Impact of Low Testosterone and SHBG Levels on Heart Failure Risk: A Systematic Review and Meta-Analysis

Area of Science:

• Endocrinology
• Cardiovascular Medicine
• Epidemiology

Background:

• Emerging evidence suggests a potential link between diminished testosterone and sex hormone-binding globulin (SHBG) levels and adverse cardiovascular events.
• However, the precise nature of this relationship, particularly concerning heart failure (HF), remains incompletely understood.

Purpose of the Study:

• To systematically review and evaluate the predictive capability of baseline testosterone, dihydrotestosterone (DHT), and SHBG concentrations for incident heart failure (HF).
• To elucidate the role of hormonal factors in the risk of developing HF.

Main Methods:

• A comprehensive systematic search of major scientific databases (MEDLINE, Scopus, Web of Science) was performed.
• Included were cohort and nested case-control studies measuring hormone levels in adults without pre-existing HF.
• Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated using random-effects models, with risk of bias assessed via the ROBINS-E tool.

Main Results:

• Analysis of six studies encompassing 233,474 participants revealed a modest association between a one-standard deviation decrease in testosterone and increased HF risk in men (HR 1.10).
• No significant association was observed in women, nor were SHBG levels found to be significant predictors of HF risk.
• Bayesian analysis indicated weak evidence supporting the testosterone-HF association (Bayes factor = 0.99).

Conclusions:

• Low testosterone levels show a modest association with increased HF risk in men, indicating a potentially significant but under-researched area in cardiovascular health.
• Significant heterogeneity across studies and the observed weak associations necessitate further rigorous investigation.
• Randomized controlled trials are crucial for validating these findings and exploring the biological pathways involved.