Management of Normal SHBG with Reduced Total Morning Testosterone

Diagnostic Approach

For patients with normal sex hormone-binding globulin (SHBG) but reduced total morning testosterone levels, free testosterone measurement is essential to determine if true testosterone deficiency exists, as normal SHBG with low total testosterone may indicate normal free testosterone levels in some cases 1, 2
Confirm low total testosterone with a second morning measurement (between 8-10 AM) as testosterone levels show diurnal variation with highest levels in the morning 3, 4
Measure free testosterone levels by equilibrium dialysis to determine if true testosterone deficiency exists despite normal SHBG 1, 2
Measure serum luteinizing hormone (LH) levels to help establish the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 3, 4
Clinical diagnosis of testosterone deficiency requires both consistently low total testosterone (<300 ng/dL on at least two separate morning measurements) AND presence of symptoms/signs 3, 4

Document symptoms associated with low testosterone, including reduced energy, endurance, physical performance, fatigue, depression, reduced motivation, poor concentration, impaired memory, reduced sex drive, changes in erectile function, and infertility 3
Perform targeted physical examination for signs of low testosterone, including body habitus and virilization status, body mass index/waist circumference, gynecomastia, testicular evaluation (size, consistency), and prostate examination 3

In obese patients, low total testosterone with normal SHBG often occurs due to increased aromatization of testosterone to estradiol in adipose tissue 1, 2
Consider measuring total testosterone in patients with specific risk factors even without symptoms, including unexplained anemia, bone density loss, diabetes, exposure to chemotherapy or testicular radiation, HIV/AIDS, chronic narcotic or corticosteroid use, male infertility, and pituitary dysfunction 3

If free testosterone is normal despite low total testosterone, testosterone replacement therapy is not indicated 1, 2
If free testosterone is confirmed low on at least two separate assessments, consider testosterone replacement therapy 1, 2
Treatment options include transdermal preparations (gel, patch), intramuscular injections, and implantable testosterone pellets 5, 6

After initiating treatment, monitor testosterone levels at 2-3 months to ensure normal serum testosterone concentrations are achieved 5

Screening questionnaires are not recommended for identifying candidates for testosterone therapy due to variable specificity and sensitivity 3