Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs that act by blocking prostaglandin production. They inhibit the action of cyclooxygenase (COX), an enzyme responsible for the formation of prostaglandins. The COX enzyme exists in two forms, COX-1 and COX-2. Traditional NSAIDs are considered 'non-selective' because they inhibit both COX-1 and COX-2 enzymes. More selective NSAIDs that solely target COX-2 enzymes (COX-2-specific inhibitors) were launched in 1999 with the aim of reducing side effects commonly reported in association with NSAIDs, such as indigestion, headaches and drowsiness. OBJECTIVES: To determine the effectiveness and safety of NSAIDs in the treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the following databases in January 2015: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, November 2014 issue), MEDLINE, EMBASE and Web of Science. We also searched clinical trials registers (ClinicalTrials.gov and ICTRP). We checked the abstracts of major scientific meetings and the reference lists of relevant articles. SELECTION CRITERIA: All randomised controlled trial (RCT) comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed their risk of bias and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). We used inverse variance methods to combine data. We assessed the overall quality of the evidence using GRADE methods. MAIN RESULTS: We included 80 randomised controlled trials (5820 women). They compared 20 different NSAIDs (18 non-selective and two COX-2-specific) versus placebo, paracetamol or each other. NSAIDs versus placeboAmong women with primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I(2) = 53%, low quality evidence). This suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so.However, NSAIDs were associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, I(2) = 0%, low quality evidence; gastrointestinal adverse effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I(2) = 30%; neurological adverse effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I(2) = 0%, low quality evidence). The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. NSAIDs versus other NSAIDsWhen NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety. However, the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. Non-selective NSAIDs versus COX-2-specific selectorsOnly two of the included studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty. NSAIDs versus paracetamolNSAIDs appeared to be more effective for pain relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I(2) = 0%, low quality evidence). There was no evidence of a difference with regard to adverse effects, though data were very scanty.Most of the studies were commercially funded (59%); a further 31% failed to state their source of funding. AUTHORS' CONCLUSIONS: NSAIDs appear to be a very effective treatment for dysmenorrhoea, though women using them need to be aware of the substantial risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.

Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. OBJECTIVES: The purpose of this review is to compare nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea versus placebo, versus paracetamol and versus each other, to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched the following databases to May 2009: Cochrane Menstrual Disorders and Subfertility Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science. The National Research Register and the Clinical Trials Register were also searched. Abstracts of major scientific meetings and the reference lists of relevant articles were checked. SELECTION CRITERIA: All randomised controlled comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). Inverse variance methods were used to combine data. MAIN RESULTS: Seventy-three randomised controlled trials were included. Among women with primary dysmenorrhoea, NSAIDs were significantly more effective for pain relief than placebo (OR 4.50, 95% CI: 3.85, 5.27). There was substantial heterogeneity for this finding (I(2) statistic =53%): exclusion of two outlying studies with no or negligible placebo effect reduced heterogeneity, resulting in an odds ratio of 4.14 (95% CI: 3.52, 4.86, I(2)=40%). NSAIDs were also significantly more effective for pain relief than paracetamol (OR 1.90, 95% CI:1.05 to 3.44). However, NSAIDS were associated with significantly more overall adverse effects than placebo (OR 1.37, 95% CI: 1.12 to 1.66). When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain-relief or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. AUTHORS' CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea.

Oral contraceptive pill for primary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea (painful menstrual cramps) is common. Combined OCPs are recommended in the management of primary dysmenorrhoea. OBJECTIVES: To determine the effectiveness and safety of combined oral contraceptive pills for the management of primary dysmenorrhoea. SEARCH STRATEGY: We conducted electronic searches for randomised controlled trials (RCTs) in the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials CENTRAL, CCTR, MEDLINE, EMBASE, and CINAHL (first conducted in 2001, updated on 5 November 2008). SELECTION CRITERIA: RCTs comparing all combined OCPs with other combined OCPs, placebo, no management, or management with nonsteroidal anti-inflammatories (NSAIDs) were considered. DATA COLLECTION AND ANALYSIS: Twenty three studies were identified and ten were included. Six compared the combined OCP with placebo and four compared different dosages of combined OCP. MAIN RESULTS: One study of low dose oestrogen and four studies of medium dose oestrogen combined OCPs compared with placebo, for a combined total of 497 women, reported pain improvement. For the outcome of pain relief across the different OCPs the pooled OR suggested benefit with OCPs compared to placebo (7 RCTs: Peto OR 2.01 [95% CI 1.32, 3.08]).The Chi-squared test for heterogeneity showed there is significant heterogeneity with an I(2) statistic of 64% and a significant chi-square test (14.06, df=5, p=0.02). A sensitivity analysis removing the studies with inadequate allocation concealment suggested significant benefit of treatment with the pooled OR of 2.99 (95% CI 1.76, 5.07) and heterogeneity no longer statistically significant and I(2) statistic of 0%.Three studies reported adverse effects (Davis 2005; Hendrix 2002; GPRG 1968) The adverse effects were nausea, headaches and weight gain. Two studies reported if women experienced any side effect and no evidence of an effect was found (3 RCTs: OR = 1.45 (95% 0.71, 2.94). There was no evidence of statistical heterogeneity.There were no studies identified that compared combined OCP versus non steroidal anti-inflammatory drugsThere was no evidence of a difference for the pooled studies for 3rd generation pro gestagens (OR = 1.11 (95% CI 0.79 - 1.57)). For the 2nd generation versus 3rd generation the OR was 0.44 (95% CI 0.23-0.84) suggesting benefit of the 3rd generation OCP but this was for a single study (Winkler 2003). AUTHORS' CONCLUSIONS: There is limited evidence for pain improvement with the use of the OCP (both low and medium dose oestrogen) in women with dysmenorrhoea. There is no evidence of a difference between different OCP preparations.

