Flash of Greater Stroke Risk at Initiation of Oral Contraceptives

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Flash of Greater Stroke Risk at Initiation of Oral Contraceptives

Risk with hormone replacement therapy lingers in the long run, though

by Nicole Lou, Senior Staff Writer, MedPage Today June 24, 2022

The upfront stroke risk associated with oral contraceptives and hormone replacement therapy (HRT) waned to varying degrees after the first year of use, an observational study found.

U.K. Biobank participants on birth control were at higher risk of any stroke during the first year of use (HR 2.49, 95% CI 1.44-4.30), after which strokes were no longer at an excess compared with nonusers (HR 1.00, 95% CI 0.86-1.14), according to researchers led by PhD student Therese Johansson, MSc, of Uppsala University in Sweden.

As for HRT, the first year of therapy was tied to an increased risk of stroke (HR 2.12, 95% CI 1.66-2.70) that declined in remaining years. The risk nevertheless remained modestly elevated over time (HR 1.18, 95% CI 1.05-1.32), even after HRT discontinuation (HR 1.16, 95% CI 1.02-1.32), Johansson's group reported in the journal Stroke.

The study supports prior work linking exogenous hormone use and stroke. Unlike other groups, however, Johansson and colleagues were able to show that HRT was associated with both ischemic and subarachnoid hemorrhage stroke subtypes.

"The increased rate of ischemic stroke during the first year of use could be a result of an immediate prothrombotic effect of the treatment that gradually declines due to adaptation of the hemostatic imbalance during remaining years of use," the authors suggested.

"However, the underlying mechanism through which HRT confers an immediate increased risk of subarachnoid hemorrhage is less clear," they said. "The short-term increased risk could be explained by cerebral vasodilation together with a transient elevation in systemic blood pressure following HRT initiation, causing rupture of preexisting aneurysm."

HRT is commonly used to treat menopause symptoms in clinical practice and has been suggested to improve cardiovascular health in some individuals.

Johansson and colleagues reported that the stroke risk associated with HRT didn't change in relation to menopause onset. This is consistent, they said, with the thinking that entering menopause increases the risk of stroke among nonusers, but women who have been on HRT are not at increased risk when they enter menopause.

Johansson and colleagues noted that the small number of strokes recorded among the relatively young group of oral contraceptive users precluded an analysis by stroke subtype in this group.

The study included more than 250,000 women ages 37-73 years from the U.K. Biobank. First occurrence of stroke was tracked in the database, which categorized events as ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage.

Use of oral contraceptives (81%) and HRT (37%) was self-reported by participants, which left room for recall bias in the study, Johansson's group acknowledged.

Additionally, this was a relatively healthy population, limiting the generalizability of the results, and the authors could not differentiate between the various formulations of HRT and oral contraceptives used.

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  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded by the Swedish Brain Foundation. The work was also funded by the Swedish Heart Lung Foundation, the Swedish Research Council, and the Uppsala University center for women's mental health.

Johansson had no disclosures.

Primary Source

Stroke

Source Reference: Johansson T, et al "Oral contraceptives, hormone replacement therapy, and stroke risk" Stroke 2022; DOI: 10.1161/STROKEAHA.121.038659.