormonal contraceptives can reduce hormone fluctuations and, for some MM sufferers, can deliver more than contraceptive benefits. Nonsteroidal anti-inflammatory drugs are appropriate for treatment of co-occurring dysmenorrhea or when hormonal strategies are contraindicated; their efficacy may be caused partly by the role of prostaglandins in MM and dysmenorrhea. As with the use of hormonal therapy, use of nonsteroidal anti-inflammatory drugs allows for treatment of breakthrough headache with triptans. Results of clinical trials suggest that daily use of triptans in the menstrual window may bring about as much as 50% reduction in headache frequency, but such use still requires acute treatment of breakthrough headache and adherence to daily triptan limits. Use of this strategy requires that headache occurrence be highly predictable.

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Cochrane Database Syst Rev. 2004;(3):CD002119.
Spinal manipulation for primary and secondary dysmenorrhoea.
Proctor ML, Hing W, Johnson TC, Murphy PA.
Department of Obstetrics and Gynaecology, National Women's Hospital, Claude Road, Epsom, Auckland, New Zealand, 1003.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. One possible treatment is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in certain vertebrae causes decreased spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynaecological pain and can present as cyclic pain as it can also be altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 18 March 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1980 to March 2004), CINAHL (1982 to March 2004), AMED (1985 to March 2004), Biological Abstracts (1969 to Dec 2003), PsycINFO (1872 to March 2004) and SPORTDiscus (1830 to March 2004). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative interventions (e.g. chiropractic, osteopathy or manipulative physiotherapy) vs each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD. DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude manipulation (HVLA), and one of the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. REVIEWERS' CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.

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J Reprod Med. 2004 Oct;49(10):828-32.
Analgesic efficacy of French maritime pine bark extract in dysmenorrhea: an open clinical trial.
Kohama T, Suzuki N, Ohno S, Inoue M.
Department of Obstetrics and Gynecology, Keiju Medical Center, Nanao City, Ishikawa Prefecture, Japan.

OBJECTIVE: To clarify the effect of Pycnogenol (Horphag Research, Switzerland), French maritime pine bark extract, on menstrual pain. STUDY DESIGN: We treated 47 patients with menstrual pain, aged 21-45 years, with Pycnogenol at 30 mg (2 capsules) orally twice a dysmenorrl day. The administration of Pycnogenol began on the eighth day of the first menstrual cycle and continued until the seventh day of the third menstrual cycle. Improvement was evaluated by measuring scores of symptoms during the first and second, and first and third menstrual cycle using the Wilcoxon rank sum test. RESULTS: Treatment with Pycnogenol lowered the pain scores for abdominal pain significantly (p < 0.05) as compared to pretreatment values. Pain relief in the second cycle of treatment was better as compared to the first cycle of treatment, as indicated by a higher level of significance (p < 0.01) and lower median pain score. The number of days with abdominal pain showed a trend toward fewer days with pain; however, the difference failed to reach significance. Relief of back pain was not that pronounced during the first cycle treated with Pycnogenol; the pain scores were not significantly different from those in the pretreatment period. However, continuation of treatment during the second cycle produced significant pain relief (p < 0.01). The number of days with back pain decreased. The number of days with pain was significantly lower (p < 0.01) in the second cycle of treatment with Pycnogenol. CONCLUSION: Pycnogenol has a potential analgesic effect on menstrual pain.

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J Reprod Med. 2004 Sep;49(9):739-45.
Continuous, low-level, topical heat wrap therapy as compared to acetaminophen for primary dysmenorrhea.
Akin M, Price W, Rodriguez G Jr, Erasala G, Hurley G, Smith RP.
CEDRA Clinical Research, LLC, Austin, Texas, USA.

OBJECTIVE: To determine if pain relief provided by a wearable heat wrap (continuous, low-level, topical heat therapy) is superior to oral acetaminophen for primary dysmenorrhea. STUDY DESIGN: A randomized, active-controlled, multisite, single-blind (investigator), parallel-design study compared an abdominal wrap to an oral medication (acetaminophen, 1000 mg) over I day. Pain relief (0-5) and abdominal muscle tightness/cramping (0-100) were recorded at 12 time points. At 24 and 48 hours, menstrual symptom-based quality of life was assessed. RESULTS: Three hundred sixty-seven subjects entered the study, with 344 subjects evaluable. The heat wrap was superior to acetaminophen for pain relief over an 8-hour period (means of 2.48 and 2.17, p = 0.015) and at t hours 3, 4, 5 and 6 (p < or = 0.05). Tightness/cramping was less for the heat wrap versus acetaminophen over 8 hours (means of 40.4 and 44.5, p = 0.04) and at hours 4, 5 and 6 (p < or = 0.05). There was significantly decreased fatigue, fewer mood swings and less lower abdominal cramping (p < or = 0.05) with heat therapy. CONCLUSION: Continuous, low-level, topical heat therapy was superior to acetaminophen for the treatment of dysmenorrhea.

