What are the treatment guidelines for a female patient of reproductive age diagnosed with Polycystic Ovary Syndrome (PCOS)?

Treatment Guidelines for PCOS

First-Line Treatment: Multicomponent Lifestyle Intervention

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. 1

Dietary Management

• Target an energy deficit of 30% or 500-750 kcal/day (approximately 1,200-1,500 kcal/day total) for women with overweight or obesity 1
• No specific diet type is superior—any balanced dietary approach creating an energy deficit is acceptable, including low glycemic index foods, high-fiber diets, omega-3 fatty acid-rich diets, ketogenic diets, Mediterranean diets, and anti-inflammatory diets 1, 2
• Focus on patient preferences and cultural needs while following general healthy eating principles 1
• Avoid unduly restrictive or nutritionally unbalanced diets 1
• Even modest weight loss of 5-10% in those with excess weight yields significant clinical improvements in hormonal, metabolic, and reproductive outcomes 1, 3

Physical Activity Prescription

• Prescribe at least 150 minutes/week of moderate-intensity exercise or 75 minutes/week of vigorous-intensity activity, performed in at least 10-minute bouts 1
• Include muscle-strengthening activities involving major muscle groups on 2 non-consecutive days per week 1
• For modest weight loss and greater health benefits, recommend at least 250 minutes/week of moderate-intensity activities or 150 minutes/week of vigorous-intensity activity 1
• Target 10,000 steps daily, including 30 minutes of structured physical activity 1
• Minimize sedentary, screen, and sitting time throughout the day 1
• Both aerobic and resistance exercises show benefits in PCOS, improving insulin sensitivity even without significant weight loss 1, 4

Behavioral Strategies

• Implement SMART (specific, measurable, achievable, realistic, timely) goal setting with self-monitoring using fitness tracking devices 1
• Include behavioral change techniques: goal-setting, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 1
• Consider comprehensive behavioral or cognitive behavioral interventions to increase engagement and adherence 1
• Address psychological factors including anxiety, depression, body image concerns, and disordered eating, as these dramatically reduce adherence to lifestyle interventions 1
• Screen for eating disorders such as binge eating disorder and night eating syndrome, which are highly prevalent in PCOS 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

• A typical COCP dosing regimen is drospirenone 3 mg/ethinyl estradiol 20 μg in a 24-active/4-inert pill regimen, taken daily 5
• COCs reduce the risk of endometrial cancer but are associated with increases in circulating triglyceride and HDL cholesterol levels 1
• Women with PCOS have a 1.5-times higher baseline risk of venous thromboembolic disease and a 3.7-fold greater effect with OCP use compared to non-PCOS subjects 6
• Medroxyprogesterone acetate suppresses circulating androgen and pituitary gonadotropin levels, though optimal progestin, duration, and frequency to prevent endometrial cancer in PCOS is not known 1

Insulin-Sensitizing Agents

• Metformin 500-2000 mg daily improves glucose tolerance over time and may have a positive impact on risk factors for diabetes and cardiovascular disease 5, 1
• Start with 500 mg daily and titrate up to 1000-2000 mg daily in divided doses 5
• Metformin reduces features of metabolic syndrome in premenopausal PCOS women 6

Anti-Obesity Pharmacological Agents

• GLP-1 receptor agonists (liraglutide 1.8-3 mg daily, semaglutide 1-2 mg weekly, or exenatide 5-10 μg twice daily or 2 mg weekly) in combination with lifestyle interventions improve weight loss and metabolic control 5
• Orlistat 120 mg three times daily plus lifestyle intervention can be considered 5

Hyperandrogenism Management

• Combined medical interventions (antiandrogen plus ovarian suppression agent) may be most effective for hirsutism 1
• Statins lower testosterone levels either alone or in combination with OCPs but have not shown improvement in menses, spontaneous ovulation, hirsutism, or acne 6

Medical Management for Women ATTEMPTING to Conceive

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, 7

• Start with 50 mg daily for 5 days, beginning on or about day 5 of the cycle 7
• If ovulation does not occur after the first course, increase to 100 mg daily for 5 days 7
• Increasing the dosage or duration beyond 100 mg/day for 5 days is not recommended 7
• A low dosage or duration is particularly recommended if unusual sensitivity to pituitary gonadotropin is suspected, such as in PCOS patients 7
• If ovulation does not occur after three courses of therapy, further treatment with clomiphene citrate is not recommended 7
• Long-term cyclic therapy is not recommended beyond a total of about six cycles 7

Alternative Fertility Treatments

• If clomiphene treatment fails, low-dose gonadotropin therapy should be used, which induces a high rate of monofollicular development with lower risk of ovarian hyperstimulation 1
• Letrozole (an aromatase inhibitor) is an alternative oral agent for ovulation induction 6
• Metformin 1 g twice daily for 12 weeks or until pregnancy can be used in the pregestational stage 5

Preconception Management

• Weight loss of at least 5% body weight through lifestyle modification should be achieved before attempting conception 3
• Screen and treat for hypertension and diabetes prior to attempting conception 6
• Evaluate for other common infertility issues including semen analysis 6

Metabolic Screening and Cardiovascular Risk Management

Baseline Assessment

• Calculate BMI and measure waist circumference using ethnic-specific cutoffs (Asian, Hispanic, and South Asian populations require lower thresholds) 1
• All women with PCOS require evaluation for metabolic syndrome and its components, including type 2 diabetes, hypertension, and hyperlipidemia 6
• Perform baseline oral glucose tolerance test every 1-2 years based on family history of type 2 diabetes and BMI, and yearly in women with impaired glucose tolerance 6
• Obese women with PCOS have impaired glucose tolerance rates of 31-35% and type 2 diabetes rates of 7.5-10% 6

Ongoing Monitoring

• Regular monitoring of weight and waist circumference during weight loss and maintenance 1
• Rates of progression from normal glucose tolerance to impaired glucose tolerance, and in turn to type 2 diabetes, may be as high as 5-15% within 3 years 6

Special Population Considerations

Lean Women with PCOS

Do not dismiss lifestyle intervention in lean PCOS patients simply because they have normal BMI—insulin resistance requires management regardless of weight. 1

• Insulin resistance is present irrespective of BMI and affects both lean and overweight women with PCOS 1
• Focus on diet quality rather than caloric restriction for thin women 1
• Healthy lifestyle behaviors should be recommended to achieve and maintain a healthy weight and optimize hormonal outcomes 1

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 activities that strengthen muscle and bone at least 3 times weekly 1
• Family support improves outcomes, and activities should be structured considering family routines and cultural preferences 1

Ethnic Populations at High Cardiometabolic Risk

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

Critical Pitfalls to Avoid

• Do not neglect metabolic screening even in normal-weight PCOS patients, as insulin resistance can occur independent of obesity 3
• Do not use thiazolidinediones in pregnancy, as their effects on early pregnancy are poorly documented compared to metformin 3
• Do not exceed recommended clomiphene dosage and duration to minimize risk of ovarian hyperstimulation syndrome 7
• Do not delay lifestyle intervention—it must be implemented first as the foundation, not as an afterthought 3
• Ensure health professional interactions are respectful and patient-centered, avoiding weight-related stigma which negatively impacts treatment engagement 1
• Persistent bleeding should always be investigated for pregnancy and/or uterine pathology, including transvaginal ultrasound and endometrial biopsy 6
• If ovarian enlargement occurs during clomiphene therapy, additional treatment should not be given until ovaries return to pretreatment size 7
• Visual symptoms during clomiphene therapy require immediate discontinuation and complete ophthalmological evaluation 7

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
• Regular monitoring of weight and waist circumference is essential 1