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

Abstract

Etonogestrel contraceptive implants are highly effective but many users experience bothersome bleeding. Few strategies exist to clinically manage this bleeding, likely due to a multifactorial mechanism. Tranexamic acid, an antifibrinolytic, is well known for treatment of obstetrical and gynecologic-related acute and chronic bleeding. Tranexamic acid has not been evaluated for bleeding related to the etonogestrel contraceptive implant. To evaluate whether tranexamic acid decreases frequent or prolonged bleeding and/or spotting in contraceptive etonogestrel-implant users. The study was a randomized, double-blind, placebo-controlled trial. We enrolled etonogestrel-implant users with frequent (defined as 2 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 three times a day or placebo three times a day 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if no bleeding or spotting occurred within 30 days of enrollment, no study drug was initiated and subjects were withdrawn.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. From January 2024 to August 2025, 65 individuals were randomized with 83% (n=54) completing 30 days of monitoring post-treatment initiation (tranexamic acid, placebo). Four individuals in the tranexamic acid arm and 5 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arm did not experience a qualifying bleeding event and thus never initiated treatment and, per protocol, they were withdrawn from the study.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 (tranexamic acid: 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: tranexamic acid 19 [interquartile range, 10-21], placebo 19 [interquartile range, 14-23], P=.38; median bleeding or spotting days while on study drug, tranexamic acid 5 [interquartile range, 4-5], placebo 5 [interquartile range, 3-5], P=.71; bleeding episodes: tranexamic acid 2 [interquartile range, 1-2], placebo 2 [interquartile range, 1-3], P=.71). Poststudy satisfaction with the implant as contraception and acceptability of bleeding over the study period also did not differ by study group (P=.98 and P=.83, respectively). A 5-day treatment course of tranexamic acid did not improve bleeding in contraceptive etonogestrel-implant users experiencing frequent or prolonged bleeding patterns.