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 Fennel's fruit with 2% concentration (25 drops q4h orally), was prescribed at the beginning of the cycle. These cycles were compared day by day for the effect, potency, time of initiation of action and also complications associated with each treatment modality, by using a self-scoring system. Intensity of pain was reported by using a 10-point linear analog technique. Statistical analyses were performed by the independent sample t-test, paired t-test and repeated measurement analysis method. RESULTS: In the study group the mean age of menarche was 12.5+/-1.3 years, the mean duration of menstruation was 6.6+/-1.4 days with the mean cycle days of 27+/-3. The findings observed during menses were as follows: headache in 26.7%, nausea in 63.3%, vomiting in 23.3%, diarrhea in 33.3%, fatigue in 93.3% and leaving the daily tasks undone was reported in 86.9% of the cases. Both of the drugs effectively relieved menstrual pain as compared with the control cycles (P<0.001). The mean duration of initiation of action was 67.5+/-46.06 min for mefenamic acid and 75+/-48.9 min for fennel. The difference was not statistically significant (P=0.57). Mefenamic acid had a more potent effect than fennel on the second and third menstrual days (P<0.05), however, the difference on the other days was not significant. No complication was reported in mefenamic acid treated cycles, but five cases (16.6%) withdrew from the study due to fennel's odor and one case (3.11%) reported a mild increase in the amount of her menstrual flow. CONCLUSIONS: The essence of fennel can be used as a safe and effective herbal drug for primary dysmenorrhea, however, it may have a lower potency than mefenamic acid in the dosages used for this study.

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Fertil Steril. 2003 Aug;80(2):310-9.
Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial.
Vercellini P, Aimi G, Busacca M, Apolone G, Uglietti A, Crosignani PG.
Reproductive Surgery Unit, First Department of Obstetrics and Gynecology, University of Milan, Milan, Italy

To evaluate the efficacy of laparoscopic resection of the uterosacral ligaments in women with endometriosis and predominantly midline dysmenorrhea.Randomized controlled trial.Two academic departments.One hundred eighty patients undergoing operative laparoscopy as first-line therapy for stage I to IV symptomatic endometriosis.Operative laparoscopy including uterosacral ligament resection or conservative surgery alone.Proportion of women with recurrence of moderate or severe dysmenorrhea 1 year after surgery.No complications occurred. Among the patients who were evaluable 1 year after operative laparoscopy, 23 of 78 (29%) women who had uterosacral ligament resection and 21 of 78 (27%) women who had conservative surgery only reported recurrent dysmenorrhea. The corresponding numbers of patients at 3 years were 21 of 59 (36%) women and 18 of 57 (32%) women, respectively. Time to recurrence was similar in the two groups. Pain was substantially reduced, and patients in both groups experienced similar and significant improvements in health-related quality of life, psychiatric profile, and sexual satisfaction. Overall, 68 of 90 (75%) patients in the uterosacral ligament resection group and 67 of 90 (74%) patients in the conservative surgery group were satisfied at 1 year.Addition of uterosacral ligament resection to conservative laparoscopic surgery for endometriosis did not reduce the medium- or long-term frequency and severity of recurrence of dysmenorrhea.

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Semin Arthritis Rheum. 2002 Dec;32(3 Suppl 1):15-24.
Coxibs: Evolving role in pain management.
Katz N.
Department of Anesthesia, Harvard Medical School, Boston, MA, USA.

Traditional pain management strategies have relied on the use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen, as well as other adjuvant analgesics. However, the limited activity of these drugs and the substantial adverse effects associated with their use has left many patients without dependable options for effective treatment. Recent advances in the understanding of pain and its pathophysiologic mechanisms have led to the development of novel therapeutic options. Cyclooxygenase (COX)-2-specific inhibitors (coxibs) have an established efficacy in the treatment of chronic arthritic pain comparable to that of traditional NSAIDs, without the degree of gastrointestinal (GI) complications commonly attributed to NSAID use. Recent trials also have shown the effectiveness of 1 of the coxibs for relief of chronic lower back pain. Numerous studies have shown that coxibs are efficacious for the management of acute pain in various clinical settings, including orthopedic surgery, dental surgery, and dysmenorrhea. The superior safety profile of coxibs in conjunction with a comparable efficacy to nonselective NSAIDs supports the use of coxibs in balanced analgesic regimens. Decreased GI and antiplatelet effects of coxibs compared to traditional NSAIDs provide the potential to incorporate coxibs into the pain management algorithm used to treat cancer pain. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Paediatr Drugs. 2002;4(12):797-805.
A contemporary approach to dysmenorrhea in adolescents.
Harel Z.
Division of Adolescent Medicine, Hasbro Children's Hospital, 593 Eddy Street, Providence, RI 02903, USA. Zharel@Lifespan.org

Dysmenorrhea is the most common gynecologic complaint among adolescent girls. Despite progress in understanding the physiology of dysmenorrhea and the availability of effective treatments, many adolescent girls do not seek medical advice or are undertreated. Dysmenorrhea in adolescents is usually primary (functional), and is associated with normal ovulatory cycles and no pelvic pathology. In approximately 10% of adolescents with severe dysmenorrhea, pelvic abnormalities such as endometriosis or uterine anomalies may be found. Potent prostaglandins from the second series and potent leukotrienes from the fourth series play an important role in generating dysmenorrhea symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common pharmacologic treatment for dysmenorrhea. A loading dose of NSAIDs (typically twice the regular dose) should be used as initial treatment for dysmenorrhea in adolescents followed by a regular dose until symptoms abate. Adolescents with symptoms that do not respond to treatment with NSAIDs for three menstrual periods should be offered combined estrogen/ progestin oral contraceptive pills for three menstrual cycles. Adolescents with dysmenorrhea who do not respond to this treatment should be evaluated for secondary causes of dysmenorrhea. Adolescent care providers have the important roles of educating adolescent girls about menstruation-associated symptoms, as well as evaluating and effectively treating patients with dysmenorrhea.

