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.