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

Treatment Options for Polycystic Ovary Syndrome (PCOS)

First-Line Treatment: Multicomponent Lifestyle Intervention for ALL Patients

All women with PCOS, regardless of body weight or BMI, 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 weight. 1, 2

Why Lifestyle Intervention is Universal

• Insulin resistance is present in PCOS irrespective of BMI and affects both lean and overweight women, contributing to hyperandrogenism through effects on the pituitary, liver, and ovaries 1
• Critical pitfall to avoid: Do not dismiss lifestyle intervention in lean PCOS patients simply because they have normal BMI—insulin resistance requires management regardless of weight 1
• Healthy lifestyle may contribute to health and quality of life benefits even in the absence of weight loss 1, 3

Dietary Management

Caloric Targets for Weight Loss (When Indicated)

• For patients with overweight or obesity, aim for an energy deficit of 30% or 500-750 kcal/day (1,200-1,500 kcal/day), considering individual energy requirements 1, 3, 2
• Achievable goals of 5-10% weight loss in those with excess weight can yield significant clinical improvements within 6 months 3

Dietary Composition

• No specific diet type has proven superior; any diet aimed at reducing weight benefits women with PCOS 1, 4
• Evidence supports low glycemic index foods, high-fiber diets, omega-3 fatty acid-rich diets, ketogenic diets, Mediterranean diets, and anti-inflammatory diets for improving insulin sensitivity and hormonal balance 1, 4
• Focus on individual preferences and cultural needs while maintaining nutritional balance 1, 2
• Avoid unduly restrictive or nutritionally unbalanced diets 1

Physical Activity Prescription

Minimum Requirements for Health Maintenance

• Prescribe at least 150 minutes/week of moderate-intensity exercise (brisk walking, cycling 8-15 km/h, low-impact aerobics, yoga) OR 75 minutes/week of vigorous-intensity activity (jogging/running, high-impact aerobics, competitive sports) 1, 3, 2
• Include muscle-strengthening activities involving major muscle groups on 2 non-consecutive days per week 1, 3
• Activity should be performed in at least 10-minute bouts, aiming for at least 30 minutes daily on most days 1

Enhanced Targets for Weight Loss

• For patients with overweight or obesity seeking weight loss, prescribe at least 250 minutes/week of moderate-intensity activities OR 150 minutes/week of vigorous-intensity activities 1, 3
• Target 10,000 steps daily, including 30 minutes of structured physical activity 1
• Minimize sedentary, screen, and sitting time throughout the day 1

Exercise Benefits

• Both aerobic and resistance exercises improve insulin sensitivity and metabolic outcomes in PCOS, with benefits occurring independently of significant weight loss 1, 3

Behavioral Strategies

• Implement SMART (specific, measurable, achievable, realistic, timely) goal setting with self-monitoring using fitness tracking devices for step count and exercise intensity 1, 3
• Include behavioral change techniques: goal-setting, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 1, 2
• Start with realistic 10-minute activity bouts, progressively increasing physical activity by 5% weekly up to and above recommendations 1
• Consider comprehensive behavioral or cognitive behavioral interventions to increase support and adherence 1

Medical Management for Women NOT Attempting to Conceive

Hormonal Therapy

Combined oral contraceptive pills are first-line hormonal therapy for women with PCOS not attempting to conceive, as they suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne. 1, 2

• Typical dosing regimen: drospirenone 3 mg/ethinyl estradiol 20 μg in a 24-active/4-inert pill regimen, taken daily 1
• Combined oral contraceptives reduce the risk of endometrial cancer 1
• Be aware that COCs are associated with significant increases in circulating triglyceride and HDL cholesterol levels 1

Insulin-Sensitizing Agents

• Metformin 500-2000 mg daily for patients with insulin resistance or glucose intolerance, starting at 500 mg daily and titrating up to 1000-2000 mg daily in divided doses 1, 2
• Metformin improves glucose tolerance over time and may have a positive impact on risk factors for diabetes and cardiovascular disease 1
• Thiazolidinediones may also improve insulin sensitivity and decrease circulating androgens 1, 2