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Gynecol Obstet Invest. 2002;54 Suppl 1:11-6; discussion 16-7.
Investigation of the localization of nerves in the uterosacral ligament: determination of the optimal site for uterosacral nerve ablation.
Fujii M, Sagae S, Sato T, Tsugane M, Murakami G, Kudo R.
Department of Gynecology and Obstetrics, Sapporo Medical University School of Medicine, Sapporo, Japan.

We select surgical treatment for cases for which severe dysmenorrhea persists following medical treatment. Many reports have described the use of neurectomies by cutting off pain conducting nerve pathways using laparoscopic surgery. Laparoscopic uterosacral nerve ablation (LUNA) has been associated with a high success rate for pain control, but there are few reports of anatomical studies in the uterosacral ligament. Using an immunohistochemical method, we examined the number and types of nerve fiber bundles in the uterosacral ligaments and its surrounding tissue in cadavers. The greatest number of nerve fiber bundles was found at a distance of 16.5-33 mm and at a depth of 3-15 mm distal to the site of attachment of the uterosacral ligament to the uterine cervix. Furthermore, there were many more sympathetic and parasympathetic nerve fiber bundles than sensory ones in the uterosacral ligament and its surrounding tissue. These results show the appropriate site of transection of uterosacral ligaments when performing LUNA. Copyright 2002 S. Karger AG, Basel

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J Tradit Chin Med. 2002 Sep;22(3):205-10.
Effects of acupressure and ibuprofen on the severity of primary dysmenorrhea.
Pouresmail Z, Ibrahimzadeh R.
Shaheed Beheshti University of Medical Sciences and Health Services, Tehran-Iran.

The present study aims at comparing the effects of acupressure using new combination of acupoints, and Ibuprofen on the severity of primary dysmenorrhea (PD). 216 female high school students, aged between 14 to 18 years, were randomly selected and divided into three groups. Each group underwent different treatment techniques: acupressure, Ibuprofen and sham acupressure as a placebo. The results indicated that the three therapeutic techniques were significantly effective in reducing the pain. However the therapeutic efficacies of acupressure and Ibuprofen were similar with no significant difference, and were significantly better than the placebo. Thus acupressure, with no complications, is recommended as an alternative and also a better choice in the decrease of the severity of PD.

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Prim Care. 2002 Jun;29(2):297-321, vi.
Gynecology: select topics.
Sidani M, Campbell J.
Department of Family Medicine, LSU School of Medicine-New Orleans, 200 West Esplanade, Suite 510, Kenner, LA 70065, USA. msidan@luhsc.edu

Menopause, premenstrual syndrome, dysmenorrhea, female fertility, and mastalgia are common problems not easily treated by conventional medicine. Women often seek alternative therapies to help address these conditions. Some evidence points to the efficacy of black cohosh, exercise, and possibly Kava and St. John's wort, in the treatment of menopausal symptoms. Clinical trials indicate that symptoms of premenstrual syndrome may be alleviated with calcium, magnesium, vitamin E. Thiamine, omega-3 fatty acids, the Japanese herbal concoction, TSS, and calcium have proved useful in treating women with dysmenorrhea. Symptoms of mastalgia may be attenuated by evening primrose oil, chaste tree and flaxseed oil may be helpful.

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Minerva Pediatr. 2002 Dec;54(6):525-38.
[Dysmenorrhea, endometriosis and premenstrual syndrome]
[Article in Italian]
Tonini G.
Centro di Endocrinologia Pediatrica-Auxologia, Clinica Pediatrica, IRCCS Burlo Garofolo, Trieste, Italy.

Dysmenorrhea is the most frequent gynaecological problem in adolescent girls (the prevalence is 80-90%). Genetic influence, style of life (diet and physical activity) social, economical and cultural factors can affect symptoms. Prostaglandins and leucotrienes produced by endometrium, abnormal uterine smooth muscle contractility and modifications of the local blood flow are responsible for abdominal pain. Frequently daily activities are negatively affected (missing time at school) dysmenorrhoea can be primary or secondary to anatomical anomalies of internal genitalia or presence of synechie (post surgery or inflammatory pelvic diseases). Therapy may consist of traditional medicine (relaxing techniques such as yoga, agopuncture, mild analgesic drugs or more effective FANS). In case of therapeutical failure, contraceptive and/or GnRH agonists can represent the last choice. Endometriosis is less frequent, etiopatogenesis is not completely understood, but the anatomical lesions consist of an oestrogen-dependent neo-angiogenesis. Oestrogen inhibitors, oral contraceptives or GnRH agonists may be useful in treating this pathology. In case of drug failure surgery is suggested. For the effective diagnosis laparoscopy and biopsy are absolutely necessary. Premenstrual syndrome is cyclical, extremely complex, unusual in adolescent girls, sometimes associated to pre-existent psychic disorders. It can be treated with symptomatic drugs or, more recently, using drugs that alter the levels of serotonin, but their use in the adolescent patient is not yet recommended.

