What is the workup for secondary amenorrhea?

Workup for Secondary Amenorrhea

The workup for secondary amenorrhea should begin with pregnancy testing, followed by measuring serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone (TSH). This systematic approach helps identify the most common causes while prioritizing conditions that impact morbidity and mortality 1.

Initial Assessment

• Definition: Secondary amenorrhea is the cessation of previously regular menses for three months or previously irregular menses for six months 1.

• Pregnancy test: Must be performed first in all women of reproductive age with amenorrhea 2, 1.

• Medical history: Focus on:

  • Menstrual patterns and onset 1
  • Weight changes and nutritional status 3
  • Exercise habits (especially excessive exercise) 3
  • Psychological stressors 3
  • Medication use (including hormonal contraceptives) 1
  • Galactorrhea (suggests hyperprolactinemia) 3
  • Chronic illness 1

• Physical examination: Assess:

  • Body mass index (BMI) and weight trends 3
  • Signs of androgen excess (hirsutism, acne) 1
  • Thyroid examination 2
  • Breast examination for galactorrhea 3
  • Pelvic examination to rule out outflow tract obstruction 3

Laboratory Testing

First-line laboratory tests:

• Pregnancy test (serum or urine hCG) 2, 1
• FSH and LH levels 3, 1
• Prolactin level 3, 1
• TSH level 3, 1

Additional testing based on initial results:

• If elevated FSH/LH: Consider primary ovarian insufficiency 2

  • Karyotype analysis to rule out chromosomal abnormalities 4
  • Antimüllerian hormone (AMH) level 3

• If low/normal FSH/LH with normal prolactin and TSH: Consider functional hypothalamic amenorrhea 3

  • Estradiol level 3
  • Bone mineral density testing if amenorrhea >6 months 3

• If elevated LH:FSH ratio >2 with normal prolactin and TSH: Consider polycystic ovary syndrome 3

  • Androgen profile (total testosterone, free testosterone, DHEAS) 1
  • Fasting glucose and lipid panel 3

• If elevated prolactin: Consider hyperprolactinemia 2

  • MRI of pituitary if significantly elevated 1

Imaging Studies

• Transvaginal ultrasound: To evaluate endometrial thickness and ovarian morphology 3

  • Helps identify polycystic ovarian morphology 3
  • Assesses endometrial thickness as indicator of estrogen status 3

• MRI: Consider when ultrasound is inconclusive or to evaluate pituitary abnormalities 3

  • Superior visualization of endometrium even in the presence of leiomyomas or adenomyosis 3
  • Essential for evaluation of pituitary tumors in hyperprolactinemia 2

• DXA scan: For bone mineral density assessment in patients with:

  • Amenorrhea lasting >6 months 3
  • History of eating disorders or BMI <18.5 kg/m² 3
  • Late menarche (≥16 years) 3

Special Tests

• Progesterone challenge test: Can help determine estrogen status 5

  • Administration of progesterone 400 mg daily for 10 days 5
  • Withdrawal bleeding indicates adequate estrogen levels 5
  • No bleeding suggests hypoestrogenic state or outflow tract obstruction 3

• Karyotype analysis: Indicated in:

  • Patients with primary ovarian insufficiency 4
  • Patients with primary amenorrhea 2
  • Patients with features suggesting chromosomal disorders 4

Common Pitfalls to Avoid

• Failing to rule out pregnancy before extensive workup 2, 1
• Overlooking eating disorders in patients with functional hypothalamic amenorrhea 3
• Neglecting bone health in patients with prolonged hypoestrogenic amenorrhea 3
• Assuming infertility in all patients with primary ovarian insufficiency (some may maintain unpredictable ovarian function) 3, 1
• Missing metabolic complications in patients with PCOS (increased risk for glucose intolerance and dyslipidemia) 3, 1

Diagnostic Algorithm

1. Pregnancy test (if positive, no further workup needed)
2. Measure FSH, LH, prolactin, and TSH
3. Based on results:
   • High FSH/LH: Primary ovarian insufficiency → karyotype, AMH
   • Normal/Low FSH/LH, normal prolactin/TSH: Functional hypothalamic amenorrhea → estradiol, bone density
   • Elevated LH:FSH ratio: PCOS → androgen profile, metabolic screening
   • Elevated prolactin: Hyperprolactinemia → pituitary imaging
   • Abnormal TSH: Thyroid dysfunction → additional thyroid testing
4. If diagnosis remains unclear: Progesterone challenge test and pelvic imaging

Remember that secondary amenorrhea is not a diagnosis but a symptom requiring thorough investigation to identify the underlying cause and prevent long-term health consequences 2.