What is the workup for primary amenorrhea?

Workup for Primary Amenorrhea

The workup for primary amenorrhea should begin with a detailed history, physical examination, pregnancy test, and laboratory assessment including FSH, LH, estradiol, prolactin, and TSH to determine the underlying cause and guide appropriate management. 1

Initial Assessment

• Primary amenorrhea is defined as the absence of menarche by age 16 years or by age 13 years in the absence of secondary sexual characteristics 1

• A thorough history should focus on:

  • Growth and development patterns
  • Presence of secondary sexual characteristics
  • Family history of delayed puberty
  • Nutritional status and exercise patterns
  • Symptoms of hyperandrogenism (acne, hirsutism)
  • Symptoms of hypothalamic dysfunction (stress, weight loss) 2

• Physical examination should include:

  • Height, weight, and BMI calculation
  • Assessment of secondary sexual characteristics (Tanner staging)
  • Examination for signs of hyperandrogenism
  • Examination of external genitalia and, if appropriate, pelvic examination to assess for anatomical abnormalities 1

Laboratory Evaluation

• Initial laboratory tests should include:
  • Pregnancy test (to exclude pregnancy as a cause) 3
  • FSH and LH levels (to differentiate between hypothalamic, pituitary, and ovarian causes) 4
  • Estradiol (to assess ovarian function) 4
  • Prolactin (to rule out hyperprolactinemia) 1
  • TSH (to exclude thyroid dysfunction) 1

Diagnostic Algorithm

Based on presence/absence of secondary sexual characteristics:

If NO secondary sexual characteristics:

• Measure FSH and LH levels 4
  • High FSH/LH: Suggests gonadal dysgenesis (e.g., Turner syndrome) - karyotype analysis recommended 1
  • Low/normal FSH/LH: Suggests hypothalamic or pituitary disorder - evaluate for constitutional delay, functional hypothalamic amenorrhea, or other central causes 1

If normal secondary sexual characteristics:

• Evaluate for outflow tract obstruction:
  • Physical examination and pelvic ultrasound to assess for imperforate hymen, transverse vaginal septum, or Müllerian agenesis 2
  • If normal outflow tract, proceed with hormonal evaluation as above 1

If abnormal secondary sexual characteristics:

• Evaluate for PCOS, adrenal disorders, or other causes of hyperandrogenism 3
• Consider testosterone levels and DHEAS if signs of androgen excess are present 1

Imaging Studies

• Pelvic ultrasound: To assess uterine and ovarian anatomy, identify structural abnormalities, and evaluate endometrial thickness 4
• MRI of the brain: Consider if hypogonadotropic hypogonadism is suspected to evaluate the hypothalamic-pituitary region 1
• Bone age assessment: Useful in cases of delayed puberty to assess skeletal maturation 1

Referral Criteria

Referral to pediatric endocrinology/gynecology is recommended for any patient who has:

• No signs of puberty by 13 years of age 4
• Primary amenorrhea by 16 years of age 4
• Failure of pubertal progression 4

Special Considerations

• Patients with primary ovarian insufficiency may maintain unpredictable ovarian function and should not be presumed infertile 1
• Patients with hypothalamic amenorrhea should be evaluated for eating disorders and are at risk for decreased bone density 4
• Consider genetic testing in cases of suspected genetic disorders (e.g., Turner syndrome, Woodhouse-Sakati syndrome) 5
• Assess bone health in patients with prolonged hypoestrogenism, as they are at increased risk for osteoporosis 4

Management Approach

Management depends on the underlying cause but generally aims to:

• Promote normal pubertal development
• Prevent complications such as osteoporosis and endometrial hyperplasia
• Preserve fertility when possible 2

For patients with hypogonadism, hormone replacement therapy may be indicated to induce puberty and maintain secondary sexual characteristics 5