Abstract
Objective
Study design
Results
Conclusion
Implications statement
Keywords
1. Introduction
United Nations Department of Economic and Social Affairs. Contraceptive Use by Method 2019. https://www.un.org/development/desa/pd/sites/www.un.org.development.desa.pd/files/files/documents/2020/Jan/un_2019_contraceptiveusebymethod_databooklet.pdf (accessed 30 June 2022).
- de Bastos M
- Stegeman BH
- Rosendaal FR
- Van Hylckama Vlieg A
- Helmerhorst FM
- Stijnen T
- et al.
- Gallo MF
- Nanda K
- Grimes DA
- Lopez LM
- Schulz KF.
- Palacios S
- Colli E
- Regidor PA.
2. Materials and methods
3. Results
3.1 Participants and compliance

Characteristic | Pooled populationn = 3409 |
---|---|
Age (years) | 27.2 ± 6.7 |
16–25 | 1629 (47.8) |
26–35 | 1393 (40.9) |
36–50 | 387 (11.4) |
BMI (kg/m2) | 24.6 ± 4.4 |
<30.0 | 2891 (84.8) |
≥30.0 | 518 (15.2) |
Smoking status | |
Current smoker | 467 (13.7) |
Former smoker | 291 (8.5) |
Never smoker | 2651 (77.8) |
Gravidity/parity | |
Nulligravid | 2024 (59.4) |
Nulliparous | 2262 (66.4) |
Recent hormonal contraceptive use | |
Switchers | 1729 (50.7) |
Starters | 1680 (49.3) |
True new users | 673 (19.7) |
Race | |
Asian | 97 (2.8) |
Black | 374 (11.0) |
White | 2828 (83.0) |
Other | 110 (3.2) |
Region | |
Canada | 152 (4.5) |
Eastern Europe | 746 (21.9) |
Russia | 280 (8.2) |
Scandinavia | 298 (8.7) |
United States of America | 1705 (50.0) |
Western Europe | 228 (6.7) |
3.2 Scheduled bleeding/spotting


