Women who used levonorgestrel-releasing intrauterine devices (LG-IUDs) were 22% less likely to have a stroke than those who did not use hormonal contraception, new research suggested.
The Danish study, which included 1.7 million women, also showed no increased risk for intracerebral hemorrhage for those using the IUDs.
“The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent (ischemic stroke),” wrote corresponding author Tom Skyhøj Olsen, MD, PhD, of Bispebjerg University Hospital, Copenhagen, Denmark, and coauthors.
The research was published online on May 16, 2024, in the journal Stroke.
A Big-Picture Look
Commonly used combined hormonal contraceptives that contain both progestins and ethinylestradiol are linked to an increased risk for ischemic stroke. Previous research suggested that progestin-only options, including LG-IUDs, are not associated with elevated risk and may even lower the risk. The IUDs had also been previously associated with lower risk for thromboembolism.
The new study was a large-scale investigation of all reproductive-age women in Denmark that compared stroke risk in those who used the progestin-only IUDs with those who didn’t use hormonal contraception. It also examined the risk for intracerebral hemorrhage, which had not been previously studied.
The historic cohort study drew on several large national databases in Denmark, including the Danish Stroke Registry, to evaluate the interplay between IUD contraception, stroke, and intracerebral hemorrhage. The study looked back at data collected on all nonpregnant Danish women aged 18-49 years who lived in Denmark for some or all of the period between 2004 and 2021.
Mean age of the 1.7 million women in the study was 30 years, and the mean follow-up period was about 7 years. More than 364,700 participants used LG-IUDs.
During the study period, 2916 women had an ischemic stroke, and 367 experienced intracerebral hemorrhage.
Among IUD users, the incidence of stroke was 19.2 per 100,000 person years. For women who didn’t use contraception, the rate was 25.2.
Overall, those who used an IUD had a 22% lower risk for ischemic stroke than those who didn’t (incidence rate ratio [IRR], 0.78; 95% CI, 0.70-0.88).
The incidence of brain bleeds was similar in both groups.
Does Age Matter?
The incidence of stroke did not differ significantly between the three age groups analyzed in the study: Women aged 18-29 years, 30-39 years, and 40-49 years. Incidence rates of intracerebral hemorrhage were similar between age groups 30-39 years and 40-49 years, but the risk was higher for those aged 18-29 years than for those aged 40-49 years (IRR, 4.49; 95% CI, 1.65-12.19).
The researchers urged caution in interpreting the apparent higher risk for brain bleeds in younger women, noting that the overall number of events was low, resulting in wide CIs.
Investigators also found that women who moved to Denmark from non-Western countries had a significantly lower stroke rate than native Danes. Incidence rates of intracerebral hemorrhage were not affected by country of origin.
The research team noted that they had only indirect information about women’s stroke risk factors including diabetes, high blood pressure, and migraine and had no information about smoking, alcohol consumption, and body mass index.
“Regarding a possible potential for stroke prevention, our study cannot stand alone and requires confirmation in further research. Even though the incidence rate for [ischemic stroke] and [intracerebral hemorrhage] did not significantly change after adjustment for various factors, bias…cannot be fully ruled out,” the researchers wrote.
The study was funded by the Aase og Ejnar Danielsens Fond and Familien Hede Nielsens Fond. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.