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Contraception. 2002 Dec;66(6):393-9.
Primary dysmenorrhea treatment with a desogestrel-containing low-dose oral contraceptive.
Hendrix SL, Alexander NJ.
Wayne State University, Detroit, MI 48201, USA. shendrix@med.wayne.edu

This randomized, double-blind, placebo-controlled exploratory study examined the efficacy and safety of a low-dose oral contraceptive (Mircette), desogestrel/ethinyl estradiol [DSG/EE] and ethinyl estradiol [EE]) in relieving the symptoms of dysmenorrhea. Twenty-three clinics in the United States enrolled 77 women (age < or =32 years) with primary dysmenorrhea documented for at least four consecutive cycles. Forty participants received DSG/EE&EE and 37 received placebo for four consecutive 28-day cycles. The intensity of menstrual-related distress was measured with the Menstrual Distress Questionnaire (MDQ). Patient diaries were used to assess number of school/work days missed as well as the use of rescue medication. Participants receiving DSG/EE&EE recorded reduced menstrual pain severity, lower total MDQ scores, and significantly less menstrual cramping. No significant change in bloating, anxiety, loneliness, weight gain, or acne was reported. The DSG/EE&EE formulation shows promise for the treatment of primary dysmenorrhea and was well tolerated by the participants in this study. Copyright 2002 Elsevier Science Inc.

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Drugs. 2002;62(14):2059-71; discussion 2072-3.
Valdecoxib.
Ormrod D, Wellington K, Wagstaff AJ.
Adis International Limited, Mairangi Bay, Auckland, New Zealand.

In ten large, well-controlled, randomised trials (n = 203 to 1089), valdecoxib, a selective inhibitor of cyclo-oxygenase-2, was significantly more effective than placebo in the treatment of osteoarthritis, rheumatoid arthritis and pain associated with primary dysmenorrhoea, and for postsurgical analgesia. Valdecoxib 1.25 to 10mg twice daily and valdecoxib 10mg once daily were more effective than placebo for the relief of pain in patients with osteoarthritis of the knee, and dosages above 5mg twice daily were similar in efficacy to naproxen 500mg twice daily. Similarly, valdecoxib 5 and 10 mg/day were as effective for osteoarthritis of the hip as naproxen 500mg twice daily. In patients with rheumatoid arthritis, valdecoxib 10, 20 or 40 mg/day was significantly more effective than placebo, and similar in efficacy to naproxen 500mg twice daily; there were no significant differences in efficacy between the three dosages of valdecoxib. Valdecoxib 20 or 40mg administered 1 to 3 hours before and 12, 24 and 36 hours after hip arthroplasty provided significantly better analgesia than placebo, and significantly reduced the amount of morphine taken by patients. Single doses of valdecoxib 10 to 80mg administered before foot or oral surgery provided significantly better analgesia than placebo; when administered after oral surgery, valdecoxib 20 or 40mg provided greater sustained analgesia than oxycodone 10mg/paracetamol 1000mg or rofecoxib 50mg. In contrast to three nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), valdecoxib 40mg twice daily did not cause significant changes in platelet function and bleeding times. Chronic users of NSAIDs who were switched to valdecoxib 10 or 20 mg/day for 12 weeks experienced significantly fewer gastroduodenal erosions or ulcers than patients receiving ibuprofen 2400 mg/day or diclofenac 150 mg/day for 12 weeks. Valdecoxib was generally well tolerated in clinical trials, with a similar incidence of adverse events to placebo.

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Clin Ther. 2002 Sep;24(9):1384-400.
Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies.
Milsom I, Minic M, Dawood MY, Akin MD, Spann J, Niland NF, Squire RA.
Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Goteborg, Sweden. ian.milsom@obgyn.gu.se

BACKGROUND: Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs. OBJECTIVE: The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea. METHODS: A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs). RESULTS: A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported. CONCLUSION: When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied.

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J Altern Complement Med. 2002 Jun;8(3):357-70.
A randomized clinical trial of the effectiveness of an acupressure device (relief brief) for managing symptoms of dysmenorrhea.
Taylor D, Miaskowski C, Kohn J.
Department of Family Health Care Nursing, School of Nursing, University of California-San Francisco, 94143-0606, USA. Diana.Taylor@nursing.ucsf.edu

OBJECTIVES: To develop and test the safety and effectiveness of an acupressure garment (the Relief Brief) in decreasing the pain and symptom distress associated with dysmenorrhea. DESIGN: A randomized clinical trial applied a 2 (Relief Brief use or control group) x 3 (baseline and two treatment measurement occasions) mixed factorial design. PARTICIPANTS: Sixty-one (61) women with moderately severe primary dysmenorrhea were randomly assigned to the standard treatment control group or the Relief Brief acupressure device group after one pretreatment menses, with 58 women reporting the effect on their pain during two post-treatment menstrual cycles. The acupressure garment: The Relief Brief is a cotton Lycra panty brief with a fixed number of lower abdominal and lower back latex foam acupads that provide pressure to dysmenorrhea-relieving Chinese acupressure points. OUTCOME MEASURES: Menstrual pain severity (worst pain and symptom intensity), pain medication use, and adverse effects were analyzed using between-groups and repeated measures analyses of treatment effects. Statistical and clinical significance criteria were applied a priori. RESULTS: For pain measures and pain medication use, the group main effect, time main effect and group x time interaction were statistically significant. Median pain medication use, the same for both groups at baseline (6 pills per day), dropped to 2 pills per day for the Relief Brief group but remained at 6 pills for the control group at the second treatment cycle. Predicted clinical significance criteria were surpassed: almost all (90%) women wearing the Relief Brief obtained at least a 25% reduction in menstrual pain severity (a 2-3 point drop) compared to only 8% of the control group (z = 6.07; p < 0.05). Relief Brief use was associated with at least a 50% decline in menstrual pain symptom intensity in more than two thirds of the women. CONCLUSIONS: An acupressure device is an effective and safe nonpharmacologic strategy for the treatment of primary dysmenorrhea. With design modifications, it could serve as a main treatment modality for women who suffer from primary dysmenorrhea and do not wish to or cannot use the conventional pharmacologic agents. In addition, this acupressure device may serve as an adjuvant therapy to medication in more severe cases of dysmenorrhea.

