Hyperandrogenism

Definition & Physiology - Androgen Excess 101

• Hyperandrogenism: Clinical (e.g., hirsutism, acne, alopecia) or biochemical evidence of elevated androgen levels.
• Principal Androgens & Sources:
  • Testosterone (T): Primarily ovarian & adrenal; potent.
  • DHEAS (Dehydroepiandrosterone sulfate): Exclusively adrenal; weak androgen, but good marker.
  • Androstenedione (A4): Ovarian & adrenal; precursor to T.
• Peripheral conversion in skin/adipose tissue also contributes to active androgens.

⭐ 5α-reductase converts testosterone to dihydrotestosterone (DHT), a more potent androgen, primarily in target tissues like hair follicles and skin.

Etiology & Clinical Features - Causes & Hairy Signs

Common Causes & Differentiating Features:

Other Etiologies:

• Adrenal: Cushing's Syndrome
• Drugs: Danazol, Valproate, Steroids
• Endocrine: Hyperprolactinemia, Hypothyroidism
• Idiopathic Hirsutism: Normal androgens, ↑skin sensitivity

Clinical Features (Spectrum of Androgen Excess):

• Hirsutism:
  • Excess terminal hair (male pattern: face, chest, back)
  • Ferriman-Gallwey score >8.
• Cutaneous Signs:
  • Acne, Seborrhea
  • Androgenic alopecia (temporal, vertex thinning)
• Menstrual Dysfunction:
  • Oligo/amenorrhea
• Virilization (Red Flag: Tumor/Severe Excess):
  • Clitoromegaly (>10mm length)
  • Voice deepening
  • ↑Muscle mass, male habitus
  • Breast atrophy

Diagnostic Workup - Unmasking the Source

• History & Exam: Assess symptom onset/progression (hirsutism, acne, alopecia). Note signs of virilization (clitoromegaly, voice deepening, muscle mass ↑).

• Initial Key Labs:

  • Total Testosterone (T)
  • DHEA-S (Adrenal marker)
  • 17-hydroxyprogesterone (17-OHP) (early morning, follicular phase)

• Diagnostic Algorithm:

• Further Tests (if indicated): Prolactin, TSH, Cushing's screen (e.g., 1mg overnight dexamethasone suppression test).

⭐ Basal 17-OHP >200 ng/dL warrants an ACTH stimulation test for Non-Classical Congenital Adrenal Hyperplasia (NCAH); a post-ACTH 17-OHP level >1000-1500 ng/dL is diagnostic.

Management Approaches - Taming the Hormones

• Lifestyle Modification: Weight loss (≥5% of body weight) in PCOS improves insulin sensitivity & hyperandrogenism.
• Cosmetic Measures: For hirsutism (e.g., laser, electrolysis, eflornithine cream).
• Pharmacological Therapy:
  • Oral Contraceptive Pills (OCPs): First-line for menstrual regulation & hirsutism. Suppress LH, ↑SHBG.
  • Anti-androgens: Added if OCP response is inadequate after 6 months.
    • Spironolactone: 50-200 mg/day. Androgen receptor blocker. ⚠️ Monitor K+.
    • Finasteride: 5 mg/day. 5α-reductase inhibitor (Type 2).
  • Metformin: For PCOS with metabolic syndrome, impaired glucose tolerance (IGT), or Type 2 Diabetes Mellitus (T2DM).
  • GnRH Agonists: (e.g., Leuprolide) For severe refractory hyperandrogenism (e.g., ovarian hyperthecosis).

⭐ Combined oral contraceptives (OCPs) are the first-line medical therapy for both hirsutism and menstrual cycle disturbances in women with Polycystic Ovary Syndrome (PCOS).

High‑Yield Points - ⚡ Biggest Takeaways

• PCOS is the most common cause; use Rotterdam criteria (2 of 3) for diagnosis.
• Manifests as hirsutism (Ferriman-Gallwey), acne, alopecia, and menstrual irregularity.
• Key labs: total testosterone, DHEAS; 17-OHP to exclude late-onset CAH.
• Rapid virilization (clitoromegaly, voice change) signals possible androgen-secreting tumor.
• Treatment: lifestyle changes, OCPs (first-line), spironolactone or other anti-androgens.
• Insulin resistance is a frequent comorbidity, especially with PCOS.