Review question
What is the effectiveness and safety of treatments commonly available during pandemics for heavy menstrual bleeding?
Background
Heavy menstrual bleeding is a common gynaecological condition. Treatments that can continue during pandemics include:
1. Non-steroidal anti-inflammatory drugs (NSAIDs), for example mefenamic acid or naproxen: these work by reducing prostaglandin levels, which reduces bleeding from the lining of the womb. NSAIDs can be taken as tablets.
2. Antifibrinolytics, for example tranexamic acid: these work in reducing bleeding by inhibiting clot‐dissolving enzymes in the lining of the womb. Antifibrinolytics can be taken as tablets.
3. Combined hormonal contraceptives, for example the combined oral contraceptive pill: these work by thinning the lining of the womb that is shed during menstrual periods. Combined hormonal contraceptives can be taken as tablets, or can be administered vaginally, using a vaginal ring.
4. Progestogens, for example norethisterone: these work by thinning the lining of the womb that is shed during menstrual periods. Progestogens are tablets, which can be taken for 10 days of the menstrual cycle (short-cycle), or for three to four weeks of the menstrual cycle (long-cycle).
We aimed to summarise the best evidence regarding their effectiveness and safety.
Study characteristics
We included four Cochrane Reviews (44 randomised controlled trials, 3196 women), to June 2020. We identified 11 different comparisons, including NSAIDs compared with placebo (control tablet that has no effect), antifibrinolytics compared with placebo, and combined hormonal oral contraceptives compared with placebo. All reviews reported menstrual bleeding, quality of life, patient satisfaction, side effects, and serious adverse events. We rated all the reviews as high quality.
Key results
Antifibrinolytics and combined hormonal contraceptives are probably effective in reducing heavy menstrual bleeding when compared to placebo. Of 1000 women with heavy menstrual bleeding, 109 will report improvement with placebo, and 363 (range 200 to 662) with antifibrinolytics. Of 1000 women with heavy menstrual bleeding, 29 will perceive their menstrual bleeding is back to normal with placebo, and 401 (range 118 to 771) with combined oral contraceptive. NSAIDs may be effective in reducing heavy menstrual bleeding when compared to placebo. Of 1000 women with heavy menstrual bleeding, 200 will report improvement with placebo, and 766 (range 578 to 887) with NSAIDs. Antifibrinolytics may be more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short-cycle progestogens, but we are unable to draw conclusions about the effects of antifibrinolytics compared to long-cycle progestogens.
There was poor reporting of secondary outcomes, including quality of life, and the women's satisfaction with treatment. These studies did not have enough women participating to detect serious adverse events. There is well known evidence that even though the risk of thromboembolic events is very low in the general population, it increases with oral contraceptives.
Certainty of the evidence
The certainty of the evidence for different comparisons and outcomes ranged from very low to moderate. There were significant limitations in the primary research studies, inconsistency in results between primary research studies, and imprecision in the reviews' findings.
There is moderate-certainty evidence that antifibrinolytics and combined hormonal contraceptives reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that NSAIDs reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short-cycle progestogens, but we are unable to draw conclusions about the effects of antifibrinolytics compared to long-cycle progestogens, on low-certainty evidence.
Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers.
To summarise the evidence from Cochrane Reviews evaluating interventions for heavy menstrual bleeding that are commonly available during pandemics.
We sought published Cochrane Reviews, evaluating interventions that can continue during pandemics for women with heavy menstrual bleeding with no known underlying cause. We identified Cochrane Reviews by searching the Cochrane Database of Systematic Reviews in June 2020. The primary outcome was menstrual bleeding. Secondary outcomes included quality of life, patient satisfaction, side effects, and serious adverse events.
We undertook the selection of systematic reviews, data extraction, and quality assessment in duplicate. We resolved any disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool, and the certainty of the evidence for each outcome using GRADE methods.
We included four Cochrane Reviews, with 11 comparisons, data from 44 randomised controlled trials (RCTs), and 3196 women. We assessed all the reviews to be high quality.
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs may be more effective in reducing heavy menstrual bleeding than placebo (mean difference (MD) -124 mL per cycle, 95% confidence interval (CI) -186 to -62 mL per cycle; 1 RCT, 11 women; low-certainty evidence). Mefenamic acid may be similar to naproxen (MD 21 mL per cycle, 95% CI -6 to 48 mL per cycle; 2 RCTs, 61 women; low-certainty evidence), and NSAIDs may be similar to combined hormonal contraceptives for heavy menstrual bleeding (MD 25 mL per cycle, 95% CI -22 to 73 mL per cycle; 1 RCT, 26 women; low-certainty evidence). NSAIDs may be be less effective in reducing menstrual bleeding than antifibrinolytics (relative risk (RR) 0.70, 95% CI 0.58 to 0.85; 2 RCTs, 161 women; low-certainty evidence). We are uncertain whether NSAIDs reduce menstrual blood loss more than short-cycle progestogens (RR 0.80, 95% CI 0.49 to 1.32; 1 RCT 32 women; very low-certainty evidence).
Antifibrinolytics
Antifibrinolytics appear to be more effective in reducing heavy menstrual bleeding than placebo (MD -53 mL per cycle, 95% CI -63 to -44 mL per cycle; 4 RCTs, 565 women; moderate-certainty evidence). Antifibrinolytics may be similar to placebo on the incidence of side effects (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, 297 women; low-certainty evidence), and they are probably similar on the incidence of serious adverse events (thrombotic events; RR 0.10, 95% CI 0.00 to 2.46; 2 RCT, 468 women; moderate-certainty evidence).
Antifibrinolytics may be more effective in reducing heavy menstrual bleeding than short-cycle progestogen (MD -111 mL per cycle, 95% CI -178 mL to -44 mL per cycle; 1 RCT, 46 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to short-cycle progestogens on quality of life (RR 1.67, 95% CI 0.76 to 3.64; 1 RCT, 44 women; very low-certainty evidence), patient satisfaction (RR 0.91, 95% CI 0.59 to 1.39; 1 RCT, 42 women; very low-certainty evidence), or side effects (RR 0.85, 95% CI 0.65 to 1.12; 3 RCTs, 211 women; very low-certainty evidence).
We are uncertain whether antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with long-cycle progestogen (MD -9 points per cycle, 95% CI -30 to 12 points per cycle; 2 RCTs, 184 women; low-certainty evidence). Antifibrinolytics may increase self-reported improvement in menstrual bleeding when compared with long-cycle medroxyprogesterone acetate (RR 1.32, 95% CI 1.08 to 1.61; 1 RCT, 94 women; low-certainty evidence). Antifibrinolytics may be similar to long-cycle progestogens on quality of life (MD 5, 95% CI -2.49 to 12.49; 1 RCT, 90 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to long-cycle progestogens on side effects (RR 0.58, 95% CI 0.33 to 1.00; 2 RCTs, 184 women; very low-certainty evidence).
There were no trials comparing antifibrinolytics to combined hormonal contraceptives.
Combined hormonal contraceptives
Combined hormonal contraceptives appear to be more effective for heavy menstrual bleeding than placebo or no treatment (RR 13.25, 95% CI 2.94 to 59.64; 2 RCTs, 363 women; moderate-certainty evidence). Combined hormonal contraceptives are probably similar to placebo on the incidence of side effects (RR 1.53, 95% CI 0.90 to 2.60; 2 RCTs, 411 women; moderate-certainty evidence).
Progestogens
There were no trials comparing progestogens to placebo.
Limitations in the evidence included risk of bias in the primary RCTs, inconsistency between the primary RCTs, and imprecision in effect estimates.