What are the diagnostic criteria and treatment options for polycystic ovary syndrome in women of reproductive age?

Diagnosis and Treatment of Polycystic Ovary Syndrome (PCOS)

Diagnostic Criteria

PCOS is diagnosed when at least two of the following three Rotterdam criteria are present: (1) oligo/anovulation, (2) clinical or biochemical hyperandrogenism, and (3) polycystic ovarian morphology on ultrasound—after excluding other causes of hyperandrogenism and ovulatory dysfunction. 1, 2

Clinical Assessment

• Menstrual history: Cycle length >35 days indicates chronic anovulation; cycles of 32-35 days require assessment for ovulatory dysfunction 1, 3
• Hyperandrogenism signs: Document onset and duration of acne, hirsutism (gradual onset, worsens with weight gain), male-pattern balding (vertex, crown, or bitemporal), and clitoromegaly 1, 3
• Family history: Cardiovascular disease, diabetes, and PCOS 1
• Lifestyle factors: Diet, exercise patterns, alcohol use, smoking 1
• Physical examination: Calculate BMI and waist-hip ratio; look for acanthosis nigricans (insulin resistance marker); perform pelvic exam for ovarian enlargement 1

Laboratory Testing

Total testosterone measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the single best initial biochemical marker, with 74% sensitivity and 86% specificity. 1, 2

• Calculated free testosterone using the Vermeulen equation has the highest sensitivity at 89% with 83% specificity 1
• Free androgen index (FAI): 78% sensitivity and 85% specificity, but use cautiously 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

Transvaginal ultrasound with ≥8 MHz transducer frequency showing ≥20 follicles (2-9mm diameter) per ovary is the gold standard ultrasonographic marker, with 87.64% sensitivity and 93.74% specificity. 1, 4

• Alternative marker: Ovarian volume >10 mL when accurate follicle counting is difficult 1, 4
• Critical caveat: Do NOT use ultrasound as first-line diagnostic tool in adolescents (<20 years or <8 years post-menarche) due to poor specificity and high false-positive rates 1, 3
• Important pitfall: Up to one-third of reproductive-aged women without PCOS have polycystic ovarian morphology on ultrasound, so ultrasound alone is insufficient for diagnosis 1

Exclusion of Other Conditions

Before confirming PCOS, rule out:

• Thyroid disease: Measure serum TSH 1
• Hyperprolactinemia: Obtain morning resting prolactin level (women with PCOS have 3.15-fold higher risk of elevated prolactin) 1
• Cushing's syndrome: Look for buffalo hump, moon facies, hypertension, abdominal striae 1
• Androgen-secreting tumors: Rapid onset and severe virilization, marked clitoromegaly, voice deepening require immediate evaluation 1, 2
• Non-classic congenital adrenal hyperplasia: Consider based on clinical suspicion 1

Metabolic Screening

All women with PCOS should be screened for type 2 diabetes and glucose intolerance using a 2-hour oral glucose tolerance test with 75-gram glucose load, regardless of BMI. 1, 4

• Fasting lipid profile: Total cholesterol, LDL, HDL, triglycerides to assess cardiovascular risk 1, 4
• Rationale: Metabolic syndrome occurs twice as frequently in PCOS compared to general population; four-fold increased risk of type 2 diabetes 4, 2

Special Considerations

• Adolescents: Delay evaluation until 2 years post-menarche; require all three Rotterdam criteria for diagnosis; persistent oligomenorrhea 2-3 years beyond menarche predicts ongoing dysfunction 2, 3
• Hormonal contraception: Remove or allow expiration of progestin-only implants (e.g., Implanon) before hormone testing, as they suppress the hypothalamic-pituitary-ovarian axis and make diagnostic levels unreliable 1
• AMH levels: NOT recommended for clinical diagnosis due to lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS 1

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Treatment Approach

First-Line: Lifestyle Modification

All women with PCOS, regardless of body weight, should receive multicomponent lifestyle intervention as first-line management, combining dietary modification, structured physical activity, and behavioral strategies, because insulin resistance affects all PCOS patients independent of BMI. 5, 4

Dietary Recommendations

• Energy deficit: 30% reduction or 500-750 kcal/day, targeting 1,200-1,500 kcal/day for overweight/obese patients 4
• No specific diet is superior—focus on individual preferences and cultural needs while maintaining balanced nutrition 5, 4
• Beneficial dietary patterns: Low glycemic index foods, high-fiber diets, omega-3 fatty acid-rich diets, Mediterranean diets, anti-inflammatory diets improve insulin sensitivity and hormonal balance 4
• Avoid unduly restrictive or nutritionally unbalanced diets 4
• Weight loss benefit: As little as 5% of initial weight can improve metabolic and reproductive abnormalities 1

