Curcumin not effective against implant bleeding

Curcumin not effective against implant bleeding | Image Credit: © Nikish Hiraman/peopleimages.com - © Nikish Hiraman/peopleimages.com - stock.adobe.com.

Daily curcumin use in contraceptive implant users does not improve bleeding patterns, according to a recent study published in the American Journal of Obstetrics and Gynecology.

While the etonogestrel (ENG) subdermal contraceptive implant has proven effective in preventing pregnancy, patients often discontinue it because of bleeding patterns. Improving acceptability of the product could prevent unwanted pregnancies, as the implant is 20 times more effective than an oral contraceptive for preventing pregnancy.

Tamoxifen has shown improved bleeding pattern outcomes in patients with implants, but concerns surround the drug because of its use in breast cancer management and its associated increased risk of venous thromboembolism when used long-term. This indicates a need for a product which can be used without concern over adverse events.

Impaired angiogenesis is believed to be associated with progestin-induced bleeding. Curcumin, a product with anti-angiogenic activity, has been determined as safe by the FDA. It has also shown efficacy in treating cancer, cardiovascular disease, and inflammatory conditions. However, the effects of curcumin on uterine bleeding have not been evaluated.

To determine how curcumin impacts bleeding patterns in ENG contraceptive implant users, investigators conducted a randomized, double blind, placebo-controlled trial.

The study was conducted between February 2021 and November 2022 at Oregon Health & Science University in Portland, Oregon. Participants included individuals aged 15 to 45 years with ENG 68mg subdermal contraceptive implant use for 30 days or longer.

Patients met criteria for frequent bleeding, defined as 2 or more independent bleeding or spotting episodes for at least 7 days in a 30-day period. Exclusion criteria included being less than 6 months post partum, less than 6 weeks post abortion, or currently breastfeeding. Participants did not use other therapies for bleeding management during the study.

In-person screening visits for participants included confirmed implant use, a pelvic examination, cervical cytology collection, and gonorrhea and chlamydia testing. Urine pregnancy tests were conducted at baseline, enrollment, and study exit, or if there was concern about pregnancy.

To establish baseline patterns, investigators had participants report bleeding and spotting over the 90 days before the implant was placed. A visual analog scale at baseline and study exit was used to determine patient satisfaction and acceptability with bleeding levels.

Participation began after 3 consecutive days of bleeding or spotting, or immediately for patients with 3 consecutive days of bleeding or spotting at enrollment. Participants with no bleeding or spotting in the 30 days following enrollment were removed from the study.

In the study group, participants received 600 mgTheracumin HP daily, while those in the control group received placebo.TheracuminHP 600 mg has been associated with no to minimal side effects.

Daily data on medication use and bleeding patterns was gathered using an automated text messaging service. The need for protection with a tampon, pad, or liner was used to define bleeding, while minimal blood loss without the need for these products was used to define spotting, with bleeding considered more burdensome than spotting.

Bleeding, spotting, and days without either were tracked through text message diaries, which were reviewed by research staff. The total number of days without bleeding or spotting was the primary outcome of the study, with secondary outcome including days with no bleeding or spotting, number of bleeding or spotting days, number of spotting days, number of bleeding days, and number of bleeding episodes.

There were 58 patients enrolled in the study, 54 of which completed all 30 days of treatment. Participants were aged a mean 24 years, 72% identified as non-Hispanic White, 94% were nulliparous, 72% partnered or married, and 80% reported some level of college education or more. The study and control groups had a similar average implant length.

The total number of days with bleeding or spotting were similar between both groups, at 16.7 days in the curcumin group and 17.5 days in the placebo group. Secondary outcomes were also similar between both groups, along with satisfaction and acceptability with levels of bleeding. Plans to keep the implant were indicated by 72% of participants, 82% in the placebo group, and 62% in the curcumin group.

The lack of changes between the curcumin and placebo groups impliesoral curcumin therapy throughout 30 days does not impact bleeding patterns in ENG implant users. To find more efficient therapies, investigators urged further research on progestin-only contraception associated bleeding.

Reference

Edelman A, Boniface E, Schrote K, et al.Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin. American Journal of Obstetrics and Gynecology. 2023. doi:10.1016/j.ajog.2023.04.028