Amenorrhea, Primary

KEY FEATURES

• Menarche ordinarily occurs between ages 11 and 15 years (average in United States: 12.7 years)

• Primary amenorrhea is failure of any menses to appear

• Evaluate at age 14 if no menarche or breast development or if height in lowest 3% for ethnicity, or at age 16 if menarche has still not occurred

• Causes

  • Hypothalamic-pituitary (low-normal follicle-stimulating hormone [FSH])

    • Most common cause is a constitutional delay of growth and puberty, which is a variant of normal; there is a genetic basis with strong family history of delayed puberty

    • Gonadotropin-releasing hormone or gonadotropin deficiency

    • Pituitary tumor

    • Cushing syndrome

    • Hypothyroidism

    • Hypothalamic amenorrhea (eg, severe illness, stress, weight change, vigorous exercise)

    • Anorexia nervosa

  • Hyperandrogenism (low-normal FSH)

    • Adrenal tumor or adrenal hyperplasia

    • Polycystic ovary syndrome

    • Ovarian tumor

    • Exogenous androgenic steroids

  • Uterine causes (normal FSH)

    • Absence of uterus

    • Imperforate hymen

  • Ovarian causes (high FSH)

    • Gonadal dysgenesis (Turner syndrome)

    • Autoimmune ovarian failure

  • Pseudohermaphroditism

    • 46,XY disorders of sexual development

    • Complete androgen insensitivity syndrome: individuals are born with completely normal external female genitalia, although some may have labial or inguinal swellings due to cryptorchid testes

    • Partial androgen insensitivity syndrome: individuals have variable degrees of ambiguous genitalia

  • Pregnancy (high human chorionic gonadotropin)

CLINICAL FINDINGS

• Nausea, breast engorgement suggest pregnancy

• Headaches or visual field abnormalities suggest hypothalamic or pituitary tumor

• Obesity and short stature suggest Cushing syndrome

• Hirsutism and virilization suggest excessive testosterone

• Short stature suggests growth hormone or thyroid hormone deficiency

• Short stature and gonadal dysgenesis indicate Turner syndrome

• Tall stature suggests eunuchoidism or acromegaly

• Anosmia suggests Kallmann syndrome

• Perform pelvic and rectal examination to assess for hymen patency and presence of a uterus

DIAGNOSIS

• Serum FSH, luteinizing hormone (LH), prolactin (PRL), total and free testosterone, thyroid-stimulating hormone (TSH), free T₄, and pregnancy test

• Serum electrolytes

• Further hormone evaluation if patient is virilized or hypertensive

• MRI of hypothalamus and pituitary is used to evaluate teens with primary amenorrhea and low or normal FSH and LH—especially those with high PRL levels

• Pelvic duplex/color sonography is very useful

• Karyotyping to diagnose X chromosome mosaicism

TREATMENT

• Treatment directed at underlying cause

• Hormone replacement therapy for females with permanent hypogonadism

• See Amenorrhea, Secondary & Menopause