What is the workup for primary amenorrhea?

Workup for Primary Amenorrhea

The workup for primary amenorrhea should include pregnancy testing, hormone level assessment (FSH, LH, prolactin, TSH), and pelvic ultrasound to identify the underlying cause, with subsequent management directed at the specific etiology. 1, 2

Definition and Initial Evaluation

• Primary amenorrhea is defined as no menarche by age 15 years, or by age 13 years in the absence of secondary sexual characteristics 3, 1
• Initial evaluation should include a thorough history focusing on:
  • Growth and development patterns 1
  • Nutritional status and weight changes 1, 4
  • Exercise habits, especially excessive exercise 3
  • Psychological stressors 4

Physical Examination

• Assess height, weight, and BMI to evaluate for malnutrition or excessive exercise 1
• Evaluate for presence or absence of secondary sexual characteristics to direct further workup 5
• Perform breast examination for development and to check for galactorrhea 4
• Conduct pelvic examination to rule out outflow tract obstruction (transverse vaginal septum, imperforate hymen) 3, 5

Laboratory Testing

• First-line laboratory tests should include:
  • Pregnancy test (to rule out pregnancy) 4, 2
  • FSH and LH levels (to differentiate between hypothalamic, pituitary, and ovarian causes) 1, 4
  • Prolactin level (to evaluate for hyperprolactinemia) 4
  • TSH level (to rule out thyroid dysfunction) 4
  • Estradiol level (to assess ovarian function) 1

Imaging Studies

• Pelvic ultrasound is recommended to:
  • Assess uterine and ovarian anatomy 1
  • Identify structural abnormalities 1
  • Evaluate endometrial thickness 1
  • Detect polycystic ovarian morphology (≥20 follicles of 2-9mm per ovary or ovarian volume >10ml) 3
• MRI should be considered when:
  • Ultrasound is inconclusive 4
  • Pituitary abnormalities are suspected 4

Diagnostic Algorithm Based on Findings

• If no sexual development is present:
  • Consider constitutional delay of growth and puberty 5
  • Evaluate for gonadal dysgenesis (e.g., Turner syndrome) with karyotype analysis 2
• If normal pubertal development and uterus present:
  • Investigate for outflow tract obstruction 5
• If abnormal uterine development:
  • Consider müllerian agenesis and confirm with karyotype analysis 5
• Based on hormone levels:
  • High FSH/LH: Consider primary ovarian insufficiency 4
  • Normal/Low FSH/LH: Consider functional hypothalamic amenorrhea 4
  • Elevated prolactin: Consider hyperprolactinemia 4
  • Abnormal TSH: Consider thyroid dysfunction 4

Special Considerations

• DXA scan for bone mineral density assessment is recommended for:
  • Patients with amenorrhea lasting >6 months 4
  • History of eating disorders or BMI <18.5 kg/m² 4
  • Late menarche (≥16 years) 4
• Athletes with primary amenorrhea require evaluation for Relative Energy Deficiency in Sport (RED-S) 3
• Patients with hypothalamic amenorrhea should be evaluated for eating disorders 1

Common Pitfalls to Avoid

• Failure to rule out pregnancy as the first step 2
• Missing outflow tract obstruction, which is a common cause in patients with normal pubertal development 5
• Overlooking the possibility of polycystic ovary syndrome in patients with signs of hyperandrogenism 6
• Not considering functional hypothalamic amenorrhea in athletes or patients with low body weight 3
• Assuming infertility in patients with primary ovarian insufficiency, as they can maintain unpredictable ovarian function 2