Abstract
Objectives
Study design
Results
Conclusions
Implications statement
Keywords
1. Introduction
United Nations. Contraceptive use by method. 2019. Available at: https://digitallibrary.un.org/record/3849735?ln=en (accessed June 27, 2022).
- Lundin C
- Wikman A
- Bixo M
- Gemzell-Danielsson K
- Sundström Poromaa I.
- Lawrie TA
- Helmerhorst FM
- Maitra NK
- Kulier R
- Bloemenkamp K
- Gülmezoglu AM.
- Gallo MF
- Lopez LM
- Grimes DA
- Carayon F
- Schulz KF
- Helmerhorst FM.
- Foidart JM
- Arnal JF
- Lenfant F
- Taziaux M
- Houtman R
- Jost M
- et al.
- Guivarc'h E
- Buscato M
- Guihot AL
- Favre J
- Vessieres E
- Grimaud L
- et al.
- Creinin MD
- Westhoff CL
- Bouchard C
- Chen MJ
- Jensen JT
- Kaunitz AM
- et al.
- Gemzell-Danielsson K
- Apter D
- Zatik J
- Weyers S
- Piltonen T
- Suturina L
- et al.
2. Materials and methods
- Creinin MD
- Westhoff CL
- Bouchard C
- Chen MJ
- Jensen JT
- Kaunitz AM
- et al.
- Gemzell-Danielsson K
- Apter D
- Zatik J
- Weyers S
- Piltonen T
- Suturina L
- et al.
3. Results
3.1 Participants and compliance

Characteristic | n (%) or mean ± standard deviation |
---|---|
Age (years) | 27.2 ± 6.7 |
16 to 25 | 1632 (47.8) |
26 to 35 | 1395 (40.8) |
36 to 50 | 390 (11.4) |
Body mass index (kg/m2) | 24.6 ± 4.4 |
<18.5 | 115 (3.4) |
18.5 to 24.9 | 1974 (57.8) |
25.0 to 29.9 | 807 (23.6) |
≥30.0 | 521 (15.2) |
Race | |
White | 2832 (82.9) |
Black | 377 (11.0) |
Asian | 97 (2.8) |
None of the above | 111 (3.2) |
Past contraceptive use | |
Switchers | 1732 (50.7) |
Starters | 1685 (49.3) |
None (true new users) | 674 (19.7) |
Smoking status | |
Current smoker | 468 (13.7) |
Former smoker | 292 (8.5) |
Never smoker | 2657 (77.8) |
Gravidity/Parity | |
Nulligravid | 2027 (59.3) |
Nulliparous | 2265 (66.3) |
3.2 Adverse events
Event | n (%) |
---|---|
Adverse events | |
Any AE | 1786 (52.3) |
AEs by severity | |
Mild | 924 (27.0) |
Moderate | 741 (21.7) |
Severe | 121 (3.5) |
AEs by cycle | |
Cycle 1-3 | 1105 (32.3) |
Cycle 4-6 | 621 (18.2) |
Cycle 7-9 | 487 (14.3) |
Cycle 10-13 | 332 (9.7) |
Treatment-related adverse events | |
Any treatment-related AEs | 981 (28.7) |
Treatment-related AEs in ≥ 2% of participants | |
Bleeding complaints | 323 (9.5) |
Breast pain or tenderness | 136 (4.0) |
Acne | 113 (3.3) |
Mood disturbance | 111 (3.2) |
Headache | 110 (3.2) |
Dysmenorrhea | 85 (2.5) |
Increased weight | 74 (2.2) |
Any treatment-related AEs leading to premature study discontinuation | 272 (8.0) |
Treatment-related AEs leading to premature study discontinuation in ≥ 0.5% of participants | |
Bleeding complaints | 97 (2.8) |
Mood disturbance | 38 (1.1) |
Acne | 28 (0.8) |
Decreased/loss of libido | 21 (0.6) |
3.2.1 Treatment-related adverse events by severity and cycle

Treatment-related AE | Number of participants (%) | Number of affected cycles | Percentage of affected cycles against total number of cycles |
---|---|---|---|
Bleeding complaints | 323 (9.5) | 1294 | 3.7 |
Acne | 113 (3.3) | 579 | 1.6 |
Breast pain or tenderness | 136 (4.0) | 561 | 1.6 |
Increased weight | 74 (2.2) | 482 | 1.4 |
Mood disturbance | 111 (3.2) | 429 | 1.2 |
Headache | 110 (3.2) | 388 | 1.1 |
Dysmenorrhea | 85 (2.5) | 337 | 1.0 |
Decreased/loss of libido | 62 (1.8) | 299 | 0.9 |
3.2.2 Serious adverse events
3.3 Body weight, vital signs and laboratory parameters
4. Discussion
- Lawrie TA
- Helmerhorst FM
- Maitra NK
- Kulier R
- Bloemenkamp K
- Gülmezoglu AM.
European Medicines Agency. Drovelis (estetrol /drospirenone): EPAR - public assessment report. 2021. Available at: https://www.ema.europa.eu/en/documents/assessment-report/drovelis-epar-public-assessment-report_en.pdf (accessed June 27, 2022)
NEXTSTELLIS. Prescibing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf (accessed June 27, 2022).
Drovelis (estetrol /drospirenone). Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/drovelis (accessed June 27, 2022).
Acknowledgments
Appendix. Supplementary materials
References
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Article info
Publication history
Footnotes
Declaration of Competing Interest: MJC: serves as an ad hoc speaker for 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. AMK: has served on Advisory Boards for Merck, Mithra Pharmaceuticals and Pfizer. The University of Florida College of Medicine receives research funding from Bayer, Merck, Mylan 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 Astra Zeneca, 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 and/or speaker for Bayer Pharmaceuticals (Russia), Gedeon Richter (Russia), and Bionorica (Russia). IA: serves as a consultant and/or 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. DFA: Grant Support to Eastern Virginia Medical School from AbbVie, Bayer Healthcare, Daré, Mithra, Myovant Sciences and ObsEva. Consulting fees from Agile Therapeutics, Mithra, ObsEva and TherapeuticsMD. Stock Options from Agile Therapeutics and InnovaGyn, Inc. 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 these studies. MDC: has received speaking honorarium from Gedeon Richter, Mayne and Organon, serves on an Advisory Board for Fuji Pharma, OLIC, Organon, and GlaxoSmithKline, and is a consultant for Estetra SRL (an affiliate company of Mithra Pharmaceuticals [includes support for medical and safety oversight of these studies]), Libbs, Mayne, and Medicines360. 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 affiliate company of Mithra Pharmaceuticals) funded this study. Participants received the study treatment free of charge.
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