A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls
A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls
复制标题
DOI：
10.1093/humrep/dev221
复制
发表时间：
2015-11-01
影响因子：
6.1
通讯作者：
Landoulsi, Sihem
中科院分区：
文献类型：
--
作者：
Bahamondes, Luis;Brache, Vivian;Landoulsi, Sihem
研究问题：在植入3年期间，植入3年的单棒依托诺孕酮(ENG)和5年的双棒左炔诺孕酮(LNG)释放避孕药，以及植入避孕药和宫内节育器(IUD)的临床效果有什么不同，特别是可能与激素避孕药有关的投诉？总结回答：ENG和LNG植入物3年的累积避孕效果和持续2.5年的方法没有显著差异。但在使用IUD的非随机年龄匹配组中，这两种结果都明显差于联合植入物组。已知的情况是：释放Eng和LNG的植入物是安全和高效的避孕药，怀孕率据报道为每100妇女年(W-Y)0.0-0.5。还没有对两种植入物进行面对面的比较研究，关于植入物和铜宫内节育器使用者副作用投诉的比较信息也很少。研究设计、大小、持续时间：这是一项开放的平行组随机对照试验，ENG和LNG植入物的分配比例为1：1，选择TCu380A宫内节育器的妇女为非随机对照组，以解决缺乏关于典型地归因于使用孕激素避孕药的常见副作用的可靠数据。在放置(S)节育器后，分别在2周、3个月和6个月进行一次随访，此后每半年随访一次，为期3年或直到怀孕、取出或拔除植入物/宫内节育器。寻求长期避孕的妇女在资格审查和知情同意后入选，2982名妇女入选：ENG植入组、LNG植入组和IUD组分别为1003、1005和974人；995、997和971人分别纳入本文报告的按方案分析。MAIN结果和机会的作用：ENG和LNG植入物的3年累积妊娠率均为每100W-Y 0.4[95%可信区间(CI)0.1-1.4]。入院时体重70公斤与怀孕无关。方法ENG和LNG种植体2.5年的续用率分别为69.8(95%CI 66.8~72.6)和71.8/100W-Y(68.8~74.5)，3年分别为12.1(95%CI 5.2~22.0)和52.0/100W-Y(95%CI 41.8~61.2)。出血障碍是停用方法的最常见原因，ENG组[16.7(95%CI14.4~19.3)]明显高于LNG组[12.5(95%CI10.5~14.9)](P 0.019)。ENG组的3年累积随访率低于LNG组，分别为8.1(95%可信区间6.4~10.2)和14.4‰(95%可信区间12.1~17.1)。植入眼压的患者平均取出种植体的时间比植入液化天然气的患者短50 S(P，0.0001)。在宫内节育器和植入物使用者的观察比较中，宫内节育器组与联合植入物组相比，3年妊娠相对危险度为5.7‰(95%CI4.4~7.3)(P=0.0003)。放置宫内节育器的3年脱落率为17.8个/100W-Y(95%可信区间14.5~21.9)，止血率为8.5(95%可信区间6.7~10.9)。放置者头痛、头晕的发生率与放置者无显著差异(P分别为0.16和0.77)，痤疮和出血异常的发生率高于放置者(P<0.0001)，而放置者大出血和下腹痛的发生率高于放置者(P<；0.0001)。
STUDY QUESTION: Is there any difference in the clinical performance of the 3-year one-rod etonogestrel (ENG)-and the 5-year two-rod levonorgestrel (LNG)-releasing contraceptive implants during 3 years of insertion, and between implant and intrauterine device (IUD) contraception, in particular complaints possibly related to hormonal contraceptives?SUMMARY ANSWER: The cumulative contraceptive effectiveness after 3 years and method continuation through 2.5 years were not significantly different between ENG and LNG implants, but both outcomes were significantly worse in the non-randomized age-matched group of IUD users than in the combined implant group.WHAT IS KNOWN ALREADY: ENG- and LNG-releasing implants are safe and highly efficacious contraceptives with pregnancy rates reported to be 0.0-0.5 per 100 women-years (W-Y). No head-to-head comparative study of the two implants has been undertaken, and little information is available on comparisons of complaints of side effects of implant and copper IUD users.STUDY DESIGN, SIZE, DURATION: This was an open parallel group RCT with 1:1 allocation ratio of the ENG and the LNG implants with non-randomized control group of women choosing TCu380A IUD to address lack of reliable data on common side effects typically attributed to the use of progestogen-only contraceptives. After device(s) placement, follow-ups were at 2 weeks, 3 and 6 months, and semi-annually thereafter for 3 years or until pregnancy, removal or expulsion of the implant/IUD occurred.PARTICIPANTS, SETTING, METHODS: The study took place in family planning clinics in Brazil, Chile, Dominican Republic, Hungary, Thailand, Turkey and Zimbabwe. Women seeking long-term contraception were enlisted after an eligibility check and informed consent, and 2982 women were enrolled: 1003, 1005 and 974 in the ENG-implant, LNG-implant and IUD groups, respectively; 995, 997 and 971, respectively, were included in the per protocol analysis reported here.MAIN RESULTS AND THE ROLE OF CHANCE: ENG and LNG implants each had the same 3-year cumulative pregnancy rate of 0.4 per 100 W-Y [95% confidence interval (CI) 0.1-1.4]. A weight of >= 70 kg at admission was unrelated to pregnancy. Method continuation rates for ENG and LNG implants at 2.5 years were 69.8 (95% CI 66.8-72.6) and 71.8 per 100W-Y(68.8-74.5), and at 3 years 12.1 (95% CI 5.2-22.0) and 52.0 per 100 W-Y (95% CI 41.8-61.2), respectively. Bleeding disturbances, the most frequent reason for method discontinuation, were significantly more common in the ENG group [16.7 (95% CI 14.4-19.3)] than in the LNG group [12.5 (95% CI 10.5-14.9)] (P 0.019). The 3-year cumulative loss to follow-up was lower in the ENG-than in the LNG-implant group, 8.1 (95% CI 6.4-10.2) and 14.4 per 100 W-Y (95% CI 12.1-17.1), respectively. The median duration of implant removal was 50 s shorter among women with ENG than among women with LNG implant (P, 0.0001). In the observational comparison between IUD and implant users, the 3-year relative risk for pregnancy in IUD group compared with the combined implant group was 5.7 per 100W-Y (95% CI 4.4-7.3) (P = 0.0003). The 3-year expulsion rate of the IUD was 17.8 per 100 W-Y (95% CI 14.5-21.9), while the discontinuation rate for bleeding disturbances was 8.5 (95% CI 6.7-10.9). Frequency of complaints of headache and dizziness was not significantly different between implant and IUD users (P = 0.16 and 0.77, respectively), acne and bleeding irregularities were more frequent among implant users (P, 0.0001), while heavy bleeding and lower abdominal pain occurred more often among IUD than implant users (P < 0.0001).LIMITATIONS, REASONS FOR CAUTION: Few women were = 19 years old or nulligravida, the proportion of implant users >= 70 kg was