What is the initial workup for a female patient of reproductive age suspected of having Polycystic Ovary Syndrome (PCOS)?

Initial Workup for Polycystic Ovary Syndrome (PCOS)

Hormonal Assessment

Measure total testosterone or free/bioavailable testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which demonstrates 92% specificity compared to 78% for direct immunoassays, as the primary test for biochemical hyperandrogenism. 1

• Obtain sex hormone-binding globulin (SHBG) levels to calculate the free androgen index 1
• Measure LH and FSH between cycle days 3-6 (average of three measurements taken 20 minutes apart), with LH/FSH ratio >2 suggesting PCOS 1
• Check mid-luteal phase progesterone (day 21 of a 28-day cycle or 7 days before expected menses) where levels <6 nmol/L indicate anovulation 1
• Measure androstenedione if levels exceed 10.0 nmol/L to rule out adrenal or ovarian tumors 1
• Check DHEAS using age-specific thresholds: >3800 ng/mL for ages 20-29, >2700 ng/mL for ages 30-39 to exclude non-classical congenital adrenal hyperplasia 1

Exclusion of Other Conditions

• Measure TSH to exclude thyroid disease as a cause of menstrual irregularity 1
• Check prolactin (morning resting levels, not postictal) to exclude hyperprolactinemia, with levels >20 μg/L being abnormal 1
• Obtain 17-hydroxyprogesterone to exclude non-classical congenital adrenal hyperplasia 1

Metabolic Evaluation

Perform a 2-hour oral glucose tolerance test with 75g glucose load in all women with suspected PCOS regardless of BMI, as insulin resistance occurs independently of body weight. 1

• Calculate fasting glucose/insulin ratio, where a ratio >4 suggests reduced insulin sensitivity 1
• Fasting glucose >7.8 mmol/L is suggestive of diabetes 1
• Obtain fasting lipid profile to assess cardiovascular risk, as women with PCOS have increased risk of dyslipidemia and metabolic syndrome 1

Imaging Studies

Transvaginal ultrasound is the preferred imaging modality using transducers with frequency ≥8 MHz, looking for ≥20 follicles (2-9mm diameter) per ovary and/or ovarian volume ≥10 mL. 2

• The 2014 Androgen Excess and Polycystic Ovary Syndrome Society revised criteria require 25 follicles that are 2-9mm in diameter in at least one ovary, assuming ovaries are well visualized transvaginally with an 8 MHz or higher transducer 2
• Ovarian volume >10 mL can also be used to suggest the diagnosis of polycystic ovarian morphology 2
• Transabdominal ultrasound may be used as an alternative, focusing on ovarian volume with threshold ≥10 mL, though it is generally not suitable for accurate follicle counting 2, 1
• MRI pelvis without contrast may be considered when ovaries cannot be adequately visualized by ultrasound, particularly in obese adolescents or patients in whom transvaginal ultrasound is unacceptable 2, 1

Critical Imaging Considerations

• Ultrasound should not be used for the diagnosis of PCOS in those with a gynecological age of <8 years (<8 years after menarche), due to the high incidence of multi-follicular ovaries in this life stage 2
• Ensure no corpora lutea, cysts, or dominant follicles are present when assessing for polycystic ovarian morphology 2
• Increased echogenicity of the ovarian stroma has been reported as the most sensitive and specific sign of polycystic ovaries, though this is a subjective finding 2

Physical Examination

• Calculate BMI and waist-to-hip ratio (WHR >0.9 indicates truncal obesity) to assess for metabolic risk 1
• Examine for acanthosis nigricans on neck, axillae, under breasts, and vulva, which indicates underlying insulin resistance 1
• Assess for hirsutism using Ferriman-Gallwey scoring, acne, male-pattern alopecia, and clitoromegaly 1

Critical Diagnostic Pitfalls

Rapid onset or marked virilization requires immediate evaluation for androgen-secreting tumors with testosterone typically >2.5 nmol/L warranting further investigation. 1

• Consider dexamethasone suppression test if Cushing's syndrome is suspected based on physical findings (buffalo hump, moon facies, abdominal striae) 1
• AMH levels should not yet be used as an alternative for the detection of polycystic ovarian morphology or as a single test for the diagnosis of PCOS 2
• In patients with irregular menstrual cycles and hyperandrogenism, an ovarian ultrasound is not necessary for PCOS diagnosis; however, ultrasound will identify the complete PCOS phenotype 2

Diagnostic Criteria Application

The Rotterdam criteria require two of the following three factors for diagnosis: oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries identified on ultrasonography, after exclusion of other conditions 3, 4