Anemia and testosterone deficiency risk: insights from NHANES data analysis and a Mendelian randomization analysis

Previous research has shown that testosterone deficiency (TD) increases the risk of anemia, but it is unclear whether anemia affects testosterone levels. This study investigated the influence of anemia on testosterone levels. Utilizing data from six NHANES cycles, including demographic, testosterone levels, and hemoglobin concentrations, we employed multivariable-adjusted logistic regression to investigate the relationship between anemia and testosterone levels. Moreover, a two-sample Mendelian randomization (MR) study employing genome-wide association study (GWAS) data examined the causal relationship. Kaplan–Meier survival estimation was used to compared the overall survival (OS) of anemic and nonanemic patients with low testosterone and normal testosterone levels. The inclusion of 21,786 participants (2318 with anemia and19,468 without anemia) revealed that nonanemic patients exhibited higher testosterone levels than did anemic patients (<i>β</i> = 22.616, 95% CI: 3.873–41.359, <i>p</i> = 0.01807). MR analysis confirmed anemia as a cause of TD (OR = 1.045, 95% CI: 1.020–1.071, <i>p</i> &lt; 0.001). Anemic males with low testosterone had reduced OS compared to those with normal levels (<i>p</i> &lt; 0.001). Anemia emerged as a potential risk factor for TD, highlighting a bidirectional relationship between these conditions. Additional prospective investigations are essential for the validation and reinforcement of our findings.

既往研究表明，睾酮缺乏症（testosterone deficiency, TD）会增加贫血的发病风险，但目前尚不清楚贫血是否会对睾酮水平产生影响。本研究旨在探讨贫血对睾酮水平的影响。本研究利用6个周期的美国国家健康与营养调查（National Health and Nutrition Examination Survey, NHANES）数据，涵盖人口统计学信息、睾酮水平及血红蛋白浓度等指标，采用多变量校正logistic回归分析，探究贫血与睾酮水平之间的关联。此外，本研究还借助全基因组关联研究（genome-wide association study, GWAS）数据开展了两样本孟德尔随机化（Mendelian randomization, MR）分析，以检验二者之间的因果关联。本研究采用Kaplan-Meier生存分析法，对比了睾酮水平低下与睾酮水平正常的贫血患者及非贫血患者的总生存期（overall survival, OS）。本研究共纳入21786名研究对象，其中贫血患者2318名，非贫血患者19468名。分析结果显示，非贫血患者的睾酮水平显著高于贫血患者（β=22.616，95%置信区间[CI]：3.873–41.359，p=0.01807）。孟德尔随机化分析证实，贫血是导致睾酮缺乏症的危险因素（比值比[OR]=1.045，95%CI：1.020–1.071，p<0.001）。睾酮水平低下的贫血男性患者，其总生存期相较于睾酮水平正常的同类患者显著缩短（p<0.001）。本研究结果表明，贫血可作为睾酮缺乏症的潜在危险因素，提示二者之间存在双向关联。未来需开展更多前瞻性研究，以验证并强化本研究的结论。