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Obstet Gynecol. 2002 Aug;100(2):350-8.
Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea.
Daniels SE, Talwalker S, Torri S, Snabes MC, Recker DP, Verburg KM.
From the Scirex Corporation, Austin, Texas, USA.

OBJECTIVE: To compare the efficacy of the cyclooxygenase (COX)-2-specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea. METHOD: This single-center, double-blind, placebo-controlled, randomized, crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg, or placebo, with an option of treatment for up to 3 days, twice daily. Efficacy was assessed by time-weighted sum of total pain relief, sum of pain intensity difference, time-specific pain relief, and pain intensity difference over 12 hours, time to rescue medication or first re-medication, the percentage of patients taking rescue medication, and patient's global evaluation of study medication. RESULTS: Mean time-weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg (P <.01) and 40 mg (P <.001). Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures. Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance, with the exception of sum of pain intensity difference-12. Both doses of valdecoxib were well tolerated. CONCLUSIONS: Both valdecoxib 20- and 40-mg doses were effective and well tolerated for the treatment of primary dysmenorrhea. Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy, based on onset, magnitude, and duration of analgesia that is similar to naproxen sodium, making it a potential choice for treating women with primary dysmenorrhea.

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Gynecol Endocrinol. 2002 Feb;16(1):39-43.
A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.
Facchinetti F, Sgarbi L, Piccinini F, Volpe A.
Departments of Gynecological, Obstetrics and Pediatric Sciences, Unit of Psychobiology of Reproduction, University of Modena and Reggio Emilia, Italy.

Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.

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Cochrane Database Syst Rev. 2002;(1):CD002123.
Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhoea.
Proctor ML, Smith CA, Farquhar CM, Stones RW.
Department of Obstetrics and Gynaecology, National Women's Hospital, Claude Road, Epsom, Auckland, New Zealand, 1003. m.proctor@auckland.ac.nz

BACKGROUND: Dysmenorrhoea is the occurrence of painful menstrual cramps of the uterus. Medical therapy for dysmenorrhoea commonly consists of nonsteroidal anti-inflammatory drugs or the oral contraceptive pill both of which work by reducing myometrial (uterine muscle) activity. However, these treatments are accompanied by a number of side effects, making an effective non-pharmacological method of treating dysmenorrhoea of potential value. Transcutaneous electrical nerve stimulation (TENS) is a treatment that has been shown to be effective for pain relief in a variety of conditions. Electrodes are placed on the skin and electric current applied at different pulse rates (frequencies) and intensities is used to stimulate these areas so as to provide pain relief. In dysmenorrhoea. TENS is thought to work by alteration of the body's ability to receive or perceive pain signals rather than by having a direct effect on the uterine contractions. Acupuncture may also be indicated as a useful, non-pharmacological method for treating dysmenorrhoea. Acupuncture is thought to excite receptors or nerve fibres which, through a complicated interaction with mediators such as serotonin and endorphins, blocks pain impulses. Acupuncture typically involves penetration of the skin by fine, solid metallic needles, which are manipulated manually or by electrical stimulation. OBJECTIVES: To determine the effectiveness of high and low frequency transcutaneous electrical nerve stimulation and acupuncture when compared to each other, placebo, no treatment, or medical treatment for primary dysmenorrhoea. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, CCTR (Cochrane Library Issue 3, 2001), MEDLINE, EMBASE, CINAHL, Bio extracts, PsycLIT and SPORTDiscus were performed in August 2001 to identify relevant randomised controlled trials (RCTs). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the UK National Research Register, the Clinical Trial Register 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 controlled trials of transcutaneous electrical nerve stimulation and acupuncture that compared these treatments to each other, placebo, no treatment, or medical treatment for primary dysmenorrhoea. Exclusion criteria were: mild, infrequent or secondary dysmenorrhoea and dysmenorrhoea associated with an IUD. DATA COLLECTION AND ANALYSIS: Nine RCTs were identified that fulfilled the inclusion criteria for this review, seven involving TENS, one acupuncture, and one both treatments. 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 was reported as descriptive data and was also included for discussion. The outcome measures were pain relief (dichotomous, visual analogue scales, descriptive), adverse effects, use of analgesics additional to treatment and absence from work or school. MAIN RESULTS: Overall high frequency TENS was shown to be more effective for pain relief than placebo TENS. Low frequency TENS was found to be no more effective in reducing pain than placebo TENS. There were conflicting results regarding whether high frequency TENS is more effective than low frequency TENS. One small trial showed acupuncture to be significantly more effective for pain relief than both placebo acupuncture and two no treatment control groups. REVIEWER'S CONCLUSIONS: High frequency TENS was found to be effective for the treatment of dysmenorrhoea by a number of small trials. The minor adverse effects reported in one trial requires further investigation. There is insufficient evidence to determine the effectiveness of low frequency TENS in reducing dysmenorrhoea. There is also insufficient evidence to determine the effectiveness of acupuncture in reducing dysmenorrhoea, however a single small but methodologically sound trial of acupuncture suggests benefit for this modality.