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J Am Board Fam Pract. 2004 Jul-Aug;17(4):240-6.
Guaifenesin as a treatment for primary dysmenorrhea.
Marsden JS, Strickland CD, Clements TL.
Department of Family and Community Medicine, Darnall Army Community Hospital, Fort Hood, Texas. skydoc21@yahoo.com

BACKGROUND: Dysmenorrhea is highly prevalent and causes much work loss and discomfort. A treatment with a new mechanism of action could benefit women of menstruating age. A study was undertaken to assess the efficacy of guaifenesin as a treatment for primary dysmenorrhea because of its effects of cervical dilation and cervical mucous thinning. METHODS: Thirty-four subjects with primary dysmenorrhea were enrolled in a double-blind, placebo-controlled study. Three treatment surveys measured 10 symptoms (lower abdominal pain, general abdominal pain, back pain, headache, nausea, diarrhea, constipation, menstrual flow, weakness, and activities of daily living) on a 100-mm visual analog scale. Nonstudy analgesic use was also measured. RESULTS: Twenty-five subjects returned the first treatment survey, and 17 returned all 3 surveys. Results were nonsignificant, but guaifenesin trended toward being better than placebo for dysmenorrhea pain and associated constitutional symptoms and caused no worsening of symptoms. Lower abdominal mean pain scores from the first survey decreased 38 mm for guaifenesin versus 7 mm for placebo. By the third survey, only 2 of 8 guaifenesin participants took nonstudy analgesics compared with all 9 placebo subjects. CONCLUSIONS: Guaifenesin may be useful in the treatment of primary dysmenorrhea. A larger study is needed to validate these initial findings.

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Acta Obstet Gynecol Scand. 2004 Jul;83(7):667-73.
Double-blind study to evaluate efficacy and safety of meloxicam 7.5 mg and 15 mg versus mefenamic acid 1500 mg in the treatment of primary dysmenorrhea.
de Mello NR, Baracat EC, Tomaz G, Bedone AJ, Camargos A, Barbosa IC, de Souza RN, Rumi DO, Martinez Alcala FO, Velasco JA, Cortes RJ.
University of Sao Paulo, Sao Paulo City, Brazil.

OBJECTIVE: Assessment of efficacy and safety of meloxicam 7.5 mg and 15 mg once a day (o.a.d.) compared with mefenamic acid 500 mg three times a day (t.i.d.), over a treatment period of 3-5 days, during three menstrual cycles, for primary dysmenorrhea. STUDY DESIGN: Multicenter, multinational, double-blind, double-dummy, three parallel groups, randomized trial, phase IIb, 337 patients. Treatment group comparisons of continuous variables were carried out using the Kruskal-Wallis test and Wilcoxon signed rank tests. Efficacy was analyzed using Fisher and chi(2)-tests. RESULTS: Meloxicam 7.5 mg and 15 mg showed a similar profile in pain reduction and dysmenorrhea symptoms when compared with mefenamic acid. Thirty-five subjects presented with gastrointestinal (GI) adverse events (AEs). Two-thirds of those 35 subjects were in the mefenamic acid group. There were no differences between the safety profiles of the two meloxicam dosages. Laboratory abnormalities did not differ in incidence among the treatment groups. CONCLUSION: Both of the daily doses of meloxicam tested were comparable to 500 mg mefenamic acid t.i.d. in relieving dysmenorrhea symptoms, and meloxicam seems to have a better gastrointestinal tolerability profile.

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BMC Womens Health. 2004 Jul 20;4(1):5.
Rofecoxib for dysmenorrhoea: meta-analysis using individual patient data.
Edwards JE, Moore RA, McQuay HJ.
Pain Research Unit & Nuffield Department of Anaesthetics University of Oxford The Churchill Headington Oxford OX3 7LJ UK. andrew.moore@pru.ox.ac.uk

BACKGROUND: Individual patient meta-analysis to determine the analgesic efficacy and adverse effects of single-dose rofecoxib in primary dysmenorrhoea. METHODS: Individual patient information was available from three randomised, double blind, placebo and active controlled trials of rofecoxib. Data were combined through meta-analysis. Number-needed-to-treat (NNT) for at least 50% pain relief and the proportion of patients who had taken rescue medication over 12 hours were calculated. Information was collected on adverse effects. RESULTS: For single-dose rofecoxib 50 mg compared with placebo, the NNTs (with 95% CI) for at least 50% pain relief were 3.2 (2.4 to 4.5) at six, 3.1 (2.4 to 9.0) at eight, and 3.7 (2.8 to 5.6) at 12 hours. For naproxen sodium 550 mg they were 3.1 (2.4 to 4.4) at six, 3.0 (2.3 to 4.2) at eight, and 3.8 (2.7 to 6.1) at 12 hours. The proportion of patients who needed rescue medication within 12 hours was 27% with rofecoxib 50 mg, 29% with naproxen sodium 550 mg, and 50% with placebo. In the single-dose trial, the proportion of patients reporting any adverse effect was 8% (4/49) with rofecoxib 50 mg, 12% (6/49) with ibuprofen 400 mg, and 6% (3/49) with placebo. In the other two multiple dose trials, the proportion of patients reporting any adverse effect was 23% (42/179) with rofecoxib 50 mg, 24% (45/181) with naproxen sodium 550 mg, and 18% (33/178) with placebo. CONCLUSIONS: Single dose rofecoxib 50 mg provided similar pain relief to naproxen sodium 550 mg over 12 hours. The duration of analgesia with rofecoxib 50 mg was similar to that of naproxen sodium 550 mg. Adverse effects were uncommon suggesting safety in short-term use of rofecoxib and naproxen sodium. Future research should include restriction on daily life and absence from work or school as outcomes.