Exercise Recommendations

• Minimum: 150 minutes/week of moderate-intensity exercise OR 75 minutes/week of vigorous-intensity activity, performed in at least 10-minute bouts 4
• Muscle-strengthening: Activities involving major muscle groups on 2 non-consecutive days per week 4
• Daily target: 10,000 steps including 30 minutes of structured physical activity 4
• For weight loss: At least 250 minutes/week of moderate-intensity or 150 minutes/week of vigorous-intensity activity 4
• Minimize sedentary time: Reduce screen and sitting time throughout the day 4
• Practical approach: Start with realistic 10-minute activity bouts, progressively increasing by 5% weekly 4

Behavioral Strategies

• SMART goal setting: Specific, measurable, achievable, realistic, timely goals with self-monitoring using fitness tracking devices 4
• Behavioral techniques: Goal-setting, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, relapse prevention 4
• Psychological support: Address anxiety, depression, body image concerns, disordered eating 4
• Avoid weight-related stigma: Ensure health professional interactions are respectful and patient-centered 4

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Pharmacologic Treatment: Based on Patient Goals

For Patients NOT Seeking Pregnancy

Combination oral contraceptive pills are first-line therapy for long-term management of menstrual irregularities, anovulation, hirsutism, and acne. 1, 2, 6

• Mechanism: Suppress ovarian androgen production and increase sex hormone-binding globulin 3
• Second-line for hirsutism: Add antiandrogens (spironolactone, cyproterone acetate, flutamide) to oral contraceptives for better efficacy 1, 3
• Alternative for menstrual regulation: Medroxyprogesterone acetate (depot or intermittent oral therapy) to suppress circulating androgen levels 1
• Mechanical hair removal: Electrolysis and laser vaporization for cosmetic management of hirsutism 1

For Patients Seeking Pregnancy

Letrozole is first-line therapy for ovulation induction in women with PCOS attempting to conceive. 6

• Alternative: Clomiphene citrate achieves 80% ovulation rate and 50% conception rate 1
• Second-line: Low-dose gonadotropin therapy for patients who fail clomiphene, with lower risk of ovarian hyperstimulation 1

For Metabolic Complications

Metformin (insulin-sensitizing agent) is first-line therapy for patients with metabolic complications such as insulin resistance, to improve insulin sensitivity, glucose tolerance, and ovulation frequency. 1, 2, 6

• Dosing in lean adolescents: 850 mg daily may be effective 3
• Dosing in overweight/obese patients: Escalate to 1.5-2.5 g daily 3
• Synergistic effect: More potent when combined with lifestyle interventions 7

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Long-Term Monitoring

International guidelines recommend comprehensive cardiovascular risk screening including weight monitoring every 6-12 months, at least annual blood pressure checks, fasting lipid panels, and glycemic control screening. 4

• Weight and waist circumference: Monitor regularly with ethnic-specific categories 4
• Blood pressure: At least annually 4
• Fasting lipid panel: Screen for dyslipidemia 4
• Glycemic control: Fasting glucose, HbA1c, or oral glucose tolerance test based on cardiovascular risk stratification 4
• Psychological screening: Assess for anxiety, depression, body image concerns, and treatment adherence 4
• Obstructive sleep apnea: Screen patients with PCOS due to increased risk 6
• Endometrial cancer surveillance: Ovulatory dysfunction increases risk of endometrial hyperplasia and cancer 3

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Critical Clinical Pitfalls

• Do NOT dismiss lifestyle intervention in lean PCOS patients simply because they have normal BMI—insulin resistance requires management regardless of weight 4
• Do NOT rely on ultrasound alone for diagnosis, as polycystic ovarian morphology is common in women without PCOS 1
• Do NOT use ultrasound in adolescents <20 years or <8 years post-menarche as first-line diagnostic tool 1, 3
• Do NOT test hormones while on hormonal contraception—progestin suppresses the hypothalamic-pituitary-ovarian axis 1
• Do NOT use direct immunoassay for free testosterone—calculated free testosterone is more accurate 1
• Recognize red flags for androgen-secreting tumors: Rapid onset, severe virilization, marked clitoromegaly require immediate evaluation 1, 2