Mortality in COVID-19 among women on hormone replacement therapy: a retrospective cohort study

  1. Hajira Dambha-Miller
  2. William Hinton
  3. Christopher R Wilcox
  4. Mark Joy
  5. Michael Feher
  6. Simon de Lusignan

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Abstract

Background

Limited recent observational data have suggested that there may be a protective effect of oestrogen on the severity of COVID-19 disease. Our aim was to investigate the association between hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP) use and the likelihood of death in women with COVID-19.

Methods

We undertook a retrospective cohort study using routinely collected computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. We identified a cohort of 1,863,478 women over 18 years of age from 465 general practices in England. Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use and all-cause mortality among women diagnosed with confirmed or suspected COVID-19 in unadjusted and adjusted models.

Results

There were 5,451 COVID-19 cases within the cohort. HRT was associated with a reduction in all-cause mortality in COVID-19 (adjusted OR 0.22, 95% CI 0.05 to 0.94). There were no reported events for all-cause mortality in women prescribed COCPs. This prevented further examination of the impact of COCP.

Conclusions

We found that HRT prescription within 6 months of a recorded diagnosis of COVID-19 infection was associated with a reduction in all-cause mortality. Further work is needed in larger cohorts to examine the association of COCP in COVID-19, and to further investigate the hypothesis that oestrogens may contribute a protective effect against COVID-19 severity.

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  1. Version published to 10.1093/fampra/cmac041
  2. ScreenIT

    SciScore for 10.1101/2021.02.16.21251853: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approval: This study received approval from the Oxford-RCGP RSC study approval committee (RSC_0920) and the University of Southampton Research Ethics committee (56309)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableWithin the database, we identified a cohort of women registered on the 1st January 2020 who were aged over 18 years with confirmed or probable COVID-19.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and limitation: A major strength of this study is the use of a population-based cohort from 465 practices across England representing wide coverage with a denominator population of 3.6 million people. This included heterogeneity in sociodemographic and clinical variables. The data used is of high quality and completeness with twice-weekly updates that are also used by Public Health England to monitor the current and previous pandemics.[9] The availability of wide-ranging and precise data means that we were able to adjust for several confounders, although residual confounding is still possible. We considered both laboratory-confirmed and clinically probable cases as a single cohort due to the national inconsistency in testing availability. It is plausible that not all those with clinically probable cases had SARS-CoV-2. Recent work in Oxford RCGP database suggests that outcomes are similar in those with clinically probable and laboratory-confirmed cases.[17] Serology testing, if available nationally in the future could also be helpful. Our cohort is likely to reflect women with more severe COVID-19 symptoms who went for testing or made contact with a general practice for review. If asymptomatic or with milder symptoms, they may not have sought health advice and will not be captured in this cohort. In terms of the exposure, we examined medications based on prescriptions within the last 6 months rather than dispensed medications so there could be some over-ascertainmen...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.02.16.21251853v1 on medRxiv