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Comparison is key: the risk of thromboembolism following the AstraZeneca vaccine needs quantifying against combined hormonal contraception. traZeneca vaccine

Dear Editor

Thank you for this commentary on the implications of the Pottegård et al. study, reporting an increased risk of venous thromboembolic events including cerebral venous thrombosis following administration of the Oxford-AstraZeneca COVID-19 vaccine [1]. While I agree that a vital next step is to ‘quantify the comparative risk associated with other vaccines” to contextualise these findings, I do not believe this will go far enough to alleviate public concern. Indeed, when presented to the public, I advise that comparisons should be extended to other medical interventions, particularly the risk of blood clots associated with the combined oral contraceptive pill.

The announcement from the Joint Committee on Vaccination and Immunisation (JCVI) that the AstraZeneca vaccine should not be offered to adults under the age of 40 where an alternative is available [2] has revived the spread of misinformation and public mistrust in the COVID-19 vaccines. Rather than bolstering public confidence that appropriate interventions are being taken to safeguard individuals, this scaremongering exacerbates the significance of a marginal elevation in clotting cases. Furthermore, it highlights the void in communication between the research community and the general population awaiting vaccination, and should instigate a re-emphasis on the hypercoagulability of COVID-19 infection itself. As the author addresses, the reported incidence of cerebral venous thrombosis from COVID-19 is almost double the incidence post-vaccination [3].

If both infection and vaccination increase clotting risk, it begs the question, what level of risk is deemed acceptable, which is where wider comparisons are key.

An estimated 2 million women in the UK take the combined oral contraceptive pill (COCP) to avoid unwanted or unplanned pregnancy and it remains the most popular form of contraception [4]. COCPs contain the hormones progesterone and oestrogen in varying preparations, and are known to interfere with clotting factors and platelet aggregation to increase coagulability. The risk of VTE is highest in the first twelve months after introduction of the pill and is quoted at around 7-12 adverse events per 10,000 women [5], a rate that is almost 100 times greater than the rate of clotting cases reported by the MHRA from the AstraZeneca vaccine [6].

While the media have made it nearly impossible to ignore the debate around the AstraZeneca vaccine, are we to believe that all of these women are as acutely aware of the risk associated with a medicine they were prescribed by a physician and rely on daily?

In actuality, UK Medical Eligibility Criteria (UKMEC) framework demonstrates our pre-existing understanding of what constitutes an unacceptable risk, as this form of contraception is contraindicated in smokers over the age of 35, but not in those under 35, where “the advantages generally outweigh the disadvantages” [7], because we appreciate the compounding effect of these two variables.

Pottegård and colleagues even comment on female sex and use of systemic hormonal contraceptives as confounders capable of artificially increasing vaccine-related clotting risk; yet the media fail to report such nuances nor acknowledge the plausible risk of clotting these same individuals may have been at had they instead contracted COVID-19. In comparison to both infection and contraception, any genuine risk posed by the AstraZeneca vaccine is negligible.

While European and UK regulators continue to advocate against the AstraZeneca vaccine, public confidence is sure to dwindle not just towards AstraZeneca but in the vaccination programme at large. Furthermore, by promoting vaccine abstinence due to a perceived level of danger, what message does this send to women on the COCP about their health and safety?

Relatable comparisons are needed urgently in the public domain to 1) empower individuals to interpret the degree of risk posed by COVID-19 infection and vaccination and 2) facilitate frank discussion around women’s health priorities. This should not be misconstrued as acceptance or justification of the risk posed by AstraZeneca vaccine, but rather prompt outcry around the dearth of public education on hormonal contraception and the minimising of women’s health concerns and risks. Both of these require urgent attention as we exit this pandemic.

[1] Pottegård A, Lund LC, Karlstad Ø, et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ2021;373:n1114

[2] BBC News: Health. James Gallagher. Under 40s to be offered alternative to AZ vaccine. Available at: [Accessed 08/05/2021]

[3] Taquet M, Husain M, Geddes JR, Luciano S, Harrison PJ. Cerebral venous thrombosis: a retrospective cohort study of 513 284 confirmed COVID-19 cases and a comparison with 489 871 people receiving a COVID-19 mRNA vaccine.

[4] NHS Digital. Sexual and Reproductive Health Services, England (Contraception) 2019/20 national statistics. 2020. Available at [Accessed 08/05/2021]

[5] Sitruk-Ware, R. Hormonal contraception and thrombosis. Fertility and Sterility 2016;106:1289-1294 DOI:

[6] Press release: JCVI advises on COVID-19 vaccine for people aged under 40. 2021. Available at: [Accessed 08/05/21]

[7] Faculty of Sexual and Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists: Standards & Guidance. UK Medical Eligibility Criteria for Contraceptive Use (UKMEC) 2016. Available at: [Accessed 08/05/2021]

Competing interests: No competing interests

08 May 2021
Rebecca Murphy Lonergan
Medical Student
University of Edinburgh
Edinburgh Medical School, Little France, Edinburgh