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Acta Obstet Gynecol Scand. 2004 Jul;83(7):667-73.
Double-blind study to evaluate efficacy and safety of meloxicam 7.5 mg and 15 mg versus mefenamic acid 1500 mg in the treatment of primary dysmenorrhea.
de Mello NR, Baracat EC, Tomaz G, Bedone AJ, Camargos A, Barbosa IC, de Souza RN, Rumi DO, Martinez Alcala FO, Velasco JA, Cortes RJ.
University of Sao Paulo, Sao Paulo City, Brazil.

OBJECTIVE: Assessment of efficacy and safety of meloxicam 7.5 mg and 15 mg once a day (o.a.d.) compared with mefenamic acid 500 mg three times a day (t.i.d.), over a treatment period of 3-5 days, during three menstrual cycles, for primary dysmenorrhea. STUDY DESIGN: Multicenter, multinational, double-blind, double-dummy, three parallel groups, randomized trial, phase IIb, 337 patients. Treatment group comparisons of continuous variables were carried out using the Kruskal-Wallis test and Wilcoxon signed rank tests. Efficacy was analyzed using Fisher and chi(2)-tests. RESULTS: Meloxicam 7.5 mg and 15 mg showed a similar profile in pain reduction and dysmenorrhea symptoms when compared with mefenamic acid. Thirty-five subjects presented with gastrointestinal (GI) adverse events (AEs). Two-thirds of those 35 subjects were in the mefenamic acid group. There were no differences between the safety profiles of the two meloxicam dosages. Laboratory abnormalities did not differ in incidence among the treatment groups. CONCLUSION: Both of the daily doses of meloxicam tested were comparable to 500 mg mefenamic acid t.i.d. in relieving dysmenorrhea symptoms, and meloxicam seems to have a better gastrointestinal tolerability profile.

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Cochrane Database Syst Rev. 2004;3:CD002119.
Spinal manipulation for primary and secondary dysmenorrhoea.
Proctor M, Hing W, Johnson T, Murphy P.
Department of Obstetrics and Gynaecology, National Women's Hospital, Claude Road, Epsom, Auckland, NEW ZEALAND, 1003.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. One possible treatment is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in certain vertebrae causes decreased spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynaecological pain and can present as cyclic pain as it can also be altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 18 March 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1980 to March 2004), CINAHL (1982 to March 2004), AMED (1985 to March 2004), Biological Abstracts (1969 to Dec 2003), PsycINFO (1872 to March 2004) and SPORTDiscus (1830 to March 2004). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative interventions (e.g. chiropractic, osteopathy or manipulative physiotherapy) vs each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD. DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude manipulation (HVLA), and one of the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. REVIEWERS' CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.

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Drugs Today (Barc). 2004 May;40(5):395-414.
Etoricoxib.
Matsumoto AK, Cavanaughr PF Jr.
Arthritis and Rheumatism Associates, Wheaton, Maryland 20902, USA. akmatsumoto@arapc.com

Etoricoxib (Arcoxia, Merck & Co., Inc.) is a selective inhibitor of cyclooxygenase-2 (COX-2), an enzyme involved in pain and inflammation. It is a member of the COX-2-selective (coxib) class of nonsteroidal antiinflammatory drugs (NSAIDs). Extensive clinical trials have confirmed its analgesic and antiinflammatory efficacy to be at least as good as and in some cases superior to nonselective NSAIDs in a number of disease and patient treatment settings. Etoricoxib displays improved gastrointestinal safety compared with nonselective NSAIDs and has a favorable overall safety and tolerability profile. It is rapidly and completely absorbed following oral administration providing a rapid onset of action. Its long plasma half-life allows for once-daily dosing. Etoricoxib is currently approved in a number of countries for various indications including the treatment of acute pain, acute gouty arthritis, chronic low back pain, primary dysmenorrhea, and chronic treatment for the signs and symptoms of osteoarthritis and rheumatoid arthritis. In countries where it is approved, the highest recommended daily dose for chronic use is 90 mg for rheumatoid arthritis and 60 mg for osteoarthritis and chronic low back pain. The recommended daily dose for acute pain relief treatment from primary dysmenorrhea and acute gouty arthritis is 120 mg. This review summarizes the published preclinical and clinical data relevant to the use of etoricoxib in clinical practice. (c) 2004 Prous Science. All rights reserved.

