What are the treatment options for patients with Polycystic Ovary Syndrome (PCOS)?

Treatment Options for PCOS

All patients with PCOS, regardless of body weight or reproductive goals, should begin with multicomponent lifestyle intervention as mandatory first-line therapy, combining dietary modification (500-750 kcal/day deficit), structured physical activity (at least 150 minutes/week moderate-intensity exercise), and behavioral strategies, because insulin resistance affects all PCOS patients independent of BMI. 1

First-Line Treatment: Lifestyle Modification (Mandatory for All Patients)

Dietary Management

• Target an energy deficit of 500-750 kcal/day with total intake of 1,200-1,500 kcal/day, adjusted for individual energy requirements 1
• Any balanced dietary approach creating an energy deficit is acceptable—no specific diet type has proven superior 1
• Focus on low glycemic index foods, high fiber, omega-3 fatty acids, and anti-inflammatory dietary patterns 2
• Avoid overly restrictive or nutritionally unbalanced diets 1

Physical Activity Prescription

• For weight maintenance and health: At least 150 minutes/week of moderate-intensity activity OR 75 minutes/week of vigorous-intensity activity 1
• For weight loss: At least 250 minutes/week of moderate-intensity activity OR 150 minutes/week of vigorous-intensity activity 1
• Include muscle-strengthening activities on 2 non-consecutive days per week 1
• Minimize sedentary, screen, and sitting time throughout the day 1
• Start with realistic 10-minute activity bouts, progressively increasing by 5% weekly 1

Behavioral Strategies

• Implement SMART goal setting with self-monitoring using fitness tracking devices 1
• Include goal-setting, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 1
• Address psychological factors including anxiety, depression, body image concerns, and disordered eating 1

Critical Pitfall: Even 5% weight loss yields significant clinical improvements in metabolic and reproductive outcomes, so do not delay treatment waiting for larger weight loss targets 1

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Medical Management: Based on Reproductive Goals

For Women NOT Attempting to Conceive

Hormonal Therapy (First-Line)

• Combined oral contraceptives (COCs) are first-line hormonal therapy because they suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne 3, 4
• Typical regimen: Drospirenone 3 mg/ethinyl estradiol 20 μg in a 24-active/4-inert pill regimen, taken daily 1
• COCs reduce endometrial cancer risk but increase circulating triglycerides and HDL cholesterol 3

Alternative Hormonal Options

• Medroxyprogesterone acetate (depot or intermittent oral) suppresses circulating androgen and pituitary gonadotropin levels, though optimal progestin, duration, and frequency to prevent endometrial cancer is unknown 3

Insulin-Sensitizing Agents

• Metformin 500-2000 mg daily improves glucose tolerance over time and may positively impact risk factors for diabetes and cardiovascular disease 3, 4
• Start with 500 mg daily and titrate up to 1000-2000 mg daily in divided doses to minimize gastrointestinal side effects 1
• Metformin is particularly indicated for documented insulin resistance, glucose intolerance, or established type 2 diabetes 2

Antiandrogen Therapy for Hirsutism

• Spironolactone 50-200 mg daily or finasteride for persistent bothersome hirsutism, combined with mechanical hair removal methods 2
• Topical eflornithine hydrochloride cream is FDA-approved for hirsutism and can be used adjunctively 2
• Combined medical interventions (antiandrogen plus ovarian suppression agent) may be most effective for hirsutism 3

For Women ATTEMPTING to Conceive

First-Line Ovulation Induction

• Clomiphene citrate is the first-line pharmacological treatment due to its effectiveness, safety, and ease of administration 3, 5
• Approximately 80% of patients ovulate and 50% of those conceive with clomiphene 3, 5
• Start treatment on or about the 5th day of the cycle 5
• Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles) 5

Critical Pitfall: Patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of clomiphene citrate, so start with the lowest recommended dose and shortest treatment duration for the first course 5

Second-Line Ovulation Induction

• If clomiphene treatment fails, use low-dose gonadotropin therapy rather than high-dose, because low-dose treatment induces high rates of monofollicular development with lower risk of ovarian hyperstimulation 3

Adjunctive Therapy

• Metformin 1 g twice daily for 12 weeks or until pregnancy can be used in the pregestational stage to improve fertility outcomes 1
• Metformin appears safe in early pregnancy, though documentation is poor for its purported effect in reducing miscarriage rate 3

Critical Warning: The benefit and role of laparoscopic ovarian drilling by laser or diathermy are undetermined in women with PCOS 3

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Emerging Anti-Obesity Pharmacotherapy

• GLP-1 receptor agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement when combined with lifestyle interventions 2, 1, 4
• Consider these newer anti-obesity agents when lifestyle interventions alone are insufficient 2
• Orlistat 120 mg three times daily plus lifestyle intervention is another potential option for weight loss 1

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Mandatory Metabolic Screening (All Patients)

Initial Assessment

• Screen for type 2 diabetes using fasting glucose followed by 2-hour glucose level after 75-gram oral glucose load 2
• Obtain comprehensive fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides 2
• Calculate BMI and waist-hip ratio using ethnic-specific cutoffs for high-risk populations (Asian, Hispanic, South Asian require lower thresholds) 2, 1

Ongoing Monitoring

• Repeat diabetes screening annually or every 1-2 years based on BMI and family history 2
• Monitor lipid profile regularly 2
• Regular monitoring of weight and waist circumference during treatment 1

Critical Pitfall: Do not neglect metabolic screening even in normal-weight PCOS patients, as insulin resistance affects all PCOS phenotypes regardless of BMI 1, 4

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Psychological and Quality of Life Management

• Screen for depression, anxiety, body image concerns, and eating disorders (binge eating disorder, night eating syndrome), as PCOS has significant negative impact on psychological wellbeing 2, 1
• Refer patients with moderately severe depression to psychiatry or behavioral health for evaluation and potential pharmacotherapy, as depression dramatically reduces adherence to lifestyle interventions 1
• Ensure health professional interactions are respectful and patient-centered, avoiding weight-related stigma which negatively impacts treatment engagement 1

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Special Population Considerations

Adolescents

• Prevention of weight gain and monitoring should begin from adolescence, as weight gain escalates from this period 1
• Adolescents should aim for at least 60 minutes of moderate to vigorous intensity physical activity daily, including muscle and bone strengthening activities at least 3 times weekly 1

Ethnic Groups at High Cardiometabolic Risk

• Asian, Hispanic, and South Asian populations require lower BMI and waist circumference thresholds and greater consideration for lifestyle intervention 2, 1

Postmenopausal Women

• Standard menopausal hormone therapy (HRT) guidelines apply—transdermal 17-β estradiol is preferred over oral formulations to minimize thrombotic risk 2
• Continue metformin for documented insulin resistance, glucose intolerance, or established type 2 diabetes to reduce cardiovascular and metabolic risk 2