What are the treatment options for symptoms of hyperandrogenism due to elevated testosterone levels?

Treatment Options for Symptoms of Hyperandrogenism Due to Elevated Testosterone

The primary treatment approach for hyperandrogenism due to elevated testosterone includes anti-androgens, 5α-reductase inhibitors, and medications that increase sex hormone binding globulin (SHBG), with selection based on specific symptoms and laboratory findings. 1

Clinical Presentation of Hyperandrogenism

Elevated testosterone levels can manifest through various symptoms depending on the severity and individual sensitivity:

• Dermatological manifestations:

  • Acne (particularly severe in patients with elevated DHT) 2
  • Seborrhea (oily skin)
  • Androgenetic alopecia (more common with elevated DHT levels) 2
  • Hirsutism (excessive terminal hair growth in androgen-dependent areas) 3

• Metabolic effects:

  • Insulin resistance
  • Hypercholesterolemia
  • Hypertension
  • Increased cardiovascular risk 3

Diagnostic Approach

Before initiating treatment, a thorough diagnostic evaluation is essential:

1. Laboratory assessment:

   • Total testosterone (first-line test) 4
   • Free testosterone calculation (more sensitive indicator of hyperandrogenism) 5
   • SHBG (often reduced in overweight patients or those with metabolic syndrome) 4
   • DHT levels (particularly important for alopecia and severe acne) 2
   • DHEAS (to evaluate adrenal contribution) 4
   • Androstenedione 3
   • LH/FSH ratio 2

2. Rule out serious underlying causes:

   • Adrenal or ovarian tumors (particularly if testosterone >2x upper limit of normal) 4, 3
   • Cushing's syndrome
   • Congenital adrenal hyperplasia
   • Ovarian hyperthecosis 3

3. Imaging studies (when indicated by laboratory results):

   • MRI of adrenal glands or ovaries if tumor suspected 3

Treatment Options

1. Pharmacological Interventions

• Anti-androgens:

  • Spironolactone: Blocks androgen receptors and inhibits 5α-reductase
  • Cyproterone acetate: Potent anti-androgen that blocks androgen receptors
    • For severe acne and hirsutism, higher doses (25-100 mg/day) may be required
    • For androgenetic alopecia, lower doses are typically effective 6
  • Flutamide: Androgen receptor antagonist (less commonly used due to hepatotoxicity risk)

• 5α-reductase inhibitors:

  • Finasteride: Blocks conversion of testosterone to DHT
  • Dutasteride: Dual inhibitor of both type I and II 5α-reductase isoenzymes
  • Particularly effective for androgenetic alopecia and seborrhea 6

• SHBG-increasing agents:

  • Oral contraceptives: Reduce androgen production and increase SHBG, resulting in decreased free testosterone 6
    • OCs with predominant estrogen effect improve mild to moderate acne, seborrhea, hirsutism, and androgenetic alopecia
    • OCs containing anti-androgenic progestogens (like cyproterone acetate) are more effective for severe symptoms 6

• Insulin sensitizers:

  • Metformin: Particularly useful when hyperandrogenism is associated with insulin resistance

2. Aromatase Inhibitors

• Anastrozole: Can be considered to reduce conversion of testosterone to estradiol 1
• Must be used cautiously as they may potentially increase testosterone levels

3. Selective Estrogen Receptor Modulators (SERMs)

• Clomiphene citrate: Modulates the hypothalamic-pituitary-gonadal axis 1
• May be beneficial in certain cases of hyperandrogenism

4. GnRH Agonists/Antagonists

• Reserved for severe cases or when the source of elevated testosterone cannot be identified
• Particularly useful in patients unfit for surgery when a tumor is suspected 3

5. Surgical Intervention

• Required for androgen-secreting tumors of adrenal or ovarian origin 3

Treatment Duration and Monitoring

• Clinical improvement timeline varies by symptom:

  • Acne and seborrhea: Improvement within 3-6 months
  • Hirsutism: Significant improvement after 6-12 months
  • Androgenetic alopecia: Optimal effect after at least 12 months 6

• Regular monitoring should include:

  • Testosterone levels (total and free)
  • SHBG levels
  • DHT levels when indicated
  • Clinical assessment of symptoms 1

Important Considerations

• Symptoms may recur after treatment discontinuation, requiring maintenance therapy 6
• Treatment selection should be based on predominant symptoms (e.g., 5α-reductase inhibitors for DHT-mediated symptoms like alopecia)
• Combination therapy may be necessary for patients with multiple symptoms or inadequate response to monotherapy
• Potential side effects of anti-androgens (including hepatotoxicity, electrolyte disturbances) require monitoring

Caution

• Alkylated oral testosterone should not be prescribed due to risk of liver toxicity 1
• Patients should be informed about potential side effects of anti-androgen therapy, including gynecomastia, erectile dysfunction, and decreased libido in males