Hypogonadism

Epidemiology

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Etiology

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• Primary Hypogonadism (Hypergonadotropic Hypogonadism)
  • Pathophysiology: Testicular or ovarian failure. The problem is in the gonads themselves.
  • Labs: ↓ Testosterone/Estrogen, ↑↑ LH & FSH (due to loss of negative feedback).
  • Causes in Males:
    • Klinefelter Syndrome (47, XXY): Most common congenital cause. Features include tall stature, small/firm testes, gynecomastia, and infertility.
    • Cryptorchidism: Undescended testes.
    • Orchitis: e.g., Mumps virus.
    • Trauma, radiation, chemotherapy.
    • Hemochromatosis.
  • Causes in Females:
    • Turner Syndrome (45, XO): Features include short stature, webbed neck, shield chest, and streak ovaries.
    • Premature Ovarian Failure.
    • Pelvic radiation or chemotherapy.
    • Autoimmune oophoritis.
    • Galactosemia.
• Secondary Hypogonadism (Hypogonadotropic Hypogonadism)
  • Pathophysiology: Pituitary or hypothalamic failure. The gonads are normal but are not being stimulated.
  • Labs: ↓ Testosterone/Estrogen, ↓ or inappropriately normal LH & FSH.
  • Causes (affecting hypothalamus/pituitary):
    • Congenital:
      • Kallmann Syndrome: A genetic disorder characterized by defective migration of GnRH-releasing neurons. It is associated with anosmia (impaired sense of smell).
      • Prader-Willi Syndrome.
    • Acquired:
      • Pituitary tumors (e.g., prolactinoma, craniopharyngioma).
      • Head trauma, pituitary surgery, or radiation.
      • Infiltrative diseases: Sarcoidosis, hemochromatosis.
      • Functional: Severe systemic illness, malnutrition, excessive exercise, obesity, opioid use.

Pathophysiology

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Diminished functional activity of the gonads → reduced biosynthesis of sex hormones → impaired secondary sexual characteristics and infertility

• Hypergonadotropic hypogonadism: gonadal insufficiency → insufficient sex steroid production (↓ testosterone, ↓ estrogen) → increased gonadotropin secretion (↑ FSH and ↑ LH) from the anterior pituitary → lack of negative feedback from the impaired gonads → further ↑ FSH and ↑ LH levels
• Hypogonadotropic hypogonadism
  • In Kallmann syndrome: impaired migration of GnRH cells and defective olfactory bulb → ↓ GnRH in hypothalamus → ↓ FSH and ↓ LH → ↓ testosterone and ↓ estrogen
  • In hypothalamic and/or pituitary lesions: ↓ pituitary gonadotropins (↓ FSH and ↓ LH) → ↓ testosterone and ↓ estrogen

Clinical features

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Diagnostics

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• Hypergonadotropic hypogonadism: ↑ GnRH, ↑ LH/FSH
• Hypogonadotropic hypogonadism: ↓ GnRH, ↓ LH/FSH

Tip

• Normally LH/FSH = 1
• LH is more sensitive to hypothalamic GnRH

Treatment

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