Incidence and outcomes associated with menopausal status in COVID-۱۹ patients: A systematic review and meta-analysis

Introduction: Menopausal status and estrogen levels can reportedly influence COVID-۱۹ infection and its outcomes via different mechanisms. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-۱۹ patients. Materials and methods: Combinations of keywords "COVID-۱۹", "menopause", and "estrogen" were used to search PubMed, Embase, Web of Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-۱۹ (discharge, length of admission, intensive care, or mortality) in pre-menopausal and premenopausal women, available through December ۲۹, ۲۰۲۲. Data from studies comparing the incidence of COVID-۱۹ infection with the age-matched male population were pooled and meta-analyzed using a random-effects model.Results: Overall, ۱۵۶۴ studies were retrieved, of which ۱۲ were finally included in the systematic review to compare disease outcomes, and six were meta-analyzed for the incidence of COVID-۱۹ in premenopausal and postmenopausal women. All studies reported better COVID-۱۹ associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-۱۹ outcomes. Our meta-analysis found higher incidence of COVID-۱۹ infection among pre- menopausal women than post- menopausal women, when compared with age-matched men (odds ratio=۱.۲۷۰; ۹۵% confidence interval [۱.۰۸۶, ۱.۴۸۶]; P=۰.۰۰۳). Conclusions: The incidence of COVID-۱۹ was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-۱۹ associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-۱۹ in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.