What are the signs and treatment options for hypogonadism (low testosterone)?

Signs and Treatment Options for Hypogonadism (Low Testosterone)

Men with symptoms of hypogonadism such as decreased sexual desire (libido), decreased sexual activity, or erectile dysfunction should be screened with a morning serum testosterone level. 1

Clinical Signs and Symptoms of Low Testosterone

Sexual Symptoms

• Decreased sexual desire (libido)
• Reduced sexual activity
• Erectile dysfunction
• Decreased volume of ejaculate
• Reduced morning erections

Physical Signs

• Decreased muscle mass and strength
• Increased body fat (especially central adiposity)
• Decreased bone mineral density
• Loss of body and facial hair
• Fatigue and decreased energy levels
• Hot flushes/sweats

Psychological Symptoms

• Decreased vitality
• Depressed mood
• Reduced cognitive function
• Irritability
• Poor concentration
• Sleep disturbances

Diagnostic Approach

Laboratory Testing

• Measure morning total testosterone level using an accurate and reliable assay 1
• If total testosterone levels are close to the lower limit:
  • Check sex hormone-binding globulin (SHBG), which is often low in diabetes and associated with lower testosterone levels 1
  • Consider further testing (luteinizing hormone and follicle-stimulating hormone) to determine if hypogonadism is primary or secondary 1

Diagnostic Thresholds

• Total testosterone levels <8 nmol/L (230 ng/dL) highly support diagnosis of hypogonadism 2
• Levels >12 nmol/L (350 ng/dL) are likely normal 2
• Levels between 8-12 nmol/L require further evaluation of free or bioavailable testosterone 2

Treatment Options

When to Consider Treatment

• Treatment should be considered for men with symptomatic hypogonadism with confirmed low testosterone levels 1
• Treatment is specifically recommended for men with sexual dysfunction who want to improve sexual function 1
• Treatment is not recommended for improving energy, vitality, physical function, or cognition alone 1

Testosterone Replacement Therapy (TRT) Options

1. Intramuscular Formulations

   • Testosterone enanthate/cypionate: 50-100 mg weekly 3
   • Recommended as first-line due to lower cost with similar effectiveness and safety profile 1
   • Caution: May cause fluctuations in testosterone levels

2. Transdermal Formulations

   • Testosterone gel 1%: 50 mg daily (range 50-100 mg) 3
   • More consistent testosterone levels but higher cost
   • Caution: Risk of transfer to women and children through skin contact 4

Monitoring During Treatment

• Reevaluate symptoms within 12 months and periodically thereafter 1
• Discontinue treatment if no improvement in sexual function 1
• Target total testosterone level: 450-600 ng/dL 3
• Monitor:
  • Hematocrit/hemoglobin (discontinue if hematocrit exceeds 54%) 3, 5
  • PSA in men over 40 (consider biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year) 3
  • Cardiovascular risk factors 3

Important Considerations and Cautions

Cardiovascular Risk

• Long-term clinical safety trials have not conclusively determined cardiovascular risk 4, 5
• Some studies show increased coronary artery plaque volume and cardiovascular events with testosterone replacement in older men 1
• Assess all testosterone deficient patients for cardiovascular disease risk factors 3
• Avoid initiating therapy for 3-6 months after recent cardiac events 3

Fertility Considerations

• Testosterone therapy suppresses spermatogenesis 3
• Consider alternative approaches for men wishing to preserve fertility:
  • Human chorionic gonadotropin (hCG)
  • Selective estrogen receptor modulators
  • Aromatase inhibitors 6

Contraindications

• Active prostate or breast cancer
• Hematocrit >50%
• Severe untreated sleep apnea
• Uncontrolled heart failure 3

Special Populations

• Men with diabetes: Mean testosterone levels are lower compared to age-matched men without diabetes, but obesity is a major confounder 1
• Older patients require more vigilant monitoring due to potentially higher risk of adverse events 3

Lifestyle Modifications

• Weight loss for overweight/obese patients
• Regular aerobic exercise
• Adequate sleep hygiene 3
• These modifications can increase total testosterone levels and/or reduce symptoms associated with testosterone deficiency 3