What are the diagnostic criteria and treatment options for Polycystic Ovary Syndrome (PCOS)?

Diagnostic Criteria for Polycystic Ovary Syndrome (PCOS)

Use the Rotterdam criteria requiring at least 2 of 3 features: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound, after excluding other androgen-excess disorders. 1, 2

Clinical History and Physical Examination

Document these specific elements:

• Menstrual history: Cycle length >35 days indicates chronic anovulation 1
• Hyperandrogenism onset: Gradual development intensifying with weight gain suggests PCOS; rapid onset with clitoromegaly suggests androgen-secreting tumor 1, 3
• Hirsutism assessment: Look for excess terminal hair growth in androgen-sensitive areas 1
• Acne patterns: Severe or treatment-resistant acne (including isotretinoin failure) carries 40% likelihood of PCOS 3
• Hair loss: Vertex, crown, or diffuse pattern; bitemporal loss suggests severe hyperandrogenemia 3
• BMI and waist-hip ratio: Calculate both as metabolic risk indicators 1
• Family history: Cardiovascular disease and diabetes 1

Biochemical Testing

Total testosterone measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the preferred initial test, offering 74% sensitivity and 86% specificity. 1

Recommended androgen panel:

• Calculated free testosterone (cFT): Highest sensitivity at 89% with 83% specificity using Vermeulen equation from high-quality total testosterone and SHBG 1
• Free androgen index (FAI): 78% sensitivity and 85% specificity, but avoid when SHBG <30 nmol/L 1
• Androstenedione: 75% sensitivity and 71% specificity, useful when SHBG is low 1
• DHEAS: 75% sensitivity and 67% specificity, most reliable for adrenal androgen production, particularly in women <30 years 1

Ultrasound Criteria

Follicle number per ovary (FNPO) ≥20 follicles is the gold standard ultrasonographic marker with 87.64% sensitivity and 93.74% specificity. 4, 1

Technical specifications:

• Transvaginal ultrasound with ≥8 MHz transducer in adults (18-50 years) 4, 1
• Alternative markers when accurate follicle counting impossible: ovarian volume >10 mL or follicle number per single cross-section 4, 1
• Avoid ultrasound in adolescents (<17 years) as first-line due to poor specificity; rely on clinical/biochemical hyperandrogenism plus menstrual irregularity 4, 3

Differential Diagnosis to Exclude

Rule out these conditions before confirming PCOS:

• Cushing's syndrome: Buffalo hump, moon facies, hypertension, abdominal striae 1
• Androgen-secreting tumors: Rapid onset, severe hyperandrogenism 1
• Non-classic congenital adrenal hyperplasia: Measure 17-hydroxyprogesterone 1, 3
• Thyroid disease and hyperprolactinemia: Check TSH and prolactin 1
• Primary ovarian failure: Assess FSH 1

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Treatment Options for PCOS

First-Line: Lifestyle Modification

Implement weight loss of at least 5% initial body weight through diet and regular exercise before initiating drug therapy, as this improves both metabolic and reproductive abnormalities. 1, 5

• Diet modification: First-choice treatment; only proceed to pharmacotherapy if dietary intervention fails 5
• Regular exercise: Essential component of management 1
• Sleep quality and stress reduction: Important adjunctive measures 5

Menstrual Irregularity Management

Use combination oral contraceptive pills as first-line therapy for long-term management of menstrual irregularities and anovulation. 1, 3

Mechanism and alternatives:

• OCPs suppress ovarian androgen production and increase SHBG, effectively lowering free androgens 3
• Medroxyprogesterone acetate (depot or intermittent oral): Alternative to suppress circulating androgens 1
• Metformin: Improves menstrual irregularities but has limited benefit for hirsutism, acne, or infertility 2

Infertility Treatment

Clomiphene citrate is first-line treatment for women with PCOS attempting to conceive, achieving 80% ovulation rate and 50% conception rate. 1, 6

FDA-approved protocol for clomiphene:

• Start on day 5 of cycle after establishing ovulation timing 6
• Limit to 6 total cycles (including 3 ovulatory cycles) 6
• Contraindications: Pregnancy, ovarian cysts (except in PCOS), abnormal vaginal bleeding, liver dysfunction 6
• Monitor for ovarian hyperstimulation syndrome (OHSS): Abdominal pain/distention, nausea, vomiting, weight gain are early warning signs 6

Second-line options:

• Low-dose gonadotropin therapy: For clomiphene failures, lower risk of ovarian hyperstimulation 1
• Metformin: Can improve ovulation frequency but inferior to clomiphene for fertility 1, 2

Hyperandrogenism and Cosmetic Management

Oral contraceptives are first-line therapy for hirsutism and acne in women with PCOS. 1, 3

Enhanced treatment strategies:

• Combination anti-androgen plus ovarian suppression: More effective than monotherapy 1
• Spironolactone, cyproterone acetate, or flutamide: Competitive androgen receptor antagonists 3
• Finasteride: Inhibits 5α-reductase, preventing testosterone conversion to dihydrotestosterone 3
• Mechanical methods: Electrolysis and laser vaporization for permanent hair reduction 1

Metabolic Complications Management

Screen all women with PCOS for type 2 diabetes and glucose intolerance regardless of symptoms. 1, 2

Comprehensive metabolic screening:

• Fasting glucose and oral glucose tolerance test: Mandatory screening 1
• Fasting lipid profile: Screen for dyslipidemia 1
• Metformin: Consider for improving insulin sensitivity and glucose tolerance in those with insulin resistance 1, 2
• Cardiovascular risk assessment: Regular screening for hypertension and cardiovascular risk factors 1
• Sleep apnea screening: Higher prevalence in PCOS 7

Special Population: Adolescents

In adolescents with PCOS, use hormonal contraceptives and metformin as treatment options, avoiding ultrasound for diagnosis. 3, 2

Adolescent-specific considerations:

• Diagnosis requires persistent oligomenorrhea 2-3 years beyond menarche plus hyperandrogenism 3
• Metformin dosing: 850 mg daily in lean adolescents; escalate to 1.5-2.5 g daily in overweight/obese 3
• Anti-androgen therapy: Short-term data suggest no bone loss, but monitor carefully 3

Medications with Unfavorable Risk-Benefit

Thiazolidinediones have an unfavorable risk-benefit ratio overall and should not be used routinely. 2

• Statins: Require further study before routine recommendation 2