What is the initial step in the workup of a patient presenting with amenorrhea (absence of menstruation)?

Initial Workup for Amenorrhea

The initial step in the workup of a patient presenting with amenorrhea should be a pregnancy test, followed by measurement of serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH). 1, 2

Diagnostic Approach

Step 1: Rule Out Pregnancy

• Pregnancy testing should always be the first step regardless of sexual history 3
• This is the most common cause of secondary amenorrhea in women of reproductive age

Step 2: Basic Laboratory Assessment

• Measure serum levels of:
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Prolactin
  • Thyroid-stimulating hormone (TSH)

Step 3: Interpret Results to Guide Further Evaluation

If FSH/LH elevated:

• Suggests primary ovarian insufficiency 3
• Consider karyotype analysis, especially in younger patients
• Evaluate for autoimmune disorders

If Prolactin elevated:

• Evaluate for galactorrhea and visual field defects
• Brain imaging to rule out pituitary adenoma 3
• Review medications that can cause hyperprolactinemia

If TSH abnormal:

• Further thyroid function tests
• Treat underlying thyroid disorder

If normal laboratory values with normal weight:

• Consider polycystic ovary syndrome (PCOS)
• Evaluate for clinical signs of hyperandrogenism
• Consider pelvic ultrasound

If normal laboratory values with low weight or excessive exercise:

• Consider functional hypothalamic amenorrhea
• BMI calculation (BMI ≤17.5 kg/m² is high-risk) 3
• Assess for weight loss ≥10% body weight in 1 month 3
• Evaluate for disordered eating behaviors
• Consider bone mineral density testing if amenorrhea persists >6 months 3

Classification-Based Approach

Primary Amenorrhea (no menarche by age 16)

• Evaluate presence/absence of sexual development
• If normal development with uterus present: consider outflow tract obstruction
• If abnormal uterine development: consider müllerian agenesis 4
• If no sexual development: consider chromosomal disorders or constitutional delay 4

Secondary Amenorrhea (cessation of menses for ≥3 months if previously regular, or ≥6 months if previously irregular)

• Most common causes:
  • Polycystic ovary syndrome
  • Hypothalamic amenorrhea
  • Hyperprolactinemia
  • Primary ovarian insufficiency 1

Common Pitfalls to Avoid

• Failing to rule out pregnancy as the first step 3
• Missing eating disorders in patients with functional hypothalamic amenorrhea 3
• Assuming patients with primary ovarian insufficiency are infertile (they may maintain unpredictable ovarian function) 1, 2
• Overlooking metabolic risks in PCOS patients (glucose intolerance, dyslipidemia) 1
• Neglecting bone health assessment in patients with prolonged amenorrhea 3

By following this systematic approach to amenorrhea evaluation, clinicians can efficiently identify the underlying cause and develop an appropriate treatment plan to address both the amenorrhea and any associated health risks.