Epidemiology

Etiology

Hypergonadotropic hypogonadism (primary hypogonadism)

Hypergonadotropic hypogonadism is caused by insufficient sex steroid production in the gonads.

• Primary gonadal insufficiency: Turner syndrome (females), Klinefelter syndrome (males), anorchia
• Secondary gonadal insufficiency (damage to Leydig cells or ovarian tissue): chemotherapy, pelvic irradiation, trauma/surgery, autoimmune disease (e.g, autoimmune polyglandular syndrome), infections (e.g., mumps, tuberculosis)

Hypogonadotropic hypogonadism (secondary hypogonadism)

Hypogonadotropic hypogonadism is caused by an insufficient gonadotropin-releasing hormone (GnRH) and/or gonadotropin release at the hypothalamic-pituitary axis.

• Genetic disorders
  • Kallmann syndrome
  • Idiopathic hypogonadotropic hypogonadism (IHH): a genetic disorder characterized by a defect in GnRH production/action in the absence of anosmia
  • Prader-Willi syndrome and Angelman syndrome
  • Gaucher disease
• Hypothalamic and/or pituitary lesions
  • Neoplasm (e.g. prolactinoma, craniopharyngioma, astrocytoma)
  • Trauma, surgery, irradiation

Pathophysiology

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

Diagnostics

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

Treatment