COCO3 & COCO3-PCOS
The women’s health team has a long history of researching hormonal contraceptives. The CoCo3 and CoCo3-PCOS trials are our most recent efforts to fill the critical gaps in current knowledge on hormonal contraception.
CoCo3 and CoCo3‑PCOS are investigator‑initiated clinical research projects studying the broad effects of modern hormonal contraceptives. The studies focus on comparing a novel estrogen component, estetrol (E4), with the traditionally used ethinylestradiol (EE), as well as progestin‑only contraception, in order to generate independent, high‑quality evidence to support safer and more individualized contraceptive choices.
The CoCo3 study is conducted in healthy women with regular menstrual cycles, while the parallel CoCo3‑PCOS study focuses on women with polycystic ovary syndrome (PCOS), a common endocrine disorder associated with increased metabolic and cardiovascular risk. Both studies use an identical randomized clinical trial design, enabling direct comparison of results between healthy participants and those with PCOS. Studied contraceptives are Drovelis (E4+ drospirenone, DRSP), Daylette (EE+DRSP) and Slinda (DRSP-only).
The projects evaluate a wide range of outcomes, including blood coagulation, inflammation, metabolism, endocrine function, bone health biomarkers, and quality of life. By addressing both short‑ and longer‑term biological effects of different contraceptive formulations, the CoCo3 projects aim to fill critical gaps in current knowledge on hormonal contraception.
The studies are conducted at Oulu University Hospital and Helsinki University Hospital by an experienced multidisciplinary research team in obstetrics & gynecology and clinical research. As fully independent, non‑commercial academic trials, CoCo3 and CoCo3‑PCOS are designed to provide objective, peer‑reviewed evidence to support future clinical guidelines and improve long‑term health outcomes for contraceptive users.
Related Publications
Mosorin ME, Ollila MM, Nordström T, Jokelainen J, Piltonen T, Auvinen J, Morin-Papunen L, Tapanainen J. Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: Aprospective, population-based cohort study. Acta Obstet Gynecol Scand. 2023 Aug11. doi: 10.1111/aogs.14636. Epub ahead of print. PMID: 37568273.
Mosorin ME, Piltonen T, Rantala AS, Kangasniemi M, Korhonen E, Bloigu R, Tapanainen JS, Morin-Papunen L.Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial. J Clin Med. 2023 Apr 12;12(8):2827. doi: 10.3390/jcm1208282, PMID: 37109164
Kangasniemi MH, Arffman RK, Joenväärä S, Haverinen A, Luiro K, Tohmola T, Renkonen R, Heikinheimo O, Tapanainen JS, Piltonen TT. Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial. Hum Reprod. 2023 Jan 5;38(1):89-102. doi: 10.1093/humrep/deac250. PMID: 36416543; PMCID: PMC9825269.
Kangasniemi MH, Arffman RK, Haverinen A, Luiro K, Hustad S, Heikinheimo O, Tapanainen JS, Piltonen TT. Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids: A randomized trial. Contraception. 2022 Dec;116:59-65. doi: 10.1016/j.contraception.2022.08.009. PMID: 36084710.
Haverinen AH, Luiro KM, Szanto T, Kangasniemi MH, Hiltunen L, Sainio S, Piltonen TT, Lassila R, Tapanainen JS, Heikinheimo O. Combined oral contraceptives containing estradiol valerate vs ethinylestradiol on coagulation: A randomized clinical trial. Acta Obstet Gynecol Scand. 2022 Jul 31. doi: 10.1111/aogs.14428. Epub ahead of print. PMID: 35909329.
Haverinen A, Luiro K, Kangasniemi MH, Piltonen TT, Hustad S, Heikinheimo O, Tapanainen JS.Estradiol Valerate vs Ethinylestradiol in Combined Oral Contraceptives: Effects on the Pituitary-Ovarian Axis. J Clin Endocrinol Metab. 2022 Jun 16;107(7) PMID: 35279718
Haverinen A, Kangasniemi M, Luiro K, Piltonen T, Heikinheimo O, Tapanainen JS. Ethinyl estradiol vs estradiol valerate in combined oral contraceptives – Effect on glucose tolerance: A randomized, controlled clinical trial. Contraception. 2021 Jan;103(1):53-59. doi: 10.1016/j.contraception.2020.10.014. Epub 2020 Oct 21. PMID: 33098852.
Kangasniemi MH, Haverinen A, Luiro K, Hiltunen JK, Komsi EK, Arffman RK, Heikinheimo O, Tapanainen JS, Piltonen TT. Estradiol Valerate in COC Has More Favorable Inflammatory Profile Than Synthetic Ethinyl Estradiol: A Randomized Trial. J. Clin. Endocrinol. Metab. 105(7):dgaa186, 2020. doi: 10.1210/clinem/dgaa186.
Mosorin ME, Haverinen A, Ollila MM, Nordström T, Jokelainen J, Keinänen-Kiukaanniemi S, Puukka K, Ruokonen A, Auvinen J, Piltonen T, Morin-Papunen L, Tapanainen JS. Current use of combined hormonal contraception is associated with glucose metabolism disorders in perimenopausal women. Eur J Endocrinol. 2020 Dec;183(6):619-626. doi: 10.1530/EJE-20-0406. PMID: 33105101
Kallio S, Puurunen J, Ruokonen A, Vaskivuo T, Piltonen T, Tapanainen JS. Antimullerian hormone levels decrease in women using combined contraception independently of administration route. Fertil Steril. 99(5):1305-1310, 2013. doi: 10.1016/j.fertnstert.2012.11.034.
Piltonen T, Puurunen J, Hedberg P, Ruokonen A, Mutt SJ, Herzig KH, Nissinen A, Morin-Papunen L, Tapanainen JS. Oral, transdermal and vaginal combined contraceptives induce an increase in markers of chronic inflammation and impair insulin sensitivity in young healthy normal-weight women: a randomized study. Hum. Reprod. 27:3046-56, 2012.
See also:
The Estrogens and Combined Oral Contraceptives Expert Committee (ESCONEC) Project brings together international experts to examine how the estrogen component shapes the acceptability, safety, and effectiveness of CHCs. Read more at:
https://natural-estrogens.org/
The Finnish Current Care Guideline for Contraception was published in 2026. Professor Piltonen led the process as the chair of the committee board. Guideline in Finnish: https://www.kaypahoito.fi/hoi50104?tab=suositus
CoCo3 team:
Oulu University Hospital
Sponsor-investigator & Principal investigator:
Terhi Piltonen, Professor in obstetrics and gynecology, MD, PhD
Coordinating investigator:
Marika Kangasniemi, MD, PhD, Specialist in obstetrics and gynecology
Sub-investigators:
Katja Alanärä, MD, PhD student, doctor specializing in obstetrics and gynecology
Lotta Vuokila, Research nurse
Tiina Leppälä, Research nurse
Helsinki University Hospital
Principal investigator:
Kaisu Luiro, MD, PhD, Associate Professor in obstetrics and gynecology
Sub-investigators:
Oskari Heikinheimo, Professor in obstetrics and gynecology,
Janina Kaislasuo, MD, PhD, Specialist in obstetrics and gynecology
Juha Tapanainen, MD, PhD, Professor emeritus in obstetrics and gynecology
Minna Vakkuri, MD, PhD student, doctor specializing in obstetrics and gynecology
Eeva Haapiainen, Research nurse
Sirpa Nolvi, Research nurse
website: www.coco3tutkimus.fi
EUCT: 2025-523359-71-00 & 2025-523358-15-00