GLP-1 Receptor Agonists

• GLP-1 receptor agonists (liraglutide, semaglutide, exenatide) in combination with lifestyle interventions for weight loss and metabolic control 1

Antiandrogen Therapy for Hirsutism

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

Medical Management for Women ATTEMPTING to Conceive

First-Line Ovulation Induction

Clomiphene citrate is first-line pharmacological treatment for ovulation induction in women with PCOS attempting to conceive, with approximately 80% of patients ovulating and 50% conceiving. 1, 5

• Weight control and regular exercise programs should be started before medication 1
• Each course of clomiphene citrate should be started 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
• Properly timed coitus in relationship to ovulation is important 5

Preconception Metformin

• Metformin 1 g twice daily for 12 weeks or until pregnancy in the pregestational stage 1

Second-Line Therapy

• If clomiphene treatment fails, low-dose gonadotropin therapy should be used, which induces a high rate of monofollicular development with a lower risk of ovarian hyperstimulation 1

Critical Safety Considerations with Clomiphene

• Patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of clomiphene citrate and should be started on the lowest recommended dose and shortest treatment duration 5
• The ovarian hyperstimulation syndrome (OHSS) has been reported with clomiphene citrate therapy and may progress rapidly (within 24 hours to several days) to become a serious medical disorder 5
• Early warning signs of OHSS include abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain 5
• If ovarian enlargement occurs, additional clomiphene citrate therapy should not be given until the ovaries have returned to pretreatment size 5
• Visual symptoms (blurring, scotomata, phosphenes) have been reported; patients with any visual symptoms should discontinue treatment and have a complete ophthalmological evaluation 5

Mental Health and Psychological Management

Screening and Referral

• Refer patients with PCOS and moderately severe depression to psychiatry or behavioral health for evaluation and potential pharmacotherapy, as depression dramatically reduces adherence to lifestyle interventions 1
• Screen patients for eating disorders (binge eating disorder, night eating syndrome), which are highly prevalent in PCOS and create a vicious cycle worsening both obesity and hormonal disturbances 1
• Address body image concerns and psychological distress related to hair loss and PCOS symptoms, as these significantly impact treatment adherence 1

Integration with Lifestyle Treatment

• Address psychological factors (anxiety, depression, body image concerns, disordered eating) to optimize engagement and adherence to lifestyle interventions 1, 2

Monitoring and Follow-Up

Initial Intensive Phase

• 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

Ongoing Monitoring

• Regular monitoring of weight and waist circumference during weight loss and maintenance 1, 3, 2
• Regular assessment of metabolic syndrome elements: blood pressure, HbA1c, and lipid status 2

Respectful Patient-Centered Care

• Critical pitfall to avoid: Ensure health professional interactions are respectful and patient-centered, avoiding weight-related stigma which negatively impacts treatment engagement 1
• Value women's individualized preferences and cultural differences 1

Special Population Considerations

High-Risk Ethnic Groups

• Asian, Hispanic, and South Asian populations require lower BMI and waist circumference thresholds for intervention due to high cardiometabolic risk 1, 2
• Use ethnic-specific BMI and waist circumference categories when optimizing lifestyle and weight 1, 3

Adolescents

• Prevention of weight gain and monitoring should begin from adolescence, as weight gain escalates from this period 1
• Adolescents with PCOS should 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
• Family support improves outcomes; structure recommended activities considering family routines and cultural preferences 1

Initial Diagnostic Workup Before Treatment

• Exclude other causes of androgen excess: Cushing's syndrome, androgen-secreting tumors, nonclassic congenital adrenal hyperplasia, thyroid disease, hyperprolactinemia, and acromegaly 2
• Essential laboratory tests: TSH, prolactin, total testosterone or free/bioavailable testosterone, fasting glucose, and fasting lipid panel 2
• Pelvic examination is necessary prior to the first and each subsequent course of clomiphene citrate treatment 5
• Endometrial biopsy should always be performed prior to clomiphene citrate therapy in patients with abnormal vaginal bleeding or in older patients where endometrial carcinoma risk increases 5