How do you diagnose and treat hypogonadism (low testosterone)?

Diagnosing and Treating Hypogonadism (Low Testosterone)

Diagnosis of Testosterone Deficiency

The diagnosis of testosterone deficiency requires both consistently low testosterone levels (<300 ng/dL on at least two early morning measurements) and the presence of specific symptoms and/or signs. 1

Symptoms to Evaluate

• Reduced energy and endurance
• Diminished work/physical performance
• Fatigue
• Depression and reduced motivation
• Poor concentration and impaired memory
• Irritability
• Reduced sex drive
• Changes in erectile function
• Infertility 1

Physical Examination Findings

• Body habitus and virilization status
• Body mass index/waist circumference
• Gynecomastia
• Testicular size, consistency, and masses
• Presence of varicocele
• Prostate size and morphology 1

Diagnostic Testing Algorithm

1. Initial Testing:

   • Measure total testosterone in early morning (before 10 AM)
   • Confirm with repeat measurement if low
   • Diagnostic threshold: <300 ng/dL on at least two measurements 1

2. Secondary Testing:

   • Luteinizing hormone (LH) levels to establish etiology:
     • High LH = Primary hypogonadism (testicular failure)
     • Normal/Low LH = Secondary hypogonadism (pituitary/hypothalamic issue) 1

3. Consider Additional Testing in Equivocal Cases:

   • Free or bioavailable testosterone with reliable assay 2
   • Sex hormone binding globulin (SHBG) levels 1

Normal Reference Ranges

Testosterone Level	Normal Range
Total Testosterone	300-950 ng/dL
Free Testosterone	50-200 pg/mL
SHBG	10-50 nmol/L

High-Risk Populations for Screening

Testosterone levels should be measured in men with:

• Unexplained anemia
• Bone density loss
• Diabetes
• Exposure to chemotherapy or testicular radiation
• HIV/AIDS
• Chronic narcotic use
• Male infertility
• Pituitary dysfunction
• Chronic corticosteroid use 1

Treatment of Testosterone Deficiency

Indications for Treatment

• Men with symptoms and consistently low testosterone levels 1

Contraindications for Treatment

• Breast or prostate cancer
• Hematocrit >50%
• Severe untreated sleep apnea
• Severe lower urinary tract symptoms
• Uncontrolled heart failure
• Desire for current or future fertility (if using traditional testosterone therapy) 1

Treatment Options

Testosterone Replacement Therapy (TRT)

• Starting dose: 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms 3
• Dose adjustment: Can be adjusted between 20.25 mg and 81 mg based on pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment 3
• Target range: 450-600 ng/dL 1

Application Instructions

• Apply to clean, dry, intact skin of the upper arms and shoulders
• Do not apply to abdomen, genitals, chest, armpits, or knees
• Cover application site with clothing after gel has dried
• Avoid swimming or showering for at least 2 hours after application 3

Monitoring Protocol

1. Initial Monitoring (3-6 months):

   • Testosterone levels
   • Hematocrit
   • PSA
   • Symptom response 1

2. Long-term Monitoring (annually):

   • Testosterone levels
   • Hematocrit (discontinue therapy if >54%)
   • PSA (in men ≥40 years)
   • Symptom evaluation 1

3. Action Thresholds:

   • PSA: Biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year
   • Hematocrit: Discontinue if >54%; consider therapeutic phlebotomy for rapid correction 1

Benefits and Risks

Benefits

• Improved sexual function
• Enhanced sense of well-being
• Increased lean body mass
• Decreased body fat
• Increased bone density 1, 4

Risks

• Increased PSA
• Mood swings
• Hypertension
• Increased red blood cell count
• Skin irritation
• Gynecomastia
• Potential for blood clots 1

Cardiovascular Considerations

• Delay TRT for 3-6 months after acute cardiovascular events 1
• Recent high-quality evidence suggests TRT does not increase the risk of myocardial infarction or stroke, even in high-risk patients 4

Lifestyle Modifications

• Weight management
• Regular exercise
• Mediterranean diet
• Limit alcohol consumption to less than 21 units per week 1

Cautions and Pitfalls

• Secondary exposure risk: Children should avoid contact with unwashed or unclothed application sites 3
• Different testosterone products have different doses, strengths, and application instructions that may result in different systemic exposure 3
• Morning testosterone measurements are essential due to diurnal variation 1
• Testosterone levels between 8-12 nmol/L (230-350 ng/dL) represent a "grey zone" requiring clinical correlation and possibly free testosterone measurement 5