PCOS Workup
The initial workup for suspected PCOS requires documenting at least two of three Rotterdam criteria through clinical assessment, hormonal testing, and pelvic ultrasound, while systematically excluding alternative diagnoses. 1, 2
Clinical History Assessment
Document menstrual patterns with specific attention to cycle length >35 days, which indicates chronic anovulation. 1, 2 Record the onset and duration of oligomenorrhea or amenorrhea, as gradual onset suggests PCOS while rapid onset raises concern for androgen-secreting tumors. 1, 3
Key historical elements to obtain:
- Timing and progression of hyperandrogenic signs (hirsutism, acne, alopecia) - gradual worsening with weight gain suggests PCOS, while rapid onset with clitoromegaly suggests neoplasm 1, 4
- Medication review to exclude exogenous androgen use 1, 2
- Family history of cardiovascular disease, diabetes, and reproductive disorders 1, 2
- Lifestyle factors including diet, exercise, alcohol use, and smoking status 1, 2
Physical Examination
Systematically assess for clinical hyperandrogenism including hirsutism distribution, acne patterns, male-pattern alopecia, and clitoromegaly. 1, 2 Calculate BMI and waist-hip ratio to identify obesity and central fat distribution. 1, 2
Screen for signs of alternative diagnoses:
- Cushing's syndrome: buffalo hump, moon facies, abdominal striae, easy bruising, proximal myopathy 1, 5
- Insulin resistance: acanthosis nigricans 2
- Pelvic examination: evaluate for ovarian enlargement 1
Laboratory Testing
First-Line Hormonal Tests
Measure total testosterone or free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the preferred method, which shows superior specificity (92%) compared to direct immunoassays (78%). 5 Total testosterone demonstrates 74% sensitivity and 86% specificity, while free testosterone shows 89% sensitivity and 83% specificity for PCOS diagnosis. 5
If LC-MS/MS is unavailable, calculate Free Androgen Index (FAI) using total testosterone and sex hormone-binding globulin (SHBG). 5
Measure thyroid-stimulating hormone (TSH) to exclude thyroid disease as a cause of menstrual irregularity. 1, 2, 5
Measure prolactin using morning resting serum levels to exclude hyperprolactinemia, with levels >20 μg/L considered abnormal. 1, 2, 5
Second-Line Hormonal Tests (if clinical suspicion remains high despite normal testosterone)
Consider measuring androstenedione (75% sensitivity, 71% specificity) and DHEAS (75% sensitivity, 67% specificity) only as adjunctive tests, as they have poorer specificity than testosterone. 5 Androstenedione levels >10.0 nmol/L suggest adrenal/ovarian tumor. 5
Measure 17-hydroxyprogesterone to exclude non-classic congenital adrenal hyperplasia. 2, 4
Metabolic Screening
Perform a 2-hour oral glucose tolerance test with 75g glucose load in all PCOS patients regardless of BMI to screen for type 2 diabetes and glucose intolerance. 1, 2, 5 This is mandatory given the fourfold increased risk of type 2 diabetes in PCOS patients. 3
Obtain fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides to assess dyslipidemia driven by insulin resistance. 1, 2, 5
Imaging Studies
Transvaginal ultrasound is the preferred imaging modality using an 8MHz or higher frequency transducer. 1, 2 The diagnostic threshold for polycystic ovarian morphology (PCOM) is ≥20 follicles (2-9mm diameter) per ovary and/or ovarian volume ≥10mL, with 87.64% sensitivity and 93.74% specificity. 6, 1, 5
Document three dimensions of each ovary and ensure no corpora lutea, cysts, or dominant follicles ≥10mm are present when measuring. 6, 1
Use transabdominal ultrasound as an alternative (focusing on ovarian volume ≥10mL threshold) in adolescents, obese patients, or when transvaginal approach is unacceptable. 1, 2
Consider MRI pelvis without contrast when ovaries cannot be adequately visualized by ultrasound. 1
Critical Ultrasound Limitations
Do not use ultrasound for PCOS diagnosis in patients with gynecological age <8 years (less than 8 years post-menarche) due to high incidence of multifollicular ovaries in this life stage. 6 In adolescents, ultrasound should be avoided as a first-line diagnostic tool due to poor specificity and high false-positive rates. 5
Diagnostic Algorithm
Confirm PCOS diagnosis when at least two of three Rotterdam criteria are present:
- Clinical or biochemical hyperandrogenism
- Ovulatory dysfunction (oligomenorrhea/amenorrhea)
- Polycystic ovarian morphology on ultrasound 2, 3, 7
Important clinical caveat: A woman can be diagnosed with PCOS based solely on clinical hyperandrogenism plus irregular menstrual cycles without any abnormal laboratory values, as total testosterone is abnormal in only 70% of confirmed PCOS cases. 5 When clinical features and ultrasound findings are present, the absence of biochemical hyperandrogenism does not exclude PCOS. 5
Exclusion of Alternative Diagnoses
Systematically rule out conditions that mimic PCOS:
- Cushing's syndrome: if buffalo hump, moon facies, hypertension, or abdominal striae present 1, 5, 8
- Androgen-secreting tumors: if rapid symptom onset, severe hirsutism, or very high testosterone levels 1, 5, 8
- Non-classic congenital adrenal hyperplasia: via 17-hydroxyprogesterone measurement 2, 8
- Hyperprolactinemia: via prolactin measurement 1, 2
- Thyroid disease: via TSH measurement 1, 2
- Primary ovarian failure: via FSH measurement 5
Anti-Müllerian Hormone (AMH) Considerations
Do not use serum AMH levels as an alternative for detecting PCOM or as a single test for PCOS diagnosis, despite AMH ≥35 pmol/L showing 92% sensitivity and 97% specificity. 6, 1, 5 AMH lacks assay standardization and requires validation across different populations before clinical implementation. 6, 5
Long-Term Surveillance Considerations
Monitor for endometrial cancer risk in patients with obesity, chronic anovulation, and hyperinsulinemia, as PCOS patients have at least a twofold increased risk of endometrial cancer. 2, 7 Screen for depression and obstructive sleep apnea, as these conditions are more prevalent in PCOS patients. 7