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

Symptoms and Treatment of Polycystic Ovary Syndrome (PCOS)

Clinical Presentation and Symptoms

PCOS presents with a characteristic triad of menstrual irregularities, hyperandrogenic features, and metabolic disturbances that affect approximately 10% of reproductive-age women. 1, 2

Menstrual and Reproductive Symptoms

• Irregular or absent menstrual cycles due to oligo- or anovulation are hallmark features 2, 3
• Infertility is common, resulting from chronic anovulation 2, 3

Hyperandrogenic Manifestations

• Hirsutism (excess male-pattern hair growth) affects the majority of patients due to elevated androgen levels 2
• Acne occurs frequently as a manifestation of androgen excess 1, 2
• Male pattern hair loss or balding may be present 1

Metabolic and Dermatologic Signs

• Acanthosis nigricans appears as darkened, velvety skin patches (typically on neck, axillae, groin) and indicates underlying insulin resistance—this is a critical physical exam finding 1, 2, 4
• Insulin resistance occurs in a significant proportion of patients regardless of body weight, affecting both lean and overweight women 2, 4
• Obesity and central adiposity are common but not universal features 4

Associated Comorbidities

• Increased risk for type 2 diabetes due to insulin resistance 1, 4
• Dyslipidemia with elevated triglycerides, increased small dense LDL, and decreased HDL 4
• Cardiovascular disease risk factors accumulate over time 1, 2
• Obstructive sleep apnea risk is elevated 5
• Mood disorders occur with increased frequency 5

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Diagnostic Workup

Required Laboratory Testing

• Thyroid-stimulating hormone and prolactin levels to exclude other causes of hyperandrogenism 1, 2
• Total testosterone or free/bioavailable testosterone to assess androgen excess severity 1, 2
• Fasting glucose followed by 2-hour glucose level after 75-gram oral glucose load to detect type 2 diabetes and glucose intolerance 1, 4
• Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) to assess cardiovascular risk 1, 4

Physical Examination Findings

• Look specifically for acanthosis nigricans on neck, axillae, and groin as a marker of insulin resistance 4
• Calculate BMI and waist-hip ratio to assess central obesity 4

Critical pitfall: Do not overlook acanthosis nigricans, as it may rarely indicate associated insulinoma or malignancy, particularly gastric adenocarcinoma 4

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Treatment Algorithm

Step 1: Lifestyle Intervention (Foundation for All Patients)

Initiate multicomponent lifestyle intervention before or concurrent with any pharmacologic therapy—this is the foundation of treatment. 4

• Target weight loss of just 5% of initial body weight, which improves metabolic parameters, ovulation rates, and pregnancy outcomes 2, 4
• Implement diet, exercise, and behavioral strategies together rather than any single component 4
• Screen every PCOS patient for metabolic dysfunction regardless of body weight, as insulin resistance occurs independent of BMI 4

Step 2: Treatment Based on Primary Concern

For Women NOT Attempting Conception

Combination oral contraceptive pills (COCs) are first-line therapy for regulating menstrual cycles, providing endometrial protection, and suppressing androgen secretion 1, 2

• COCs regulate cycles and reduce androgen levels, improving hirsutism and acne 2
• Be aware that COCs may increase triglycerides and HDL cholesterol, though they do not appear to increase cardiovascular events compared to the general population 2, 4

Add metformin when metabolic dysfunction is prominent:

• Use metformin as the preferred insulin-sensitizing agent when pharmacologic intervention is warranted 4
• Metformin improves insulin sensitivity, glucose tolerance over time, and decreases circulating androgen levels 4
• Metformin tends to decrease weight, unlike thiazolidinediones which increase weight 4
• Note: Metformin lacks FDA approval specifically for PCOS but has the most data supporting its effectiveness 2, 4, 6

For Women Attempting Conception

Letrozole (aromatase inhibitor) is now first-line treatment for PCOS-related anovulation (off-label use) 3

• If letrozole is unavailable or fails, clomiphene citrate induces ovulation in approximately 80% of women, with 50% achieving pregnancy 2
• Metformin can be added to clomiphene to improve ovulation rates and metabolic outcomes 4, 6

If clomiphene fails:

• Use low-dose gonadotropins to minimize ovarian hyperstimulation risk 2
• Consider laparoscopic ovarian drilling as a surgical alternative 7

For Hirsutism Management

Beyond COCs as first-line:

• Spironolactone (off-label) for moderate to severe hirsutism 3, 6
• Topical eflornithine for facial hirsutism 6
• Finasteride (off-label) as an alternative anti-androgen 3
• Topical cosmetic treatments (laser hair removal, electrolysis) 3

For Acne Management

• COCs provide first-line hormonal management 2
• Routine acne treatments (topical retinoids, benzoyl peroxide, antibiotics) are also used 3

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Ongoing Screening and Monitoring

Metabolic Surveillance

• All women with PCOS require screening for type 2 diabetes using fasting glucose and 2-hour oral glucose tolerance test 1, 2
• Regular fasting lipid profiles to monitor the particularly atherogenic lipid profile created by insulin resistance 4
• Regular blood pressure monitoring due to increased cardiovascular disease risk 1, 2

Endometrial Protection

• Women with chronic anovulation require endometrial protection to prevent endometrial hyperplasia and cancer risk 1
• COCs provide this protection; if COCs are contraindicated, consider cyclic progestin therapy 1

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Key Clinical Pitfalls to Avoid

• Do not use thiazolidinediones as first-line agents given their tendency to increase weight and unfavorable risk-benefit profile compared to metformin 4, 5
• Do not skip lipid screening—insulin resistance in PCOS creates a particularly atherogenic lipid profile requiring monitoring 4
• Do not forget endometrial protection in women with chronic anovulation who are not on COCs 1
• Do not overlook screening for mood disorders and obstructive sleep apnea, which occur with increased frequency 5