Let’s Talk about COVID’s VTE Risk for Women on the Pill

Women have appeared protected from COVID-19 in some way compared with men, but how the thrombotic risk shakes out for those on contraceptives, hormone therapy, and in pregnancy remains an important question.

Combined oral contraceptives carry a two- to six-fold increased risk for venous thromboembolic events (VTEs), with similar risks seen with oral hormone replacement therapy for menopause and other indications. Pregnancy increases the risk four- to five-fold.

Together those cover a large population of women potentially at risk, so it’s a pressing question as to whether COVID-19 exacerbates the VTE and stroke risk associated with those factors, noted Daniel Spratt, MD, of the Maine Medical Center in Portland, and Rachel Buchsbaum, MD, of Tufts University in Boston, in a commentary in Endocrinology.

Women have consistently racked up fewer of the COVID-19 hospitalizations and deaths than men, but why still isn’t clear.

Female sex hormones may actually be protective overall, as estrogen improves the immune response to infection and there have also been signals that menstruation has beneficial effects on COVID-19. At least some research is looking at giving estrogen specifically to address the virus, but people with a history of thromboembolic events have been excluded.

The University of California San Francisco’s PRIORITY registry for COVID-19 in pregnancy (looking at symptoms, duration, and impact on the pregnancy and delivery) should help answer some questions, Spratt and Buchsbaum noted.

However, overall research into the hypercoagulability of COVID-19 remains largely observational, they pointed out. Large randomized trials into antithrombotic efficacy and optimal agents and dosing are underway but are at least months away from providing even those general answers.

“Establishing models for basic research into mechanisms of hypercoagulability in COVID-19, let alone intersecting effects of COVID-19 and estrogen therapy or pregnancy, has several hurdles and will require innovative novel animal and tissue models,” Spratt and Buchsbaum noted.

For example, they said, coagulation physiology differs between humans and animals. Also, pregnancy and probably estrogen therapy-related hypercoagulability does not naturally occur in other animals.

“We do not know how long the current pandemic will endure and can be reasonably certain that, like the H1N1 virus causing the 1918-1919 influenza pandemic, SARS-CoV-2 will return cyclically for years if not decades,” Spratt and Buchsbaum wrote. “Thus, the importance of undertaking research to answer these questions will continue with findings likely to be applicable in a wide range of clinical situations.”