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