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Clin Rheumatol. 2001 Nov;20 Suppl 1:S15-21.
Overview on clinical data of dexibuprofen.
Phleps W.
Gebro Pharma GmbH, Fieberbrunn, Austria. walter.phleps@gebro.com

Several clinical trials, post-marketing surveillance studies and a meta-analysis were performed to obtain information about dose finding, pharmacokinetics, special indications, tolerability and compliance. In eight clinical trials, according to GCP, 1463 patients were included. Six of the trials were double-blind studies against placebo, racemic ibuprofen and diclofenac; the pharmacokinetic study and a long-term safety study were open studies. A meta-analysis of five clinical trials compared tolerability and safety data between dexibuprofen and racemic ibuprofen. Three PMS studies collected data on 7133 outpatients. All clinical trials and PMS studies have been published. In the dosage ratio 0.5:1, dexibuprofen was found to be at least as efficacious as racemic ibuprofen; 75% of the maximum daily dose of dexibuprofen was equally efficacious as 100% of MDD of diclofenac; no influence was found of meals on bioavailability and a significant doseresponse relationship; there was clinical efficacy in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis of the hip, osteoarthritis of the knee, lumbar vertebral syndrome, distortion of the ankle joint and dysmenorrhoea; there was good tolerability compared to other NSAIDs: racemic ibuprofen showed a 30% and diclofenac a 90% higher incidence of adverse drug reactions; the long-term study stated a 15.2% adverse drug event incidence; the incidence of adverse drug reactions in the PMS studies was between 5.5% and 7.4%, and withdrawals were between 2.3% and 2.7%. In conclusion, dexibuprofen (Seractil) has the stature of a modern NSAID, combining the high efficacy of diclofenac with the good tolerability of ibuprofen, and need not hide behind the new generation of COX-2 inhibitors.

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BJOG. 2001 Nov;108(11):1181-3.
A randomised placebo-controlled trial to determine the effect of vitamin E in treatment of primary dysmenorrhoea.
Ziaei S, Faghihzadeh S, Sohrabvand F, Lamyian M, Emamgholy T.
Department of Obstetrics and Gynaecology, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, IR, Iran.

OBJECTIVE: To determine whether vitamin E is effective in the treatment of primary dysmenorrhoea. DESIGN: A randomised placebo-controlled trial. PARTICIPANTS: One hundred girls, aged 16-18 years old who suffered from primary dysmenorrhoea, among 1,000 students attending a public high school in Region 5 in the Greater Tehran Municipality. METHODS: Fifty girls were given 500 units of vitamin E (five tablets) per day, and 50 were given five placebo tablets per day. The treatment began two days before the beginning of menstruation and continued through the first three days of bleeding. The severity of pain before and after the treatment was studied. Treatment in both groups was carried out in two consecutive menstrual periods. RESULTS: The severity of pain in the two groups was reduced after treatment, but the reduction was greater in the group treated with vitamin E. These differences were maintained in the second month of therapy. CONCLUSION: Both placebo and vitamin E are effective in relieving symptoms due to primary dysmenorrhoea, but the effects of vitamin E are more marked.

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Int J Clin Pharmacol Res. 2001;21(1):21-9.
Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.
de los Santos AR, Zmijanovich R, Perez Macri S, Marti ML, Di Girolamo G.
Department of Medicine, School of Medicine, Universidad de Buenos Aires, Argentina. adlsantos@intramed.net.ar

We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

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Cochrane Database Syst Rev. 2001;(4):CD002120.
Combined oral contraceptive pill (OCP) as treatment for primary dysmenorrhoea.
Proctor ML, Roberts H, Farquhar CM.
Department of Obstetrics and Gynaecology, National Women's Hospital, Claude Road, Epsom, Auckland, New Zealand, 1003. m.proctor@auckland.ac.nz