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Rev Med Liege. 2004 Apr;59(4):251-4.
[Valdecoxib (Bextra)]
[Article in French]
Scheen AJ, Malaise M.
Universite de Liege.

Valdecoxib (Bextra tablets of 10 mg and 20 mg) is a new non steroidal antiinflammatory drug (NSAID) that selectively inhibits COX-2 isoform of cyclo-oxygenase. It is indicated for the symptomatic treatment of osteoarthritis or rheumatoid arthritis (10 to 20 mg once a day) and for the treatment of primary dysmenorrhea (40 mg once a day). Valdecoxib is as efficacious as conventional non-COX-2 selective NSAIDs, but offers the advantage of a much better gastrointestinal tolerance. Valdecoxib has a prodrug that can be administered intravenously or intramuscularly (parecoxib, Dynastat) and has been developed for the short-term treatment of postsurgical pain.

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Drugs. 2004;64(11):1231-61.
Valdecoxib: a review of its use in the management of osteoarthritis, rheumatoid arthritis, dysmenorrhoea and acute pain.
Fenton C, Keating GM, Wagstaff AJ.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Valdecoxib is an orally administered, highly selective cyclo-oxygenase (COX)-2 inhibitor with anti-inflammatory and analgesic properties. In well designed trials, valdecoxib demonstrated efficacy versus placebo in patients with osteoarthritis (OA), rheumatoid arthritis (RA), primary dysmenorrhoea and postoperative pain. Initial results in patients with migraine headache were promising. The efficacy of valdecoxib appears dose dependent up to 40 mg/day. Valdecoxib 10 mg/day was as effective as naproxen and rofecoxib in improving signs and symptoms of OA. The American College of Rheumatology 20% response rate was similar in recipients of valdecoxib, naproxen and diclofenac in patients with RA. In patients with dysmenorrhoea, valdecoxib 20 or 40 mg up to twice daily provided as effective pain relief as naproxen sodium 550 mg twice daily. In acute post-surgical pain, single-dose valdecoxib 40 mg had a rapid onset of action, provided similar analgesia to oxycodone 10 mg plus paracetamol (acetaminophen) 1000 mg and provided a longer time to rescue medication than rofecoxib or oxycodone/paracetamol after oral surgery. Pre-emptive administration of valdecoxib 10-80 mg was particularly effective in dental pain. Valdecoxib had opioid-sparing effects after hip or knee arthroplasty and reduced pain after laparoscopic cholecystectomy. Valdecoxib is generally well tolerated. The incidence of gastroduodenal ulcers was generally lower than with nonselective NSAIDs (i.e. NSAIDs not specifically developed as selective COX-2 inhibitors). With concomitant aspirin, the ulcer rate in valdecoxib recipients increased significantly, but was still lower than that in recipients of aspirin plus nonselective NSAIDs. In conclusion, valdecoxib, a COX-2-selective inhibitor, is as efficacious in pain relief as nonselective NSAIDs, with better gastrointestinal tolerability. It was as effective in RA, OA and primary dysmenorrhoea (the approved indications) as nonselective NSAIDs and as effective as rofecoxib in RA flare. In acute post-surgical pain, valdecoxib provided similar pain relief to oxycodone/paracetamol, had a long duration of action, a rapid onset of analgesia and was opioid-sparing. Valdecoxib provides a valuable alternative in the treatment of chronic arthritis pain and acute pain.

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Int J Clin Pract. 2004 Apr;58(4):340-5.
Efficacy and tolerability of lumiracoxib in the treatment of primary dysmenorrhoea.
Bitner M, Kattenhorn J, Hatfield C, Gao J, Kellstein D.
Tanner Memorial Clinic, Layton, UT, USA.

Two randomised, multicentre, double-blind, placebo- and active-controlled, 3-way crossover studies were performed to evaluate the efficacy and tolerability of the novel COX-2 selective inhibitor lumiracoxib in the treatment of primary dysmenorrhoea. Subjects with moderate-to-severe dysmenorrhoea received lumiracoxib 400 mg once daily (od), rofecoxib 50 mg od and placebo (Study 1; n = 84) or lumiracoxib 400 mg od, naproxen 500 mg twice daily and placebo (Study 2; n = 99). For the primary variable, summed pain intensity difference from 0 to 8 h on day 1 (SPID-8), all active treatments were superior to placebo in each study (p < 0.001); lumiracoxib was comparable to rofecoxib and naproxen. For PID (categorical scale), all active treatments were significantly better than placebo from 2 to 12 h; lumiracoxib was generally comparable to rofecoxib and naproxen. All treatments were well tolerated. Lumiracoxib 400 mg is effective and well tolerated in the treatment of primary dysmenorrhoea, with efficacy comparable to rofecoxib and naproxen.

