How do you treat hyperandrogenism in a male patient?

Treatment of Hyperandrogenism in Male Patients

The treatment of hyperandrogenism in male patients should focus on identifying and addressing the underlying cause while avoiding exogenous testosterone therapy, which can suppress spermatogenesis and worsen the condition. 1

Diagnostic Approach

• First-line laboratory testing should include total testosterone (TT) and free testosterone (FT), preferably measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for highest accuracy 2
• Second-line testing should include androstenedione and dehydroepiandrosterone sulfate (DHEAS) if initial tests are inconclusive 2
• LH/FSH ratio assessment helps distinguish between primary and secondary causes of hyperandrogenism 2, 3
• Rule out adrenal tumors, which can be a rare but potentially serious cause of hyperandrogenism in males 4
• Consider Cushing's disease as a potential cause of hyperandrogenism, which requires specific diagnostic workup 1

Treatment Algorithm

1. For Hypogonadotropic Hypogonadism

• First-line treatment: human chorionic gonadotropin (hCG) injections (500-2500 IU, 2-3 times weekly) 1
• Add FSH injections after testosterone levels normalize on hCG 1
• Avoid exogenous testosterone therapy in males interested in current or future fertility as it inhibits intratesticular testosterone production and suppresses spermatogenesis 1

2. For Androgen-Secreting Tumors

• Surgical intervention is the primary treatment for adrenal or testicular tumors causing hyperandrogenism 4
• For adrenal carcinomas, consider mitotane therapy, which is FDA approved for treatment of adrenal cancer with endogenous Cushing's syndrome 1

3. For Cushing's Disease

• Medical therapy options include:
  • Ketoconazole (400–1200 mg/day PO, dosing BID) - achieves approximately 65% UFC normalization initially 1
  • Osilodrostat (2–7 mg/day BID PO) - achieves 86% UFC normalization in phase 3 studies 1
  • Metyrapone (500 mg/day to 6 g/day; dosing every 6–8 hours) - achieves approximately 70% UFC normalization 1
• Monitor for side effects including GI disturbances, increased liver enzymes, and adrenal insufficiency 1

4. For Castration-Resistant Prostate Cancer with Hyperandrogenism

• For non-metastatic CRPC: observation with continued androgen deprivation therapy 1
• For metastatic CRPC: abiraterone plus prednisone, enzalutamide, or docetaxel-based chemotherapy depending on prior treatments 1
• Consider secondary hormonal therapy with antiandrogens, ketoconazole with/without glucocorticoids, or estrogens/progesterone 1

Important Clinical Considerations

• Recovery of spermatogenesis after cessation of testosterone therapy may take months or even years 1
• Monitor for metabolic complications associated with hyperandrogenism, particularly insulin resistance 2, 3
• Consider neuroendocrine differentiation in patients who do not respond to androgen deprivation therapy, especially those with high Gleason scores (9-10) 1
• For patients with hyperandrogenism related to adrenal dysfunction, surgical approach is often necessary due to the frequent malignant origin 4

Potential Pitfalls

• Exogenous testosterone therapy is commonly prescribed but can worsen fertility outcomes by suppressing spermatogenesis 1
• Failure to identify androgen-secreting tumors can lead to delayed treatment of potentially life-threatening conditions 4, 5
• Hyperandrogenism can manifest with various clinical presentations including hirsutism, acne, and androgenic alopecia, which may be overlooked in male patients 6, 7
• Drug interactions with ketoconazole and other medications require careful review before initiating treatment 1