30 October 2023

New research shows how women with a certain genetic predisposition may be at raised risk of venous thromboembolism (VTE) because of oral contraceptives, Swedish researchers have reported.

Researchers at Uppsala University investigated how genetics impact the VTE risk from oral contraceptive use over time.

They write in the American Journal of Obstetrics and Gynecology that: “More than 150 million women worldwide use oral contraceptives.

“Women with inherited thrombophilia and carriers of certain thrombophilia gene variants, such as factor V Leiden and the prothrombin, are at an increased risk for venous thromboembolism.”

The team aimed to use ‘polygenic risk scores’ to quantify the disease risk caused by a range of other genetic variations which are also known to increase VTE risk. They analysed data from 244,420 women enrolled in the UK Biobank study.

When not considering genetics, the overall risk of venous thromboembolism tripled in the first two years of oral contraceptive use. However, over time this risk returned to the rate for women not on the pill.

But when genetic risk was considered, women in the highest polygenic risk group had a six times higher risk in the first two years of oral contraceptive use, compared to those with the lowest genetic risk score. Women with a high genetic liability also had an increased VTE risk during continued use (over two-fold increased risk) but it was less pronounced.

The authors state: “Evaluating polygenic risk can identify additional venous thromboembolism risk that is not captured in the commonly investigated genes for inherited thrombophilia.

“Our results suggest that the polygenic risk score could be used to identify women who are at high risk for developing a venous thromboembolism and advise them on alternative methods of contraception.”

First author, Dr Valeria Lo Faro, added: “This is important knowledge for women’s health and may be important in contraception counselling.”


Lo Faro V, Johansson T, Johansson Å. (2023) “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.” American Journal of Obstetrics and Gynecology, doi: 10.1016/j.ajog.2023.09.012

Link: https://www.ajog.org/article/S0002-9378(23)00618-X/fulltext

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