Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding

Abstract

Heavy menstrual bleeding is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Nonsteroidal anti-inflammatory drugs or prostaglandin synthetase inhibitors reduce prostaglandin levels which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea. The primary objective of this review was to investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB). Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were approached for unpublished data. In most cases, the first author of each included trial was contacted for additional information. The inclusion criteria were randomised comparisons of individual NSAIDs with either each other, placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment induced) causes for their heavy menstrual blood loss. Sixteen RCTs were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The remaining seven trials were of crossover design with data unsuitable for pooling and their individual results were described in text form. As a group, NSAIDs were more effective than placebo at reducing heavy menstrual bleeding but less effective than either tranexamic acid or danazol. Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There was a non significant trend towards greater efficacy of NSAIDs compared to oral progestogen (luteal phase) and ethamsylate but no differences were demonstrated between NSAIDs and the progesterone releasing intra-uterine system (IUS) and the oral contraceptive pill, although these results were based on very small studies. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. NSAIDs reduce heavy menstrual bleeding when compared with placebo but are less effective than either tranexamic acid or danazol. However, adverse events are more severe with danazol therapy. In the limited number of small scale studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral progestogen given in the luteal phase, ethamsylate, oral contraceptive pill and the progesterone releasing IUS.