At what levels of free testosterone and total testosterone should a patient with hyperandrogenism be started on treatment, and what type of treatment is recommended?

Treatment Thresholds and Management for Hyperandrogenism

Treatment for hyperandrogenism should be initiated when free testosterone exceeds 25 pg/mL and total testosterone exceeds 450-600 ng/dL, with anti-androgen therapy being the first-line treatment approach. 1, 2

Diagnostic Thresholds and Evaluation

• The American Urological Association (AUA) defines hyperandrogenism as total testosterone levels consistently above the normal physiologic range of 450-600 ng/dL 1
• Free testosterone levels above 25 pg/mL are considered elevated and indicative of hyperandrogenism requiring intervention 2, 3
• Diagnosis should be confirmed with at least two separate morning testosterone measurements to account for diurnal variation 1
• When evaluating hyperandrogenism, both total and free testosterone should be measured, as free testosterone better reflects bioavailable androgen 3

Pre-Treatment Assessment

• Before initiating treatment, perform a comprehensive evaluation including:
  • Measurement of hemoglobin/hematocrit (withhold treatment if hematocrit >50%) 1
  • Assessment for cardiovascular disease risk factors 1
  • PSA testing for patients over 40 years 1
  • Reproductive health evaluation if fertility is a concern 1
  • DHEAS assay if testosterone is twice the upper limit of normal to rule out adrenal causes 2

Treatment Options

First-Line Treatment:

• Anti-androgen therapy is the first-line treatment for hyperandrogenism with significantly elevated testosterone levels 2, 4
• Options include:
  1. Spironolactone (100-200 mg daily)
  2. Finasteride (5 mg daily) - particularly effective for patients with elevated DHT 5
  3. Flutamide (250 mg daily) - though less commonly used due to hepatotoxicity risk

Adjunctive Treatments:

• Lifestyle modifications should be recommended to all patients with hyperandrogenism 1

  • Weight loss and increased physical activity can help reduce testosterone levels 1
  • Dietary changes to reduce insulin resistance may be beneficial 4

• Hormonal therapy may be considered in specific cases:

  • Combined oral contraceptives for women with hyperandrogenism 4
  • GnRH analogues for severe cases unresponsive to other treatments 5

Monitoring During Treatment

• Monitor testosterone levels every 3-6 months during treatment 1

  • Target total testosterone levels in the middle tertile of normal range (450-600 ng/dL) 1
  • Free testosterone should be maintained below 25 pg/mL 3

• Regular monitoring should include:

  • Hemoglobin/hematocrit (discontinue or reduce dose if hematocrit >54%) 1
  • Liver function tests, especially with oral anti-androgens 1
  • PSA in men over 40 years 1
  • Blood pressure and cardiovascular risk assessment 1

Special Considerations

• Fertility concerns: Anti-androgen therapy can impair spermatogenesis; patients interested in fertility should have a reproductive health evaluation prior to treatment 1

  • Exogenous testosterone should not be used in patients trying to conceive 1

• Cardiovascular risk: Patients with recent cardiovascular events should wait 3-6 months before initiating treatment 1

  • Current evidence does not definitively show increased cardiovascular risk with treatment, but careful monitoring is advised 1

• Prostate health: For men over 40, PSA should be monitored regularly during treatment 1

  • Consider prostate biopsy if PSA increases by >1.0 ng/mL in the first year of treatment or >0.4 ng/mL per year thereafter 1

Treatment Efficacy and Expectations

• Patients should be informed that treatment may take 3-6 months to show significant clinical improvement 4
• If symptoms persist despite normalized testosterone levels, consider alternative diagnoses or additional treatments 1
• Treatment should be continued as long as hyperandrogenism persists, with periodic attempts to reduce dosage to determine if continued therapy is necessary 1, 5