Amenorrhea risk factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

The most common risk factor in the development of primary amenorrhea include chromosomal disorders and the most common risk factor in the development of secondary amenorrhea is breastfeeding. Common risk factors in the development of amenorrhea include risk factors related to hypothalamus, pituitary, ovaries, and also functional amenorrhea. Most common hypothalamic risk factors are Kallmann syndrome and chronic disorders. Most common pituitary risk factors are hyperprolactinemia and pituitary microadenoma.

• The most common risk factor in the development of primary amenorrhea is chromosomal disorder and the most common risk factor in the development of secondary amenorrhea is breastfeeding.
• Common risk factors in the development of amenorrhea include risk factors related to hypothalamus, pituitary, ovaries, and also functional amenorrhea. The risk factors in the development of amenorrhea, in an order from most common to least common, are as following:^[1][2]

• Kallmann syndrome
• Chronic disorders
  • Crohn disease
  • Cystic fibrosis
  • Sickle cell disease
  • Thalassemia major

• Congenital gonadotropin-releasing hormone deficiency

• Irradiation to the hypothalamus

• Infiltrative disorders of the hypothalamus
  • Langerhans cell granulomatosis
  • Lymphoma
  • Sarcoidosis
  • Tuberculosis (TB)

• Tumors of the hypothalamus
• Tumors of the brain
  • Meningioma
  • Craniopharyngioma
  • Gliomas
• Traumatic brain injury

• Hyperprolactinemia
• Pituitary microadenoma
• Cushing syndrome

• GnRH receptor gene mutations
• Infiltrative disorders of the pituitary
  • Hemochromatosis
  • Langerhans cell granulomatosis
  • Sarcoidosis
  • TB

• Isolated gonadotropin deficiency
• Postpartum pituitary necrosis (Sheehan syndrome)
• Traumatic brain injury
• Aneurysms of the pituitary

• Turner syndrome

• Androgen insensitivity syndrome (testicular feminization)
• Autoimmune disorders
  • Autoimmune oophoritis (in myasthenia gravis, thyroiditis, or vitiligo)

• Chemotherapy (e.g., high-dose alkylating drugs)
• Congenital adrenal virilism
• Gestational trophoblastic disease
• Drug-induced virilization
  • Androgens
  • Antidepressants
  • Danazol
  • High-dose progestins

• Prader-Willi syndrome
• Fragile X syndrome
• Idiopathic accelerated ovarian follicular atresia

• Gonadal dysgenesis
• Irradiation to the pelvis
• True hermaphroditism

• Tumors producing androgens (ovarian or adrenal)

• Viral infections (mumps)

• Family history of anatomical defects
• Radiation within pregnancy
• Dilation and curettage (D & C)
• Prior complicated Cesarean section
• Severe pelvic inflammatory disease (PID)-induced adhesion
• Uterus scarring

• Stress
• Excessive exercise
• Dieting
• Obesity
• Cachexia

• Eating disorders
  • Anorexia nervosa
  • Bulimia

• Malnutrition

• Hyperthyroidism
• Hypothyroidism

• HIV infection
• Drug abuse

• Alcohol
• Cocaine
• Marijuana
• Opioids

• Immunodeficiency

• Metabolic disorders
  • Addison disease
  • Diabetes mellitus
  • Galactosemia

• Psychiatric disorders
  • Stress
  • Depression
  • Obsessive-compulsive disorder
  • Schizophrenia
  • Psychoactive drugs

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• All other intense and strenuous sports

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