What is the initial workup for secondary amenorrhea?

Initial Workup for Secondary Amenorrhea

The initial workup for secondary amenorrhea should begin with a pregnancy test, followed by measuring serum FSH, LH, prolactin, and TSH levels to identify the underlying cause. 1, 2

First-Line Assessment

• Pregnancy test is the first step as pregnancy is the most common cause of missed menses 1
• Detailed history focusing on:
  • Recent weight changes or low BMI (potential trigger for functional hypothalamic amenorrhea) 1, 3
  • Exercise patterns, especially excessive exercise 1, 2
  • Psychological stressors 1, 3
  • Caloric restriction or energy deficit 1, 3
• Physical examination should include:
  • BMI assessment 2
  • Breast examination for galactorrhea (sign of hyperprolactinemia) 2
  • Pelvic examination to rule out outflow tract obstruction 2

Laboratory Testing

• First-line laboratory tests include:
  • FSH and LH levels (differentiates between hypothalamic-pituitary and ovarian causes) 1, 2
  • Prolactin level (hyperprolactinemia accounts for ~20% of secondary amenorrhea cases) 1, 3
  • TSH level (thyroid dysfunction can cause amenorrhea) 1, 2
• Interpretation of gonadotropin levels:
  • Low/normal FSH and LH suggest hypothalamic amenorrhea 1, 3
  • LH:FSH ratio >2 suggests PCOS 1, 3
  • Elevated FSH and LH suggest primary ovarian insufficiency 3

Imaging and Additional Testing

• Transvaginal ultrasound to evaluate:
  • Endometrial thickness (indicator of estrogen status) 1, 2
  • Ovarian morphology (polycystic ovarian morphology is defined as ≥20 follicles of 2-9mm per ovary or ovarian volume >10ml) 1, 2
  • Uterine abnormalities 1
• Progestin challenge test may be used to determine estrogen status 3, 2
• Consider DXA scan for bone mineral density assessment in patients with:
  • Amenorrhea lasting >6 months 2
  • History of eating disorders or BMI <18.5 kg/m² 2
  • Late menarche (≥16 years) 2

Differential Diagnosis

Functional Hypothalamic Amenorrhea (FHA)

• Accounts for 20-35% of secondary amenorrhea cases 3
• Characterized by low/normal FSH and LH levels 1, 3
• Negative progestin challenge test 3
• Associated with stress, excessive exercise, weight loss, and caloric restriction 1, 3

Polycystic Ovary Syndrome (PCOS)

• Common cause of secondary amenorrhea 3
• Characterized by LH:FSH ratio >2 1, 3
• Polycystic ovarian morphology on ultrasound 3
• May have clinical or biochemical hyperandrogenism 3

Hyperprolactinemia

• Accounts for approximately 20% of secondary amenorrhea cases 3
• May present with galactorrhea 3
• Elevated serum prolactin levels 3
• May require pituitary imaging 2

Primary Ovarian Insufficiency (POI)

• Characterized by elevated FSH and LH levels 3
• May require additional testing such as karyotype analysis and AMH level 2

FHA-PCOM (Special Entity)

• Affects 40-47% of women with FHA 1, 3
• Features characteristics of both FHA and PCOM 3
• Can be misdiagnosed as PCOS as they fulfill Rotterdam criteria 1, 3
• Differentiation based on typical FHA triggers, negative progestin challenge, and lower LH levels 3

Common Pitfalls and Caveats

• Failure to perform a pregnancy test as the first step can lead to unnecessary testing 1, 4
• Misdiagnosing FHA-PCOM as PCOS can lead to inappropriate treatment 1, 3
• Not considering hyperprolactinemia, which accounts for approximately 20% of cases 3
• Overlooking thyroid dysfunction as a potential cause 1, 3
• Not evaluating bone mineral density in patients with prolonged hypoestrogenic states 2
• Assuming patients with primary ovarian insufficiency are infertile, as they can maintain unpredictable ovarian function 4

By following this systematic approach to the evaluation of secondary amenorrhea, clinicians can efficiently identify the underlying cause and develop an appropriate management plan that addresses both the immediate symptoms and potential long-term health consequences.