Clinical Inquiries

Which medications work best for menorrhagia?

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References

Danazol linked to weight gain and other adverse effects

A 2010 Cochrane review evaluated 9 RCTs, including 1 (66 patients) comparing danazol 200 mg with placebo that showed a significant decrease in subjectively assessed MBL in the danazol group.6 The study, which only 22 women finished, didn’t address ­intention-to-treat and used an unidentified scoring system. Patients also reported a significant 6.7-kg weight gain (95% CI, 1-12.4) after 3 months of treatment.

In addition to the 2013 meta-analysis showing danazol to be superior to NSAIDs, several studies6 compared danazol favorably with oral progesterone, although not all results reached significance. One study (37 patients) showed that women were more likely to rate the efficacy of danazol as moderate or high compared with progesterone (OR = 4.3; 95% CI, 1.1-17.0), but the mean difference in MBL (–36 mL; 95% CI, −102 to 31 mL) wasn’t statistically significant.

Of note, both a meta-analysis of 4 of the studies (117 patients) and another study comparing danazol with NSAIDs (20 patients) found significantly more adverse effects in the danazol group. Commonly reported adverse effects were acne, weight gain, headache, nausea, and tiredness.

RECOMMENDATIONS

A comparative effectiveness review by the Agency for Healthcare Research and Quality concluded that evidence showed efficacy for 4 primary care interventions for heavy cyclic bleeding: LNG-IUS, NSAIDs, tranexamic acid, and combination OCPs.7

The United Kingdom’s National Institute for Health Care and Excellence (NICE) recommends pharmaceutical treatment when no structural or histologic abnormality is present or when fibroids are < 3 cm in diameter.8 NICE advises considering pharmaceutical treatments in the following order: first, LNG-IUS if long-term use (at least 12 months) is anticipated; second, tranexamic acid or NSAIDs; and third, combination OCPs, norethisterone (15 mg) daily from Days 5 to 26 of the menstrual cycle, or injected long-acting progestogen.

Editor’s takeaway

I was taught to use combination OCPs as first-line treatment for menorrhagia, but better evidence supports using any of these 4: LNG-IUS, tranexamic acid, danazol, or NSAIDs. In the absence of clear evidence demonstrating differences in efficacy, I would use them in the reverse order for cost-effectiveness reasons.

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