Hormone replacement therapy linked to lower COVID-19 mortality risk

Receiving hormone replacement therapy within 6 months of a COVID-19 diagnosis was associated with a reduction in mortality, according to researchers.

The findings mark a step forward in understanding the sex-based disparity in COVID-19 mortality rates, researchers said.

Based on the findings, Hajira Dambha-Miller, MRCGP, PhD, FHEA, a general practitioner and a National Institute for Health and Care Research Clinical Lecturer in Primary Care at the University of Southampton, and colleagues reported in Family Practice that there is no reason to discontinue hormone replacement therapy (HRT) due to COVID-19.

“This study supports the theory that estrogen may offer some protection against severe COVID-19,” Christopher R. Wilcox, BSc (Hons), MBBCh, DCH, of the Primary Care Research Centre at the University of Southampton and one of the paper’s authors, said in a press release about the study. “We hope that this study can provide reassurance to patients and clinicians that there is no indication to stop hormone replacement therapy because of the pandemic.”

The researchers noted that, while men and women are equally susceptible to COVID-19, recent data show that mortality in men is 1.7 times higher than the average woman. This is similar to previous pandemics, like the SARS-CoV and MERS-CoV outbreaks, but the reason for the discrepancies is unclear.

Previous research has also shown a link between estrogen therapy and lowered COVID-19 mortality risks, with researchers suggesting that, even after adjusting for confounding risk factors, women appear to be more protected from COVID-19 compared with men.

The current study was prompted by recent, limited observational data that have suggested there may be a “protective effect of estrogen on the severity of COVID-19 disease,” and the researchers aimed to investigate the association between HRT or combined oral contraceptive pill use and the likelihood of death in women with COVID-19.

Dambha-Miller, Wilcox and colleagues evaluated outcomes among a cohort of 1,863,478 women over 18 years of age from 465 general practices in England. They used mixed-effects logistic regression models to quantify the association.

There were 5,451 cases of COVID-19 within the cohort. The mean age was 59 years, and the self-identified ethnicity was predominantly white (64.8%). Of the 5,451 cases, there were 235 women with HRT prescriptions — about 4.3%.

HRT use was associated with a lower likelihood of all-cause mortality in patients diagnosed with COVID-19 within unadjusted models (OR = 0.15; 95% CI, 0.06-0.37) and models adjusted for age, sex, ethnicity, socioeconomic status, household size, BMI, comorbidities and smoking status (OR = 0.22; 95% CI, 0.05-0.94). The researchers also observed that all-cause mortality risk was higher among women with COVID-19 who were older, underweight, from larger households, had hypertension or were on immunosuppressants.

Although the researchers also aimed to analyze the effects of oral contraceptive pill use, there were no reported events for the outcome of interest (all-cause mortality) in that group, and “further work is needed in larger cohorts” to investigate the hypothesis further, they wrote.

References:

• Dambha-Miller H, et al. Family Practice. 2022;doi.org/10.1093/fampra/cmac041.
• Estrogen treatment associated with reduced COVID deaths. https://www.eurekalert.org/news-releases/952438. Published May 17, 2022. Accessed June 2, 2022.