3.3 Unscheduled bleeding/spotting

3.4 Absence of bleeding/spotting
Table A. Absence of scheduled bleeding/spotting | |||||||
---|---|---|---|---|---|---|---|
Parameter | Comparator | Cycles | Proportion* | Reference | Cycles | Proportion* | Adjusted OR (95% CI) |
Compliance† | 1 missed pill | 402 | 11.9% | No missed pills | 25,584 | 9.4% | 1.31 (1.00–1.71) |
2 missed pills | 131 | 16.0% | 1.82 (1.25–2.64) | ||||
3 missed pills | 59 | 18.6% | 1.79 (0.96–3.33) | ||||
4 missed pills | 40 | 37.5% | 3.23 (1.60–6.51) | ||||
≥5 missed pills | 52 | 55.8% | 5.35 (2.95–9.72) | ||||
BMI | ≥30 kg/m2 | 3,541 | 17.8% | <30 kg/m2 | 22,727 | 8.3% | 1.68 (1.37–2.05) |
Recent CHC use‡ | |||||||
Cycle 2§ | Switcher from CHC | 1,445 | 8.2% | Starter | 1383 | 10.1% | 1.01 (0.77–1.31) |
Cycle 3§ | Switcher from CHC | 1,403 | 9.8% | Starter | 1267 | 10.5% | 1.06 (0.83–1.37) |
Cycle 4§ | Switcher from CHC | 1,386 | 8.4% | Starter | 1239 | 10.3% | 0.93 (0.71–1.21) |
Table B. Unscheduled bleeding/spotting | |||||||
Parameter | Comparator | Cycles | Proportion* | Reference | Cycles | Proportion* | Adjusted OR (95% CI) |
Compliance† | 1 missed pill | 402 | 25.4% | No missed pills | 25,584 | 16.7% | 1.40 (1.11–1.77) |
2 missed pills | 131 | 26.0% | 1.70 (1.13–2.56) | ||||
3 missed pills | 59 | 42.4% | 3.15 (1.86–5.33) | ||||
4 missed pills | 40 | 40.0% | 2.44 (1.26–4.71) | ||||
≥5 missed pills | 52 | 38.5% | 2.40 (1.36–4.23) | ||||
BMI | ≥30 kg/m2 | 3541 | 20.4% | <30 kg/m2 | 22,727 | 16.4% | 1.16 (0.98–1.36) |
Recent CHC use‡ | |||||||
Cycle 2§ | Switcher from CHC | 1445 | 20.2% | Starter | 1383 | 20.7% | 0.95 (0.79–1.15) |
Cycle 3§ | Switcher from CHC | 1403 | 20.5% | Starter | 1267 | 17.3% | 1.19 (0.97–1.45) |
Cycle 4§ | Switcher from CHC | 1386 | 19.4% | Starter | 1239 | 19.2% | 0.98 (0.80–1.19) |
3.5 Bleeding patterns by treatment compliance and region
A. Absence of scheduled bleeding/spotting | ||||||||
---|---|---|---|---|---|---|---|---|
Region | N* | # | Proportion† | Reference | N | # | Proportion† | Adjusted |
Cycles | Cycles | OR (95% CI)‡ | ||||||
Canada | 123 | 1008 | 10.0% | Non-Canada | 2844 | 25,260 | 9.6% | 1.57 (1.03–2.38) |
Eastern Europe | 712 | 6733 | 6.9% | Non-Eastern Europe | 2255 | 19,535 | 10.5% | 1.04 (0.82–1.32) |
Russia | 265 | 2653 | 1.9% | Non-Russia | 2702 | 23,615 | 10.4% | 0.21 (0.13–0.33) |
Scandinavia | 256 | 2150 | 7.9% | Non-Scandinavia | 2711 | 24,118 | 9.7% | 1.32 (0.92–1.90) |
US | 1400 | 11,640 | 13.5% | Non-US | 1567 | 14,628 | 6.4% | 1.93 (1.57–2.37) |
Western Europe | 211 | 2084 | 7.3% | Non-Western Europe | 2756 | 24,184 | 9.8% | 1.15 (0.77–1.70) |
B. Unscheduled bleeding/spotting | ||||||||
Region | N* | # | Proportion† | Reference | N | # | Proportion† | Adjusted |
Cycles | Cycles | OR (95% CI)‡ | ||||||
Canada | 123 | 1008 | 19.4% | Non-Canada | 2844 | 25,260 | 16.9% | 1.27 (0.94–1.73) |
Eastern Europe | 712 | 6733 | 15.8% | Non-Eastern Europe | 2255 | 19,535 | 17.4% | 1.04 (0.88–1.23) |
Russia | 265 | 2653 | 7.8% | Non-Russia | 2702 | 23,615 | 18.0% | 0.39 (0.30–0.52) |
Scandinavia | 256 | 2150 | 22.3% | Non-Scandinavia | 2711 | 24,118 | 16.5% | 1.65 (1.33–2.06) |
US | 1400 | 11,640 | 18.7% | Non-US | 1567 | 14,628 | 15.6% | 1.13 (0.98–1.29) |
Western Europe | 211 | 2084 | 16.0% | Non-Western Europe | 2756 | 24,184 | 17.1% | 1.03 (0.80–1.33) |
4. Discussion
Acknowledgments
Appendix. Supplementary materials
References
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Article info
Publication history
Footnotes
Conflict of Interest: AMK has served on Advisory Board 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, Merck and has received honoraria from Astra Zeneca, Exeltis, Ferring, Merck, and MSD. 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, Searchlight, BioSyent Pharma Inc., Estetra SRL (an affiliate company of Mithra Pharmaceuticals), and has received honoraria for medical lectures from Merck Canada and Pfizer, and research grants from Astellas, Endoceutics, Estetra SRL (an affiliate company of Mithra Pharmaceuticals), Ipsen, and Inovio Pharmaceuticals.
MJC has received speaker fees from Mayne Pharma.
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.
CLW serves on an Advisory Board for Mayne and TherapeuticsMD, is a consultant to HRA Pharms, and serves as a DSMB member for studies evaluating Merck and Bayer products. Columbia University receives research funding for contraceptive research from Medicines360 and Sebela.
MJ is 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 this study.
MDC has received speaking honorarium from Gedeon 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 this study]), 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: The clinical trials and pooled analysis were funded by Estetra SRL (an affiliate company of Mithra Pharmaceuticals).
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