Initial Investigations for Suspected PCOS
For a patient with suspected PCOS, begin with a focused history and physical examination, followed by hormonal evaluation (total or free testosterone, TSH, prolactin), metabolic screening (2-hour 75g oral glucose tolerance test and fasting lipid profile), and transvaginal ultrasound to assess ovarian morphology. 1, 2
Clinical History Assessment
Document specific menstrual patterns, as cycle length >35 days indicates chronic anovulation, which is a core diagnostic criterion for PCOS 1, 3. Assess the onset and progression of hyperandrogenic symptoms—gradual onset suggests PCOS, while rapid onset with severe symptoms raises concern for androgen-secreting tumors 1. Review medication use, particularly exogenous androgens, and obtain family history of cardiovascular disease and diabetes 1. Evaluate lifestyle factors including diet, exercise patterns, and assess for eating disorders or excessive exercise that could suggest functional hypothalamic amenorrhea as an alternative diagnosis 4.
Physical Examination Findings
Examine for clinical hyperandrogenism including hirsutism (using Ferriman-Gallwey scoring), acne, and androgenic alopecia 1, 5. Calculate BMI and measure waist-hip ratio to identify central obesity, noting that a waist-hip ratio >0.9 indicates truncal obesity 1, 2. Look specifically for acanthosis nigricans on the neck, axillae, under breasts, and vulva, which indicates underlying insulin resistance 6. Screen for Cushing's syndrome features including buffalo hump, moon facies, and abdominal striae 1, 2.
Laboratory Testing
Hormonal Evaluation
Measure total testosterone or free testosterone as the first-line androgen test, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) when available, as this method shows superior specificity (92%) compared to direct immunoassays (78%) 2, 6. Total testosterone demonstrates pooled sensitivity of 74% and specificity of 86%, while free testosterone shows superior sensitivity of 89% with specificity of 83% 2. If testosterone levels are normal but clinical suspicion remains high, measure androstenedione and DHEAS as second-line tests 2.
Obtain TSH to exclude thyroid disease as a cause of menstrual irregularity 1, 2. Measure prolactin levels using morning resting serum samples to exclude hyperprolactinemia 1, 2. Consider measuring LH and FSH between days 3-6 of the menstrual cycle, as an LH/FSH ratio >2 suggests PCOS, though this finding is present in only 35-44% of PCOS patients 2.
Metabolic Screening
Perform a 2-hour oral glucose tolerance test with 75g glucose load regardless of BMI, as insulin resistance occurs independently of body weight in PCOS patients 1, 6, 5. Obtain a fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides 1, 2. These metabolic evaluations are critical because PCOS patients have increased risk of type 2 diabetes, dyslipidemia, and cardiovascular disease 6.
Imaging Studies
Transvaginal ultrasound is the preferred imaging modality, using an 8MHz or higher frequency transducer 4, 1. The updated diagnostic threshold for polycystic ovarian morphology is ≥20 follicles (2-9mm diameter) per ovary and/or ovarian volume ≥10mL 4, 1, 6. Document three dimensions of each ovary and ensure no corpus luteum, cyst, or dominant follicle is present 6.
For patients where transvaginal ultrasound is not acceptable or feasible, transabdominal ultrasound can be used as an alternative, focusing on ovarian volume with a threshold of ≥10mL 4, 1. MRI pelvis without contrast may be considered when ovaries cannot be adequately visualized by ultrasound, particularly in obese patients 4, 1.
Important caveat: Ultrasound should not be used for diagnosis in patients with gynecological age <8 years due to high incidence of multifollicular ovaries at this developmental stage 6, 3.
Differential Diagnosis Exclusion
Measure 17-hydroxyprogesterone to exclude non-classic congenital adrenal hyperplasia 6. Consider dexamethasone suppression testing if Cushing's syndrome is suspected based on clinical features 1, 6. Evaluate for androgen-secreting tumors if there is rapid symptom onset, severe hirsutism, or very high testosterone levels (androstenedione >10.0 nmol/L) 2.
Critical Clinical Pitfalls
Do not rely on ultrasound findings alone for diagnosis, as polycystic ovarian morphology may be present in up to one-third of reproductive-aged women without PCOS 1. Serum AMH levels should not be used as a single diagnostic test despite emerging evidence showing high sensitivity (92%) and specificity (97%) at thresholds ≥35 pmol/L, as this requires further validation 2, 6.
Recognize that 30% of women with confirmed PCOS have normal testosterone levels, so the diagnosis can be established based on clinical hyperandrogenism plus irregular menstrual cycles without abnormal laboratory values, according to Rotterdam criteria 2. The diagnosis requires only two of three features: oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology 6, 3.
Screen all PCOS patients for metabolic complications regardless of body weight, as insulin resistance and metabolic dysfunction occur in both lean and obese patients 6, 5. Monitor for endometrial cancer risk in patients with chronic anovulation 1.