Dehydroepiandrosterone Sulfate/Cortisol Ratio as a Biomarker of Depressive Symptoms in Late-Onset Hypogonadism: An Analysis of 3,005 Males

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PURPOSE: Depressive symptoms related to late-onset hypogonadism (LOH) have attracted attention due to their impact on absenteeism and presenteeism. Although LOH symptoms are not consistently associated with serum testosterone levels, elevated cortisol and decreased dehydroepiandrosterone sulfate (DHEA-S) are frequently observed in depressed individuals, suggesting their potential as biomarkers. We investigated the relationship between depressive symptoms and the DHEA-S/cortisol (D/C) ratio in a large cohort of males with LOH symptoms. MATERIALS AND METHODS: We retrospectively analyzed data from 3,005 males with LOH symptoms who visited our hospital or affiliates between May 2016 and March 2024. Symptoms were assessed using the Aging Male Symptoms (AMS) scale, Sexual Health Inventory for Men, International Prostate Symptom Score, and Beck Depression Inventory (BDI). Endpoints included correlations between serum testosterone and D/C ratio, associations between the D/C ratio and AMS and BDI scores, and multivariable-adjusted relationships between the D/C ratio and symptom scores. RESULTS: The mean age was 47.5±12.3 years, mean serum testosterone of 5.4±2.4 ng/mL and mean D/C ratio of 33.8±29.2. No significant correlation was observed between testosterone and D/C ratio (p=0.368). In contrast, the D/C ratio showed significant negative correlations with AMS (r=-0.058, p=0.001) and BDI (r=-0.085, p<0.001) scores. Trend analysis demonstrated a decline in the D/C ratio with increasing AMS and BDI severity (p for trend<0.001). Testosterone showed no association with AMS or BDI scores. After adjusting for age, aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, triglyceride, hemoglobin A1c, only the BDI score remained associated with the D/C ratio (β=-0.054, p=0.002). CONCLUSIONS: The D/C ratio demonstrates a significant association with depressive symptoms and may serve as a potential biomarker. Its assessment may improve psychological evaluations and management in this population.

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