25 September 2023

The Factor V Leiden gene variation can combine with other factors to place some women at risk of blood clots when using oestrogen-based drugs, according to a new study.

It is already known that multimorbidity – the co-occurrence of two or more chronic conditions – oestrogen use, and the Factor V Leiden variation are independent risk factors for venous thromboembolism (VTE). However, little is known about the risks of these factors combined.

To investigate this, Dr Emma Magavern and colleagues from Queen Mary University of London used figures on 20,048 British-Bangladeshi and British-Pakistani women in the ongoing Genes & Health project.

Overall, 30% of the women were prescribed oestrogens, and 3% were carriers of the Factor V Leiden gene variation. In total, 439 participants (2.2%) had a VTE.

Analysis showed that the risk of VTE was increased for women with obesity, hypertension, dyslipidaemia, or chronic kidney disease, and with oestrogen use, and the Factor V Leiden gene mutation.

The increase in VTE risk went up according to the number of co-morbidities. Having all four conditions studied results in an 8 times greater risk compared to a woman with none of the conditions. Three medical conditions combined results in a 5-fold greater risk, while two conditions meant a 2-fold greater risk.

Findings appear in the journal iScience. The authors write: “Exogenous oestrogens are commonly prescribed to women. Multi-morbidity and the Factor V Leiden gene mutation compound risk of venous thromboembolism with oestrogen use.

“This is important for women in deprived populations with high multi-morbidity burden.”

Dr Magavern said: “Many women will take oestrogen at some point in their lifetime. Overall, this is very safe and there are far more positives to taking it than negatives when it’s prescribed.

“But these women may not be aware of the combined risk of their genetics and overall health and how it affects their risk of developing a blood clot, which could be life-threatening for some individuals.

“It’s important that women have all the information they need to make an informed choice. While our results are important for women everywhere, they are especially relevant for South Asian women with multiple existing health conditions.”


Magavern EF, Genes & Health Research Team, Smedley D, Caulfield MJ (2023) “Factor V Leiden, estrogen, and multimorbidity association with venous thromboembolism in a British-South Asian cohort.” iScience, doi: 10.1016/j.isci.2023.107795

Link: https://www.cell.com/iscience/fulltext/S2589-0042(23)01872-2   

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