What are the diagnostic criteria and treatment options for a woman of reproductive age presenting with irregular menstrual periods, weight gain, acne, and excess hair growth, suspected of having Polycystic Ovary Syndrome (PCOS)?

Diagnosis of Polycystic Ovary Syndrome (PCOS)

Diagnose PCOS using the Rotterdam criteria: at least 2 of 3 features must be present—oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound—after excluding other causes of hyperandrogenism. 1, 2

Diagnostic Criteria

Clinical Assessment

• Document menstrual history: cycle length >35 days indicates chronic anovulation, which is a core feature of PCOS 2
• Assess signs of hyperandrogenism: look specifically for hirsutism (excessive terminal hair in male-pattern distribution), persistent or treatment-resistant acne, androgenic alopecia (vertex/crown pattern or bitemporal hair loss), and clitoromegaly 1, 3
• Calculate BMI and waist-hip ratio: obesity and central fat distribution are common metabolic features 2
• Evaluate onset and duration of symptoms: gradual onset with intensification during weight gain suggests PCOS, whereas rapid onset with severe virilization raises concern for androgen-secreting tumors 1, 4
• Obtain family history: specifically ask about cardiovascular disease, diabetes, and PCOS in relatives 2

Laboratory Testing

First-line hormonal testing:

• Measure total testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS): this is the single best initial biochemical marker with 74% sensitivity and 86% specificity 2, 3
• Calculate free testosterone using the Vermeulen equation: this has the highest sensitivity at 89% with 83% specificity when derived from high-quality total testosterone and SHBG measurements 2, 3
• Avoid direct immunoassay methods for free testosterone: these have poor accuracy at low serum concentrations typical in women 3

Second-line hormonal testing (if total and free testosterone are not elevated but clinical suspicion remains high):

• Measure androstenedione (A4): 75% sensitivity and 71% specificity 2, 3
• Measure DHEAS: 75% sensitivity and 67% specificity, most useful in women <30 years for assessing adrenal androgen production 1, 2, 3
• Calculate LH/FSH ratio: ratio >2 suggests PCOS 3

Exclusion of other conditions:

• Measure TSH: to rule out thyroid disease 1, 2
• Measure prolactin: to exclude hyperprolactinemia 1, 2
• Measure 17-hydroxyprogesterone: to rule out non-classic congenital adrenal hyperplasia 1, 2
• Screen for Cushing's syndrome if clinical signs present: buffalo hump, moon facies, hypertension, abdominal striae, easy bruising 1, 2
• Consider androgen-secreting tumors if testosterone >150-200 ng/dL or DHEAS >600 μg/dL: these present with rapid-onset severe hyperandrogenism and virilization 1, 3

Ultrasound Assessment

In adults (≥18 years):

• Use transvaginal ultrasound with ≥8 MHz transducer frequency: this provides optimal resolution 2
• Count follicle number per ovary (FNPO): ≥20 follicles (2-9mm diameter) is the gold standard marker with 87.64% sensitivity and 93.74% specificity 2
• Measure ovarian volume as alternative: >10 mL threshold when accurate follicle counting is difficult 2
• Perform ultrasound on days 3-9 of menstrual cycle: this timing provides most accurate assessment 1

In adolescents (<20 years or <8 years post-menarche):

• Do NOT use ultrasound as first-line diagnostic tool: poor specificity and high false-positive rates due to normal multifollicular ovaries in this age group 2
• Base diagnosis on persistent oligomenorrhea (2-3 years beyond menarche) plus clinical or biochemical hyperandrogenism 1, 2, 4

Important Diagnostic Pitfalls

• Do not confuse isolated polycystic ovaries with PCOS: 17-33% of normal women have polycystic ovarian morphology on ultrasound without symptoms or hormonal abnormalities 1, 2
• Recognize that hormonal contraception interferes with diagnosis: progestin-containing contraceptives suppress the hypothalamic-pituitary-ovarian axis, making hormone levels unreliable; remove or allow expiration before testing 2
• Consider hypothalamic amenorrhea in women with excessive exercise: working out twice daily can cause amenorrhea through hypothalamic suppression rather than PCOS 2
• Anti-Müllerian hormone (AMH) is NOT recommended for diagnosis: lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS 2, 3

Metabolic Screening

All women diagnosed with PCOS require metabolic evaluation:

• Screen for type 2 diabetes: fasting glucose followed by 2-hour glucose level after 75-gram oral glucose load 1, 2
• Measure fasting lipid panel: assess for dyslipidemia including elevated LDL cholesterol and triglycerides 1, 2
• Assess for insulin resistance: fasting glucose/insulin ratio >4 suggests reduced insulin sensitivity 1
• Screen for non-alcoholic fatty liver disease 5
• Evaluate for sleep apnea: occurs more commonly in women with PCOS 5

Treatment Options

Lifestyle Modification (First-Line for All Patients)

• Implement weight loss of 5-10% of initial body weight: this improves metabolic and reproductive abnormalities even with modest reduction 2, 6
• Prescribe regular exercise and dietary modification before initiating drug therapy 2

Menstrual Regulation and Endometrial Protection

• Use combination oral contraceptives (COCs) as first-line therapy: these regulate menstrual cycles, suppress ovarian androgen production, increase SHBG, and provide endometrial protection against hyperplasia 2, 4, 6
• Alternative: medroxyprogesterone acetate (depot or intermittent oral): suppresses circulating androgen levels and protects endometrium 2
• Menstrual cycle control is necessary to prevent endometrial hyperplasia and cancer 5

Management of Hirsutism and Acne

• First-line: oral contraceptives effectively manage both hirsutism and acne through androgen suppression 2, 4
• Add anti-androgen therapy for better efficacy: spironolactone (competitive androgen receptor antagonist) or finasteride (5α-reductase inhibitor) 4, 6
• Use combination of anti-androgen plus ovarian suppression agent for optimal results 2
• Employ mechanical hair removal methods: electrolysis and laser vaporization for cosmetic management 2, 5
• Apply routine acne treatments as adjunctive therapy 6

Ovulation Induction for Infertility

• First-line: clomiphene citrate achieves 80% ovulation rate and 50% conception rate in women with PCOS attempting to conceive 2, 7
• Alternative first-line: letrozole (aromatase inhibitor) is now recommended as first-line treatment for PCOS-related anovulation 6
• Second-line: low-dose gonadotropin therapy for women who fail clomiphene, with lower risk of ovarian hyperstimulation 2
• Adjunctive: metformin improves insulin sensitivity, glucose tolerance, and ovulation frequency 2, 4
• Start clomiphene on day 5 of cycle; limit to 6 total cycles (including 3 ovulatory cycles) 7

Insulin Sensitizers

• Consider metformin for metabolic management: improves insulin sensitivity and glucose tolerance 2, 4
• Dose in lean adolescents: 850 mg daily may be effective 4
• Dose in overweight/obese patients: escalate to 1.5-2.5 g daily 4
• Can be used as monotherapy or combined with oral contraceptives 4

Long-Term Monitoring

• Screen regularly for cardiovascular risk factors: PCOS is associated with dyslipidemia, hypertension, and increased cardiovascular disease risk 1, 2
• Monitor for progression to type 2 diabetes: repeat glucose tolerance testing periodically 2
• Assess mental health: depression and eating disorders occur more commonly in women with PCOS 5