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Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a valuable marker for identifying individuals at increased risk of metabolic dysfunction, liver-related complications, and cardiovascular disease. However, the association between MAFLD and testosterone deficiency (TD) in aging men remains poorly understood. This study aimed to investigate the association between MAFLD and the risk of TD in aging Taiwanese men, with a specific focus on those without metabolic syndrome (MetS)., Methods: A free health screening program was conducted for Taiwanese men aged over 40 years in Kaohsiung, Taiwan. Participants underwent physical examinations, completed questionnaires regarding demographics, medical history, and clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. Fatty liver index was used to evaluate the risk of fatty liver. Diagnostic criteria for MAFLD included fatty liver along with overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation., Results: A total of 631 men (mean age: 54.4 ± 8.4 years) were enrolled. The prevalence rates of TD and MetS were significantly higher in men with MAFLD compared to those without (both p < 0.001). Additionally, the presence of MAFLD showed a significant correlation with adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol-binding protein-4 (RBP-4) levels (all p < 0.001). Among men without MetS, those with MAFLD had a 3.89- and 4.74-fold higher risk of total testosterone < 300 ng/dL and TD, respectively, after adjusting for potential covariates., Conclusion: MAFLD is associated with an elevated risk of TD in aging Taiwanese men, particularly in the absence of MetS. This finding suggests that MAFLD could serve as an early predictor of TD, facilitating the identification of high-risk individuals and enabling timely interventions. Further research is needed to validate these findings and explore the underlying mechanisms linking MAFLD, TD, and MetS in diverse populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Huang, Lee, Lee, Huang, Geng, Chang, Lin, Juan, Wu and Hsieh.)

Objectives: Non‐alcoholic fatty liver disease (NAFLD) is suggested to be a precursor of metabolic syndrome (MetS) and could influence the risk of testosterone deficiency (TD). Fatty liver index (FLI) is a simple and useful screening tool for NAFLD. We determined the association between the risk of NAFLD assessed by FLI and TD in aging Taiwanese men, especially those without MetS. Materials and Methods: A free health screening program was conducted for men (age: >40 years) in a medical center in Kaohsiung, Taiwan. All participants underwent a physical examination; answered a questionnaire assessing demographics, medical history, and clinical symptoms of TD; and provided 20‐mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. The risk of NAFLD was evaluated using FLI. The presence of NAFLD was ruled out if FLI value was <25 and ruled in if FLI value was ≥35. Results: A total of 552 men (mean age: 54.7 ± 7.7 years) were enrolled. The prevalence rates of TD and MetS were significantly higher among men with NAFLD than those without NAFLD (both p < 0.001). FLI was significantly correlated with total testosterone (TT) and adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol‐binding protein‐4 (RBP‐4) levels, respectively (all p < 0.001). Among men without MetS, those at risk of and with NAFLD had a 3.82 and 8.50 times higher risk of TD, respectively, than those without NAFLD after adjusting for potential covariates. Conclusion: The FLI is associated with the risk of TD in aging Taiwanese men, especially in those without MetS. Our findings also suggest that insulin resistance may be an important link among the inter‐relationships of NAFLD, MetS, and TD. Further population‐based studies with larger sample sizes of different ethnicities are warranted to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocyte nuclear factor-4α (HNF4A) can influence the risk of insulin resistance that is postulated to be an important link between metabolic syndrome (MetS) and testosterone deficiency (TD) in men. Aim To investigate the relationship between single-nucleotide polymorphisms (SNPs) of HNF4A and the risk of developing MetS and TD in a population of aging Taiwanese men. Methods A free health screening of men over 40 years of age was conducted in a medical center in Kaohsiung City, Taiwan. All participants underwent a physical examination, answered a questionnaire on demographics and medical history, completed the Androgen Deficiency in The Aging Male questionnaire to assess clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, hormonal, and genetic evaluation. Main Outcome Measure 3 common SNPs (rs11574736, rs1884613, and rs2144908) of HNF4A were selected and identified using a TaqMan 5' allelic discrimination assay. Results 559 men were enrolled for this study (mean age, 55.8± 4.9 years). Prevalence of TD was significantly higher (P =.031) in subjects with MetS (16.8%) than those without MetS (10.1%). In SNP rs1884613 of HNF4A, subjects with the C allele carried a 1.31- and 1.50-times higher risk of developing MetS and TD, respectively, compared to those with the G allele, after adjusting for potential covariates. In addition, subjects with the CC genotype were exposed to a 1.91- and 2.20-times higher risk of developing MetS and TD, respectively, compared to those with the GG genotype. Clinical Implications Our findings may point to the importance of the role played by insulin resistance in the link between MetS and TD. Strength & Limitations Our current work is the first report with adequate sample size to evaluate the role of genetic variants of HNF4A on the risk of both MetS and TD in men. The limitations included subjects enrolled from a free health screening and single measurement of serum testosterone levels. Conclusion The rs1884613 SNP marker of HNF4A is significantly associated with an increased risk for developing both MetS and TD in aging Taiwanese men. Further population-based studies utilizing larger samples of different ethnicities may be needed to confirm these preliminary results. Liu C-C, Lee Y-C, Hung S-P. Hepatocyte Nuclear Factor-4α P2 Promoter Variants Are Associated With the Risk of Metabolic Syndrome and Testosterone Deficiency in Aging Taiwanese Men. J Sex Med 2018;15:1527–1536. [ABSTRACT FROM AUTHOR]