Are Reference Intervals for Calculated Free Testosterone in Healthy Men Reliable Also in Men With Erectile Dysfunction? Findings From a Cross‐Sectional Study

Background: Reference intervals for calculated free testosterone (cFT) in healthy, nonobese men have been released, but have not been validated in men with erectile dysfunction (ED). Objectives: To assess the clinical impact of new cFT reference intervals in men with new-onset ED. Methods: Data from 410 healthy, nonobese men were analyzed (2015-2023). cFT was assessed using Vermeulen's formula and compared to Jasuja et al.'s (2022) reference values, using the 2.5th percentile as a pathological threshold. At baseline, all patients completed the International Index of Erectile Function (IIEF) and Beck Depression Inventory (BDI). Descriptive statistics and linear regression analyses were applied. Results: Median (IQR) age and total testosterone at presentation were 48 (38-59) years and 4.7 (3.3-6.1) ng/mL. Median IIEF-EF score was 18 (8-23), with 134 patients (32.8%) reporting severe ED. Percentiles of cFT in ED men were: 2.5th = 10, 10th = 50, 50th = 90, 90th = 150, and 97.5th = 227.5 pg/mL, compared to 66, 91, 141, 240, and 309 pg/mL in healthy controls. Seventy-four had cFT between 10 and 66 pg/mL, normal for ED distribution but pathological by healthy reference. This group was older (p<0.01), had lower IIEF-EF (p<0.001), and higher BDI (p<0.01) versus those with cFT >66 pg/mL, though other parameters were similar. Severe ED rates were 72.7%, 44.6%, and 28.7% in men with cFT <10, 10-66, and >66 pg/mL (p<0.01). At multivariable regression, cFT >66 pg/mL was linked to higher IIEF-EF (p = 0.02), while cFT >66 pg/mL (p = 0.03) and younger age (p = 0.01) were associated with lower BDI scores. Conclusions: Reference thresholds for cFT derived from healthy men identify, among men with ED, a subgroup showing a less favorable erectile and psychometric profile. These findings suggest that healthy-derived cFT reference values may provide clinically useful information in the assessment of men presenting with ED.