Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic...

Area of Science:

• Urology
• Endocrinology
• Genetics

Background:

• Benign prostatic hyperplasia (BPH) risk factors like dyslipidemia, diabetes, hypertension, and obesity have conflicting evidence.
• A reliable method is needed to identify precise factors contributing to BPH development.

Purpose of the Study:

• To investigate the causal associations between nine phenotypes and benign prostatic hyperplasia (BPH) using a robust Mendelian randomization design.
• To validate the role of bioavailable testosterone in BPH pathogenesis.

Main Methods:

• Employed a Mendelian randomization (MR) design utilizing large-scale genome-wide association studies (GWAS) data.
• Assessed causal relationships between testosterone levels (total, bioavailable), sex hormone-binding globulin, lipid profiles, diabetes, hypertension, and BMI with BPH.
• Conducted two-sample MR, bidirectional MR, and multivariate MR (MVMR) analyses.

Main Results:

• Elevated bioavailable testosterone levels were consistently associated with an increased risk of BPH across multiple analytical methods.
• Higher triglyceride levels showed a potential association with increased bioavailable testosterone.
• In multivariate MR, bioavailable testosterone remained a significant predictor of BPH occurrence.

Conclusions:

• This study provides the first validation of bioavailable testosterone's central role in the development of benign prostatic hyperplasia.
• Further research is warranted to elucidate the intricate relationships between other identified traits and BPH.