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

Treatment for PCOS

Multicomponent lifestyle intervention combining diet, exercise, and behavioral strategies is the mandatory first-line treatment for all women with PCOS, regardless of body weight or fertility goals, because insulin resistance affects all patients independent of BMI. 1

First-Line Treatment: Lifestyle Modification

Dietary Management

• Create an energy deficit of 500-750 kcal/day, targeting 1,200-1,500 kcal/day total intake, adjusted for individual energy requirements 1, 2
• 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 intake, and omega-3 fatty acids to improve insulin sensitivity and hormonal balance 1
• Avoid overly restrictive or nutritionally unbalanced diets 1
• Even modest weight loss of 5-10% yields significant clinical improvements in menstrual regularity, ovulation, and metabolic parameters 1, 2

Physical Activity Prescription

• Prescribe at least 150 minutes/week of moderate-intensity exercise OR 75 minutes/week of vigorous-intensity activity 1, 2
• Include muscle-strengthening activities on 2 non-consecutive days per week 1
• For weight loss and prevention of regain, increase to at least 250 minutes/week of moderate-intensity activity 1
• Perform activity in at least 10-minute bouts, aiming for 10,000 steps daily including 30 minutes of structured activity 1
• Both aerobic and resistance exercises show benefits in PCOS 1
• Minimize sedentary, screen, and sitting time throughout the day 1

Behavioral Strategies

• Implement SMART (specific, measurable, achievable, realistic, timely) goal setting with self-monitoring using fitness tracking devices 1, 2
• Include stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 1
• Address psychological factors including anxiety, depression, body image concerns, and eating disorders (binge eating disorder and night eating syndrome are highly prevalent in PCOS) 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

Monitoring Schedule

• Fortnightly review for the first 3 months with structured dietary and physical activity plans 1
• Regular review for the first 12 months to ensure adherence and adjust interventions 1
• Monitor weight and waist circumference regularly using ethnic-specific cutoffs (Asian, Hispanic, and South Asian populations require lower thresholds) 1, 2

Medical Management: Based on Reproductive Goals

For Women NOT Attempting to Conceive

Combined oral contraceptives (COCs) are first-line hormonal therapy for women with PCOS not attempting to conceive. 1, 3

• COCs suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne 1, 3
• Typical dosing: drospirenone 3 mg/ethinyl estradiol 20 μg in a 24-active/4-inert pill regimen, taken daily 1
• COCs reduce the risk of endometrial cancer but are associated with increases in circulating triglyceride and HDL cholesterol levels 1

Add metformin 500-2000 mg daily when:

• Insulin resistance or glucose intolerance is documented 1, 3
• Lifestyle modifications alone are insufficient for metabolic control 3
• Patient has obesity or elevated cardiovascular risk factors 3
• Start with 500 mg daily and titrate up to 1000-2000 mg daily in divided doses 1
• Metformin improves glucose tolerance and may positively impact risk factors for diabetes and cardiovascular disease 1, 3

For severe hirsutism:

• Combined medical interventions (antiandrogen plus ovarian suppression agent) may be most effective 1

For Women ATTEMPTING to Conceive

Clomiphene citrate is first-line pharmacological treatment for ovulation induction in women with PCOS attempting to conceive. 1, 2, 3, 4

• Approximately 80% of patients ovulate and 50% conceive with clomiphene citrate 1, 2, 3
• Start each course on or about the 5th day of the cycle 4
• Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles) 4
• Patients with polycystic ovary syndrome should be started on the lowest recommended dose and shortest treatment duration for the first course of therapy due to unusual sensitivity to gonadotropin 4
• Pelvic examination is necessary prior to the first and each subsequent course of treatment 4

If clomiphene treatment fails:

• Use low-dose gonadotropin therapy rather than high-dose to induce monofollicular development with lower risk of ovarian hyperstimulation 1, 2, 3

Metformin in preconception:

• Metformin 1 g twice daily for 12 weeks or until pregnancy can be used in the pregestational stage to improve fertility outcomes 1
• Metformin and thiazolidinediones improve ovulation frequency and may positively impact diabetes and cardiovascular risk factors 2

Emerging Pharmacological Options

GLP-1 receptor agonists show promise for weight reduction and metabolic improvement when combined with lifestyle interventions. 1, 3

• Liraglutide 1.8-3 mg daily, semaglutide 1-2 mg weekly, or exenatide 5-10 μg twice daily or 2 mg weekly 1
• These agents appear superior to placebo for anthropometric outcomes 3
• Orlistat 120 mg three times daily plus lifestyle intervention is another potential option for weight loss 1

Mandatory Metabolic Screening

All patients with PCOS require comprehensive metabolic surveillance regardless of weight. 3

• Screen for type 2 diabetes with fasting glucose 3
• Obtain fasting lipid profile 3
• Calculate BMI and waist-hip ratio to assess central obesity 1, 3
• Use ethnic-specific BMI and waist circumference categories for Asian, Hispanic, and South Asian populations 1, 2
• Repeat screening at least annually 3
• Perform endometrial biopsy prior to treatment in women with increasing age due to increased incidence of endometriosis and endometrial carcinoma 3

Critical Pitfalls to Avoid

• Do not dismiss lifestyle intervention in normal-weight PCOS patients—insulin resistance requires management regardless of BMI 1, 2
• Do not recommend herbal supplements (including evening primrose oil) as primary therapy instead of evidence-based interventions 1
• Do not exceed recommended clomiphene dosage and duration due to risk of ovarian hyperstimulation syndrome 3, 4
• Do not neglect metabolic screening even in normal-weight PCOS patients 3
• Ensure health professional interactions are respectful and patient-centered, avoiding weight-related stigma which negatively impacts treatment engagement 1
• Recognize that weight gain accelerates over time in PCOS, making early intervention crucial starting from adolescence 1, 2
• If ovarian enlargement occurs with clomiphene, do not give additional therapy until ovaries return to pretreatment size 4
• Discontinue clomiphene immediately if visual symptoms occur and perform complete ophthalmological evaluation 4

Special Population Considerations

Adolescents

• Prevention of weight gain and monitoring should begin from adolescence 1
• Aim for at least 60 minutes of moderate to vigorous intensity physical activity daily, including activities that strengthen muscle and bone at least 3 times weekly 1

High Cardiometabolic Risk Ethnic Groups

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