What labs should be checked for a patient with a 9-month history of amenorrhea (absence of menstruation)?

Laboratory Evaluation for 9-Month Amenorrhea

For a patient with a 9-month history of amenorrhea, a comprehensive laboratory workup should include pregnancy test, FSH, LH, estradiol, prolactin, and TSH as the initial screening panel to determine the underlying cause. 1

Initial Laboratory Testing

The following laboratory tests should be ordered for all patients with secondary amenorrhea:

• Pregnancy test - Must be performed first to exclude pregnancy 2
• FSH and LH levels - To differentiate between hypothalamic, pituitary, and ovarian causes 1
• Estradiol - To assess ovarian function 1
• Prolactin - To rule out hyperprolactinemia 1
• TSH - To exclude thyroid dysfunction 1, 3

Interpretation of Initial Results

Based on the initial laboratory results, the cause of amenorrhea can be categorized:

• Elevated FSH (>35 IU/L): Suggests primary ovarian insufficiency 1
• Normal/Low FSH with normal/low LH: Suggests hypothalamic amenorrhea 1, 3
• LH/FSH ratio >2: Suggests polycystic ovary syndrome (PCOS) 1
• Elevated prolactin (>20 μg/L): Suggests hyperprolactinemia 2, 1
• Abnormal TSH: Suggests thyroid dysfunction 1, 3

Second-Tier Laboratory Testing

Based on initial results, additional testing may be indicated:

For suspected PCOS:

• Testosterone and free testosterone - Values >2.5 nmol/L suggest hyperandrogenism 1
• Androstenedione - Values >10.0 nmol/L suggest adrenal or ovarian androgen excess 1
• DHEAS - To assess adrenal androgen production 1
• Fasting glucose/insulin ratio - To assess insulin resistance 1
• Lipid profile - To assess cardiovascular risk 1, 4

For suspected primary ovarian insufficiency:

• Anti-Müllerian hormone (AMH) - Low levels indicate diminished ovarian reserve 2
• Karyotype - To rule out chromosomal abnormalities, especially in younger patients 4

For suspected hypothalamic amenorrhea:

• Complete blood count - To assess for anemia or other systemic conditions 3
• Comprehensive metabolic panel - To assess liver and kidney function 3

Imaging Studies

Based on laboratory findings, the following imaging may be indicated:

• Transvaginal ultrasound - To evaluate ovarian morphology, follicle count, and endometrial thickness 1

  • Look for ≥20 follicles per ovary and/or ovarian volume ≥10ml (suggestive of PCOS)
  • Assess endometrial thickness and rule out structural abnormalities

• Pituitary MRI - Indicated if prolactin is elevated or if there are symptoms suggesting a pituitary disorder 2

Common Pitfalls to Avoid

1. Failing to rule out pregnancy first - Always perform a pregnancy test before proceeding with other testing 2

2. Misinterpreting FSH levels - A single FSH measurement may not be diagnostic; consider repeating in 4-6 weeks if results are equivocal 3

3. Overlooking medication effects - Many medications can cause amenorrhea, including hormonal contraceptives, antipsychotics, and certain antidepressants 4

4. Ignoring timing of blood tests - Hormonal measurements should ideally be performed during the early follicular phase (days 3-6) of the cycle in women with irregular cycles 2

5. Missing eating disorders or excessive exercise - These are common causes of hypothalamic amenorrhea and require specific questioning 4

By following this systematic laboratory approach, the underlying cause of amenorrhea can be identified in most cases, allowing for appropriate management and treatment to reduce long-term health risks associated with untreated amenorrhea, including osteoporosis and cardiovascular disease.