COVID-19 infection may reduce serum testosterone levels and increase the risk of erectile dysfunction: A two-sample Mendelian randomization study

Investig Clin Urol. 2025 Mar;66(2):152-160. doi: 10.4111/icu.20240384.

Abstract

Purpose: Coronavirus disease 2019 (COVID-19) infection may affect serum hormones levels and male sexual function. This study aims to provide evidence for the causal relationship between COVID-19 infection, serum testosterone levels and the risk of erectile dysfunction (ED) using a two-sample Mendelian randomization (MR) approach.

Materials and methods: Summary-level data for serum testosterone levels (199,569 samples and 12,321,875 single nucleotide polymorphisms [SNPs]) were obtained from Rebecca's study, while data for ED (6,175 cases and 217,630 controls) were sourced from Bovijn's study. Genetic variations linked to COVID-19 were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 6,406 cases and 902,088 controls from the COVID-19 Host Genetics Initiative. The inverse-variance weighted (IVW) method was primarily employed to evaluate the potential associations between COVID-19 infection, serum testosterone levels, and the risk of ED. The weighted mode, weighted-median and simple-median method were employed to evaluate the sensitivity. Heterogeneity and pleiotropic outlier were assessed using Cochran's Q test and MR-Egger regression.

Results: The MR analysis demonstrated that COVID-19 infection was associated with reduced serum testosterone levels (odds ratio [OR] 0.966, 95% confidence interval [CI] 0.938-0.993, p=0.016) and an increased risk of ED (OR 1.205, 95% CI 1.063-1.367, p=0.004) when using IVW methods. Sensitivity analyses utilizing various IV sets and MR approach remained consistent.

Conclusions: COVID-19 infection is associated with a decrease in serum testosterone levels and an increased risk of ED. Male patients recovering from COVID-19 need to pay special attention to their sex hormone levels and sexual health.

Keywords: COVID-19; Erectile dysfunction; Mendelian randomization analysis; SARS-CoV-2; Testosterone.

MeSH terms

  • COVID-19* / blood
  • COVID-19* / complications
  • COVID-19* / epidemiology
  • COVID-19* / genetics
  • Erectile Dysfunction* / blood
  • Erectile Dysfunction* / epidemiology
  • Erectile Dysfunction* / etiology
  • Erectile Dysfunction* / genetics
  • Genome-Wide Association Study
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • SARS-CoV-2
  • Testosterone* / blood

Substances

  • Testosterone