Age-Dependent Effects of Homocysteine on Erectile Dysfunction Risk Among U.S. Males: A NHANES Analysis

Abstract

Erectile dysfunction (ED) is a common problem that seriously impacts men's quality of life and mental health. Earlier studies have indicated that homocysteine (HCY) levels might be linked to the risk of ED, although these studies are limited by small sample sizes and insufficient correction for confounding factors. This study uses data from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) to evaluate the relationship between HCY levels and ED risk in U.S. adult males. The analysis involved using a weighted generalized linear model to assess main effects and restricted cubic splines (RCS) to explore nonlinear relationships. Results showed that the association between HCY and ED was not statistically significant after adjusting for covariates. However, interaction analyses between age and the HCY-ED relationship showed that as age increases, the impact of HCY on ED strengthens. Based on this, subgroup analysis by age was carried out, revealing that in people aged 50 and above, HCY levels were significantly positively correlated with ED, especially when HCY levels exceeded 9.22 μmol/L, significantly increasing the risk of ED. Sensitivity analysis further confirmed the robustness of these findings. This study indicates that controlling HCY levels, especially in middle-aged and older men, might help prevent and treat ED, providing a foundation for future preventive strategies.

Keywords: National Health and Nutrition Examination Survey; cross-sectional study; erectile dysfunction; homocysteine.

Figure 1.

Flowchart of the Participant Selection

Figure 2.

Analysis of Homocysteine Levels and Erectile Dysfunction Risk Note.Figure 2A: ROC Curve showing strong predictive accuracy with an AUC of 0.854. Figure 2B: Residual Plot indicating potential nonlinearity between HCY levels and ED risk. Figure 2C: RCS Analysis revealing nonlinear relationship between HCY levels and ED risk.

Figure 3.

RCS Analysis of HCY and ED Risk by Age Note.Figure 3A Nonlinear relationship in participants aged 50+. Figure 3B No significant relationship was observed among participants below 50 years of age.

Figure 4.

RCS Analyses Across Different Phases and Subgroups Note.Figure 4A RCS for overall analysis in the first phase. Figure 4B RCS for participants aged 50 and older during the first phase. Figure 4C RCS for participants below 50 years of age during the first phase. Figure 4D RCS for the critical subset aged 50 and above in the second phase.