What is the initial workup and treatment approach for a young male with hypogonadism (low testosterone)?

Initial Workup and Treatment Approach for Young Male with Hypogonadism

The initial workup for a young male with suspected hypogonadism requires morning total testosterone measurements on at least two separate days, along with free testosterone, LH, and FSH levels to distinguish between primary and secondary hypogonadism, followed by appropriate treatment based on the underlying cause and fertility desires. 1

Diagnostic Evaluation

Laboratory Assessment

• Measure morning total testosterone concentration between 8 AM and 10 AM on at least two separate days 1, 2
• Measure free testosterone level by equilibrium dialysis, especially in obese patients 1
• Measure sex hormone-binding globulin (SHBG) levels, particularly in obesity 1
• If testosterone levels are subnormal, measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1
• For secondary hypogonadism (low testosterone with low/normal LH/FSH), additional tests include 1:
  • Serum prolactin
  • Iron saturation
  • Pituitary function testing
  • MRI of sella turcica

Clinical Assessment

• Evaluate for signs and symptoms of hypogonadism 1:
  • Decreased energy/vitality
  • Decreased libido/sexual activity
  • Decreased muscle mass
  • Reduced body hair
  • Hot flashes
  • Gynecomastia
  • Infertility
  • Erectile dysfunction
• Assess for potential causes 1, 3:
  • Obesity and metabolic disorders
  • Medications affecting the hypothalamic-pituitary-gonadal axis
  • Prior anabolic steroid use 4
  • Chronic illnesses
  • Pituitary or testicular disorders

Treatment Approach

For Men Not Concerned About Fertility

1. Testosterone Replacement Therapy (TRT) 1, 2

   • Confirm diagnosis with at least two morning testosterone measurements below normal range 2
   • Starting dose of testosterone gel 1.62% is 40.5 mg applied topically once daily in the morning 2
   • Apply to clean, dry skin of shoulders and upper arms 2
   • Monitor testosterone levels at 2-3 months after initiation and after any dose adjustment 1
   • Once stable levels achieved, monitor every 6-12 months 1

2. Formulation Selection 1

   • Transdermal preparations (gel, patch) provide stable day-to-day testosterone levels
   • Intramuscular injections require less frequent administration but cause fluctuating levels
   • Implantable pellets offer long-term option but require implantation procedure

For Men Desiring Fertility Preservation

1. Alternative Therapies 1, 5
   • Human chorionic gonadotropin (hCG) - FDA approved for use in males 1
   • Selective estrogen receptor modulators (SERMs) like clomiphene citrate 1, 5
   • Aromatase inhibitors 1
   • These agents promote endogenous testosterone production without suppressing spermatogenesis 1

For Reversible Causes

1. Lifestyle Modifications 1
   • Weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism 1
   • Physical activity shows benefits correlating with exercise duration and weight loss 1
   • However, testosterone increases from lifestyle changes alone are modest (1-2 nmol/L) 1

Monitoring and Follow-up

• Measure testosterone levels 2-3 months after treatment initiation 1
• For patients on testosterone gel, levels can be measured at any time 1
• For patients on testosterone injections, measure levels midway between injections 1
• Monitor for potential adverse effects 2:
  • PSA elevation
  • Erythrocytosis (increased hematocrit/hemoglobin)
  • Emotional lability
  • Hypertension
  • Contact dermatitis (with topical preparations)

Important Considerations and Pitfalls

• Fertility Impact: Exogenous testosterone suppresses spermatogenesis through negative feedback on the hypothalamic-pituitary axis 1, 3
• Contraindications to TRT 2:
  • Prostate cancer
  • Breast cancer
  • Uncontrolled congestive heart failure
  • Severe lower urinary tract symptoms
  • Erythrocytosis
• Secondary Exposure Risk: Topical testosterone can be transferred to others through skin contact; patients should wash hands after application and cover application sites with clothing 2
• Commercially manufactured testosterone products are preferred over compounded testosterone due to potential variations in potency and quality 1
• Consider discontinuing TRT after 3-6 months if target testosterone levels are achieved but symptoms don't improve 1

By following this systematic approach to diagnosis and treatment, clinicians can effectively manage hypogonadism in young males while considering individual needs regarding fertility and potential risks of therapy.