Diagnosis and Treatment of Hypogonadism in Middle-Aged to Older Males

Key Diagnostic Considerations

Total testosterone represents the sum of all testosterone in circulation: bound to sex hormone-binding globulin (SHBG) (60-70%), bound to albumin (30-40%), and unbound/free (1-3%) 1
Total testosterone can be measured using standard immunoassays in most clinical laboratories 2
Free testosterone, which represents only the biologically active, unbound fraction available to tissues, should be measured by equilibrium dialysis (gold standard) or calculated using total testosterone, SHBG, and albumin concentrations 1, 2
The American College of Endocrinology recommends measuring free testosterone in men over 60 years with hypogonadal symptoms, regardless of total testosterone level 1

Low testosterone is defined as <300 ng/dL, and requires two separate morning measurements (8-10 AM) to confirm 1, 2
Free testosterone levels correlate significantly with age, hematocrit, gonadotropins, BMI, erectile dysfunction, and low libido 1
The Endocrine Society recommends using the Vermeulen formula to calculate free testosterone, which requires total testosterone, SHBG, and albumin concentrations 1, 2

Men with obesity (BMI >30) and diabetes should have their free testosterone measured, as these conditions can alter SHBG metabolism and increase the risk of hypogonadism 1, 2
Testosterone replacement therapy can produce small but significant improvements in sexual function, with a standardized mean difference of 0.35 1
The American Urological Association recommends that treatment decisions be based on both biochemical confirmation (low free testosterone) and specific symptoms, particularly diminished libido and erectile dysfunction 1