What are the diagnosis and treatment options for hyperandrogenism?

Diagnosis and Treatment of Hyperandrogenism

For diagnosing biochemical hyperandrogenism, free testosterone (FT) and total testosterone (TT) should be used as first-line laboratory tests, preferably measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for highest accuracy. 1

Diagnostic Approach

Clinical Assessment

• Evaluate for common clinical manifestations of hyperandrogenism including hirsutism (using modified Ferriman-Gallwey scoring), acne, androgenic alopecia, and in severe cases, virilization 2, 3
• Assess for menstrual irregularities, as hyperandrogenism often presents with oligo/anovulation 4, 5
• Record body mass index and blood pressure, as metabolic complications are common with hyperandrogenic conditions 4

Laboratory Testing

• First-line testing should include:

  • Total testosterone (TT) and free testosterone (FT) measured by LC-MS/MS 1
  • Where mass spectrometry is unavailable, free androgen index (FAI) can be employed with good diagnostic accuracy 1

• Second-line testing (if TT or FT not elevated):

  • Androstenedione (A4) and dehydroepiandrosterone sulfate (DHEAS), noting their poorer specificity 1
  • LH/FSH ratio (>2 suggests PCOS) 4
  • 17-hydroxyprogesterone to screen for non-classic congenital adrenal hyperplasia 5, 6

• For severe or rapidly progressive hyperandrogenism with virilization:

  • Consider additional testing to rule out androgen-secreting tumors 3, 6
  • Overnight dexamethasone suppression test or 24-hour urinary free cortisol to exclude Cushing's disease 6

Differential Diagnosis

• Polycystic ovary syndrome (PCOS) - most common cause of hyperandrogenism 4, 6
• Non-classic congenital adrenal hyperplasia (NCCAH) 6
• Cushing's disease 6
• Androgen-secreting tumors (ovarian or adrenal) 3, 6
• Idiopathic hyperandrogenism 5
• Physiologic hyperandrogenism of puberty 5

Treatment Options

Pharmacological Approaches

• First-line treatment: Combined oral contraceptives (COCs)

  • Effectively regulate menstrual cycles and reduce hyperandrogenism 4
  • Improve acne and hirsutism by suppressing androgen production 4, 2

• Antiandrogen therapy:

  • Options include cyproterone acetate, spironolactone, and flutamide 3
  • Consider for patients with persistent symptoms despite COC therapy 2
  • 5α-reductase inhibitors may be used to block conversion of testosterone to dihydrotestosterone 2

Cosmetic Management for Hirsutism

• Short-term options: shaving, chemical depilation, plucking, threading, waxing, and bleaching 2
• Long-term options: electrolysis, laser therapy, and intense pulse light therapy 2
• Topical eflornithine hydrochloride can be used as adjunctive therapy 2

Metabolic Management

• Screen for and manage metabolic complications, particularly insulin resistance 4
• Consider lifestyle modifications including diet and exercise for overweight/obese patients 4

Treatment Response Timeline

• Acne typically responds relatively quickly to therapy 2
• Hirsutism improvement may be observed as early as 3 months, but typically requires 6-8 months of consistent therapy 2
• Female pattern hair loss (FPHL) is slowest to respond, potentially requiring 12-18 months of therapy, and may not improve in all cases 2

Important Clinical Considerations

• Virilization (clitoromegaly, deepening voice, increased muscle mass) is uncommon in typical hyperandrogenism and warrants investigation for androgen-secreting tumors 3, 6
• The psychological impact of hyperandrogenism symptoms should be addressed as part of comprehensive care 4
• Treatment should not be withheld during ongoing evaluation for underlying causes 5
• Patient expectations regarding treatment timeline and efficacy should be discussed before initiating therapy 5