What is the initial approach for managing low free testosterone levels, considering other testosterone lab results?

Initial Laboratory Workup for Low Free Testosterone

When free testosterone is confirmed low, you must measure serum luteinizing hormone (LH) levels to distinguish primary from secondary hypogonadism, followed by serum prolactin if LH is low or low-normal. 1

Essential Follow-Up Laboratory Tests

Luteinizing Hormone (LH) - Required for All Patients

• Measure serum LH in all patients with confirmed low testosterone to establish the etiology of testosterone deficiency (Strong Recommendation; Evidence Level: Grade A) 1
• LH levels distinguish between:
  • Primary hypogonadism: Elevated LH (testicular failure) 1
  • Secondary hypogonadism: Low or low-normal LH (pituitary-hypothalamic dysfunction) 1
• LH measurement determines whether additional pituitary evaluation is needed and identifies candidates for selective estrogen receptor modulator therapy, particularly men wishing to preserve fertility 1

Prolactin - Required for Secondary Hypogonadism

• Measure serum prolactin in all patients with low testosterone AND low or low-normal LH levels (Strong Recommendation; Evidence Level: Grade A) 1
• If prolactin is elevated, repeat the measurement to confirm it was not spurious 1
• Persistently elevated prolactin requires endocrinology referral to evaluate for prolactinomas or other pituitary tumors 1
• Men with total testosterone <150 ng/dL combined with low or low-normal LH should undergo pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be present 1

Follicle-Stimulating Hormone (FSH) - For Fertility Concerns

• Measure FSH in men interested in fertility to assess underlying reproductive health status 1
• Elevated FSH with low testosterone (hypergonadotropic hypogonadism) indicates impaired spermatogenesis 1
• Consider semen analysis in patients with elevated FSH 1
• Patients with severe oligospermia (<5 million sperm/mL) or non-obstructive azoospermia should receive karyotype testing and Y-chromosome microdeletion analysis 1

Estradiol - For Breast Symptoms Only

• Measure serum estradiol only in testosterone-deficient patients presenting with breast symptoms or gynecomastia prior to starting therapy (Expert Opinion) 1
• Men with elevated baseline estradiol should be referred to endocrinology 1

Hemoglobin and Cardiovascular Risk Assessment

• Measure hemoglobin before offering testosterone therapy (Strong Recommendation; Evidence Level: Grade A) 1
• Assess for atherosclerotic cardiovascular disease (ASCVD) risk factors including dyslipidemia, hypertension, diabetes, and smoking 1

Critical Pitfalls to Avoid

• Do not skip LH measurement - this is the single most important test to guide further workup and determine treatment approach 1
• Do not order pituitary imaging without first checking LH and prolactin, unless total testosterone is <150 ng/dL with low/low-normal LH 1
• Do not routinely measure estradiol - it is only indicated for patients with breast symptoms before treatment 1
• Do not use screening questionnaires as substitutes for laboratory testing - they have variable specificity and sensitivity 1