Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant
Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant
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DOI：
10.1093/humrep/dew222
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发表时间：
2016-11-01
影响因子：
6.1
通讯作者：
Hubacher, David
中科院分区：
文献类型：
--
作者：
Ali, Moazzam;Akin, Ayse;Hubacher, David
是否有可能将3年单杆依托孕烯（ENG）释放皮下避孕植入剂的使用延长至5年？单杆含ENG缓释剂皮下埋植剂的长期使用在第4年和第5年显示出100%的有效性。20世纪90年代进行的含ENG缓释剂皮下埋植剂的初始监管试验旨在测量累积的3年有效性。ENG植入物在长达3年的时间内具有良好的安全性和有效性。ENG的药代动力学数据显示3年时的水平较高，一些既往临床研究证实了超过目前批准的3年持续时间的疗效。今天，许多妇女，因为标签的持续时间已经达到，有ENG植入物删除在3年，增加成本，不便和风险。在前3年，这项研究是一个开放标签，多中心随机试验比较3年ENG植入物5年左炔诺孕酮（LNG）释放植入物。3年后，390名ENG参与者同意延长使用。我们比较了两种种植体的疗效、副作用和取出程序。我们使用Kaplan-Meier（K-M）分析。我们纳入了一个观察队列的铜宫内节育器（IUD）的用户作为非用户的激素避孕方法进行比较purposes.The研究发生在全球七个国家的计划生育诊所。在资格检查和知情同意后，招募了1328名妇女：ENG植入组、LNG植入组和IUD组分别为390名、522名和416名。ENG或LNG植入组在额外2年随访期间未发生妊娠。ENG和LNG植入体的总体5年K-M累积妊娠率分别为0.6/100女性-年（W-Y）[95%置信区间（CI）：0.2-1.8]和0.8/100 W-Y [95% CI：0.2-2.3]。出血变化的投诉相似;然而，ENG使用者比LNG使用者更有可能经历严重出血（p < 0.05）。与双棒LNG产品（IQR = 77.0，180.0）相比，单棒ENG植入物（四分位距（IQR）= 30.5，117.5）的植入物取出手术的中位持续时间短64秒。IUD组2年妊娠率为4.1/100 W-Y [95%CI：2.5-6.5]，19岁以上妇女和初产妇很少。虽然没有体重限制，但参与研究的女性人数很少，每千日元70公斤。这项研究的结果证实了以前的证据，表明ENG植入物在4年内具有高避孕效果。5年的数据是一个新的贡献，进一步证明了该产品能够提供安全有效的避孕措施，可与目前的5年LNG皮下植入剂相媲美。这些发现为政策制定者、计划生育程序员和临床医生提供了有价值的信息，即ENG释放皮下植入物在植入后5年内仍然非常有效。与以前的努力相比，我们的研究人群在地理上是多样化的，我们的研究有最多的参与者完成了至少5年的使用。该试验注册为ISRCTN 33378571。避孕装置和进行研究的资金由联合国开发计划署/联合国人口基金/世界卫生组织（WHO）/联合国儿童基金会/世界银行特别研究计划提供，卫生组织生殖健康和研究部人类生殖发展和研究培训。本报告包含一个国际专家组的集体观点，并不一定代表世界卫生组织的决定或声明的政策。所有声明的作者都没有利益冲突，除了Hubacher博士在研究进行期间报告了美国国际开发署的赠款;其他来自咨询委员会（Teva，Bayer，OCON），在提交的工作之外。
Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years?The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5.The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks.For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan-Meier (K-M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes.The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively.Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K-M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2-1.8] and 0.8 per 100 W-Y [95% CI: 0.2-2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more likely than LNG-users to experience heavy bleeding (p < 0.05). The median duration of the implant removal procedure was 64 seconds shorter for the one-rod ENG-implant (inter-quartile range (IQR) = 30.5, 117.5) compared to the two-rod LNG product (IQR = 77.0, 180.0). The 2-year rate for pregnancy in the IUD group compared with the two implant groups combined was 4.1 per 100 W-Y [95% CI: 2.5-6.5].Few women were a parts per thousand currency sign19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women a parts per thousand yen70 kg were few.The results from this study corroborate previous evidence showing high contraceptive efficacy through 4 years for the ENG-implant. Data through 5 years are a novel contribution and further proof of the product's capability to provide safe and effective contraception that rivals the current 5-year LNG-subdermal implant. The findings provide valuable information for policy makers, family planning programmers and clinicians that the ENG-releasing subdermal implant is still highly effective up to 5 years after insertion. Compared to previous efforts, our study population was geographically diverse and our study had the highest number of participants completing at least 5 years of use.The trial was registered as ISRCTN33378571.The contraceptive devices and funds for conduct of the study were provided by the United Nations Development Programme/United Nations Population Fund/World Health Organization (WHO)/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), WHO. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the WHO. All stated authors have no conflict of interest, except Dr Hubacher who reported grants from United States Agency for International Development, during the conduct of the study; other from Advisory Boards (Teva, Bayer, OCON), outside the submitted work.