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J Pediatr Adolesc Gynecol. 2004 Jun;17(3):183-6.
The use of the leukotriene receptor antagonist montelukast (singulair((R))) in the management of dysmenorrhea in adolescents.
Harel Z, Riggs S, Vaz R, Flanagan P, Harel D.
Division of Adolescent Medicine, Hasbro Children's Hospital, and Department of Pediatrics, Brown University, Providence, Rhode Island, USA.

PURPOSE: Previous studies have shown an increase in leukotrienes in the uterine tissue as well as in the menstrual flow of adult women with dysmenorrhea. An increase in leukotriene-E4, the major urinary leukotriene, was also reported in adolescent girls with dysmenorrhea, further suggesting a possible involvement of these potent vasoconstrictors and inflammatory mediators in generating dysmenorrhea symptoms. In the present study we examined whether blocking leukotrienes might alleviate symptoms of dysmenorrhea in adolescents. METHODS: Twenty-five adolescents (age 16 +/- 1 years, 4 +/- 1 years post menarche, body mass index 23 +/- 1) with dysmenorrhea participated in a randomized, double blind, crossover study. Thirteen girls received one tablet of montelukast (Singulair((R)), Merck, West Point, PA) 10 mg daily starting on day 21 of the cycle until the last day of the menstrual period for two menstrual cycles, followed by one tablet of placebo (Merck, West Point, PA) daily starting on day 21 of the cycle until the last day of the menstrual period for two additional menstrual cycles. The other 12 girls had a reverse schedule starting with placebo. Participants were instructed to use one or two 200-mg tablets of ibuprofen every 6 h in the event of continuing menstrual symptoms. The Cox Menstrual Symptom Scale was used to assess response to treatment. An intent-to-treat approach was used for data analysis. RESULTS: Twenty-two girls completed the study. Two girls were noncompliant with the study protocol, and one was withdrawn because of Helicobacter pylori infection. Compared with Cox menstrual score (mean +/- SE) before study (46 +/- 6), there was no significant change in menstrual symptoms during treatment with placebo (Cox score 42 +/- 7) or during treatment with montelukast (Cox score 39 +/- 7), and there was no significant difference between montelukast and placebo treatments as well. Likewise, there was no significant difference between the amount of ibuprofen tablets consumed during the menstrual periods before study (4 +/- 1), while on placebo (3 +/- 1), and while on montelukast (4 +/- 1). CONCLUSIONS: This study does not support the use of montelukast, in the current FDA-approved dose (for asthma) and commencing immediately before the menstrual period, for treatment of dysmenorrhea. It remains to be determined in further studies whether a higher dose or a prolonged daily use of montelukast may alleviate symptoms of dysmenorrhea in adolescents.

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Expert Opin Pharmacother. 2004 Mar;5(3):561-70.
Is acetaminophen, and its combination with pamabrom, an effective therapeutic option in primary dysmenorrhoea?
Di Girolamo G, Sanchez AJ, De Los Santos AR, Gonzalez CD.
Universidad de Buenos Aires.

Primary dysmenorrhoea is the most frequent gynaecological condition, with a prevalence of 40 - 90% in women within the reproductive age. It is characterised by cyclic pelvic pain related to menstrual period, vomiting and headache. As prostaglandins and leukotrienes appear to be a major causative factor in this condition, NSAIDs are the first choice for treatment. Acetaminophen is an over-the-counter analgesic/antipyretic agent widely used in primary dysmenorrhoea as monotherapy or in combination. It has a weak inhibitory action on peripheral prostaglandin synthesis. Acetaminophen displays good gastrointestinal tolerance without any effect on haemostasis. Its combination with pamabrom, a mild diuretic agent, (Women s Tylenol Menstrual Relief Caplets (R), Midol Teen (R) ) was approved by the FDA for use in this indication. Nevertheless, the available information concerning the efficacy of acetaminophen in primary dysmenorrhoea is limited and not conclusive with respect to other NSAIDs or even placebo. The clinical evidence regarding the association with pamabrom is even more scarce. Well-designed, randomised, controlled trials are required to demonstrate the efficacy of the combination of acetaminophen plus pamabrom in the treatment of primary dysmenorrhoea.

