What investigations should be included in the workup of amenorrhea?

Comprehensive Workup for Amenorrhea

The initial workup for amenorrhea should include pregnancy testing, followed by measurement of FSH, LH, prolactin, TSH, and estradiol levels to determine the underlying cause. 1

Initial Evaluation

• Pregnancy test: Must be performed first as pregnancy is the most common cause of amenorrhea 2, 3
• Hormonal panel:
  • FSH and LH: To differentiate between hypothalamic, pituitary, and ovarian causes 2, 1
  • Prolactin: To rule out hyperprolactinemia 2, 1
  • TSH: To assess thyroid function 2, 1
  • Estradiol: To evaluate ovarian function 1
  • Testosterone (total and free): If signs of hyperandrogenism are present 1

Clinical Assessment

• Menstrual history: Document duration of amenorrhea (>6 months of no bleeding or >3 months of missed regular cycles) 3
• Signs of hormonal imbalance:
  • Hirsutism, acne, male-pattern hair loss (suggests PCOS or other androgen excess disorders) 2
  • Galactorrhea (suggests hyperprolactinemia) 2
  • Signs of estrogen deficiency (vaginal dryness, hot flashes) 2
• Weight changes: Recent weight loss, low BMI, or excessive exercise (suggests functional hypothalamic amenorrhea) 2

Imaging Studies

• Pelvic ultrasonography: Indicated when clinical features or hormonal tests suggest ovarian pathology 2

  • Transvaginal ultrasound is more sensitive than transabdominal for identifying structural abnormalities 2
  • Evaluates endometrial thickness (thin endometrium suggests hypoestrogenism) 2
  • Identifies polycystic ovarian morphology 2

• Pituitary MRI: Indicated if hyperprolactinemia is present or if clinical features suggest hypothalamic-pituitary abnormality 2

Specialized Testing

• Progesterone challenge test: To assess endogenous estrogen status and outflow tract patency 4

  • Positive withdrawal bleeding indicates adequate estrogen and patent outflow tract
  • Negative test suggests hypoestrogenism or outflow tract obstruction

• Bone density assessment (DXA scan): Recommended for patients with ≥6 months of amenorrhea, BMI <18.5 kg/m², history of disordered eating or excessive exercise 2, 1

Diagnosis-Specific Investigations

For Suspected PCOS

• LH:FSH ratio (often >2 in PCOS) 2
• Fasting glucose and insulin levels to assess insulin resistance 2
• Lipid profile to evaluate metabolic risks 2

For Suspected Functional Hypothalamic Amenorrhea (FHA)

• Calculate energy availability (energy intake minus exercise energy expenditure) 2
• Assess for disordered eating patterns 2
• Evaluate stress levels and psychological factors 2

For Suspected Primary Ovarian Insufficiency

• Anti-Müllerian hormone (AMH) levels 5
• Karyotype analysis if premature ovarian failure is suspected, especially in younger patients 5

For Suspected Liver Disease

• Liver function tests (in women with advanced liver disease, altered estrogen metabolism can lead to amenorrhea) 2

Common Pitfalls to Avoid

• Failing to rule out pregnancy before extensive workup 1
• Misdiagnosing functional hypothalamic amenorrhea with polycystic ovarian morphology (FHA-PCOM) as PCOS 1
• Neglecting to assess bone health in patients with prolonged amenorrhea 1
• Overlooking the possibility of hyperprolactinemia due to medication effects 1
• Assuming amenorrhea in female athletes is normal without proper investigation (amenorrhea may occur in up to 66% of athletes but should not be accepted as inevitable) 2

By following this systematic approach to the workup of amenorrhea, clinicians can efficiently identify the underlying cause and initiate appropriate management to prevent long-term complications such as bone loss and endometrial hyperplasia.