What laboratory tests should be included in the initial evaluation of a patient presenting with amenorrhea?

Initial Laboratory Evaluation for Amenorrhea

The initial laboratory evaluation for a patient presenting with amenorrhea should include pregnancy test, FSH, LH, estradiol, prolactin, and TSH as the core diagnostic tests, with additional targeted testing based on clinical suspicion. 1

Primary vs. Secondary Amenorrhea Assessment

Initial Core Laboratory Tests

• Pregnancy test (first step in all cases)
• FSH (follicle-stimulating hormone)
• LH (luteinizing hormone)
• Estradiol
• Prolactin
• TSH (thyroid-stimulating hormone)

Additional First-Line Tests Based on Clinical Presentation

• Complete blood count
• Androgen profile (total and free testosterone, DHEAS) if signs of hyperandrogenism
• Fasting glucose and insulin if PCOS is suspected
• Progesterone challenge test to assess estrogen status and outflow tract patency

Diagnostic Algorithm

1. Rule out pregnancy - Always the first step regardless of history

2. Evaluate hormonal status:

   • High FSH/LH (>35 IU/L): Suggests primary ovarian insufficiency
   • Normal/Low FSH/LH with high prolactin (>20 μg/L): Suggests hyperprolactinemia
   • Normal/Low FSH/LH with normal prolactin: Consider hypothalamic amenorrhea or PCOS
   • LH:FSH ratio >2: Suggests PCOS 1
   • Abnormal TSH: Suggests thyroid dysfunction

3. If prolactin is elevated: Brain MRI with contrast to rule out pituitary adenoma 1

4. If androgen levels are elevated:

   • Testosterone >2.5 nmol/L
   • Androstenedione >10.0 nmol/L
   • DHEAS >3800 ng/ml (age 20-29) or >2700 ng/ml (age 30-39)
   • Consider PCOS or other causes of hyperandrogenism 1

Imaging Studies

• Pelvic/transvaginal ultrasound: Indicated to evaluate ovarian morphology (looking for ≥20 follicles per ovary and/or ovarian volume ≥10ml) and rule out structural anomalies 1
• Brain MRI with contrast: Indicated if prolactin is elevated or multiple pituitary hormone abnormalities are present 1

Special Considerations

Functional Hypothalamic Amenorrhea (FHA)

For patients with suspected FHA (history of stress, excessive exercise, or weight loss):

• Evaluate LH:FSH ratio (typically <1 in 82% of FHA patients) 2
• Assess for signs of estrogen deficiency
• Consider bone density testing if prolonged hypoestrogenic state 2, 1

Athletes

For athletes with amenorrhea:

• Assess energy availability
• Laboratory assessment should include hemoglobin, LH, FSH, prolactin, estradiol, T4, TSH 2
• Consider bone mineral density testing if amenorrhea persists >6 months 2

Common Pitfalls to Avoid

1. Failing to rule out pregnancy before extensive workup
2. Overlooking thyroid dysfunction - Always check TSH in all patients with amenorrhea 1, 3
3. Missing hyperprolactinemia - Check prolactin levels in all cases 3, 4
4. Incomplete evaluation of PCOS - Remember to assess metabolic parameters (glucose, insulin) 1
5. Assuming infertility in all cases - Patients with primary ovarian insufficiency can maintain unpredictable ovarian function 5
6. Not considering medication effects - Always review current medications as potential causes 1

When to Refer

• Gynecology referral: For suspected anatomic abnormalities or persistent symptoms despite normal laboratory values 1
• Endocrinology referral: For elevated FSH levels, suspected PCOS with metabolic concerns, or suspected chromosomal abnormalities 1

By following this systematic approach to laboratory evaluation, the underlying cause of amenorrhea can be identified in most cases, allowing for appropriate treatment and management of associated health risks.