Oral contraceptive pill as treatment for primary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea (painful menstrual cramps) is common. Combined OCPs are recommended in the management of primary dysmenorrhoea. OBJECTIVES: To determine the effectiveness and safety of combined oral contraceptive pills for the management of primary dysmenorrhoea. SEARCH STRATEGY: We conducted electronic searches for randomised controlled trials (RCTs) in the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials CENTRAL, CCTR, MEDLINE, EMBASE, and CINAHL (first conducted in 2001, updated on 5 November 2008). SELECTION CRITERIA: RCTs comparing all combined OCPs with other combined OCPs, placebo, no management, or management with nonsteroidal anti-inflammatories (NSAIDs) were considered. DATA COLLECTION AND ANALYSIS: Twenty three studies were identified and ten were included. Six compared the combined OCP with placebo and four compared different dosages of combined OCP. MAIN RESULTS: One study of low dose oestrogen and four studies of medium dose oestrogen combined OCPs compared with placebo, for a combined total of 497 women, reported pain improvement. For the outcome of pain relief across the different OCPs wthe pooled OR suggested benefit with OCPs compared to placebo (7 RCTs: Peto OR 2.01 [95% CI 1.32, 3.08]).The Chi-squared test for heterogeneity showed there is significant heterogeneity with an I(2) statistic of 64% and a significant chi-square test (14.06, df=5, p=0.02). A sensitivity analysis removing the studies with inadequate allocation concealment suggested significant benefit of treatment with the pooled OR of 2.99 (95% CI 1.76, 5.07) and hereterogeneity no longer statistically significant and I(2) statistic of 0%.Three studies reported adverse effects (Davis 2005; Hendrix 2002; GPRG 1968) The adverse effects were nausea, headaches and weight gain. Two studies reported if women experienced any side effect and no evidence of an effect was found (3 RCTs: OR = 1.45 (95% 0.71, 2.94). There was no evidence of statistical heterogeneity.There were no studies identified that compated combined OCP versus non steroidal anti-inflammatory drugs. There was no evidence of a difference for the pooled studies for 3rd generation progestagens (OR = 1.11 (95% CI 0.79 - 1.57)). For the 2nd generation versus 3rd generation the OR was 0.44 (95% CI 0.23-0.84) suggesting benefit of the 3rd generation OCP but this was for a single study (Winkler 2003). AUTHORS' CONCLUSIONS: There is limited evidence for pain improvement with the use of the OCP (both low and medium dose oestrogen) in women with dysmenorrhoea. There is no evidence of a difference between different OCP preparations.

Dysmenorrhoea.

INTRODUCTION: Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure, acupuncture, aspirin, behavioural interventions, combined oral contraceptives, compound analgesics, fish oil, herbal remedies, magnesium, magnets, non-steroidal anti-inflammatory drugs, paracetamol, spinal manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki-shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS), vitamin B12, and vitamin E.

Recombinant versus urinary gonadotrophins for triggering ovulation in assisted conception.

BACKGROUND: The objective of this systematic review was to assess the safety and efficacy of subcutaneous recombinant (r) HCG and high-dose rLH compared with intramuscular urinary (u) uHCG for inducing final oocyte maturation and triggering ovulation. METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (August 27, 2003), the Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, issue 4, 2003), MEDLINE (1966 to February 2004) and EMBASE (1980 to February 2004). Searches were not limited by language. The bibliographies of included and excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. Only truly randomized controlled trials (RCTs) were included. Assessment of inclusion/exclusion, quality assessment and data extraction were performed independently by at least two reviewers. RESULTS: Seven RCTs were identified, four comparing rHCG and uHCG and three comparing rhLH and uHCG. There was no statistically significant difference between rHCG and uHCG regarding the ongoing pregnancy/live birth rate [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.69-1.39], clinical pregnancy rate, miscarriage rate or incidence of ovarian hyperstimulation syndrome (OHSS). There was no statistically significant difference between rhLH and uHCG regarding the ongoing pregnancy/live birth rate (OR 0.94; 95% CI 0.50-1.76), pregnancy rate, miscarriage rate or incidence of OHSS. rHCG was associated with a reduction in the incidence of local site reactions (OR 0.47; 95% CI 0.32-0.70). CONCLUSIONS: According to these data, there is no evidence of a difference in clinical outcomes between urinary and recombinant gonadotrophins used for induction of final follicular maturation. Additional factors should be considered when choosing gonadotrophin type, including safety, cost and drug availability.