Utility of Directly Measured Free Testosterone in Predicting Benefit of Testosterone Therapy in Men with Hypogonadal Symptoms and Normal Total Testosterone

Abstract

Introduction: Currently symptomatically hypogonadal men with normal total testosterone (TT) levels but low enzyme-linked immunoassay (EIA) free testosterone (FT) are not offered Testosterone Therapy (TTh), despite the evidence that they may benefit. Objective: To determine whether low EIA-FT could help predict response to TTh in men with hypogonadal symptoms and TT >300. Methods: A total of 86 consecutive men with hypogonadal symptoms were prospectively analyzed with normal TT (>300 ng/dL) and low FT (<7.9 pg/mL). The TT and FT were measured by a single laboratory (LabCorp). Subjects began testosterone cypionate intramuscular 200 mg q2 weeks with 3- and 6-month follow-up. The population was divided into two groups based on initial TT levels: Group 1: 300–399 ng/dL; Group 2: 400–660 ng/dL. Clinical response to TTh was determined by improvements in hypogonadal symptoms, changes in International Index of Erectile Function (IIEF-5) questionnaire, and subjective changes in libido, energy, and vitality. Safety parameters were assessed with periodic checks of T, estradiol, hematocrit, and prostate-specific antigen (PSA). Results: Mean age was 62 years. Mean IIEF-5 score before TTh was 12.8; after 3 and 6 months, the scores were 14.1 and 14.7, respectively. Eighty-seven percent of men reported subjective improvement in energy/libido after 3 months of TTh, 61% of patients reported substantial improvement, 26% reported a modest improvement, and 13% reported no improvement. After 6 months of TTh, 77 patients (89.5%) reported substantial improvement, 7 (8.1%) with more mild but noticeable improvement, and only 2 (2.3%) with no improvement. Erectile function after 6 months of TTh improved, but it did not reach statistical significance (mean 12.8 ≥ 14.7, p = 0.07). Group 1 showed a greater rise in their IIEF-5 score after 6 months compared with patients in Group 2. Ten men (11.6%) and 3 men (4.8%) developed erythrocytosis and a rise in PSA respectively at 6 months. Conclusion: Our data suggest that many men with hypogonadal symptoms, normal TT, and low EIA-FT respond well, and safely, to TTh.