Tags

Type your tag names separated by a space and hit enter

Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant.
Hum Reprod 2016; 31(11):2491-2498HR

Abstract

STUDY QUESTION

Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years?

SUMMARY ANSWER

The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5.

WHAT IS KNOWN ALREADY

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.

STUDY DESIGN SIZE, DURATION

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.

PARTICIPANTS/MATERIALS, SETTING, METHODS

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.

MAIN RESULTS AND THE ROLE OF CHANCE

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].

LIMITATIONS, REASONS FOR CAUTION

Few women were ≤19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women ≥70 kg were few.

WIDER IMPLICATIONS OF THE FINDINGS

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.

TRIAL REGISTRATION

The trial was registered as ISRCTN33378571.

STUDY FUNDING/COMPETING INTERESTS

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.

Authors+Show Affiliations

UNDP, UNICEF, UNFPA, WHO, World Bank Special Programme of Research Development and Research Training in Human Reproduction, Geneva, Switzerland alimoa@who.int.Faculty of Medicine, Baskent University, Ankara, Turkey.Family Planning Clinic, Department of Obstetrics and Gynaecology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.PROFAMILIA, Santo Domingo, Dominican Republic.UNDP, UNICEF, UNFPA, WHO, World Bank Special Programme of Research Development and Research Training in Human Reproduction, Geneva, Switzerland.UNDP, UNICEF, UNFPA, WHO, World Bank Special Programme of Research Development and Research Training in Human Reproduction, Geneva, Switzerland.FHI 360, Durham, NC, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27671673

Citation

Ali, Moazzam, et al. "Extended Use Up to 5 Years of the Etonogestrel-releasing Subdermal Contraceptive Implant: Comparison to Levonorgestrel-releasing Subdermal Implant." Human Reproduction (Oxford, England), vol. 31, no. 11, 2016, pp. 2491-2498.
Ali M, Akin A, Bahamondes L, et al. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant. Hum Reprod. 2016;31(11):2491-2498.
Ali, M., Akin, A., Bahamondes, L., Brache, V., Habib, N., Landoulsi, S., & Hubacher, D. (2016). Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant. Human Reproduction (Oxford, England), 31(11), pp. 2491-2498.
Ali M, et al. Extended Use Up to 5 Years of the Etonogestrel-releasing Subdermal Contraceptive Implant: Comparison to Levonorgestrel-releasing Subdermal Implant. Hum Reprod. 2016;31(11):2491-2498. PubMed PMID: 27671673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant. AU - Ali,Moazzam, AU - Akin,Ayse, AU - Bahamondes,Luis, AU - Brache,Vivian, AU - Habib,Ndema, AU - Landoulsi,Sihem, AU - Hubacher,David, AU - ,, Y1 - 2016/09/26/ PY - 2016/05/07/received PY - 2016/07/28/revised PY - 2016/08/09/accepted PY - 2016/9/28/pubmed PY - 2018/1/13/medline PY - 2016/9/28/entrez KW - etonogestrel KW - extended use KW - intrauterine device KW - levonorgestrel KW - subdermal contraceptive implants SP - 2491 EP - 2498 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 31 IS - 11 N2 - STUDY QUESTION: Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? SUMMARY ANSWER: The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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]. LIMITATIONS, REASONS FOR CAUTION: Few women were ≤19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women ≥70 kg were few. WIDER IMPLICATIONS OF THE FINDINGS: 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. TRIAL REGISTRATION: The trial was registered as ISRCTN33378571. STUDY FUNDING/COMPETING INTERESTS: 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. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/27671673/Extended_use_up_to_5_years_of_the_etonogestrel_releasing_subdermal_contraceptive_implant:_comparison_to_levonorgestrel_releasing_subdermal_implant_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dew222 DB - PRIME DP - Unbound Medicine ER -