Abstract
The relationship between hormonal contraception and cardiovascular events, particularly ischemic stroke and myocardial infarction (MI), has been a subject of extensive research and debate. A recent nationwide prospective cohort study conducted in Denmark provides valuable insights into this association. This article delves into the study's methodology, findings, and implications, offering a comprehensive analysis of the risks associated with contemporary hormonal contraceptive methods.
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Introduction
Hormonal contraception is a cornerstone of reproductive health, offering women control over fertility and contributing to various health benefits. However, concerns have been raised regarding the potential cardiovascular risks associated with these contraceptives, especially in relation to ischemic stroke and myocardial infarction. Understanding these risks is crucial for informed decision-making by both healthcare providers and patients.
Background
The introduction of combined oral contraceptives (COCs) in the 1960s revolutionized family planning. Over time, formulations have evolved to include lower doses of estrogen and various types of progestins to minimize adverse effects. Despite these advancements, studies have indicated a potential increase in the risk of arterial thrombotic events among users. A meta-analysis by Roach et al. (2015) reported a 1.6-fold increase in the risk of myocardial infarction or ischemic stroke among COC users, with higher risks associated with pills containing more than 50 micrograms of estrogen.
Study Overview
A comprehensive nationwide prospective cohort study was conducted in Denmark to assess the association between contemporary hormonal contraception and the risk of ischemic stroke and myocardial infarction. The study encompassed all Danish women aged 15-49 years without a history of arterial or venous thrombosis, thrombophilia, or cancer, spanning from 1996 to 2021. Data on hormonal contraception use, diagnoses of stroke and myocardial infarction, and potential confounders were meticulously collected from nationwide registers.
Methodology
Cohort Selection
The study identified 2,205,794 women who met the inclusion criteria. Women with prior diagnoses of arterial or venous thrombosis, thrombophilia, or cancer were excluded to eliminate confounding factors that could independently increase the risk of cardiovascular events.
Data Collection
Data were sourced from multiple nationwide registers:
National Prescription Register: Provided detailed information on prescriptions for hormonal contraceptives, including type, dosage, and duration.
National Patient Register: Offered data on hospital admissions and diagnoses, enabling identification of incident cases of ischemic stroke and myocardial infarction.
Civil Registration System: Supplied demographic information and vital status, ensuring accurate follow-up.
Exposure Assessment
Hormonal contraceptive use was categorized based on formulation:
Combined Oral Contraceptives (COCs): Containing both estrogen (ethinyl estradiol) and various progestins.
Progestin-Only Pills (POPs): Containing only progestin.
Non-Oral Methods: Including vaginal rings, transdermal patches, and intrauterine devices (IUDs).
The estrogen component in COCs was further stratified by dosage:
Low Dose: 20 μg of ethinyl estradiol.
Moderate Dose: 30-40 μg of ethinyl estradiol.
Outcome Assessment
The primary outcomes were first-time diagnoses of ischemic stroke and myocardial infarction during the study period. These were identified using International Classification of Diseases (ICD) codes from the National Patient Register.
Statistical Analysis
Incidence rates of ischemic stroke and myocardial infarction were calculated per 100,000 person-years. Poisson regression models were employed to estimate adjusted incidence rate ratios (IRRs), controlling for potential confounders such as age, education level, calendar year, hypertension, statin use, diabetes, and atrial fibrillation.
Findings
Demographics
The cohort was followed over 23,700,659 person-years. The median age was 33 years (interquartile range: 24-41) for non-users and 25 years (IQR: 20-34) for users of hormonal contraception.
Incidence Rates
The study reported the following incidence rates among non-users:
Ischemic Stroke: 24.2 per 100,000 person-years.
Myocardial Infarction: 13.2 per 100,000 person-years.
Risk Associated with COCs
When compared to non-use, COCs containing 30-40 μg of ethinyl estradiol were associated with increased risks of ischemic stroke and myocardial infarction, varying by progestin type:
Levonorgestrel: IRR of 1.9 for ischemic stroke and 2.0 for myocardial infarction.
Norgestimate: IRR of 1.9 for ischemic stroke and 1.9 for myocardial infarction.
Desogestrel: IRR of 2.4 for ischemic stroke and 2.2 for myocardial infarction.
Gestodene: IRR of 1.9 for ischemic stroke and 1.9 for myocardial infarction.
Drospirenone: IRR of 2.0 for ischemic stroke and 1.8 for myocardial infarction.
Cyproterone Acetate: IRR of 1.7 for ischem
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