Background
Heavy menstrual bleeding and cramping are the most common reasons why women stop using an intrauterine device (IUD) for birth control. We reviewed studies to find out whether pain relief or other medicines, or other methods could reduce bleeding and pain related to IUD use.
Study characteristics
The evidence is up-to-date to January 2021. We included studies that investigated the treatment or prevention of heavy menstrual bleeding or pain related to IUD use. The treatment could be compared with another medicine, no treatment or a placebo (dummy medicine).
Key results
This review includes 21 studies with 3689 women. Eleven studies investigated treatment, while 10 looked at prevention of heavy bleeding and pain. Most of the evidence was obtained from single studies with few participants. We have little to no confidence in the results of the studies. Our confidence is limited because some studies involved only a few people, had varied interventions or had no clear reports on how the study was conducted.
Treatment of heavy menstrual bleeding
Copper IUD
Vitamin B1 may reduce the duration of bleeding, number of spotting days and number of pads used per day while. Mefenamic acid may reduce the volume but not the duration of bleeding when compared to tranexamic acid. Naproxen may not reduce the amount of menstrual bleeding associated with copper IUD.
Levonorgestrel IUD
Among levonorgestrel IUD users, ulipristal may not reduce the duration of bleeding.
Unknown IUD type
In one study with an unknown IUD type, we found that mefenamic acid may not reduce the volume of menstrual bleeding.
Treatment of painful menstruation
Copper IUD
Treatment with tranexamic acid and sodium diclofenac may not reduce the occurrence of painful menstruation associated with copper IUD.
Unknown IUD type
Naproxen may reduce pain associated with an unknown IUD type
Prevention of heavy menstrual bleeding
Copper IUD
Tolfenamic acid may prevent heavy menstrual bleeding while ibuprofen made little to no difference to the volume and duration of menstrual bleeding when compared to placebo. Aspirin in comparison to paracetamol, may not prevent the occurrence of heavy menstrual bleeding.
Levonorgestrel IUD
Studies on tranexamic acid, estradiol, naproxen and mifepristone could not tell us whether they prevented heavy menstrual bleeding associated with levonorgestrel IUD use.
Prevention of painful menstruation
Copper IUD
Tolfenamic acid and ibuprofen may not be effective to prevent painful menstruation compared with placebo.
Authors' conclusions
Heavy menstrual bleeding among copper IUD users may be treated with vitamin B and mefenamic acid while tranexamic acid and diclofenac may not alleviate painful menstruation. As for levonorgestrel IUD users, ulipristal may not reduce or prevent heavy menstrual bleeding. Tolfenamic acid may prevent heavy menstrual bleeding but not pain associated with levonorgestrel IUD. Our confidence in the evidence is low to very low. More studies are needed in the future to generate higher-quality evidence regarding effective medicines to treat and prevent heavy menstrual bleeding and painful menstruation associated with IUD use. Evidence from further studies is likely to change our results.
Findings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.
Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non-steroidal anti-inflammatory drugs (NSAIDs), anti-fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use.
To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies.
We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021.
We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention.
Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE.
This review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding.
Treatment of heavy menstrual bleeding
Cu IUD
Vitamin B1 resulted in fewer pads used per day (mean difference (MD) −7.00, 95% confidence interval (CI) −8.50 to −5.50) and fewer bleeding days (MD −2.00, 95% CI –2.38 to −1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence).
Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD −64.26, 95% CI −105.65 to −22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI −0.27 to 0.42, 2 trials, 152 women; low-certainty evidence).
LNG IUD
The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD −9.30 days, 95% CI −26.76 to 8.16; 1 trial, 24 women; low-certainty evidence).
Unknown IUD type
Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD −2.40, 95% CI −13.77 to 8.97; 1 trial; 84 women; low-certainty evidence).
Treatment of pain
Cu IUD
Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence).
Unknown IUD type
Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence).
Prevention of heavy menstrual bleeding
Cu IUD
We found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD −14.11, 95% CI −36.04 to 7.82) and duration of bleeding (MD −0.2 days, 95% CI −1.40 to 1.0; 1 trial, 28 women, low-certainty evidence).
Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD −0.30, 95% CI −26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence).
LNG IUD
Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B.
There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol.
Prevention of pain
Cu IUD
There was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence).