Abstract
Objective
Study design
Results
Conclusion
Implications Statement
Keywords
1. Introduction
2. Materials and methods
3. Results
16–25 years (n = 1632) | 26–35 years (n = 1395) | Total 16–35 years (n = 3027) | |
---|---|---|---|
Age (years) | 21.8 ± 2.2 | 29.7 ± 2.8 | 25.4 ± 4.6 |
Body mass index | 23.8 ± 4.2 | 25.2 ± 4.6 | 24.5 ± 4.4 |
<25.0 kg/m2 | 1113 (68.2) | 765 (54.8) | 1878 (62.0) |
25.0 to 29.9 kg/m2 | 333 (20.4) | 365 (26.2) | 698 (23.1) |
≥ 30.0 kg/m2 | 186 (11.4) | 265 (19.0) | 451 (14.9) |
Gravidity | |||
Nulligravid | 1378 (84.4) | 606 (43.4) | 1984 (65.6) |
History of dysmenorrhea | 480 (29.4) | 388 (27.8) | 868 (28.7) |
Past hormonal contraceptive use | |||
>3 months before initiating study drug (starters) | 779 (47.7) | 714 (51.2) | 1493 (49.3) |
None (true new users) | 376 (23.0) | 245 (17.6) | 621 (20.5) |
≤3 months before initiating study drug (switchers) | 853 (52.3) | 681 (48.8) | 1534 (50.7) |
Race | |||
Asian | 53 (3.2) | 37 (2.7) | 90 (3.0) |
Black | 145 (8.9) | 189 (13.5) | 334 (11.0) |
Other | 45 (2.8) | 50 (3.6) | 95 (3.1) |
White | 1389 (85.1) | 1119 (80.2) | 2508 (82.9) |
Region | |||
Canada | 83 (5.1) | 60 (4.3) | 143 (4.7) |
Europe | 680 (41.7) | 433 (31.0) | 1113 (36.8) |
Russia | 113 (6.9) | 127 (9.1) | 240 (7.9) |
United States | 756 (46.3) | 775 (55.6) | 1531 (50.6) |
Smoking status | |||
Current smoker | 242 (14.8) | 226 (16.2) | 468 (15.5) |
Former smoker | 90 (5.5) | 153 (11.0) | 243 (8.0) |
Never smoker | 1300 (79.7) | 1016 (72.8) | 2316 (76.5) |

Contraceptive efficacy assessments | 16–25 years | 26–35 years | Total 16–35 years | ||
---|---|---|---|---|---|
PI for ‘at risk cycles’ according to FDA | |||||
Subjects (n) | 1518 | 1319 | 2837 | ||
Cycles (n) | 13,759 | 12,696 | 26,455 | ||
On-treatment pregnancies (n) | 17 | 14 | 31 | ||
PI (95% CI) | 1.61 (0.94–2.57) | 1.43 (0.78–2.40) | 1.52 (1.04–2.16) | ||
PI for ‘at risk cycles’ according to EMA | |||||
Subjects (n) | 1,573 | 1,362 | 2935 | ||
Cycles (n) | 15,013 | 13,725 | 28,738 | ||
On-treatment pregnancies (n) | 17 | 14 | 31 | ||
PI (95% CI) | 1.47 (0.86–2.36) | 1.33 (0.72–2.22) | 1.40 (0.95–1.99) | ||
Method failure PI for ‘at risk cycles’ according to FDA, | |||||
Subjects (n) | 1518 | 1319 | 2837 | ||
Cycles (n) | 13,759 | 12,696 | 26,455 | ||
On–treatment pregnancies (n) | 9 | 8 | 17 | ||
PI (95% CI) | 0.85 (0.39–1.61) | 0.82 (0.35–1.61) | 0.84 (0.49–1.34) | ||
Cumulative pregnancy rate at cycle 13 | |||||
Cumulative on-treatment pregnancy rate (% [95% CI]) | 1.29 (0.80–2.08) | 1.26 (0.75–2.13) | 1.28 (0.83–1.73) | ||
Cumulative on-treatment method failure pregnancy rate (% [95% CI]) | 0.69 (0.36–1.34) | 0.77 (0.38–1.54) | 0.73 (0.38–1.08) |
Variable | Statistic | 16–25 years | 26–35 years | Total 16–35 years |
---|---|---|---|---|
Body mass index | ||||
<25.0 kg/m2 | Subjects, n | 1044 | 727 | 1771 |
Cycles | 9809 | 7275 | 17,084 | |
On-treatment pregnancies | 11 | 4 | 15 | |
Pearl Index (95% CI) | 1.46 (0.73–2.61) | 0.71 (0.19–1.83) | 1.14 (0.64–1.88) | |
