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

Abstract

Background

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.

Methods

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.

Results

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 (β = 22.616, 95% CI: 3.873–41.359, p = 0.01807). MR analysis confirmed anemia as a cause of TD (OR = 1.045, 95% CI: 1.020–1.071, p < 0.001). Anemic males with low testosterone had reduced OS compared to those with normal levels (p < 0.001).

Conclusions

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.

Keywords:

• Anemia
• testosterone deficiency
• bidirectional relationship
• NHANES
• Mendelian randomization

Acknowledgments

We gratefully acknowledge the NHANES and GWAS project participants for providing valuable data and information. We also thank the staff members involved in database maintenance and management. Our appreciation extends to all the contributors who provided valuable insights and feedback on this article.

Ethical statement

The data for this study were sourced from the NHANES database, which operates under a survey protocol approved by the NCHS Ethics Review Board (https://www.cdc.gov/nchs/nhanes/irba98.htm). Consequently, no additional ethical review is required.

Consent to participate

The data for this study was obtained from the NHANES public database, and participants in the survey had already received and signed an informed consent form. Therefore, this study is exempt from the need for consent to participate.

Consent to publish

Not applicable, as this study does not include any personal identifiers or private information.

Figures raw data

The data for this study were sourced from the public databases NHANES and GWAS, with a portion of the raw data uploaded in Supplementary Tables 1 and 2. More comprehensive raw data can be accessed and downloaded from the official websites of the databases at NHANES (https://www.cdc.gov/nchs/nhanes/index.htm) and GWAS (https://gwas.mrcieu.ac.uk/).

Author contributions

ZZ, JP, and XZ conceptualized and designed the study; ML, ZC, JG, and LZ collected and analyzed the data; JP and ML interpreted the results; ZZ drafted the manuscript; and PG and XZ critically revised the manuscript for important intellectual content. All authors approved the final version of the manuscript for submission.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used in this study are available at the official websites of the NHANES (https://www.cdc.gov/nchs/nhanes/index.htm) and GWAS (https://gwas.mrcieu.ac.uk/) projects.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant 82071637.