What is the management for a patient with low total testosterone (260.84 ng/dL) and free testosterone (2.9 ng/dL) levels, with a Sex Hormone-Binding Globulin (SHBG) level of 17 nmol/L?

Management of Low Testosterone with Low SHBG

You need to confirm the diagnosis with a second early morning testosterone measurement, assess for symptoms, measure free testosterone and LH levels, and if confirmed with symptoms present, initiate testosterone replacement therapy. 1, 2

Diagnostic Confirmation Required

Your patient has a total testosterone of 260.84 ng/dL, which is below the diagnostic threshold of 300 ng/dL established by the American Urological Association. 1 However, diagnosis cannot be made on a single measurement alone. 1, 2

Required Next Steps:

• Obtain a second early morning (8-10 AM) total testosterone measurement to confirm the diagnosis, as guidelines mandate two separate low measurements before establishing testosterone deficiency. 1, 2

• Measure free testosterone by equilibrium dialysis (the gold standard method) because your patient has a low SHBG of 17 nmol/L, which can affect the interpretation of total testosterone. 2, 3 Low SHBG typically results in higher free testosterone relative to total testosterone, so free testosterone measurement is essential to determine if true deficiency exists. 4

• Measure serum LH levels to distinguish between primary testicular failure (elevated LH) and secondary hypogonadism from pituitary/hypothalamic dysfunction (low or inappropriately normal LH). 2

Clinical Assessment

The diagnosis requires both biochemical confirmation AND presence of symptoms/signs. 1 You must document whether your patient has:

Symptoms to Assess:

• Reduced libido and erectile dysfunction 1, 2
• Decreased energy, endurance, and physical performance 1, 2
• Fatigue and reduced motivation 1, 2
• Poor concentration, impaired memory, depression, irritability 1
• Infertility concerns 1

Physical Examination Findings:

• Body mass index or waist circumference (obesity is a major confounder) 1, 4
• Testicular size and consistency 1, 2
• Gynecomastia 1, 2
• Body hair patterns in androgen-dependent areas 1

Treatment Decision Algorithm

If Free Testosterone is Normal:

• Do not initiate testosterone replacement therapy, as treatment is not indicated when free testosterone is normal despite low total testosterone. 4

If Free Testosterone is Confirmed Low (on two separate measurements) AND Symptoms Present:

Initiate testosterone replacement therapy to improve sexual function, sense of well-being, muscle mass and strength, and bone mineral density. 1, 3

Contraindications to Exclude First:

• Breast or prostate cancer 3
• Prostate-specific antigen >4 ng/mL (or >3 ng/mL in high-risk patients) 3
• Hematocrit >50% 3
• Untreated severe obstructive sleep apnea 3
• Severe lower urinary tract symptoms (International Prostate Symptom Score >19) 3
• Uncontrolled or poorly controlled heart failure 3

Treatment Options:

• Transdermal testosterone gel 1.62%: Starting dose 40.5 mg daily (two pump actuations), with dose titration based on follow-up levels to achieve mid-normal range (350-750 ng/dL). 5
• Intramuscular testosterone enanthate: Administered every 2-4 weeks. 6
• Transdermal patches or implantable pellets as alternatives. 4

Target testosterone levels during treatment in the mid-normal range (approximately 400-700 ng/dL). 5, 3

Monitoring Protocol

• Check testosterone levels at 2-3 months after initiating therapy to ensure achievement of normal serum concentrations. 4, 5
• Monitor hematocrit, prostate-specific antigen, and symptom response using a standardized plan. 3

Critical Pitfalls to Avoid

• Do not rely on screening questionnaires to determine candidacy for testosterone therapy, as they lack adequate specificity and sensitivity. 1, 4

• Do not start treatment without confirming low testosterone on two separate occasions, as single measurements can be misleading due to diurnal variation and assay variability. 1, 2

• In obese patients with low SHBG, low total testosterone often occurs due to increased aromatization to estradiol in adipose tissue, making free testosterone measurement particularly important. 4

• Total testosterone between 280-350 ng/dL is not sensitive enough to reliably exclude hypogonadism, and levels must exceed 350-400 ng/dL to reliably predict normal free testosterone. 7