25.0 to 29.9 kg/m2 | Subjects, n | 311 | 345 | 656 |
Cycles | 2610 | 3325 | 5935 | |
On-treatment pregnancies | 5 | 5 | 10 | |
Pearl Index (95% CI) | 2.49 (0.81–5.81) | 1.95 (0.63–4.56) | 2.19 (1.05–4.03) | |
≥30.0 kg/m2 | Subjects, n | 163 | 247 | 410 |
Cycles | 1340 | 2096 | 3436 | |
On-treatment pregnancies | 1 | 5 | 6 | |
Pearl Index (95% CI) | 0.97 (0.025–5.40) | 3.10 (1.01–7.24) | 2.27 (0.83–4.94) | |
Past hormonal contraceptive use | ||||
Starters | Subjects, n | 704 | 664 | 1368 |
Cycles | 5924 | 5859 | 11,783 | |
On-treatment pregnancies | 12 | 5 | 17 | |
Pearl Index (95% CI) | 2.63 (1.36–4.60) | 1.11 (0.36–2.59) | 1.88 (1.09–3.00) | |
Switchers | Subjects, n | 814 | 655 | 1469 |
Cycles | 7835 | 6837 | 14,672 | |
On-treatment pregnancies | 5 | 9 | 14 | |
Pearl Index (95% CI) | 0.83 (0.27–1.94) | 1.71 (0.78–3.25) | 1.24 (0.68–2.08) | |
Race | ||||
Asian | Subjects, n | 48 | 34 | 82 |
Cycles | 352 | 332 | 684 | |
On-treatment pregnancies | 1 | 1 | 2 | |
Pearl Index (95% CI) | 3.69 (0.09–20.58) | 3.92 (0.10–21.82) | 3.80 (0.46–13.73) | |
Black | Subjects, n | 119 | 165 | 284 |
Cycles | 795 | 1161 | 1956 | |
On-treatment pregnancies | 9 | 3 | 12 | |
Pearl Index (95% CI) | 14.72 (6.73–27.94) | 3.36 (0.69–9.82) | 7.98 (4.12–13.93) | |
Other | Subjects, n | 41 | 44 | 85 |
Cycles | 312 | 380 | 692 | |
On-treatment pregnancies | 0 | 1 | 1 | |
Pearl Index (95% CI) | 0 (0 –15.37) | 3.42 (0.09–19.06) | 1.88 (0.05–10.47) | |
White | Subjects, n | 1310 | 1076 | 2386 |
Cycles | 12,300 | 10,823 | 23,123 | |
On-treatment pregnancies | 7 | 9 | 16 | |
Pearl Index (95% CI) | 0.74 (0.30–1.52) | 1.08 (0.49–2.05) | 0.90 (0.51–1.46) | |
Smoking status | ||||
Current smoker | Subjects, n | 221 | 215 | 436 |
Cycles | 1,991 | 2,057 | 4048 | |
On-treatment pregnancies | 3 | 4 | 7 | |
Pearl Index (95% CI) | 1.96 (0.40–5.72) | 2.53 (0.69–6.47) | 2.25 (0.90–4.63) | |
Former smoker | Subjects, n | 83 | 140 | 223 |
Cycles | 660 | 1,229 | 1889 | |
On-treatment pregnancies | 2 | 2 | 4 | |
Pearl Index (95% CI) | 3.94 (0.48–14.23) | 2.12 (0.26–7.64) | 2.75 (0.75–7.05) | |
Never smoker | Subjects, n | 1,214 | 964 | 2178 |
Cycles | 11,108 | 9,410 | 20,518 | |
On-treatment pregnancies | 12 | 8 | 20 | |
Pearl Index (95% CI) | 1.40 (0.73–2.45) | 1.10 (0.48–2.18) | 1.27 (0.77–1.96) |
Variable | Hazard ratio | % Wald confidence limits | |
---|---|---|---|
Comparator | Reference | ||
Age | |||
16 to <25 years | 25 to 35 years | 2.37 | 1.09–5.15 |
Body mass index | |||
≥30 kg/m2 | <30 kg/m2 | 0.79 | 0.31–2.01 |
Past contraceptive use | |||
Starters | Switchers | 0.92 | 0.45–1.92 |
Gravidity | |||
1 | 0 | 3.61 | 1.56–8.38 |
Smoking status | |||
Current smoker | Never Smoker | 1.83 | 0.74–4.50 |
Former Smoker | Never Smoker | 1.48 | 0.49–4.46 |
Race | |||
Asian | White | 2.78 | 0.61–12.71 |
Black | White | 4.61 | 1.97–10.80 |
Other | White | 1.03 | 0.13–8.05 |
Region | |||
United States/Canada | Europe/Russia | 2.68 | 0.93–7.77 |
Compliance | |||
Low | High | 4.21 | 2.04–8.66 |
4. Discussion
Data Availability
- Data will be made available on request.
