What is the treatment approach for females with hyperandrogenism (high testosterone levels)?

Treatment Approach for Females with Hyperandrogenism (High Testosterone Levels)

The first-line treatment for females with hyperandrogenism should be based on the underlying cause, with anti-androgenic medications like spironolactone being the primary pharmacological intervention for most cases of hyperandrogenism not caused by tumors. 1

Diagnostic Evaluation

Before initiating treatment, proper diagnosis is essential:

• Measure morning total testosterone (TT) and free testosterone (FT) as first-line laboratory tests to assess biochemical hyperandrogenism, preferably using liquid chromatography with tandem mass spectrometry (LC-MS/MS) 2
• For patients with obesity, measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) level 1
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary causes 1
• Consider measuring androstenedione (A4) and dehydroepiandrosterone sulfate (DHEAS) if TT or FT are not elevated, noting their poorer specificity 2
• Rule out serious causes of severe hyperandrogenism, particularly if testosterone levels are very high (>2-3 SD above normal reference range) or if there is rapid onset of virilization 3, 4

Treatment Algorithm Based on Etiology

1. Polycystic Ovary Syndrome (PCOS)

PCOS is the most common cause of hyperandrogenism in premenopausal women 4, 5:

• First-line: Combined oral contraceptives to suppress ovarian androgen production 5
• Second-line: Spironolactone (50-200 mg daily) for anti-androgenic effects 1
• For metabolic concerns: Consider metformin if insulin resistance is present 5

2. Non-Classical Congenital Adrenal Hyperplasia (NCCAH)

• Low-dose glucocorticoids to suppress adrenal androgen production 4
• Can be diagnosed with elevated basal or ACTH-stimulated 17-hydroxyprogesterone levels 4

3. Androgen-Secreting Tumors (Ovarian or Adrenal)

• Surgical removal is the definitive treatment 3, 6
• Medical management with GnRH agonists/antagonists may be considered for patients unfit for surgery 6

4. Idiopathic Hyperandrogenism

• Anti-androgenic medications: Spironolactone (50-200 mg daily) 1
• Finasteride (5 mg daily) to prevent conversion of testosterone to dihydrotestosterone 1

Specific Treatments for Hyperandrogenism Symptoms

For Hirsutism

• Spironolactone (start at 50 mg daily, can increase to 200 mg daily) 1, 5
• Finasteride (5 mg daily) 1
• Topical eflornithine for facial hirsutism 5
• Cosmetic approaches: laser hair removal, electrolysis 5

For Acne

• Combined oral contraceptives 5
• Topical retinoids and antibiotics 5
• Oral antibiotics for moderate-to-severe cases 5

For Menstrual Irregularities

• Combined oral contraceptives to regulate cycles 5
• Cyclic progestins if contraceptives are contraindicated 5

Special Populations

Adolescents

• Careful evaluation is needed as there is overlap between normal puberty and PCOS symptoms 5
• Treatment of acne and hirsutism should not be withheld during ongoing evaluation 5

Postmenopausal Women

• Thorough investigation for androgen-secreting tumors is essential, as they are more common in this age group 6
• Elevated testosterone can lead to metabolic complications including hypercholesterolemia, insulin resistance, and hypertension 6

Monitoring and Follow-up

• Regular assessment of clinical symptoms every 3-6 months 1
• Laboratory monitoring of testosterone levels to ensure adequate suppression 1
• For patients on spironolactone, monitor potassium levels due to risk of hyperkalemia 1

Important Considerations

• Clinical improvement of hirsutism may take 6-12 months to become apparent 5
• Set realistic expectations with patients regarding timeline for treatment response 5
• Avoid exogenous testosterone therapy in women with hyperandrogenism, as this will worsen symptoms 2
• Consider fertility implications when selecting treatments, as some anti-androgens may be teratogenic 5