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps and is a common gynaecological complaint. Research as early as 1937 has shown that dysmenorrhoea responds favourably to ovulation inhibition, and that the synthetic hormones in the combined oral contraceptive pill can be used to treat dysmenorrhoea. These hormones act by suppressing ovulation and lessening the endometrial lining of the uterus. Therefore, menstrual fluid volume decreases along with the amount of prostaglandins produced, in turn effectively reducing dysmenorrhoea by decreasing uterine motility, and thus uterine cramping. The use of combined oral contraceptive pills (OCP) has been advocated as a treatment for primary dysmenorrhoea since their introduction for general use in 1960. There is evidence from epidemiological studies of general populations that combined OCPs can effectively treat dysmenorrhoea. OBJECTIVES: The objective of this review is to determine the efficacy of combined oral contraceptive pills for the treatment of primary dysmenorrhoea. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials (RCTs) of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, CCTR, MEDLINE, EMBASE, and CINAHL, were performed. Attempts were also made to identify trials from the National Research Register, the Clinical Trials Register and the citation lists of review articles and included trials. SELECTION CRITERIA: The inclusion criteria were RCTs that compared all types of combined oral contraceptives (oestrogen/progestogen) with other combined oral contraceptives, placebo, no treatment, or treatment with nonsteriodal anti-inflammatory drugs (NSAIDs) in the treatment of primary dysmenorrhoea. The main outcome measures were pain relief, adverse effects, additional analgesics required and time off work or school. DATA COLLECTION AND ANALYSIS: Nine trials were identified that appeared to fulfil the initial criteria for this review. Of these nine trials, four were excluded, two at further investigation revealed a lack of randomisation and two included combined oral contraceptives that are now discontinued due to very high oestrogen content. Of the remaining five RCTs, four were included in the meta-analysis (Buttram 1969; Cullberg 1972; GPRG 1968; Nakano 1971). The results of the other trial (Matthews 1968) were included in the text of the review for discussion because data were not available in a form that allowed it to be combined in a meta-analysis. Data for all outcomes were in dichotomous form and the Peto odds ratio was used in the meta-analysis for all comparisons. MAIN RESULTS: Combined OCPs with medium dose oestrogen (>35 mcg) and 1st/2nd generation progestogens were shown to be more effective than placebo for pain relief. However, there was significant heterogeneity in the results from different studies and when data were analysed with a random effects model, the confidence intervals increased and the results became statistically non-significant. For the other outcomes, there was a significant difference in favour of OCPs when compared to placebo for the outcome of absence from work or school, and there was no difference between the treatment groups and placebo in the number of adverse effects experienced. REVIEWER'S CONCLUSIONS: No conclusions can be made about the efficacy of commonly used modern lower dose combined oral contraceptives for dysmenorrhoea. While there is some evidence from four RCTs that combined OCPs with medium dose oestrogen and 1st/2nd generation progestogens are more effective than placebo it should be emphasised that the studies were small, of poor quality and all included much higher doses of hormones that those commonly prescribed today. Therefore no recommendations can be made regarding the efficacy of modern combined oral contraceptives.

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Cochrane Database Syst Rev. 2001;(4):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. m.proctor@auckland.ac.nz

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. The efficacy of medical treatments such as nonsteroidal anti-inflammatories (NSAIDs) or oral contraceptive pills (OCPs) is considerable, however the failure rate can still be as high as 20-25% and there are also a number of associated adverse effects. Many women are thus seeking alternatives to conventional medicine. One popular treatment modality is spinal manipulation therapy. There are several rationales for the use of musculoskeletal manipulation to treat dysmenorrhoea. The parasympathetic and sympathetic pelvic nerve pathways are closely associated with the spinal vertebrae, in particular the 2nd-4th sacral segments and the 10th thoracic to the 2nd lumbar segments. One hypothesis is that mechanical dysfunction in these 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 through an influence on the autonomic nerve supply to the blood vessels. 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 gynecological 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: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, CINAHL, Bio extracts, Psyclit and SPORTDiscus were performed to identify relevant randomised controlled trials (RCTs). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register 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 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: Five RCTs were identified that fulfilled the inclusion criteria for this review. Four trials involving high velocity, low amplitude manipulation (HVLA), and one involving 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. REVIEWER'S 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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Cochrane Database Syst Rev. 2001;(3):CD002124.
Herbal and dietary therapies for primary and secondary dysmenorrhoea.
Wilson ML, Murphy PA.
Department of Obstetrics and Gynaecology, National Women's Hospital, Claude Road, Epsom, Auckland, New Zealand, 1003. ml.wilson@auckland.ac.nz

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological complaint. Common treatment for dysmenorrhoea is medical therapy such as nonsteroidal anti-inflammatories (NSAIDs) or oral contraceptive pills (OCPs) which both work by reducing myometrial activity (contractions of the uterus). The efficacy of conventional treatments such as nonsteroidals is considerable, however the failure rate is still often 20-25%. Many consumers are now seeking alternatives to conventional medicine and research into the menstrual cycle suggests that nutritional intake and metabolism may play an important role in the cause and treatment of menstrual disorders. Herbal and dietary therapies number among the more popular complementary medicines yet there is a lack of taxonomy to assist in classifying them. In the US, herbs and other phytomedicinal products (medicine from plants) have been legally classified as dietary supplements since 1994. Included in this category are vitamins, minerals, herbs or other botanicals, amino acids and other dietary substances. For the purpose of this review we use the wider term herbal and dietary therapies to include the assorted herbal or dietary treatments that are classified in the US as supplements and also the phytomedicines that may be classified as drugs in the European Union. OBJECTIVES: To determine the efficacy and safety of herbal and dietary therapies for the treatment of primary and secondary dysmenorrhoea when compared to each other, placebo, no treatment or other conventional treatments (e.g. NSAIDS). SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, CCTR, MEDLINE, EMBASE, CINAHL, Bio extracts, and PsycLIT were performed to identify relevant randomised controlled trials (RCTs). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register 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 RCTs of herbal or dietary therapies as treatment for primary or secondary dysmenorrhoea vs each other, placebo, no treatment or conventional treatment. Interventions could include, but were not limited to, the following; vitamins, essential minerals, proteins, herbs, and fatty acids. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD. DATA COLLECTION AND ANALYSIS: Seven trials were included in the review. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were pain intensity or pain relief and the number of adverse effects. Data on absence from work and the use of additional medication was also collected if available. Data was combined for meta-analysis using Peto odds ratios for dichotomous data or weighted mean difference for continuous data. A fixed effects statistical model was used. If data suitable for meta-analysis could not be extracted, any available data from the trial was extracted and presented as descriptive data. MAIN RESULTS: MAGNESIUM: Three small trials were included that compared magnesium and placebo. Overall magnesium was more effective than placebo for pain relief and the need for additional medication was less. There was no significant difference in the number of adverse effects experienced. VITAMIN B6: One small trial of vitamin B6 showed it was more effective at reducing pain than both placebo and a combination of magnesium and vitamin B6. MAGNESIUM AND VITAMIN B6: Magnesium was shown to be no different in pain outcomes from both vitamin B6 and a combination of vitamin B6 and magnesium by one small trial. The same trial also showed that a combination of magnesium and vitamin B6 was no different from placebo in reducing pain. VITAMIN B1: One large trial showed vitamin B1 to be more effective than placebo in reducing pain. VITAMIN E: One small trial comparing a combination of vitamin E (taken daily) and ibuprofen (taken during menses) versus ibuprofen (taken during menses) alone showed no difference in pain relief between the two treatments. OMEGA-3 FATTY ACIDS: One small trial showed fish oil (omega-3 fatty acids) to be more effective than placebo for pain relief. JAPANESE HERBAL COMBINATION: One small trial showed the herbal combination to be more effective for pain relief than placebo, and less additional pain medication was taken by the treatment group. REVIEWER'S CONCLUSIONS: Vitamin B1 is shown to be an effective treatment for dysmenorrhoea taken at 100 mg daily, although this conclusion is tempered slightly by its basis on only one large RCT. Results suggest that magnesium is a promising treatment for dysmenorrhoea. It is unclear what dose or regime of treatment should be used for magnesium therapy, due to variations in the included trials, therefore no strong recommendation can be made until further evaluation is carried out. Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies considered in this review for the treatment of primary or secondary dysmenorrhoea.

