Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding

Heavy menstrual bleeding (HMB) 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. Non-steroidal anti-inflammatory drugs (NSAIDs) 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 NSAIDs in achieving a reduction in menstrual blood loss in women of reproductive years with HMB.

We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL in July 2012 and reference lists of articles. We also contacted manufacturers and researchers in the field.

The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their heavy menstrual blood loss.

Eighteen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data and one trial with missing variances were described in data tables.

As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than either tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). 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 were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system (Progestasert), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB.

NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of intrauterine system, Progestasert.