Association Between Life’s Crucial 9 and Testosterone Deficiency in U.S. Men: The Mediating Role of Central Obesity

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Abstract

Objective Testosterone deficiency (TD) is a prevalent and clinically significant condition with implications for both reproductive and cardiometabolic health. Life’s Crucial 9 (LC9) serves as an integrative indicator for evaluating overall cardiovascular health status, and the weight-adjusted waist index (WWI) is an emerging anthropometric measure that reflects central obesity. This study aimed to investigate the association between LC9 and TD, and to assess whether WWI mediates this relationship. Methods We analyzed data from 5,276 male participants aged 20–79 years from the NHANES 2013–2018 cycles. LC9 scores were calculated based on nine health domains, while WWI was derived from waist circumference and weight. Testosterone deficiency (TD) was defined as a total testosterone level below 300 ng/dL. The associations among LC9, WWI, and TD were assessed using weighted logistic regression models. Restricted cubic spline (RCS) models were applied to assess the dose–response associations. Additionally, subgroup and mediation analyses were performed to assess effect modification and to investigate whether WWI acted as a mediator. Results A 10-point rise in LC9 corresponded to a 27% lower likelihood of testosterone deficiency (OR = 0.73, 95% CI: 0.67–0.79), in contrast, every one-unit increase in WWI was associated with a 121% elevation in the likelihood of developing testosterone deficiency (OR = 2.21, 95% CI: 1.87–2.62). The observed associations remained stable across all examined subgroups and followed an approximately linear dose–response pattern. Mediation analysis revealed that WWI accounted for 52.54% of the total effect of LC9 on TD. Conclusion LC9 was inversely associated with testosterone deficiency, with central obesity (WWI) partially mediating this relationship. These findings underscore the importance of integrated strategies targeting cardiovascular health and central adiposity in efforts to prevent or mitigate testosterone deficiency.

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