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J Am Assoc Gynecol Laparosc. 2001 Nov;8(4):573-8.
Addition of laparoscopic uterine nerve ablation to laparoscopic bipolar coagulation of uterine vessels for women with uterine myomas and dysmenorrhea.
Yen YK, Liu WM, Yuan CC, Ng HT.
Department of Obstetrics and Gynecology, VGH-Taipei, National Yang Ming University, Taipei, Taiwan.

STUDY OBJECTIVE: To assess the effectiveness of laparoscopic uterine nerve ablation (LUNA) in women with dysmenorrhea caused by uterine myomas treated by laparoscopic bipolar coagulation of uterine vessels (LBCUV). DESIGN: Prospective, randomized, longitudinal study (Canadian Task Force classification II-1). SETTING: Private practice, university-affiliated hospital. PATIENTS: Eighty-five women with uterine leiomyomas and associated dysmenorrhea. INTERVENTION: Laparoscopic bipolar coagulation of uterine vessels with or without LUNA. MEASUREMENTS AND MAIN RESULTS: Of 85 patients who entered the study, 41 were assigned to undergo LBCUV-LUNA (group A), which was successful in 40 (97.6%). In 44 women assigned to have LBCUV only (group B), 43 (97.7%) underwent successful surgery. Eighty women completed 1-, 3-, and 6-month follow-up (38 group A, 42 group B). The groups did not differ significantly in age, history of abdominopelvic surgery, intraperitoneal adhesions, endometriosis, concomitant surgery, and operating time. Seven (18.4%) of 38 women in group A and 12 (28.6%) of 42 in group B experienced lower abdominal pain postoperatively. Acceptable pain was defined as a score of zero or 1: 31 and 30 women in groups A and B reported scores of zero; 3 and 2 reported scores of 1; 4 and 8 reported scores of 2; zero and 2 reported scores of 3; and no patients reported scores of 4. The frequency and severity of postoperative pain were less in group A than in group B (both p <0.05). The efficacy of both methods was almost equal in shrinking the uterus and dominant myoma, and in improving menorrhagia and bulk-related symptoms. Dysmenorrhea improvement was 84.2% and 61.9% in groups A and B at 3 months and 92.1% and 73.8% at 6 months, respectively. This was more significant in group A than in group B (p <0.05). CONCLUSION: Our results suggest that LUNA may decrease postoperative ischemic pain and improve dysmenorrhea associated with uterine myomas treated by LBCUV.

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Aust N Z J Obstet Gynaecol. 2001 May;41(2):195-7.
Laparoscopic presacral neurectomy—retrospective series.
Kwok A, Lam A, Ford R.
The Women's Institute - Endosurgery, Mater Misericordiae Hospital, North Shore Private Hospital, St Leonards, Sydney, Australia.

A retrospective audit of medical records was conducted for one surgeon (AL). All patients who underwent laparoscopic presacral neurectomy for severe midline dysmenorrhoea were identified. Details of the preoperative symptoms, clinical findings and operative records were studied. Improvement of dysmenorrhoea was assessed according to a pain scale. Twelve patients who had a laparoscopic presacral neurectomy performed were identified. Eight patients reported significant improvement of symptoms, with a further two reporting mild improvement. Two patients failed to show any improvement of symptoms. We believe that the role of laparoscopic presacral neurectomy should be limited to patients with severe midline dysmenorrhoea not responding to the medical therapy. It may be a supplementary procedure to laparoscopic resection of endometriosis or adhesiolysis.

