Elevated Endogenous Testosterone Levels are not Associated With Significant Clinical Morbidity.

Only a small proportion of men in the study population had elevated endogenous testosterone levels above 800 ng/dL.

• After excluding men with testosterone levels <300 ng/dL, 3673 men met inclusion criteria.
• Only 146 (4%) of men had a testosterone >800 ng/dL.
• Data were drawn from National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016.
• Study included men aged 18 and older not on testosterone or androgen ablation therapy.

Men with elevated endogenous testosterone had similar rates of sleep disorders, urinary symptoms, and depression compared to men with normal testosterone.

• Men with testosterone >800 ng/dL were compared to men with normal testosterone (300-800 ng/dL).
• Multivariable logistic and linear regressions were used for comparison.
• No statistically significant associations were found between elevated testosterone and these clinical outcomes.
• These outcomes are commonly associated with adverse effects of testosterone therapy.

Men with elevated endogenous testosterone had significantly higher hematocrit levels compared to men with normal testosterone.

• Regression coefficient for hematocrit: βi 1.30, 95% CI 0.69-1.90, P < .01.
• The authors characterized this elevation as not clinically significant.
• Elevated hematocrit (erythrocytosis) is a known adverse effect associated with testosterone therapy.

Men with elevated endogenous testosterone had significantly higher AST and ALT liver enzyme levels compared to men with normal testosterone.

• AST regression coefficient: βi 8.48, 95% CI 0.31-16.66, P = .04.
• ALT regression coefficient: βi 12.23, 95% CI 0.70-23.77, P = .04.
• Elevated liver enzymes are an adverse effect associated with testosterone therapy.
• The clinical significance of these elevations was not specified as clinically meaningful by the authors.

No association was found between higher endogenous testosterone levels and the adverse events commonly associated with testosterone therapy.

• The findings challenge what is considered a safe target for testosterone therapy.
• The authors suggest future prospective studies are needed to delineate the safety of elevated endogenous and exogenously modulated levels of testosterone.
• Precise thresholds above which adverse effects occur with testosterone therapy remain unknown.
• Data on the association between naturally elevated endogenous testosterone levels and physiologic effects was described as sparse prior to this study.