What are the causes and treatment options for hypergonadism (elevated serum testosterone levels)?

Causes and Treatment of Hypergonadism (Elevated Serum Testosterone)

Elevated serum testosterone (hypergonadism) requires identification of the underlying cause and targeted treatment, with primary focus on addressing any conditions that may be causing hormonal imbalance rather than directly lowering testosterone levels.

Causes of Elevated Testosterone

Primary Causes:

• Exogenous testosterone administration: Most common cause in clinical practice
  • Testosterone replacement therapy (TRT)
  • Anabolic steroid use
  • Testosterone supplements

Secondary Causes:

• Endocrine disorders:

  • Congenital adrenal hyperplasia
  • Androgen-secreting tumors (ovarian or adrenal)
  • Polycystic ovary syndrome (PCOS) in women 1
  • Hyperthyroidism (can increase sex hormone-binding globulin) 2

• Medication-related:

  • Human chorionic gonadotropin (hCG) therapy 3
  • Selective estrogen receptor modulators (SERMs) 4
  • Aromatase inhibitors (AIs) 4

• Laboratory errors:

  • Improper sample handling
  • Cross-reactivity in assays 1
  • Timing of blood draw (testosterone levels fluctuate throughout the day)

Diagnostic Approach

1. Confirm the elevation:

   • Repeat testing in the morning (when levels are highest)
   • Consider using extraction techniques to eliminate laboratory interference 1
   • Measure both total and free testosterone

2. Evaluate for symptoms:

   • In men: Increased libido, aggressive behavior, acne, hirsutism, male-pattern baldness
   • In women: Virilization, menstrual irregularities, infertility 1

3. Additional testing:

   • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
     • Low/normal with exogenous testosterone
     • High with primary hypergonadism
   • Thyroid function tests (TSH, free T4) 2
   • Liver function tests (ALT, AST, bilirubin, albumin) 2
   • Imaging studies if tumor suspected (adrenal, ovarian, testicular)

Treatment Approach

For Exogenous Testosterone Use:

• Discontinue or adjust testosterone therapy if patient is on TRT
• Monitor testosterone levels until normalization
• Consider therapeutic phlebotomy if hematocrit is elevated (>54%) 2

For Endocrine Disorders:

• Treat the underlying condition:
  • Surgical removal for androgen-secreting tumors
  • Medical management for congenital adrenal hyperplasia
  • Treatment of hyperthyroidism if present 2

For Medication-Induced Hypergonadism:

• Adjust medication regimen:
  • Reduce or discontinue hCG, SERMs, or AIs if appropriate 4, 3
  • Consider alternative treatments for the condition being managed

Lifestyle Modifications:

• Weight management and regular exercise (150 minutes weekly of moderate-intensity exercise) 2
• Mediterranean diet rich in fruits, vegetables, whole grains, and lean proteins 2
• Limit alcohol consumption to less than 21 units per week 2

Monitoring and Follow-up

• Repeat testosterone measurements every 3-6 months until stabilized
• Monitor for complications:
  • Erythrocytosis (elevated hematocrit)
  • Prostate issues in men (PSA monitoring)
  • Cardiovascular risk factors

Special Considerations

For Men:

• Elevated testosterone may increase risk of erythrocytosis 4
• Monitor prostate health with PSA testing and digital rectal examination 4
• Consider fertility implications if planning to conceive 5

For Women:

• High testosterone can cause virilization and menstrual irregularities 1
• May contribute to infertility through disruption of normal ovulation 1
• Evaluate for PCOS or ovarian/adrenal tumors

Treatment Pitfalls to Avoid

1. Don't assume laboratory error without confirmation

   • Always repeat testing before dismissing elevated results

2. Don't overlook serious underlying causes

   • Tumors can present with rapid onset of symptoms and very high testosterone levels

3. Don't focus solely on testosterone levels

   • Address the underlying cause rather than just treating the hormone elevation

4. Don't ignore cardiovascular risk

   • High testosterone levels may increase cardiovascular risk, especially with exogenous sources

5. Don't miss the opportunity to identify steroid abuse

   • Consider this possibility, especially in athletes or bodybuilders

By following this structured approach to diagnosis and treatment, hypergonadism can be effectively managed while minimizing potential complications from persistently elevated testosterone levels.