What are the treatment options for women with hyperandrogenism (high testosterone levels)?

Treatment Options for Women with Hyperandrogenism (High Testosterone Levels)

The treatment of hyperandrogenism in women should target the underlying cause, with combined oral contraceptives (COCs) being the first-line therapy for most women with polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism. 1

Diagnostic Approach

Before initiating treatment, proper diagnosis is essential:

1. Laboratory Testing:

   • Morning total and free testosterone levels
   • Dehydroepiandrosterone sulfate (DHEAS)
   • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
   • Sex hormone-binding globulin (SHBG)
   • Consider 17-hydroxyprogesterone if congenital adrenal hyperplasia is suspected 1, 2

2. Clinical Assessment:

   • Evaluate for hirsutism (excessive facial/body hair)
   • Acne
   • Androgenic alopecia (male-pattern hair loss)
   • Menstrual irregularities
   • Infertility
   • Virilization signs (clitoromegaly, deepening voice, increased muscle mass) 1, 3

3. Rule Out Serious Causes:

   • Very high testosterone levels (>2-3 SD above normal) warrant investigation for androgen-secreting tumors, especially if rapid onset of symptoms 4, 3
   • Consider imaging (MRI/ultrasound) of adrenal glands and ovaries if tumor suspected 3

Treatment Options Based on Etiology

1. Polycystic Ovary Syndrome (PCOS)

• First-line: Combined oral contraceptives (COCs)

  • Suppress ovarian androgen production
  • Increase SHBG, reducing free testosterone
  • Regulate menstrual cycles
  • Improve acne and hirsutism 1

• Second-line: Antiandrogens

  • Spironolactone (50-200 mg daily)
    • Blocks androgen receptors
    • Often combined with COCs to prevent pregnancy (teratogenic risk) 1
  • Finasteride (2.5-5 mg daily)
    • 5α-reductase inhibitor that prevents conversion of testosterone to DHT 1
  • Flutamide (used less commonly due to hepatotoxicity risk) 3

• For metabolic concerns:

  • Metformin (1500-2000 mg daily)
    • Improves insulin sensitivity
    • May help restore ovulation
    • Can be used alone or with COCs 1

2. Non-Classic Congenital Adrenal Hyperplasia

• Glucocorticoids (low-dose)
  • Suppress adrenal androgen production
  • Often combined with COCs or antiandrogens 1

3. Androgen-Secreting Tumors

• Surgical resection is curative for ovarian or adrenal tumors 3
• Post-surgical testosterone levels typically normalize within 24 hours 4

4. Idiopathic Hyperandrogenism

• Similar approach to PCOS treatment
• COCs plus antiandrogens based on symptom severity 1

Treatment Based on Specific Symptoms

For Hirsutism

• Pharmacological:

  • COCs (containing drospirenone or cyproterone acetate preferred)
  • Antiandrogens (spironolactone, finasteride)
  • Topical eflornithine hydrochloride cream (slows hair growth) 1

• Mechanical hair removal:

  • Laser therapy
  • Electrolysis
  • Waxing, shaving, plucking (temporary measures) 1

For Acne

• COCs
• Topical or systemic retinoids
• Antiandrogens
• Topical or oral antibiotics 1

For Infertility

• Weight loss (if overweight) - even 5% weight reduction can improve ovulation and pregnancy rates 1
• Clomiphene citrate - first-line ovulation induction (80% ovulate, 50% conceive) 1
• Low-dose gonadotropins if clomiphene fails (better for monofollicular development) 1
• Metformin may improve ovulation frequency 1

Monitoring and Follow-up

• Monitor testosterone levels every 3-6 months initially, then annually
• Assess clinical improvement in hirsutism, acne, and menstrual regularity
• For women on spironolactone, monitor potassium levels if other risk factors for hyperkalemia exist 1
• For women on COCs, monitor for contraindications and side effects

Special Considerations

• Pregnancy planning: Discontinue antiandrogens and COCs before attempting conception 1
• Postmenopausal women: Investigate any new-onset hyperandrogenism thoroughly, as androgen-secreting tumors are more concerning in this population 3
• Adolescents: May need more aggressive treatment to prevent long-term consequences of hyperandrogenism 2

Common Pitfalls to Avoid

1. Failing to rule out serious causes - Always investigate rapid-onset or severe hyperandrogenism for tumors
2. Inadequate treatment duration - Improvement in hirsutism may take 6-12 months
3. Overlooking metabolic complications - Screen for diabetes, dyslipidemia, and hypertension in women with PCOS
4. Ignoring fertility concerns - Avoid treatments that further suppress fertility if pregnancy is desired
5. Laboratory errors - Consider extraction procedures if testosterone levels are extremely high without clinical virilization 4

By following this structured approach to diagnosis and treatment, most women with hyperandrogenism can achieve significant improvement in both symptoms and quality of life.