Causality between COVID-19 and female reproductive function: A Mendelian randomization study

Abstract

Coronavirus disease 2019 (COVID‐19) has experienced a global pandemic, and currently, the emergence of its variants has posed challenges in terms of prevention and treatment. Nonetheless, the effect of COVID‐19 infection on female reproductive function is unclear. This study aimed to systematically evaluate for the first time the causal effect of COVID‐19 on female reproductive function. Genetic correlations were assessed using linkage disequilibrium score regression. Mendelian randomization (MR) analysis was performed using summary statistics of two variables, including COVID‐19 severity and eight female reproductive traits. The three degrees of severity had genetically significant associations with sex hormone‐binding globulin (SHBG) concentrations (rg = –0.153, p = 0.004; rg = –0.187, p < 0.001; rg = –0.180, p = 0.003). Additionally, MR showed that SHBG (β = –0.020, p = 0.040) and total testosterone levels (β = –0.061, p = 0.009) followed a decreasing trend, as the COVID‐19 infection higher. No significant genetic association was found between COVID‐19 infection and total estradiol concentrations, menstruation, and female infertility. Simultaneously, MR found no causal relationships between COVID‐19 infection and total estradiol concentrations, menstruation, and female infertility (all p > 0.05). In conclusion, COVID‐19 was causally associated with lower SHBG and total testosterone concentrations, offering invaluable insights that will help guide clinical decision‐making.