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J Pediatr Adolesc Gynecol. 2001 Feb;14(1):3-8.
Primary dysmenorrhea in adolescent girls and treatment with oral contraceptives.
Davis AR, Westhoff CL.
Department of Obstetrics and Gynecology, Columbia University, 630 W. 168th Street, New York, NY 10032, USA. ard4@columbia.edu

This review examines the prevalence, associated morbidity, and treatment of primary dysmenorrhea in adolescent girls. Relevant literature was examined by systematic, evidence-based review using MEDLINE and Cochrane Collaboration databases. Dysmenorrhea is highly prevalent during adolescence. Despite differences in measurement methods, 20%-90% of adolescent girls report dysmenorrhea and about 15% of adolescents describe their dysmenorrhea as severe. During adolescence, dysmenorrhea leads to high rates of school absence and activity nonparticipation. Most adolescents with dysmenorrhea self-medicate with over-the-counter preparations; few consult healthcare providers. Combined oral contraceptives (COC) are an accepted treatment for dysmenorrhea in nonadolescent women. However, data supporting the efficacy of COC is limited. Very small studies show decreased prostaglandin in menstrual fluid associated with high-dose COC use. Larger studies are limited to cross-sectional comparisons showing lower prevalence of dysmenorrhea in low-dose COC users compared to non-COC users. One small, randomized controlled trial including some adolescents demonstrated an improvement in dysmenorrhea with high-dose COC treatment compared to placebo. The efficacy of low-dose COC in the treatment of adolescent dysmenorrhea has yet to be determined. If effective, well-established safety and noncontraceptive health benefits may make COC an ideal treatment for dysmenorrhea in adolescent girls.

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Expert Opin Investig Drugs. 2001 May;10(5):825-34.
Development and therapeutic indications of orally-active non-peptide vasopressin receptor antagonists.
Paranjape SB, Thibonnier M.
Case Western Reserve University School of Medicine and University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, Ohio 44106-4951, USA.

Vasopressin (AVP) is a cyclic nonapeptide hormone that exhibits many physiological effects including free water reabsorption, vasoconstriction, cellular proliferation and adrenocorticotrophic hormone (ACTH) secretion. In a healthy organism, AVP plays an important role in the homeostasis of fluid osmolality and volume status. However, in several diseases or conditions such as the syndrome of inappropriate secretion of AVP (SIADH), congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome, dysmenorrhoea and ocular hypertension, AVP may play an important role in their pathophysiology. Recently, orally-active non-peptide AVP receptor antagonists were developed by random screening of chemical entities and optimisation of lead compounds. These include agents specific for the V(1)-vascular and V(2)-renal AVP receptor subtypes. Dual V(1)/V(2) AVP receptor antagonists are also being studied. Some of these non-peptide receptor antagonists have been studied extensively, while others are currently under investigation. Potential therapeutic indications for AVP receptor antagonists comprise: 1) The blockade of V(1)-vascular AVP receptors in arterial hypertension, congestive heart failure, Raynaud's syndrome, peripheral vascular disease and dysmenorrhea. 2) The blockade of V(2)-renal AVP receptors in the syndrome of inappropriate secretion of vasopressin, congestive hart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatraemia. 3) The blockade of V(3)-pituitary AVP receptors in ACTH-secreting tumours. This review examines the pharmacology of orally-active non-peptide AVP receptor antagonists and their clinical applications.

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Obstet Gynecol. 2001 Mar;97(3):343-9.
Continuous low-level topical heat in the treatment of dysmenorrhea.
Akin MD, Weingand KW, Hengehold DA, Goodale MB, Hinkle RT, Smith RP.
Health Quest Therapy and Research Institute, Austin, Texas, USA.

OBJECTIVE: To compare the efficacy of topically applied heat for menstrual pain with oral ibuprofen and placebo treatment. METHODS: We conducted a randomized placebo and active controlled (double dummy), parallel study using an abdominal patch (heated or unheated) for approximately 12 consecutive hours per day and oral medication (placebo or ibuprofen 400 mg) three times daily, approximately 6 hours apart for 2 consecutive days. Pain relief and pain intensity were recorded at 17 time points. There was at least 85% power to detect a true one-unit difference in the 2-day pain relief treatment means for comparisons with the unheated patch plus oral placebo group using a one-tailed test at the.05 level of significance, based on an observed within-group standard deviation of 1.147. RESULTS: Eighty-four patients were enrolled and 81 completed the study protocol. Over the 2 days of treatment, the heated patch plus placebo tablet group (mean 3.27, P <.001), the unheated patch plus ibuprofen group (mean 3.07, P =.001), and the combination heated patch plus ibuprofen group (mean 3.55, P <.001) had significantly greater pain relief than the unheated patch plus placebo group (mean 1.95). Greater pain relief was not observed for the combination heated patch plus ibuprofen group compared with the unheated patch plus ibuprofen group (P =.096); however, the time to noticeable pain relief was statistically significantly shorter for the heated patch plus ibuprofen group (median 1.5 hours) compared with the unheated patch plus ibuprofen group (median 2.79 hours, P =.01). CONCLUSION: Continuous low-level topical heat therapy was as effective as ibuprofen for the treatment of dysmenorrhea.

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Obstet Gynecol Surv. 2001 Feb;56(2):99-104.
Laparoscopic presacral neurectomy: a review.
Kwok A, Lam A, Ford R.
The Women's Institute-Endosurgery, North Shore Private Hospitals, St. Leonards, Australia.

Dysmenorrhea can be a severe and debilitating symptom in many women. Although most women may find adequate relief of symptoms from pharmacological approaches, there remain a few with resistant pain. Presacral neurectomy, although technically challenging, may be offered after other approaches are unsuccessful. The operation is now performed increasingly by the laparoscopic approach, which has revived this operation in some centers. The anatomy, technique, and indications as well as a review of the literature supporting this operation are reviewed. The potential complications of this operation are discussed also.

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