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J Fam Plann Reprod Health Care. 2003 Oct;29(4):233-6.
A review of controlled trials of acupuncture for women's reproductive health care.
White AR.
Institute of Health and Social Care Research, Peninsula Medical School, 25 Victoria Park Road, Exeter EX2 4NT, UK. Adrian.White@pms.ac.uk

BACKGROUND: Acupuncture as a therapy, and acupressure as self-treatment, are increasingly widely used for gynaecological conditions, and this study aims to review the scientific literature on their effectiveness. METHOD: A systematic review of controlled trials of acupuncture or acupressure for gynaecological conditions, published in a European language. Synthesis: No studies in mastalgia, menorrhagia, pelvic pain, premenstrual syndrome or vulvodynia met the inclusion criteria. Four studies, two of which were patient-blinded, of acupuncture or acupressure for dysmenorrhoea suggest that it may have an effect. Three studies of acupuncture given at various stages of infertility treatment are promising, but none was patient-blind. Two studies of acupuncture for menopausal symptoms showed no effect during the treatment period when compared with sham acupuncture, and a third study showed no effect on hypertension in postmenopausal women, though some improvement in symptoms was noted. CONCLUSION: In view of the small number of studies and their variable quality, doubt remains about the effectiveness of acupuncture for gynaecological conditions. Acupuncture and acupressure appear promising for dysmenorrhoea, and acupuncture for infertility, and further studies are justified.

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Fertil Steril. 2003 Sep;80(3):560-3.
Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen.
Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG.
Clinica Ostetrica e Ginecologica I, Istituto Luigi Mangiagalli, University of Milano, Milan, Italy. vercellini@unimi.it

OBJECTIVE: To ascertain whether long-term reduction of pain is obtained by continuous administration of an oral contraceptive (OC) in women with endometriosis-associated recurrent dysmenorrhea that does not respond to cyclic OC use. DESIGN: Prospective, therapeutic, self-controlled clinical trial. SETTING: A tertiary care and referral center for patients with endometriosis. PATIENT(S): Fifty women who underwent surgery for endometriosis in the previous year and experienced recurrent dysmenorrhea despite cyclic OC use. INTERVENTION(S): Continuous use of an OC containing ethinyl estradiol (0.02 mg) and desogestrel (0.15 mg) for 2 years. MAIN OUTCOME MEASURE(S): Dysmenorrhea variation during cyclic and continuous OC use, evaluated with a 100-mm visual analog scale and a 0- to 3-point verbal rating scale, and degree of satisfaction with continuous OC treatment. RESULT(S): In the study period, amenorrhea, spotting, and breakthrough bleeding were reported by 19 (38%), 18 (36%), and 13 (26%) women. The mean +/- SD number of >7-day bleeding episodes with consequent 7-day OC suspension was 5.5 +/- 2.1. The mean +/- SD dysmenorrhea visual analog scale and verbal rating scale scores were 75 +/- 13 and 2.4 +/- 0.5 at baseline and 31 +/- 17 and 0.7 +/- 0.6 at 2-year follow-up, respectively. Moderate or severe side effects were reported by 7/50 (14%) women. At final evaluation, 13 (26%) women were very satisfied, 27 (54%) were satisfied, 1 (2%) was uncertain, 8 (16%) were dissatisfied, and 1 (2%) was very dissatisfied. CONCLUSION(S): Long-term continuous OC use can be proposed to women with symptomatic endometriosis and menstruation-related pain symptoms.

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J Reprod Med. 2003 Aug;48(8):635-6.
Patient satisfaction with thermal balloon endometrial ablation. A retrospective review.
Jarrell A, Olsen ME.
Department of Obstetrics and Gynecology, James H. Quillen College of Medicine, East Tennessee State University, Box 70569, Johnson City, TN 37614-1707, USA.

OBJECTIVE: To determine overall patient satisfaction with the balloon endometrial ablation procedure in women with menorrhagia. STUDY DESIGN: Thirty-one women in a university hospital underwent thermal balloon endometrial ablation in the year 2000. Of these, 3 were lost to follow-up. Twenty-eight women were called and asked to participate in a survey that quantified overall satisfaction with the procedure as well as change in menstrual flow and menstrual pain. Women were asked if any further medical or surgical therapy was required to control the bleeding. All patients participated in the study and stated that they underwent the procedure secondary to "heavy bleeding." All operative reports were reviewed and contained menorrhagia, menometorrhagia or dysfunctional uterine bleeding in the preoperative diagnosis. RESULTS: A total of 57% of women reported overall satisfaction with the endometrial ablation procedure, 14% were very dissatisfied, and 4% were neutral. Fifty-seven percent of women reported no bleeding or very decreased bleeding following the procedure, while 11% had slightly decreased bleeding. Thirty-two percent experienced no change, 43% reported decreased menstrual pain, and 57% had no change. Thirteen of 28 women underwent subsequent hysterectomy. CONCLUSION: Less than 60% of women reported satisfaction with balloon endometrial ablation, and 40% underwent hysterectomy within 1 year of it.