Acknowledgments
Appendix. Supplementary materials
References
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Article info
Publication history
Footnotes
Conflicts of Interest: JTJ: has received payments for consulting from Bayer Healthcare, Evofem, Mayne Pharma, Merck, Sebela, and TherapeuticsMD. OHSU has received research support from Abbvie, Bayer Healthcare, Daré, Mayne, Medicines360, Merck, and Sebela. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. AK: has served on Advisory Boards for Merck, Mithra Pharmaceuticals and Pfizer. The University of Florida College of Medicine receives research funding from Merck and Estetra SRL (an affiliate company of Mithra Pharmaceuticals). SLA: has received consulting fees from Mayne Pharma and Merck. Magee-Womens Research Institute receives research funding from Estetra SRL (an affiliate company of Mithra Pharmaceuticals), EvoFem, and Merck. JZ: has no conflict of interest to declare. SW: serves on an advisory board for Bayer and MSD. TP: serves on an Advisory Board for Exeltis, Gedeon Richter, Merck and Roche and has received honoraria from AstraZeneca, Exeltis, Ferring, Gedeon Richter, Merck, MSD and Roche. Her research is funded by the Finnish Academy, Sigrid Jusélius Foundation, the Finnish Medical Foundation and Roche. LS: serves as a consultant for Bayer Pharmaceuticals (Russia) and for Gedeon Richter (Russia). IA: has served as an ad hoc speaker for Bayer Pharma AG (Russia), TEVA (Russia), Astellas (Russia), Roche Diagnostics Rus LLC (Russia), Avexima, Bionorica (Russia), CSC Pharma, and Aspen Health LLC. CB: serves on an Advisory Board for Merck Canada, Pfizer Canada, Searchlight, BioSyent Pharma Inc., Estetra SRL (an affiliate company of Mithra Pharmaceuticals), and has received honoraria for medical lectures from Merck Canada, Pfizer Canada and research grants from Astellas, Estetra SRL (an affiliate company of Mithra Pharmaceuticals), Ipsen, Endoceutics and Inovio Pharmaceuticals. MJC: serves as an ad hoc speaker for Mayne Pharma. DA: has been an invited speaker on an ad hoc basis for MSD/Merck, Exeltis, Bayer, and Mithra. MJ: is an employee of Estetra SRL, an affiliate company of Mithra Pharmaceuticals. JMF: is a member of the board at Mithra Pharmaceuticals and received financial support for the supervision of these studies. MDC: has received speaking honorarium from Gedeon 68 Richter, serves on an Advisory Board for Fuji Pharma and Merck, and is a consultant for Estetra SRL (an affiliate company of Mithra Pharmaceuticals [includes support for medical and safety oversight of these studies]), Mayne, Medicines360, and Merck. The Department of Obstetrics and Gynecology, University of California, Davis, receives contraceptive research funding for Dr. Creinin from Chemo Research SL, Evofem, HRA Pharma, Medicines360, Merck, and Sebela.
Funding: Estetra SRL (an affiliated company of Mithra Pharmaceuticals) funded this study. Participants received the study treatment free of charge.
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