Norethindrone Reduced Prolonged Bleeding Related to Etonogestrel Implant

Does oral norethindrone reduce prolonged uterine bleeding related to etonogestrel implant use?

Oral norethindrone, 10 mg daily reduced the duration of prolonged uterine bleeding in the first year after placement of an etonogestrel implant. It also reduced the number of bleeding days by an average of 8 days in the first 30 days after initiating treatment. However, recurrences of bleeding were frequent and occurred earlier on average than with placebo. (Level of Evidence = 1b)

In the multicenter, randomized, double-blind, placebo-controlled trial conducted in Brazil from September 2020 through May 2023, oral norethindrone (also known as norethisterone) was used to treat prolonged uterine bleeding (7 days or more) within the first year of use of an etonogestrel contraceptive implant (Implanon NXT; not available in the United States). The list of exclusion criteria included body mass index of 35 kg/m² or more; history of bariatric surgery; abnormalities on gynecologic examination, including transvaginal ultrasonography that could account for abnormal bleeding; a positive test result for chlamydia or gonorrhea; and placement of the implant less than 40 days before enrollment. After exclusions, there were 45 participants in each group. Participants received oral norethindrone (10 mg tablets) or placebo with an identical appearance. Treatment could be repeated up to three times. Data collection was by daily text message with a paper diary as backup. The norethindrone group achieved a higher rate of cessation of bleeding (at least 2 days) within 7 days of treatment (87% vs 49%; number needed to treat = 3; 95% CI, 2–5; P < .001) and required a median of fewer treatment days to achieve cessation of bleeding (3 vs 5 days; P = .01). The rate of bleeding cessation within 14 days was also higher (91% vs 64%; P = .002). However, the norethindrone group had a shorter mean duration until bleeding recurrence (5 vs 10 days; P = .008). During the first 30 days, the norethindrone group had more days without bleeding (21 vs 13 days; P = .007). Bleeding-free days during the rest of the study period (210 days) was not different between groups. There were more dropouts in the placebo group over time.

Study design: Randomized controlled trial (double-blinded)

Funding source: Unknown/not stated

Allocation: Concealed

Setting: Outpatient (primary care)

Reference: Andrade MCR, Yamaguti EMM, de Nadai MN, et al. Norethisterone for prolonged uterine bleeding associated with etonogestrel implant (IMPLANET): a randomized controlled trial. Am J Obstet Gynecol. 2026; 234(1): 101-115.