Treatment of unfavorable bleeding patterns in contraceptive implant users with tranexamic acid: randomized clinical trial.

BACKGROUND Etonogestrel (ENG) contraceptive implants are highly effective but many users experience bothersome bleeding. Few strategies exist to clinically manage this bleeding; likely due to a multi-factorial mechanism. Tranexamic acid (TXA), an antifibrinolytic, is well known for treatment of obstetrical and gynecologic-related acute and chronic bleeding. TXA has not been evaluated for bleeding related to the ENG contraceptive implant.

OBJECTIVE To evaluate whether TXA decreases frequent or prolonged bleeding and/or spotting in contraceptive ENG-implant users.

STUDY DESIGN The study was a randomized, double blind, placebo-controlled trial. We enrolled ENG-implant users with frequent (defined as two or more independent bleeding or spotting episodes) or prolonged (7 or more consecutive days of bleeding or spotting in a 30-day interval) bleeding or spotting to tranexamic acid 1300 mg TID or placebo TID for 5 days. Enrolled participants started study treatment on the third day of consecutive bleeding or spotting; if no bleeding or spotting occurred within 30-days of enrollment, no study drug was initiated and subjects were withdrawn. Participants used an e-diary to report daily bleeding patterns and study drug compliance. We defined bleeding as a day that required the use of protection with a pad, tampon, or liner, and spotting as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days following first day of treatment. Secondary outcomes included total number of bleeding or spotting days, bleeding episodes, and satisfaction. A sample size of 24 per group provided 80% power at an alpha 0.05 to demonstrate a 5-day difference between groups.

RESULTS From January 2024 to August 2025, 65 individuals were randomized with 83% (n = 54) completing 30 days of monitoring post-treatment initiation (TXA, placebo). Four individuals in the TXA arm and five in the placebo arm did not experience a qualifying bleeding event and thus never initiated treatment and, per protocol, they were withdrawn from the study. Participant characteristics did not differ between groups including the median length of implant use [TXA: 531 days (range 91-939); placebo: 645 days (range 68-1078)]. Study groups did not differ in regard to key bleeding-related outcomes [median days without bleeding or spotting: TXA 19 (interquartile range [IQR] 10-21), placebo 19 (IQR 14-23), p = 0.38; median bleeding or spotting days while on study drug, TXA 5 (IQR 4-5), placebo 5 (IQR 3-5), p = 0.71; bleeding episodes: TXA 2 (IQR1-2), placebo 2 (IQR 1-3), p = 0.71. Post-study satisfaction with the implant as contraception and acceptability of bleeding over the study period also did not differ by study group (p = 0.98 and p = 0.83, respectively).

CONCLUSION A 5-day treatment course of TXA did not improve bleeding in contraceptive ENG-implant users experiencing frequent or prolonged bleeding patterns.