Comparison of metabolic and inflammatory outcomes in women who used oral contraceptives and the levonorgestrel-releasing intrauterine device in a general population
Abstract
Objective We compared the metabolic and cardiovascular parameters of a reference group of women with those of women who used 2 contraceptive regimes that are used worldwide: the levonorgestrel-releasing intrauterine device and oral contraceptives.Study design We investigated a cohort of 2814 women at age 31 years from the general population-based Northern Finland Birth Cohort who were born in 1966. Women were classified as oral contraceptive users (n = 687 women), levonorgestrel-releasing intrauterine device users (n = 168 women), or no use of hormonal contraception (reference group; n = 1959 women). The analyses were adjusted for body mass index, current alcohol use, household income, and area of residence.Results Compared with the reference group, oral contraceptive users had higher systolic and diastolic blood pressure, raised levels of inflammatory indices (C-reactive protein), and impaired insulin sensitivity. Levonorgestrel-releasing intrauterine device users displayed a lower high-density lipoprotein and total cholesterol, but a similar cholesterol/ high-density lipoprotein ratio, and higher leukocyte count compared with the reference group. Oral contraception users were insulin-resistant compared with levonorgestrel-releasing intrauterine device users with higher blood pressure, raised lipid levels (such as total cholesterol and triglycerides) and insulin levels, and lower homeostasis model assessment and insulin sensitivity, despite smaller waist and lower waist-hip ratio.Conclusion Oral contraception usage was associated with adverse findings in several metabolic, cardiovascular, and inflammatory parameters, which is consistent with an increased future risk of cardiovascular and metabolic disease. These findings should invite more criticism of recent trends that encourage the prescription of oral contraceptives for years during reproductive life and especially in premenopausal women. In contrast, levonorgestrel-releasing intrauterine device or progestin-only pills may offer long-term health benefits over oral contraceptives and should be preferred to oral contraceptives for women in their forties and/or with metabolic risk factors for cardiovascular diseases and type 2 diabetes mellitus.
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Combined oral contraceptives increase low-grade inflammation, alter lipid metabolism and affect the coagulation system, resulting in an increased risk for thromboembolic events.
“COCs also increase low-grade inflammation, alter lipid metabolism and affect the coagulation system, resulting in an increased risk for thromboembolic events”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as Morin-Papunen et al., 2008
EE-containing contraceptives alter lipid metabolism, increasing especially high-density lipoprotein and triglycerides, but also affect glucose metabolism.
“EE-containing contraceptives alter lipid metabolism, increasing especially high-density lipoprotein and triglycerides, but also affect glucose metabolism (Morin-Papunen et al., 2008; Piltonen et al., 2012; Wang et al., 2016).”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as Morin-Papunen et al., 2008
EE-containing COCs increase low-grade inflammation, reflected by increased levels of C-reactive protein (CRP).
“EE-containing COCs have been shown to increase low-grade inflammation, reflected by increased levels of C-reactive protein (CRP) (van Rooijen et al., 2006; Morin-Papunen et al., 2008; Haarala et al., 2009; Piltonen et al., 2012; Wang et al., 2016)”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as Morin-Papunen et al., 2008
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- Authors
- Morin-Papunen, L., Martikainen, H., McCarthy, M. I., Franks, S., Sovio, U., Hartikainen, A.-L., Ruokonen, A., Leinonen, M., Laitinen, J., Järvelin, M.-R., & Pouta, A.
- Affiliations
- Oulu University Hospital (FI)
- Oxford Centre for Diabetes, Endocrinology and Metabolism (GB)
- Imperial College London (GB)
- Finnish Institute of Occupational Health (FI)
- ORCID
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 199
- Issue
- 5
- Pages
- 529.e1-529.e10
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W2094977869
- Cited by
- 78
- References
- 48
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 7 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 8.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- oral contraceptives, levonorgestrel-releasing intrauterine system, hormonal contraception, insulin resistance, C-reactive protein, inflammation, blood pressure, lipid profile, cardiovascular risk, type 2 diabetes risk, metabolic risk factors, women's health
- MeSH terms
- Adult, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, Contraceptive Agents, Female, Contraceptives, Oral, Diabetes Mellitus, Type 2, Female, Homeostasis, Humans, Inflammation, Insulin, Insulin Resistance, Intrauterine Devices, Medicated, Leukocyte Count, Lipids, Lipoproteins, HDL, Metabolic Diseases, Progestins, Levonorgestrel, Waist-Hip Ratio
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