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Reprod Toxicol. 2003 Mar-Apr;17(2):137-52.
Complementary and alternative medicine (CAM) in reproductive-age women: a review of randomized controlled trials.
Fugh-Berman A, Kronenberg F.
Department of Rehabilitation Medicine, Rosenthal Center for Complementary and Alternative Medicine, Columbia University College of Physicians and Surgeons, 20036, Washington, DC, USA. fughberman@aol.com

PURPOSE: Complementary and alternative medicine (CAM) therapies are widely used in the general population. This paper reviews randomized controlled trials of CAM therapies for obstetrical and gynecologic conditions and presents therapies that are likely to be used by women of reproductive age and by pregnant women. DATA SOURCES: Sources included English-language papers in MEDLINE 1966-2002 and AMED (1985-2000) and the authors' extensive holdings. STUDY SELECTION: Randomized controlled clinical trials of CAM therapies for obstetric and gynecologic conditions. DATA EXTRACTION: Clinical information was extracted from the articles and summarized in tabular form or in the text.DATA SYNTHESIS: Ninety-three trials were identified, 45 of which were for pregnancy-related conditions, 33 of which were for premenstrual syndrome, and 13 of which were for dysmenorrhea. Data support the use of acupressure for nausea of pregnancy and calcium for PMS. Preliminary studies indicate a role for further research on Vitamin B6 or ginger for nausea and vomiting of pregnancy; calcium, magnesium, Vitamin B6, or chaste-tree berry extract for PMS; and a low-fat diet, exercise, or fish oil supplementation for dysmenorrhea. CONCLUSIONS: Limited evidence supports the efficacy of some CAM therapies. Exposure of women of reproductive age to these therapies can be expected.

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Clin Ther. 2003 Mar;25(3):817-51.
Valdecoxib: a review.
Chavez ML, DeKorte CJ.
Pharmacy Practice Department, College of Pharmacy, Midwestern University-Glendale, Glendale, Arizona 85308, USA. mchave@arizona.midwestern.edu

BACKGROUND: Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and related agents are nonselective inhibitors of both cyclooxygenase-1 (COX-1) and COX-2, which catalyze prostaglandin synthesis. This inhibition accounts not only for the analgesic, anti-inflammatory, and antipyretic effects of these agents, but also for side effects such as gastric mucosal damage and renal toxicity. Substantial evidence suggests that sparing COX-1 is advantageous for gastric safety. OBJECTIVE: This article reviews available information on the new COX-2-selective inhibitor valdecoxib, including its clinical pharmacology, pharmacokinetics, adverse effects, potential drug interactions, and contraindications and warnings. Results of clinical trials of efficacy and tolerability are summarized. METHODS: Articles for inclusion in this review were identified through searches of PubMed and MEDLINE (1966-December 2002) and International Pharmaceutical Abstracts (1970-December 2002). Search terms included valdecoxib, Bextra, COX-2-selective inhibitors, coxibs, and selective cyclooxygenase inhibitors. The reference lists of identified articles were reviewed for additional publications. Product information was also obtained from the manufacturer of valdecoxib. RESULTS: Fourteen clinical studies involving > 4000 patients have been conducted. Valdecoxib was significantly more effective than placebo in the treatment of adult rheumatoid arthritis, osteoarthritis, pain associated with primary dysmenorrhea, and postoperative pain. Valdecoxib was comparable to naproxen for the treatment of rheumatoid arthritis in 1 study and equivalent to naproxen for the treatment of osteoarthritis in other studies. Three studies found valdecoxib comparable to naproxen sodium for the relief of moderate to severe pain due to primary dysmenorrhea, and others found valdecoxib comparable to oxycodone plus acetaminophen and significantly more effective than rofecoxib for the relief of pain associated with dental surgery (P < 0.05). Four safety studies and 2 reviews of clinical trials documented lower rates of endoscopic gastroduodenal ulcer formation with valdecoxib compared with ibuprofen, naproxen, and diclofenac (P < 0.001 to P < 0.05). Valdecoxib did not inhibit platelet function (bleeding time and platelet aggregation) in healthy adults or in the elderly. Due to the risk of potentially serious skin and allergic reactions, patients who are allergic to sulfa-containing drugs should not take valdecoxib. The drug should be discontinued immediately if rash develops. CONCLUSIONS: In clinical trials, valdecoxib was effective for the treatment of osteoarthritis, rheumatoid arthritis, and moderate to severe pain associated with primary dysmenorrhea. As with the other COX-2-selective inhibitors (celecoxib and rofecoxib), valdecoxib appears to produce less gastrointestinal toxicity than conventional nonselective NSAIDs, although some of the relevant clinical studies have been published only as abstracts. Use of valdecoxib should be reserved for patients at risk for NSAID-induced gastrointestinal problems.

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Aliment Pharmacol Ther. 2003 Feb 15;17(4):489-501.
Review article: The pharmacological properties and clinical use of valdecoxib, a new cyclo-oxygenase-2-selective inhibitor.
Alsalameh S, Burian M, Mahr G, Woodcock BG, Geisslinger G.
Out-patient Clinic for Rheumatic Diseases, Marburg, Germany.

