From the Guidelines
For the evaluation of Polycystic Ovary Syndrome (PCOS), I strongly recommend ordering a comprehensive panel including total testosterone (TT), free testosterone (FT), and free androgen index (FAI) as the first-line laboratory tests to assess biochemical hyperandrogenism, as supported by the most recent and highest quality study 1. These tests should be performed during the early follicular phase (days 3-5) of the menstrual cycle when possible. Additional tests that may be considered include:
- LH and FSH to assess for an elevated LH:FSH ratio (often >2:1 in PCOS)
- Pelvic ultrasound to evaluate for polycystic ovarian morphology
- Fasting glucose, HbA1c, lipid profile, and a 2-hour oral glucose tolerance test to assess for metabolic complications
- TSH and prolactin to rule out thyroid disorders and hyperprolactinemia
- 17-hydroxyprogesterone to rule out congenital adrenal hyperplasia
- Androstenedione and DHEAS if TT or FT is not elevated and clinical suspicion is high, noting their poorer specificity 1
- Insulin resistance testing with fasting insulin levels and calculating HOMA-IR
- Pregnancy test and testing for premature ovarian insufficiency with anti-Müllerian hormone and estradiol levels in patients with amenorrhea. It is essential to use highly accurate LC-MS/MS for assessing biochemical hyperandrogenism for TT, DHEAS, and androstenedione, while FT should be assessed by calculation, functionally by equilibrium dialysis or ammonium sulfate precipitation 1. Direct androgen immunoassays have limited accuracy, and results that are not consistent with the clinical presentation should be rechecked by an LC-MS/MS method. These tests help establish the diagnosis based on Rotterdam criteria while ruling out conditions that can mimic PCOS. The metabolic workup is particularly important as PCOS patients have increased risk for type 2 diabetes, dyslipidemia, and cardiovascular disease.
From the Research
Laboratory Tests for PCOS Evaluation
The following laboratory tests are recommended for the evaluation of Polycystic Ovary Syndrome (PCOS):
- Serum total testosterone (TT) measurement 2, 3, 4
- Free androgen index (FAI) calculation 2, 4
- Calculated free testosterone (cFT) and calculated bioavailable testosterone (cBT) measurements 2
- Luteinizing hormone (LH) and follicle stimulating hormone (FSH) measurements, including LH:FSH ratio 3, 5, 4
- Androstenedione measurement 3, 4
- Sex hormone binding globulin (SHBG) measurement 2, 3, 4
- Dehydroepiandrosterone sulfate (DHEA-S) measurement 3, 5
Diagnostic Criteria
The diagnosis of PCOS is based on a combination of clinical and laboratory findings, including:
- Hyperandrogenism, which can be assessed clinically or biochemically 2, 6, 3
- Oligomenorrhea or amenorrhea 3, 5
- Polycystic ovarian morphology on ultrasound 6, 3, 5
Test Performance
The performance of these laboratory tests in diagnosing PCOS has been evaluated using receiver operating characteristic (ROC) curve analysis:
- Calculated bioavailable testosterone (cBT) had the highest area under the curve (AUC) and specificity 2
- Free androgen index (FAI) and calculated free testosterone (cFT) also showed good correlation with each other and high specificity 2
- LH:FSH ratio had a lower AUC and specificity compared to other androgen markers 3, 4