Researchers explore mortality among women in hormone replacement therapy early in COVID-19 pandemic
Researchers explore mortality among women in hormone replacement therapy early in COVID-19 pandemic

Researchers explore mortality among women in hormone replacement therapy early in COVID-19 pandemic

A recent study published in Family practice assessed the association between hormone replacement therapy (HRT) or the use of the combined oral contraceptive pill (COCP) with mortality among women with a previous history of coronavirus disease 2019 (COVID-19).

Examination: Mortality in COVID-19 among women in hormone replacement therapy: a retrospective cohort study. Image credit: F8 studio / Shutterstock


The causative pathogen of COVID-19, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to spread. Women and men are equally vulnerable, although men show a higher rate of serious outcomes such as hospitalization and death. According to a study, COVID-19-related mortality among men was 1.7 times higher than in women.

Similarly, higher mortality was recorded in previous outbreaks caused by SARS-CoV and Middle East Respiratory Syndrome (MERS) -CoV. Although the cause of observed gender differences remains unknown, various theories have been established, including gender-based immunological variations, smoking patterns, and comorbidities. The role of estrogen is discussed and has received much attention. For example, younger women or those with high estrogen levels have lower odds of developing severe COVID-19 outcomes.

Additionally, estrogen has been reported to modulate immune responses by decreasing T-cell fatigue and suppression of the production of interleukin (IL) -6 and IL-1β, which limits cytokine storm. This may explain the lower frequency of COVID-19-related hospitalizations and intensive hospitalizations among women compared to men. Recent evidence suggests that COCP users have a lower risk of COVID-19 and associated hospitalization; nevertheless, data on HRT have not been consistent.

The study and the results

In the current retrospective study, researchers examined the associations between HRT / COCP use and the odds of COVID-19-related mortality among women in the early stages of the pandemic. They used computerized medical records from the Oxford Royal College of General Practitioners, Research and Surveillance Centers database. This database included 465 general practices in England, comprising 1.8 million women. Women with a confirmed or probable diagnosis of COVID-19 were identified.

A confirmed case was defined as having a positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result, and probable or suspected cases were those diagnosed clinically or radiologically according to the recommendations of Public Health England. The authors defined exposure as one or more prescriptions of COCP or HRT within six months of probable or confirmed diagnosis. The main result was mortality from all causes between 1 January 2020 and 21 June 2020.

Univariate logistic regression models quantified the association between HRT / COCP and mortality from all causes. Subsequently, a multivariable model was adjusted for covariates run, and a mixed-effects model was performed that took into account practice clustering. The statistical tests were two-tailed and set at a 5% significance level.

The authors identified 5451 women with COVID-19 with a mean age of 59 years. The mean follow-up time was 164.9 days; more than 64% of the subjects were white and 80.6% lived in urban areas. There were 171 women with prescriptions for COCP use and 231 with HRT prescriptions. Mortality was 12.2% at follow-up time. The researchers found that HRT had lower odds of mortality from all causes in unadjusted (Odds ratio, OR: 0.15) and adjusted (OR 0.22) models.

Mortality from all causes was higher in those who were older, underweight, with immunosuppressants or hypertension, and from larger households. Those who had asthma had a significantly lower risk of mortality. The team could not estimate the association between COCP use and mortality for all reasons as no fatalities were reported among the prescribed COCPs.


To summarize, the results revealed that HRT use was associated with lower odds of mortality in women followed up for six months after COVID-19. Some of the strengths of the study were the population-based cohort across 465 general practices in England that ensured heterogeneity in clinical and sociodemographic variables. In particular, the authors did not analyze the type of dose or preparation for HRT due to the lack of data in the database.

In addition, the duration of drug use was not investigated and the follow-up period was less than six months. Inclusion of age as only a categorical variable may have limited adjustment. Given that mortality was investigated for all reasons, some deaths may not be associated with SARS-CoV-2 infection.

In conclusion, the authors observed that HRT prescription within six months after the COVID-19 diagnosis was associated with a decrease in mortality from all causes. This meant that women did not have to stop using HRT because of the pandemic. It is important that future work should evaluate variations in the preparation and dose of HRT and investigate the association between COCP use and mortality.

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