Which medications work best for menorrhagia?
EVIDENCE-BASED ANSWER:
Four medications have been shown to reduce menstrual blood loss (MBL) significantly in placebo-controlled randomized controlled trials (RCTs): the levonorgestrel-releasing intrauterine system (LNG-IUS), tranexamic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), and danazol, a synthetic steroid (strength of recommendation: A, meta-analyses of RCTs).
A single trial showed that the LNG-IUS reduced MBL by about 100 mL, compared with placebo. In a meta-analysis of 4 placebo-controlled RCTs, tranexamic acid reduced MBL by about 53 mL, roughly a 40% to 50% decrease. The 8 NSAID trials (5 mefenamic acid, 2 naproxen, 1 ibuprofen) demonstrated effectiveness, but the effect size is difficult to quantify. The single danazol RCT used a subjective scoring system without reporting MBL.
No studies compared all effective medical therapies against one another. In head-to-head comparisons, women were more likely to experience improvement with the LNG-IUS than with tranexamic acid (number needed to treat [NNT] = 2 to 6). Both treatments are superior to NSAIDs. Danazol is also more efficacious than NSAIDs, but its use is limited by its adverse effects, including teratogenicity.
No placebo-controlled trials have studied oral contraceptive pills (OCPs) or oral progesterone to treat menorrhagia. However, multiple comparative RCTs have demonstrated that these commonly prescribed medications significantly decrease MBL. Trials have shown the reduction to be inferior to LNG-IUS and danazol and equivalent to NSAIDs.
On the other hand, tranexamic acid compared unfavorably with LNG-IUS (1 RCT, 42 patients), showing a lower likelihood of improvement (RR = 0.43; 95% CI, 0.24-0.77). Whereas 85% of women improved with LNG-IUS, only 20% to 65% of women improved with tranexamic acid (NNT = 2 to 6).
No statistical difference was found in gastrointestinal adverse effects, headache, vaginal dryness, or dysmenorrhea.4 Only 1 thromboembolic event occurred in the 2 studies that reported this outcome, a known risk that prohibits its concomitant use with combination OCPs.
Different NSAIDs, equivalent efficacy
A 2013 Cochrane review of 18 RCTs included 8 (84 patients) that compared NSAIDs (5 MFA, 2 naproxen, 1 ibuprofen) with placebo.5 In 6 trials, NSAIDs produced a significant reduction in MBL compared with placebo, although most were crossover trials that couldn’t be compiled into the meta-analysis.
One trial (11 patients) showed a mean reduction of 124 mL (95% CI, 62-186 mL) in the MFA group. In another trial, women were less likely to report no improvement in the MFA group than in the placebo group (odds ratio [OR] = 0.08; 95% CI, 0.03-0.18). No NSAID had significantly higher efficacy than the others.
Danazol was superior to NSAIDs in a meta-analysis of 3 trials (79 patients) with a mean difference of 45 mL (95% CI, 19-71 mL), as was tranexamic acid in a single trial (48 patients) with a mean difference of 73 mL (95% CI, 22-124 mL).5 Comparisons with OCPs, oral progesterone, and an older model of LNG-IUS showed no significant differences. The most common adverse effects were gastrointestinal.
Continue to: Danazol linked to weight gain and other adverse effects
