Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality: a multiregister nationwide matched cohort study in Sweden.

Publication date: Feb 27, 2024

It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4. 73, 1. 22 to 18. 32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1. 06, 1. 00 to 1. 13) or tibolone (aHR 1. 21, 1. 01 to 1. 45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2. 02,1. 45 to 2. 81) as well as for all secondary outcomes. Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. Not applicable.

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Concepts Keywords
53years COVID-19
Outpatient Estrogens
Progestogens Menopause
Sweden Menopause hormonal treatments
Women SARS-CoV-2


Type Source Name
disease MESH COVID-19
disease MESH morbidity
drug DRUGBANK Tibolone
pathway REACTOME SARS-CoV-2 Infection
disease MESH infection
disease MESH death
disease MESH comorbidity
disease MESH Long Covid
disease MESH syndrome
disease MESH Middle East respiratory syndrome
disease MESH etiology
disease IDO cell
disease MESH cytokine storm
disease VO biological sex
disease VO Hormone
drug DRUGBANK Coenzyme M
drug DRUGBANK Timonacic
disease VO population
disease IDO country
disease MESH marital status
disease MESH educational attainment
disease MESH communicable diseases
disease MESH hepatitis
disease MESH gender dysphoria
disease VO dose
disease VO Gap
drug DRUGBANK Dydrogesterone
disease VO device
disease VO time
disease MESH alcohol abuse
disease MESH obesity
disease MESH complications
drug DRUGBANK Trestolone
disease VO USA
disease MESH deep vein thrombosis
drug DRUGBANK Iron
disease MESH atrophy
disease MESH urinary tract infection
disease MESH candidiasis
drug DRUGBANK Tamoxifen
drug DRUGBANK Isoxaflutole
drug DRUGBANK Estradiol
drug DRUGBANK Piroxicam
disease IDO susceptibility
drug DRUGBANK Esomeprazole
disease MESH contraindications
disease VO organization
disease MESH fibroid
disease MESH endometriosis
disease VO age
drug DRUGBANK Arbutin
disease MESH severe acute respiratory syndrome
disease IDO symptom
disease MESH premature menopause
disease IDO blood

Original Article

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