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Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin
Edelman A, Boniface E, Schrote K, Messerle-Forbes M, O'Donnell A, Jensen JT, Han L
American journal of obstetrics and gynecology. 2023
Abstract
BACKGROUND Some users of the etonogestrel contraceptive implant experience bothersome bleeding which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown but it is likely multi-factorial (e.g. impaired angiogenesis, 'leaky' fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, anti-proliferative, and anti-angiogenic proprieties which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE To evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN The study was a randomized, double blind, placebo-controlled trial. We enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting and randomized them to either 600 mg Theracumin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. We defined "frequent" as two or more independent bleeding or spotting episodes and "prolonged" as 7 or more consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical exam as well as a negative gonorrhea/chlamydia and pregnancy test. Enrolled participants initiated study treatmentfollowing three consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30-days of enrollment, subjects were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record 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 of study drug or placebo exposure. Secondary outcomes including total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha 0.05 to demonstrate a 6-day difference between groups. RESULTS From February 2021 to November 2022, 58 individuals enrolled in the study with 93% (n=54) completing 30 days of treatment (curcumin 26, placebo 28). One individual in the curcumin arm did not experience a qualifying bleeding event and thus never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups including length of implant use at study enrollment [placebo: 521 days (SD 305), curcumin 419 days (SD 264)]. Study groups did not differ in regard to any bleeding-related outcome [mean days without bleeding or spotting: curcumin 16.7 (SD 6.9), placebo 17.5 (SD 4.8), p = 0.62; mean bleeding-free days: curcumin 23.4 (SD 4.9), placebo 22.4 (SD 4.5), p = 0.44; bleeding episodes: curcumin 2.0 (SD 0.8), placebo 2.1 (SD 0.8), p = 0.63]. Satisfaction with the implant as contraception and acceptability of bleeding over the study period also did not differ by study group (p = 0.54 and p = 0.30, respectively). CONCLUSION Daily use of curcumin did not improve bleeding patterns in users of the etonorgestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.