What is the best course of action for a patient with low testosterone and free testosterone levels, suspected hypogonadism, and normal SHBG levels?

Workup and Management of Confirmed Hypogonadism

Your patient has confirmed biochemical hypogonadism with both low total testosterone (8.7-9.6 nmol/L; reference 10-35) and low free testosterone (184 pmol/L; reference 225-725), and you must immediately measure serum LH and prolactin to determine the etiology before initiating any treatment. 1

Immediate Next Steps: Essential Laboratory Testing

The American Urological Association mandates measuring serum luteinizing hormone (LH) in all patients with confirmed low testosterone—this is the single most important test to guide your entire workup and treatment approach. 1 Do not skip this step, as it distinguishes between:

• Primary hypogonadism: Elevated LH indicates testicular failure 1
• Secondary hypogonadism: Low or low-normal LH indicates pituitary-hypothalamic dysfunction 1

Measure serum prolactin in all patients with low testosterone and low or low-normal LH levels. 1 This is critical because hyperprolactinemia can cause secondary hypogonadism and requires different management.

Additional Pre-Treatment Laboratory Work

• Hemoglobin: Required before offering testosterone therapy 1
• FSH measurement: Recommended if the patient is interested in fertility, as elevated FSH with low testosterone indicates impaired spermatogenesis 1
• Cardiovascular risk assessment: Screen for dyslipidemia, hypertension, diabetes, and smoking status before initiating testosterone therapy 1

Critical Decision Point: When to Order Pituitary MRI

The Endocrine Society recommends pituitary MRI in men with:

• Total testosterone <150 ng/dL (approximately <5.2 nmol/L) combined with low or low-normal LH, regardless of prolactin levels 1

Do not order pituitary imaging without first checking LH and prolactin, unless the testosterone is profoundly low as described above. 1

Confirming the Diagnosis Before Treatment

Prior to initiating testosterone replacement, confirm hypogonadism by ensuring serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range. 2 Your patient's lab results show two separate measurements (8.7 and 9.6 nmol/L), both below the reference range of 10-35 nmol/L, which satisfies this requirement.

Understanding the Normal SHBG Finding

Your patient's SHBG is normal (30 nmol/L; reference 10-70), which means the low free testosterone is not due to altered binding protein levels but reflects truly low testosterone production. 3 This is distinct from situations where low SHBG causes elevated free testosterone despite normal total testosterone, or where high SHBG (common in aging men) causes low free testosterone despite normal total testosterone. 4

Testosterone Replacement Therapy Initiation

Once you have confirmed the etiology with LH/prolactin testing and ruled out contraindications, testosterone replacement is indicated for primary or hypogonadotropic hypogonadism. 2

FDA-Approved Dosing for Testosterone Gel 1.62%

• Starting dose: 40.5 mg testosterone (2 pump actuations) applied topically once daily in the morning to shoulders and upper arms 2
• Dose range: Can be adjusted between 20.25 mg (1 pump) and 81 mg (4 pumps) 2
• Titration timing: Check pre-dose morning serum testosterone at approximately 14 days and 28 days after starting treatment 2
• Target range: 350-750 ng/dL (approximately 12-26 nmol/L) 2

Application Instructions

Apply to clean, dry, intact skin of the shoulders and upper arms only—do not apply to abdomen, genitals, chest, armpits, or knees. 2 Patients must wash hands immediately with soap and water after application and cover the application site with clothing after the gel has dried. 2 Avoid swimming or showering for a minimum of 2 hours after application. 2

Common Pitfalls to Avoid

• Never skip LH measurement—it is the single most important test to determine your treatment approach 1
• Do not measure estradiol routinely—it is only indicated for patients with breast symptoms before treatment 1
• Do not rely on screening questionnaires as substitutes for laboratory testing, as they have variable specificity and sensitivity 1
• Do not use total testosterone alone in older patients (>60 years), as 26.3% may have normal total testosterone with low free testosterone due to elevated SHBG 4

Monitoring After Treatment Initiation

• Testosterone levels: Check at 14 and 28 days, then periodically thereafter 2
• PSA and hemoglobin/hematocrit: Monitor periodically 2
• Liver function tests and lipid profile: Assess periodically 2
• Prostate monitoring: Watch for worsening BPH symptoms 2
• VTE risk: Evaluate patients with signs or symptoms of DVT or PE 2