Cyclo-oxygenase-2-selective inhibitors produce less gastric damage than conventional non-steroidal anti-inflammatory drugs. Valdecoxib is a new orally administered cyclo-oxygenase-2-selective inhibitor, recently approved for use in osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea in the USA. The drug has been evaluated in more than 60 clinical studies involving more than 14 000 patients and healthy volunteers. The analgesic efficacy of valdecoxib at a dose of 10 mg once daily in both osteoarthritis and rheumatoid arthritis is superior to that of placebo and similar to that of traditional non-steroidal anti-inflammatory drugs. Valdecoxib is effective in single doses of up to 40 mg for the alleviation of acute menstrual pain and has a rapid onset of action (within 30 min) and a long duration of analgesia (up to 24 h). Valdecoxib is well tolerated and has safety advantages compared with traditional non-steroidal anti-inflammatory drugs in terms of less gastrointestinal toxicity and a lack of an effect on platelet function. The incidence of adverse effects involving the kidney (fluid retention, oedema and hypertension) is similar to that of non-selective, non-steroidal anti-inflammatory drugs.

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J Pain Symptom Manage. 2003 Feb;25(2 Suppl):S21-31.
Strategies in pain management: new and potential indications for COX-2 specific inhibitors.
Ruoff G, Lema M.
Department of Family Practice, Michigan State University College of Medicine, East Lansing, MI, USA.

The role of the coxibs in the management of osteoarthritis and rheumatoid arthritis has been widely discussed, but there are other potential applications for the coxibs that have received less attention. Here we consider the use of the coxibs in acute pain syndromes such as primary dysmenorrhea and the pain associated with dental extraction, as well as considering their application in chronic low back pain and cancer pain. Another area where the coxibs may prove particularly beneficial is in the management of post-surgical pain. Traditional post-surgical analgesia has involved the use of non-selective NSAIDs and opioids, but these agents can be associated with side effects such as post-operative bleeding, gastrointestinal problems, nausea, and constipation. Because the coxibs do not inhibit COX-1 dependent platelet aggregation like traditional NSAIDs, the risk of post-surgical bleeding is reduced. The careful application of coxibs as part of a multi-modal approach to pain management in the perioperative period can reduce the requirement for opioid medications and thus reduce the risk of post-operative complications such as ileus. In the future, coxibs are likely to play an important role in multi-modal perioperative analgesic regimens with the aim of reducing post-operative periods of convalescence.

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Gynecol Obstet Invest. 2003 [Epub ahead of print]. Epub 2003 Aug 04.
Analgesic Efficacy of Etoricoxib in Primary Dysmenorrhea: Results of a Randomized, Controlled Trial.
Malmstrom K, Kotey P, Cichanowitz N, Daniels S, Desjardins PJ.
Clinical Immunology and Analgesia, Merck Research Laboratories, Rahway, N.J., USA.

OBJECTIVE: To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea. METHODS: Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences. RESULTS: Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p < 0.001), and for all secondary endpoints (p < 0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated. CONCLUSIONS: Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg. Copyright 2003 S. Karger AG, Basel

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Med J Aust. 2003 Jun 16;178(12):621-3.
The efficacy of non-contraceptive uses for hormonal contraceptives.
Fraser IS, Kovacs GT.
Department of Obstetrics and Gynaecology, University of Sydney, Sydney, NSW 2006, Australia. helena@med.usyd.edu.au

In addition to providing safe and effective contraception, both the combined oral contraceptive pill (COCP) and selected long-acting progestogen-only contraceptives have significant health benefits. The COCP may reduce menstrual blood loss, dysmenorrhoea and premenstrual syndrome; unequivocally reduces the later incidence of endometrial and ovarian cancer; appears to help protect future fertility, probably by reducing the risk of acute pelvic inflammatory disease, endometriosis and uterine fibroids. The quality of evidence for individual non-contraceptive health benefits of the COCP is very variable.

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Int J Gynaecol Obstet. 2003 Feb;80(2):153-7.
Comparison of fennel and mefenamic acid for the treatment of primary dysmenorrhea.
Namavar Jahromi B, Tartifizadeh A, Khabnadideh S.
Department of Obstetrics and Gynecology, Shiraz University of Medical Sciences, Shiraz, Iran. namavarb@sums.ac.ir

OBJECTIVES: To compare the effect of Foeniculum vulgare variety dulce (Sweet Fennel) vs. mefenamic acid for the treatment of primary dysmenorrhea. METHODS: A cohort of seventy women, 15-24 years old from a local university and high-school, who complained of dysmenorrhea were enrolled in this study. Ten cases were excluded due to evidence of secondary dysmenorrhea. The remaining 60 patients were graded mild, moderate and severe on the basis of a verbal multidimensional scoring system. Thirty patients with mild dysmenorrhea were also excluded from the study. Each of the 30 cases with moderate to severe dysmenorrhea was evaluated for three cycles. In the first cycle no medication was given (control cycle), in the second cycle the cases were treated by mefenamic acid (250 mg q6h orally) and in the third cycle, essence of Fenne