What is the recommended workup for a female patient of reproductive age presenting with symptoms suggestive of Polycystic Ovary Syndrome (PCOS), including irregular menstrual cycles, weight gain, and hirsutism?

PCOS Workup

For a reproductive-age female with irregular cycles, weight gain, and hirsutism, perform hormonal evaluation including LH/FSH ratio, free testosterone, mid-luteal progesterone, fasting glucose/insulin ratio, TSH, and prolactin, followed by transvaginal ultrasound if sexually active to confirm polycystic ovarian morphology. 1, 2

Clinical Assessment

Physical examination findings to document:

• Body mass index (BMI) and waist-to-hip ratio (WHR >0.9 indicates truncal obesity associated with PCOS) 3, 1
• Hirsutism using Ferriman-Gallwey scoring or noting male escutcheon pattern 3
• Acne and male-pattern hair loss (androgenic alopecia) 1, 4
• Acanthosis nigricans suggesting insulin resistance 4

Laboratory Evaluation

Hormonal testing (timing is critical):

• LH and FSH measured on cycle days 3-6, using three samples taken 20 minutes apart for accuracy; LH/FSH ratio >2 suggests PCOS 3, 2
• Free testosterone (more sensitive than total testosterone) measured on days 3-6; levels >2.5 nmol/L are abnormal 3, 4
• Mid-luteal progesterone (timed to menstrual cycle); levels <6 nmol/L indicate anovulation 3
• TSH and free T4 to exclude thyroid dysfunction, which commonly mimics PCOS with menstrual irregularity 2
• Prolactin using 2-3 morning resting samples taken 20-60 minutes apart (not post-ictal); levels >20 μg/L are abnormal 3, 2

Metabolic screening:

• Fasting glucose and insulin with calculation of glucose/insulin ratio; ratio >4 suggests insulin resistance 3, 1
• Lipid panel to assess cardiovascular risk 1

Additional androgen testing when indicated:

• Androstenedione if levels >10.0 nmol/L to rule out adrenal/ovarian tumor 3
• DHEAS (age-specific thresholds: age 20-29 >3800 ng/ml, age 30-39 >2700 ng/ml) to rule out non-classical congenital adrenal hyperplasia 3
• 17-hydroxyprogesterone if congenital adrenal hyperplasia is suspected 4

Ultrasound Evaluation

Transvaginal ultrasound is preferred if sexually active and acceptable to the patient (perform on cycle days 3-9): 3, 1

• Diagnostic criteria for polycystic ovaries using transducers with frequency bandwidth including 8MHz: ≥20 follicles (2-9mm diameter) per ovary and/or ovarian volume ≥10ml 3, 1
• Ensure no corpora lutea, cysts, or dominant follicles ≥10mm are present at time of examination 3
• Transabdominal ultrasound may be used if transvaginal is not feasible, focusing on ovarian volume ≥10ml (follicle counting is unreliable with this approach) 3

Ultrasound should NOT be used for PCOS diagnosis in those with gynecological age <8 years (less than 8 years post-menarche) due to high incidence of multi-follicular ovaries in this life stage 3

Diagnostic Criteria

PCOS diagnosis requires at least 2 of 3 Rotterdam criteria:

• Chronic anovulation (oligomenorrhea or amenorrhea) 4, 5
• Clinical or biochemical hyperandrogenism 4, 5
• Polycystic ovaries on ultrasound 4, 5

Critical Pitfalls to Avoid

• Do not diagnose PCOS without first excluding thyroid disorders and hyperprolactinemia, as these conditions mimic PCOS presentation 2
• Do not use ultrasound as sole diagnostic criterion in adolescents <17 years, as multicystic ovaries are common findings in normal puberty 4
• Do not confuse isolated polycystic ovaries (17-22% of general population) with PCOS syndrome, which requires symptoms and hormonal abnormalities 3
• Recognize that amenorrhea >3 months in PCOS represents unopposed estrogen exposure, significantly increasing endometrial hyperplasia and cancer risk, requiring endometrial protection 6
• Screen for metabolic complications including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular risk factors even in women with apparently regular cycles 1

Additional Screening Based on Findings

If amenorrhea is present for >3 months:

• Consider endometrial assessment for hyperplasia risk 6
• Initiate endometrial protection with combined oral contraceptives or cyclic progestin therapy 6

If significant insulin resistance is identified:

• Screen for nonalcoholic fatty liver disease 7
• Screen for obstructive sleep apnea (more common in PCOS) 7
• Assess for depression and eating disorders 7