Post-menopausal women with lower levels of the female sex hormone estrogen appear to be at higher risk of developing serious complications of COVID-19, a study has found.

Research published recently in medRxiv, led by King’s College London, has found that high levels of estrogen may have a protective effect against the novel coronavirus. 

Using the COVID Symptom Study App, researchers examined the rate of predicted COVID-19 among post-menopausal women, premenopausal women using the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT), from more than 500,000 women in the UK, between 7 May and 15 June 2020.

The sex hormone estrogen, which declines in women post-menopause, interacts with the immune system in various ways, including influencing how many immune cells are produced and how they respond to infection.

Researchers hypothesised that estrogen could serve as a protectant against COVID-19. Previous studies on SARS-CoV and MERS suggest this might explain why men of all ages are at a higher risk of severe infection, including COVID-19.

The pre-print study found post-menopausal women had a higher rate of predicted COVID-19 than other studied women. Women in the 45-50 age group were most likely to be at risk, and reported symptoms of anosmia, fever and a persistent cough, and the need for oxygen treatment in hospital were significant in this group. 

Women using the COCP, between 18-45 years, had a lower rate of predicted COVID-19 and corresponding reduced frequency of symptoms, including persistent cough, delirium, anosmia, skipped meals, severe fatigue and pain. The rate of hospitalisation was also significantly lower.

HRT use, in post-menopausal women between 50-65 years, was associated with an increased rate of predicted COVID-19 but not with hospitalisation. The researchers advised HRT results should be considered with caution due to the lack of information about HRT type, route of administration and duration of treatment. 

Joint lead author Dr Karla Lee, from King’s College London, said:

“We hypothesised that pre-menopausal women with higher estrogen levels would have less severe COVID-19 when compared to women of the same age and BMI who had been through the menopause, and our findings supported this. Additionally, when we compared a younger group of women on the combined oral contraceptive pill (COCP) with a similar group not taking the COCP we saw less severe COVID amongst those taking the COCP, suggesting hormones in the COCP may offer some protection against COVID-19. More research is certainly needed to further our knowledge.”