Current use of oral contraceptives and the risk of first-ever ischemic stroke: A meta-analysis of observational studies

FSRH Guideline (January 2019, amended October 2023) Combined Hormonal Contraception

“…This is consistent with the findings of three previous meta-analyses which reported OR for ischaemic stroke in current COC users of 1.8 (95% CI 1.2–2.8),259 2.12 (95% CI 1.56–2.86)257 and 1.90 (95% CI 1.24–2.91)210 compared to non-users. A 2015 meta-analysis260 found a higher OR (OR 2.47; 95% CI 2.04–2.99) for first-time ischaemic stroke with current COC use compared with non-current use, however the risk declined significantly with decreasing estrogen dose.…”

“…A Cochrane Review256 and a meta-analysis260 concluded that risk of ATE seemed to increase with higher doses of estrogen in COC.…”

Diagnosing migraine

“…3 9 Correct diagnosis of the type of migraine is important since migraine with aura (but not migraine without aura) is associated with a two-fold increased risk of ischaemic stroke 10 11. Use of combined oral contraceptives (COCs) is an independent risk factor for ischaemic stroke: odds ratio (OR) 1.56 [95% confidence interval (CI) 1.61–1.89] for COCs containing 20 μg ethinylestradiol and OR 1.75 (95% CI 1.36–1.79) for 30 μg COCs 12. Hence in the UK, USA and WHO Medical Eligibility Criteria, COCs are contraindicated in women with migraine aura 13–15.…”

“…Hence in the UK, USA and WHO Medical Eligibility Criteria, COCs are contraindicated in women with migraine aura 13–15. Progestogen-only methods do not increase risk of ischaemic stroke,12 and may benefit migraine with aura 16. Aura does not restrict use of physiological doses of estradiol in HRT, specifically transdermal estradiol, which is not associated with increased risk of ischaemic stroke 17…”

The clinical relevance of altered fibrinogen packaging in the presence of 17β-estradiol and progesterone

“…It is essential to understand natural hormone mechanisms since these hormones are still present in circulation while hormonal contraceptives, which have been shown to indeed negatively affect fibrin clot features and lysability [17][18][19][20], are used. Although natural female hormones like 17β-estradiol and 5 progesterone decrease with the use of hormone therapies, specifically combined oral contraceptives, it is still essential to understand the natural hormone mechanisms at physiological concentrations since this could give more insight into possible interaction of any remaining natural hormones with synthetic hormones introduced with combined oral contraceptives.…”