What is the workup for secondary amenorrhea (absence of menstruation)?

Workup for Secondary Amenorrhea

The workup for secondary amenorrhea should begin with a pregnancy test, followed by measuring FSH, LH, prolactin, and TSH levels to determine the underlying cause, which is essential for appropriate management and preventing complications like osteoporosis. 1

Initial Assessment

• Obtain a detailed menstrual history including age of menarche, previous regularity, and duration of amenorrhea (>6 months of no bleeding defines secondary amenorrhea) 2, 1
• Assess for weight changes, nutritional status, and calculate BMI (obesity: BMI >25) 2, 1
• Evaluate exercise habits, particularly excessive exercise which can lead to functional hypothalamic amenorrhea 1
• Identify psychological stressors that may contribute to hypothalamic dysfunction 2, 1
• Screen for symptoms of hyperandrogenism (hirsutism, acne) which may suggest PCOS 2
• Check for galactorrhea through breast examination, which may indicate hyperprolactinemia 2, 1
• Perform pelvic examination to rule out anatomical abnormalities and assess for signs of estrogen deficiency 1

Laboratory Testing

• Perform pregnancy test (first step in all cases of secondary amenorrhea) 1
• Measure FSH and LH levels to differentiate between hypothalamic, pituitary, and ovarian causes 1
  • High FSH/LH: Primary ovarian insufficiency
  • Normal/Low FSH/LH with low estradiol: Functional hypothalamic amenorrhea
  • Elevated LH:FSH ratio: Suggests PCOS
• Check prolactin level to rule out hyperprolactinemia 2, 1
• Measure TSH to identify thyroid dysfunction 1
• Consider additional hormone testing based on initial results:
  • Estradiol level if functional hypothalamic amenorrhea is suspected 1
  • Androgen profile (testosterone, DHEAS) if PCOS is suspected 1
  • Progesterone challenge test to determine estrogen status 1

Imaging Studies

• Transvaginal ultrasound to evaluate:
  • Endometrial thickness (indicator of estrogen status) 1
  • Ovarian morphology (polycystic ovarian morphology defined as ≥20 follicles of 2-9mm per ovary or ovarian volume >10ml) 2, 1
  • Uterine anatomy to rule out structural abnormalities 1
• Consider pituitary MRI if prolactin is elevated or central causes are suspected 2, 1
• DXA scan for bone mineral density assessment in patients with:
  • Amenorrhea lasting >6 months 2, 1
  • History of eating disorders or BMI <18.5 kg/m² 1
  • Late menarche (≥16 years) 1

Diagnostic Algorithm

1. Rule out pregnancy first with a pregnancy test 1
2. Measure FSH, LH, prolactin, and TSH to determine the underlying pathophysiology 1
3. Interpret hormone results:
   • High FSH/LH: Primary ovarian insufficiency - consider karyotype analysis and AMH level 1
   • Normal/Low FSH/LH: Functional hypothalamic amenorrhea - evaluate for stress, excessive exercise, or eating disorders 2, 1
   • Elevated LH:FSH ratio: Consider PCOS - perform androgen profile and metabolic screening 1
   • Elevated prolactin: Hyperprolactinemia - perform pituitary imaging 1
   • Abnormal TSH: Thyroid dysfunction - perform additional thyroid testing 1
4. Perform transvaginal ultrasound to assess ovarian morphology and endometrial thickness 1
5. Consider progesterone challenge test to assess estrogen status and endometrial responsiveness 1

Management Considerations

• For functional hypothalamic amenorrhea: address underlying causes (stress, excessive exercise, nutritional deficiencies) 2, 1
• For secondary amenorrhea due to decreased progesterone: progesterone capsules 400 mg daily at bedtime for 10 days may be prescribed 3
• For patients with amenorrhea >6 months: evaluate bone density and consider appropriate interventions 2, 1
• For PCOS: metabolic screening and interventions to reduce risk of glucose intolerance and dyslipidemia 1

Common Pitfalls to Avoid

• Failing to rule out pregnancy as the first step 1, 4
• Overlooking eating disorders in patients with functional hypothalamic amenorrhea 1
• Not assessing bone mineral density in patients with prolonged amenorrhea 2, 1
• Missing hyperprolactinemia by not checking prolactin levels 2, 1
• Neglecting to evaluate thyroid function 1
• Failing to recognize PCOS and its associated metabolic risks 1