What investigations should be done in a patient with Polycystic Ovary Syndrome (PCOS)?

Investigations for PCOS

All patients with suspected PCOS require a comprehensive laboratory workup including thyroid-stimulating hormone, prolactin, total or free testosterone (preferably by LC-MS/MS), a 2-hour oral glucose tolerance test with 75g glucose load, and fasting lipid profile, along with transvaginal ultrasound to evaluate ovarian morphology. 1, 2

Essential Laboratory Tests

Hormonal Evaluation

• Measure total testosterone or free testosterone as the primary androgen marker, with liquid chromatography-tandem mass spectrometry (LC-MS/MS) being the preferred method showing superior specificity (92%) compared to direct immunoassays (78%) 2
• Obtain thyroid-stimulating hormone (TSH) to exclude thyroid disease as a cause of menstrual irregularity 3, 1
• Measure prolactin level using morning resting serum samples to rule out hyperprolactinemia 3, 2
• Calculate Free Androgen Index (FAI) or measure sex hormone-binding globulin (SHBG) if LC-MS/MS is unavailable 1, 2

Metabolic Screening

• Perform a 2-hour oral glucose tolerance test with 75g glucose load to screen for type 2 diabetes and glucose intolerance, as all women with PCOS have demonstrated increased risk 3, 1
• Obtain fasting lipid profile including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, as women with PCOS frequently have dyslipidemia with disproportionately elevated LDL levels 3, 1, 2
• Calculate body mass index (BMI) and measure waist-hip ratio to assess for obesity and central fat distribution 1, 2

Additional Androgen Testing (If Initial Tests Normal)

• Measure androstenedione if testosterone levels are normal but clinical suspicion remains high, with levels >10.0 nmol/L indicating possible adrenal/ovarian tumor 2
• Obtain DHEAS (dehydroepiandrosterone sulfate) to rule out non-classical congenital adrenal hyperplasia, particularly if elevated 2
• Measure LH and FSH between days 3-6 of menstrual cycle, with an LH/FSH ratio >2 suggesting PCOS 2

Imaging Studies

Ultrasound Evaluation

• Perform transvaginal ultrasound using an 8MHz or higher transducer as the preferred approach for evaluating ovarian morphology 1
• Look for ≥20 follicles (2-9mm diameter) per ovary and/or ovarian volume ≥10mL, which suggests polycystic ovarian morphology 1, 2
• Document three dimensions of each ovary to calculate ovarian volume accurately 1
• Consider transabdominal ultrasound as an alternative if transvaginal approach is not feasible, focusing on ovarian volume with threshold of ≥10mL 1
• Consider MRI pelvis (without contrast) when ovaries cannot be adequately visualized by ultrasound 1

Differential Diagnosis Exclusion

Screening for Mimicking Conditions

• Screen for Cushing's syndrome if patient presents with buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, or proximal myopathies 3, 1, 2
• Evaluate for androgen-secreting tumors if there is rapid onset of symptoms, severe hirsutism, or very high testosterone levels 1, 2
• Rule out non-classic congenital adrenal hyperplasia particularly if DHEAS levels are elevated 2
• Exclude acromegaly if coarse facial features or enlarged hands/feet are present 3, 2
• Assess for primary ovarian failure using FSH levels 2

Clinical Assessment Components

History Taking

• Document menstrual history including cycle length (>35 days suggests chronic anovulation), regularity, and presence of amenorrhea 1
• Record onset and duration of androgen excess signs, as gradual onset suggests PCOS while rapid onset suggests androgen-secreting tumor 1
• Review all medications, particularly any exogenous androgens 3, 1
• Assess lifestyle factors including diet, exercise, alcohol use, and smoking 3, 1
• Obtain family history of cardiovascular disease and diabetes 3, 1

Physical Examination Findings

• Evaluate for clinical hyperandrogenism including hirsutism, acne, alopecia, and clitoromegaly 1
• Assess for signs of insulin resistance including acanthosis nigricans (velvety hyperpigmentation on back of neck, beneath breasts, axillae, or vulva) 3, 1
• Perform pelvic examination to evaluate for ovarian enlargement 3, 1

Critical Pitfalls to Avoid

• Do not use serum AMH levels as a single diagnostic test despite emerging evidence, as it should not yet replace standard diagnostic criteria 1
• Do not diagnose PCOS based on ultrasound findings alone, as polycystic ovarian morphology may be present in up to one-third of reproductive-aged women without PCOS 1
• Remember that chronic anovulation increases endometrial cancer risk, requiring appropriate follow-up and consideration of endometrial thickness assessment 3, 1
• Recognize that up to 64.7% of PCOS patients have insulin resistance even with normal oral glucose tolerance test, making metabolic screening essential 4
• Be aware that direct immunoassays for testosterone have lower specificity (78%) compared to LC-MS/MS (92%), potentially leading to false positives 2