Abstract
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 100 W-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 100 W-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
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2527-2538 |
| Number of pages | 12 |
| Journal | Human Reproduction |
| Volume | 30 |
| Issue number | 11 |
| DOIs | |
| State | Published - May 26 2015 |
| Externally published | Yes |
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Keywords
- contraception
- etonogestrel
- implanon
- implants
- Jadelle
- levonorgestrel
- randomized clinical trial
- TCu380A IUD
ASJC Scopus subject areas
- Rehabilitation
- Obstetrics and Gynecology
- Reproductive Medicine
Cite this
A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls. / Bahamondes, Luis; Brache, Vivian; Meirik, Olav; Ali, Moazzam; Habib, Ndema; Landoulsi, Sihem; Bahamondes, Luis M Valeria; Massai, Rebeca; Montero, Juan Carlos; Villarroel, Claudio; Kovacs, Laszlo; Pal, Attila; Koloszar, Sandor; Tooth, Marta; Orawan, Kiriwat; Akin, Ayse; Erbaydar, Nüket Paksoy; Erdost, Türküler; Aybaş, Güldali; Beksac, Sinan; Dilbaz, Berna; Haberal, Ali; Kurttekin, Cuma; Giray, Emine; Aktün, Hale; Mollamahmutoglu, Leyla; Tümay, Erdoʇan; Evran, Ayşe; Kasule, Jonathan; Chipato, Tsungai; Schmidt, Johannes; Farley, Tim; Culwell, Kelly; Jackson, Emily; Piaggio, Gilda; Hazelden, Catherine; Habib, Ndema Abu; Fersurella, Antonio Lucio; Steiner, Markus; Hubacher, David; Acevedo, Ninky; Coker, Joy; Kijkuarn, Orawan; Wojdyla, Daniel; Campodonico, Liana; Burgueno, Fernando; Pinol, Alain; Bahamondes, L.; Ali, M.; Habib, N. Abu; Landoulsi, S.
In: Human Reproduction, Vol. 30, No. 11, 26.05.2015, p. 2527-2538.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls
AU - Bahamondes, Luis
AU - Brache, Vivian
AU - Meirik, Olav
AU - Ali, Moazzam
AU - Habib, Ndema
AU - Landoulsi, Sihem
AU - Bahamondes, Luis M Valeria
AU - Massai, Rebeca
AU - Montero, Juan Carlos
AU - Villarroel, Claudio
AU - Kovacs, Laszlo
AU - Pal, Attila
AU - Koloszar, Sandor
AU - Tooth, Marta
AU - Orawan, Kiriwat
AU - Akin, Ayse
AU - Erbaydar, Nüket Paksoy
AU - Erdost, Türküler
AU - Aybaş, Güldali
AU - Beksac, Sinan
AU - Dilbaz, Berna
AU - Haberal, Ali
AU - Kurttekin, Cuma
AU - Giray, Emine
AU - Aktün, Hale
AU - Mollamahmutoglu, Leyla
AU - Tümay, Erdoʇan
AU - Evran, Ayşe
AU - Kasule, Jonathan
AU - Chipato, Tsungai
AU - Schmidt, Johannes
AU - Farley, Tim
AU - Culwell, Kelly
AU - Jackson, Emily
AU - Piaggio, Gilda
AU - Hazelden, Catherine
AU - Habib, Ndema Abu
AU - Fersurella, Antonio Lucio
AU - Steiner, Markus
AU - Hubacher, David
AU - Acevedo, Ninky
AU - Coker, Joy
AU - Kijkuarn, Orawan
AU - Wojdyla, Daniel
AU - Campodonico, Liana
AU - Burgueno, Fernando
AU - Pinol, Alain
AU - Bahamondes, L.
AU - Ali, M.
AU - Habib, N. Abu
AU - Landoulsi, S.
PY - 2015/5/26
Y1 - 2015/5/26
N2 - 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 100 W-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 100 W-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
AB - 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 100 W-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 100 W-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
KW - contraception
KW - etonogestrel
KW - implanon
KW - implants
KW - Jadelle
KW - levonorgestrel
KW - randomized clinical trial
KW - TCu380A IUD
UR - http://www.scopus.com/inward/record.url?scp=84946401503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946401503&partnerID=8YFLogxK
U2 - 10.1093/humrep/dev221
DO - 10.1093/humrep/dev221
M3 - Article
C2 - 26409014
AN - SCOPUS:84946401503
VL - 30
SP - 2527
EP - 2538
JO - Human Reproduction
JF - Human Reproduction
SN - 0268-1161
IS - 11
ER -