Etonogestrel 68mg implant

ObjectiveTo summarize evidence on the efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) in managing adenomyosis (AM), both as a monotherapy and in combination with other therapies.MethodsWe searched Medical Literature Analysis and Retrieval System On-Line: Medline, The Cochrane Library, Embase, SinoMed, China National Knowledge Infrastructure, and Wanfang from the inception to Aug 12, 2024 for articles using the LNG-IUS both alone and combined with other therapies in patients with AM. The primary outcome included dysmenorrhea, menstrual bleeding, uterine volume, endometrial thickness and quality of life. The secondary outcome was the assessment of adverse events. Data synthesis was conducted using random-effects model with significant heterogeneity (I2 > 50%), otherwise using fixed-effects model.ResultsThe final analysis included 28 studies. Compared with etonogestrel, LNG-IUS was more effective in reducing uterine volume and associated with a lower risk of weight gain, but showed no significant difference in reducing dysmenorrhea and endometrial thickness. Comparing LNG-IUS with mifepristone, there was no significant difference in terms of quality of life. The combination of LNG-IUS with Gonadotropin-releasing hormone agonists (GnRH-a) was more effective than LNG-IUS alone, providing benefits in reducing dysmenorrhea (mean deviation, MD: -1.14), menstrual bleeding (MD: -11.94), uterine volume (MD: -30.39), endometrial thickness (MD: -0.89), and adverse events. The combination of LNG-IUS with surgical excision was more effective than surgical excision alone, providing benefits in reducing dysmenorrhea (MD: -1.49), menstrual bleeding (MD: -5.13) at 12 months, reducing uterine volume at 6 (MD: -9.23), 12 (MD: -16.53) and 24 (MD: -27.17) months. The combination of LNG-IUS with focused ultrasound ablation (FUA) was more effective than FUA alone, providing benefits in reducing dysmenorrhea (MD: -0.62), menstrual bleeding (MD: 0.17).ConclusionsThis study found no clear evidence to recommend single-drug therapy for improving pain and quality of life in AM management within 12 months. Combining LNG-IUS with GnRH-a is effective in alleviating pain, controlling heavy bleeding, reducing lesion volume, reducing the probability of expulsion and irregular bleeding. Postoperative LNG-IUS helps reduce long-term pain and bleeding. In combined FUA, LNG-IUS is effective for managing short-term pain and bleeding.Trial registrationPROSPERO registration number: CRD42024578824.

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PurposeWe aimed to conduct a systematic review and meta-analysis comparing the outcomes of subdermal implants and levonorgestrel intrauterine system (LNG-IUS) in reproductive-aged women.MethodsIn April 2024, we searched Pubmed, Embase and Cochrane trials using the search terms: "etonogestrel", "levonorgestrel" and "randomized controlled trials". We identified 2862 results comparing the LNG-IUS to subdermal implants. Randomized controlled trials (RCTs) were selected with no restrictions on language or year of publication.ResultsWe include six RCTs comprising 1503 patients. R Studio was used for statistical analysis. Subdermal implants were associated with a higher risk of dissatisfaction (OR 2.42; 95% CI 1.47-3.98), acne (OR 2.21; 95% CI 1.21-4.04), weight gain (OR 4.63; 95% CI 1.96-10.63), and device removal due to side effects (OR 2.02; 95% CI 1.20-3.41) compared to the LNG-IUS group. Subgroup analysis indicated that irregular bleeding may be influenced by gynecological conditions, and the risk of new ovarian cyst detection was lower in healthy women using subdermal implants. Norplant-2 was associated with an increased risk of irregular bleeding and a decreased risk of amenorrhea or infrequent bleeding. The leave-one-out analysis and heterogeneity were well distributed among studies for all evaluated outcomes.ConclusionsReproductive-aged women in use of subdermal implants experienced a higher rate of acne, weight gain, device removal due to side effects and dissatisfaction compared to those in use of LNG-IUS.Trial registrationPROSPERO ID: CRD42024516472.

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BACKGROUND Additional progestogens are often used in some countries to stop prolonged bleeding in etonogestrel implant users, although no evidence currently supports this practice. OBJECTIVE To evaluate the efficacy and safety of oral norethisterone acetate (NETA), also known as norethindrone acetate, at a dose of 10 mg/day for prolonged bleeding associated with etonogestrel implant use. STUDY DESIGN IMPLANET is a randomized, controlled, blinded, multicenter trial conducted in Brazil. It included etonogestrel implant users aged 18-40 years who had been using the implant for at least 40 days and had experienced uterine bleeding for a minimum of 7 consecutive days at enrollment. Participants had no prior diagnosis of abnormal uterine bleeding and underwent a standardized evaluation to exclude a secondary cause for the current prolonged bleeding episode. Participants were block-randomized to receive 10 mg of oral NETA or placebo daily until they experienced no bleeding for 2 consecutive days or completed 30 consecutive days of treatment, whichever occurred first. Participants could repeat treatment up to three times over 210 days. Participants reported bleeding via daily messages. The primary outcome was the proportion of participants who achieved bleeding cessation after using up to seven consecutive pills. Secondary outcomes included the proportion of participants who achieved bleeding cessation after using up to 14 pills, treatment days required to stop the first bleeding episode, time to bleeding recurrence after the first treatment, bleeding-free days within the first 30 days, treatment failure (continued bleeding after 30 days of pill use), bleeding days and bleeding-free days after the first 30 days, and safety outcomes. Exploratory outcomes included study participation time and premature discontinuation. A sample size of 86 participants provided 80% power to detect a 30% in bleeding cessation rates after using a maximum of seven pills. The modified intention-to-treat (mITT) analysis included participants who received at least one dose of the randomized treatment and had a negative chlamydia/gonorrhea screen post-randomization. We used Chi-square and Wilcoxon tests for comparisons. The primary outcome was additionally analyzed using a multiple log-binomial regression to adjust for baseline imbalances (age, employment status, and marital status), with adjusted risk difference (RD) and 95% confidence intervals (CI). RESULTS Between September/2020 and May/2023, 114 participants were enrolled, 99 were randomized, and 90 (45 per group) were included in the mITT. Baseline characteristics were similar except for age, employment, and marital status. The NETA group had a significantly higher percentage of participants who achieved bleeding cessation after using up to 7 pills than the placebo group (86.7% vs. 48.9%, p<.001), even after adjusting for baseline imbalances (adjusted RD: 35.6% [95% CI: 17.1%-54.0%], p<.001). Bleeding cessation using up to 14 pills was higher (91.1% vs. 64.4%, p=.002) and treatment failure was lower (2.2% vs. 17.8%, p=.03) in the NETA group than in the placebo group, with fewer median treatment days to stop bleeding in the NETA group (3.0 vs. 5.0 days, p=.01). Compared to placebo, the NETA group had a shorter time to bleeding recurrence (5.0 vs. 10.5 days, p=.008), more bleeding-free days in the first 30 days (21.0 vs. 13.0 days, p=.007), longer trial participation (159.9 vs. 127.2 days, p<.001), and a lower discontinuation rate (33.3%, p=.09). CONCLUSION Short-term use of 10 mg/day NETA effectively and safely stopped prolonged bleeding in etonogestrel implant users. However, it does not prevent bleeding recurrence.

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