What labs should be ordered to diagnose and manage low testosterone in a male patient?

Laboratory Requisition for Diagnosing Low Testosterone in Males

Order two separate early morning (8:00-10:00 AM) total testosterone measurements on different days, along with LH, and establish baseline hemoglobin/hematocrit before considering any testosterone therapy. 1, 2

Essential Initial Labs

Total Testosterone (Required)

• Two separate morning measurements between 8:00-10:00 AM are mandatory to confirm diagnosis, as testosterone levels can be 20-25% lower in the afternoon in younger men and 10% lower even at age 70 2
• Both measurements must be <300 ng/dL to meet diagnostic criteria for testosterone deficiency 1, 2
• Use the same laboratory with the same method/instrumentation for both measurements to ensure consistency 1
• Do not test during acute illness, as this artificially suppresses testosterone levels 2

Luteinizing Hormone (LH) - Mandatory

• Measure serum LH in all patients with confirmed low testosterone to distinguish primary from secondary hypogonadism 1, 2
• Low or low-normal LH with low testosterone indicates secondary hypogonadism, while elevated LH with low testosterone indicates primary hypogonadism 2
• This distinction is critical because secondary hypogonadism patients can potentially achieve fertility with gonadotropin therapy, while primary hypogonadism patients require testosterone replacement which suppresses fertility 2

Baseline Hemoglobin/Hematocrit

• Measure before initiating testosterone therapy to establish baseline, as testosterone increases red blood cell mass 2

Adjunctive Labs Based on Clinical Context

For Patients with Breast Symptoms or Gynecomastia

• Measure serum estradiol only if the patient presents with breast symptoms or gynecomastia prior to starting testosterone therapy 2
• Elevated baseline estradiol requires endocrinology referral 2

For Men Interested in Fertility

• Perform testicular examination to evaluate size, consistency, and descent 2
• Measure FSH to assess underlying reproductive health status 2

For Severe Hypogonadism (Total Testosterone <150 ng/dL)

• Obtain pituitary MRI regardless of prolactin levels if LH is low or low-normal 2

Cardiovascular Risk Assessment

• Assess lipid panel if not recently checked 2

High-Risk Populations Requiring Screening

Measure testosterone even without typical symptoms in patients with: 1, 2

• Unexplained anemia
• Bone density loss
• Diabetes
• HIV/AIDS
• Exposure to chemotherapy
• Direct or scatter radiation therapy to the testes
• Chronic narcotic use
• Male infertility
• Pituitary disorders
• Chronic corticosteroid use

Critical Pitfalls to Avoid

• Do not rely on screening questionnaires alone—they lack specificity and cannot substitute for laboratory confirmation 1, 2
• Do not test during acute illness, as this suppresses the hypothalamic-pituitary-gonadal axis 2
• Do not diagnose testosterone deficiency based on laboratory values alone—the clinical diagnosis requires both low total testosterone levels combined with symptoms and/or signs 1
• Do not order testosterone testing in the afternoon—this can lead to false-positive diagnoses of testosterone deficiency 2

Symptoms to Document

Document patient-reported symptoms including: 1

• Reduced energy, endurance, or physical performance
• Fatigue
• Depression, reduced motivation, poor concentration, or impaired memory
• Irritability
• Infertility
• Reduced sex drive
• Changes in erectile function

Physical Examination Findings to Document

Conduct targeted physical exam for: 1

• General body habitus and virilization status
• Body mass index or waist circumference
• Gynecomastia
• Testicular size, consistency, and masses
• Varicocele presence
• Prostate size and morphology