Management of bleeding irregularities during contraceptive implant use: A systematic review

To systematically review literature on management of bleeding irregularities during contraceptive implant use.

We searched multiple databases through November 2022 for randomized clinical trials assessing treatment of bleeding irregularities during implant use. Primary outcomes were changes in bleeding irregularities during and after treatment and patient satisfaction. We extracted data and assessed risk of bias for each included study, narratively summarized results, and determined certainty of evidence for primary outcomes.

Twenty-one articles met inclusion criteria. Risk of bias ranged from high to low. Trials examining some non-steroidal anti-inflammatory drugs (celecoxib and mefenamic acid), tamoxifen, and ulipristal acetate (UPA) generally showed improved bleeding patterns during and after treatment compared with placebo, while ibuprofen trials showed no improvements during treatment and inconsistent results after treatment. Trials of tranexamic acid, some hormonal treatments [oral ethinyl estradiol (EE; 50 mcg), combined oral contraceptives], and mifepristone with EE or doxycycline showed improved bleeding patterns only during treatment. Mifepristone alone, doxycycline alone or with EE, oral EE (20 mcg), transdermal estradiol patch, oral levonorgestrel, aspirin, and vitamin E were not consistently effective during or after treatment. Six trials measured patient satisfaction and found improved satisfaction with bleeding patterns for tamoxifen and UPA, and improved satisfaction with treatment for celecoxib, tamoxifen, and mifepristone.

Across the different interventions assessed, certainty of evidence ranged from high to very low. The evidence summarized in this systematic review can help providers counsel patients about interventions to improve bleeding irregularities with contraceptive implant use, depending on patient preferences and goals.

Patients experiencing bothersome bleeding irregularities during contraceptive implant use may be offered different options to manage bleeding and improve their satisfaction. More data are needed on the effectiveness of specific interventions (drugs, regimens, and repeat dosing) and patient satisfaction outcomes.