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Genetics Influence Blood Clot Risk in Women Using Birth Control

A contraceptive pill pack.
Credit: Reproductive Health Supplies Coalition / Unsplash.
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Combined hormonal contraceptives and blood clot risk

An estimated 150 million people worldwide use hormonal contraceptives. Combined hormonal contraceptives, or CHCs, are known to increase the rare risk of blood clots. For individuals who carry genetic mutations associated with hereditary thrombophilia, where there is an acquired tendency for blood clots to form, this risk can be greater still.

A wide number of genes are known to influence the risk of blood clot formation. By analyzing genetic data and combining multiple risk factors, scientists can calculate how high or low such a risk is for an individual, expressed as a polygenic risk score. In the American Journal of Obstetrics and Gynecology, researchers from Uppsala University in Sweden share their work exploring the risk of venous thromboembolism (VTE) formation within the first two years of oral contraceptive use in individuals with high and low genetic risk scores.

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“To study the link between a person’s genetic risk of blood clots and their use of contraceptive pills, we investigated data from 244,420 British women from the UK Biobank,” says Dr. Valeria Lo Faro, postdoctoral researcher at the Department of Immunology, Genetics and Pathology at Uppsala University and the first author of the study.

The UK Biobank recruited over 500,000 individuals aged 37–72 years between 2006 and 2010. In this study, the researchers collected data on White European women. “Our study was designed to follow the women from birth (age, 0 years) until the first of the following events occurred: VTE diagnosis, end-of-study follow-up (ie, age at recruitment), underwent a bilateral oophorectomy or hysterectomy, or menopause started,” the researchers write.

Six times greater risk in women with higher genetic predisposition

Lo Faro and colleagues found that women with higher polygenic risk scores for VTE had a six times greater risk of developing a VTE during their first two years of oral contraceptive use, compared to individuals with the lowest genetic risk.

“This is important knowledge for women’s health and may be important in contraception counseling,” Lo Faro adds. If individuals are made aware of the added risk, they can be advised on the most appropriate and safest contraception available for them.

“Genetic risk profiles for many common diseases can now be determined all at the same time, for example, from blood tests taken at birth. We predict that this type of genetic risk projection will play an important role in counseling and risk predictions in the future,” says Åsa Johansson, associate professor at the Department of Immunology, Genetics and Pathology, and at SciLifeLab at Uppsala University.

The researchers acknowledge that by only calculating risk scores from a White European cohort, their data cannot be generalized against the wider population: “The results of the combined effect of OC and genetic risk factors should be replicated in other larger populations and among people with different ancestries,” they write. What’s more, the use of oral contraceptives was determined using self-report data, which is subject to recall bias. Lo Faro and the team emphasize that additional studies are warranted to explore this risk further.

Reference: Lo Faro V, Johansson T, Johansson Å. The risk of venous thromboembolism in oral contraceptive users: the role of genetic factors—a prospective cohort study of 240,000 women in the UK Biobank. AJOG. 2023. doi: 10.1016/j.ajog.2023.09.012

This article is a rework of a press release issued by Uppsala University. Material has been edited for length and content.