Diagnostic Workup for a 28-Year-Old Woman with Irregular Periods and Normal Ovarian Ultrasound
For a 28-year-old woman with irregular periods and no evidence of PCOS on ultrasound, the recommended bloodwork should include LH, FSH, prolactin, testosterone, thyroid function tests, and glucose metabolism assessment to identify the underlying cause of menstrual irregularity. 1
Initial Laboratory Evaluation
Gonadotropin assessment: Measure LH and FSH levels between days 3-6 of the menstrual cycle (average of three estimations taken 20 minutes apart). An LH/FSH ratio >2 may suggest ovulatory dysfunction even without polycystic ovaries on ultrasound 1
Prolactin level: Morning resting serum levels (not post-ictal) to rule out hyperprolactinemia, which can cause menstrual irregularity. Values >20 μg/L are considered abnormal 1
Thyroid function tests: TSH to exclude thyroid dysfunction as a cause of irregular periods 1
Androgen profile: Total testosterone or bioavailable/free testosterone (preferably measured on days 3-6 of cycle). Values >2.5 nmol/L suggest hyperandrogenism despite normal ovarian appearance 1
Progesterone level: Mid-luteal phase measurement to assess for anovulation. Levels <6 nmol/L indicate anovulation even without polycystic ovaries 1
Metabolic assessment:
- Fasting glucose and insulin (calculate glucose/insulin ratio)
- Two-hour oral glucose tolerance test
- Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) 1
Additional Considerations
DHEAS measurement: Consider if adrenal hyperandrogenism is suspected, especially with values >3800 ng/ml (age 20-29) 1
Androstenedione: If testosterone is elevated, to rule out adrenal/ovarian tumors (abnormal if >10.0 nmol/L) 1
Anti-Müllerian Hormone (AMH): While not diagnostic for PCOS by itself, elevated levels may provide additional information about ovarian function 1
Interpretation of Normal Ovarian Ultrasound
A normal ovarian ultrasound does not exclude all reproductive disorders. Women can have ovulatory dysfunction or hyperandrogenism with normal ovarian morphology 1
Remember that ultrasound criteria for polycystic ovarian morphology include:
- ≥20 follicles per ovary (using high-resolution transvaginal ultrasound)
- Ovarian volume ≥10 ml 1
Next Steps Based on Laboratory Results
If hyperandrogenism detected: Consider non-PCOS causes such as non-classical congenital adrenal hyperplasia, androgen-secreting tumors, or Cushing's syndrome 1
If anovulation confirmed: Consider hypothalamic amenorrhea (especially with low LH levels <7 IU/ml) 1
If metabolic abnormalities present: Address insulin resistance and cardiovascular risk factors even without PCOS diagnosis 1
If all tests normal: Consider functional hypothalamic amenorrhea related to stress, excessive exercise, or weight changes 1
Management Plan
For anovulation without hyperandrogenism: Consider cyclic progestin therapy to prevent endometrial hyperplasia 1
For metabolic abnormalities: Lifestyle modifications and possibly metformin if insulin resistance is detected 1
For persistent unexplained irregular cycles: Consider referral to reproductive endocrinologist for further evaluation 1
Follow-up imaging: If initial bloodwork is inconclusive and symptoms persist, consider sonohysterography or MRI of the pelvis to evaluate for structural abnormalities 1
Important Pitfalls to Avoid
Don't dismiss irregular periods without PCOS: Menstrual irregularity requires investigation regardless of ovarian appearance 1
Don't rely solely on ultrasound: Diagnosis of reproductive disorders requires correlation of clinical, biochemical, and imaging findings 1
Don't forget non-reproductive causes: Thyroid disorders, hyperprolactinemia, and stress can all cause menstrual irregularity 1
Don't overlook metabolic health: Women with menstrual irregularity have increased cardiovascular risk even without PCOS diagnosis 1