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

Logan Hubbard, Nivetha Chandrasekaran, Paola Bustillos, Nathan R. Starke

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
Issue number1
StatePublished - 2022


  • free testosterone
  • hypogonadal symptoms
  • IIEF-5 score
  • testosterone replacement therapy
  • total testosterone

ASJC Scopus subject areas

  • Urology
  • Reproductive Medicine
  • Endocrinology


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