Hyperandrogenism

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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:

FeaturePCOSLate-Onset CAHAndrogen-Secreting Tumor
OnsetPeri-pubertal, gradualPeri-pubertal, gradualRapid, any age (post-pubertal)
VirilizationUsually absent/mild hirsutismMild-moderate hirsutismOften severe, rapid
Key Lab↑LH/FSH, ↑Testo (mild-mod)↑17-OHP (baseline/post-ACTH)Markedly ↑Testo or DHEAS

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. Modified Ferriman-Gallwey scoring system for hirsutism
  • 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.

Practice Questions: Hyperandrogenism

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Flashcards: Hyperandrogenism

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Polycystic ovarian syndrome is a condition characterized by at least 2/3 of the following criteria:- signs of _____- irregular periods (typically oligomenorrhea)- polycystic ovaries on ultrasound

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Polycystic ovarian syndrome is a condition characterized by at least 2/3 of the following criteria:- signs of _____- irregular periods (typically oligomenorrhea)- polycystic ovaries on ultrasound

Hyperandrogenism

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