Free Testosterone Rate-of-Change Interpretation: What Your Lab Trend Actually Means

What the free fraction actually is

The Depo-Testosterone label describes testosterone in plasma as 98 percent bound to a specific testosterone-estradiol binding globulin and about 2 percent free. It states that the amount of this sex-hormone binding globulin in plasma determines the distribution of testosterone between free and bound forms [2]. The label gives no percentage target for interpreting a change in free testosterone.

Comparing two draws

Assay differences can affect testosterone results. An interlaboratory study of eight mass spectrometry assays evaluated total testosterone, not free testosterone. It found coefficients of variation under 15% above 1.53 nmol/L but under 34% at 0.3 nmol/L, and between-assay variability was the major contributor to the spread [4].

For injected testosterone, the Depo-Testosterone label lists dosing every 2 to 4 weeks for replacement and a half-life of testosterone cypionate of about eight days after intramuscular injection [2].

What the guideline follows

For diagnosis, the guideline recommends accurate fasting morning total testosterone testing and a repeat measurement. During treatment, it recommends monitoring symptoms, serum testosterone, hematocrit and prostate cancer risk in the first year. It makes a separate recommendation for men whose total testosterone is near the lower limit of normal or who have a condition that alters SHBG [1].

Hematocrit in a dose-response study

In a dose-response study, 121 men (61 aged 19 to 35 and 60 aged 60 to 75) received a monthly GnRH agonist plus weekly testosterone enanthate at 25, 50, 125, 300 or 600 mg for 20 weeks. Hemoglobin and hematocrit rose linearly with dose in both groups, and the rise was greater in older men. Changes in erythropoietin and soluble transferrin receptor were not significantly correlated with changes in total or free testosterone [3].