What is the best treatment for Polycystic Ovary Syndrome (PCOS)?

Best Treatment for Polycystic Ovary Syndrome (PCOS)

Lifestyle modification targeting 5-10% weight loss through diet and exercise is the foundational first-line treatment for all women with PCOS, regardless of their primary symptom concern, as this modest weight reduction improves metabolic, reproductive, and psychological outcomes. 1

Treatment Algorithm Based on Primary Clinical Goal

For Women NOT Seeking Pregnancy

Combined oral contraceptives (COCs) are the first-line pharmacological treatment, as they suppress ovarian androgen secretion, increase sex hormone binding globulin, and address menstrual irregularities and hyperandrogenic symptoms. 2, 3

• COCs using ethinyl estradiol/drospirenone combinations do not increase insulin resistance in clamp studies, though women with PCOS have 1.5-times higher baseline venous thromboembolic risk and 3.7-fold greater effect with OCP use compared to non-PCOS women. 3

• For hirsutism specifically, combine an antiandrogen with ovarian suppression (COC) for optimal results, as this addresses both androgen production and peripheral androgen effects. 4

• Metformin should be added to reduce insulin resistance and metabolic syndrome features, particularly in women with elevated BMI or metabolic abnormalities. 2, 3

For Women Seeking Pregnancy

Clomiphene citrate remains the first-line ovulation induction agent, with approximately 80% of patients ovulating and 50% conceiving. 2, 5

• If clomiphene fails after appropriate trials, low-dose gonadotropin therapy is second-line due to lower risk of ovarian hyperstimulation compared to higher doses. 2

• Letrozole (an aromatase inhibitor) is an alternative first-line option with comparable or superior efficacy to clomiphene citrate. 3, 5

• Laparoscopic ovarian drilling is reserved for clomiphene-resistant patients who require laparoscopy for another indication. 5

• In vitro fertilization remains the final option when other treatments fail. 6, 5

Core Lifestyle Intervention Components

Target an energy deficit of 500-750 kcal/day (total intake 1,200-1,500 kcal/day) adjusted for individual energy requirements, body weight, and physical activity levels. 1

Dietary Approach

• Any balanced dietary approach that creates an energy deficit is acceptable—there is no evidence that any specific diet type is superior in PCOS compared to general population recommendations. 1

• Follow general healthy eating principles across the life course, tailoring to food preferences while avoiding overly restrictive or nutritionally unbalanced diets. 1

Physical Activity Requirements

For weight maintenance and health: Minimum 150 minutes/week of moderate-intensity activity OR 75 minutes/week of vigorous activity, plus muscle-strengthening activities on 2 non-consecutive days/week. 1

For weight loss and prevention of regain: Minimum 250 minutes/week of moderate-intensity activity OR 150 minutes/week of vigorous activity, plus muscle strengthening on 2 non-consecutive days/week. 1

• Activities should be performed in at least 10-minute bouts, aiming for at least 30 minutes daily on most days (approximately 10,000 steps total daily, including 3,000 steps of structured activity). 1

• Minimize sedentary, screen, and sitting time. 1

Behavioral Strategies

Incorporate goal-setting, self-monitoring, stimulus control, problem-solving, assertiveness training, slower eating, reinforcement of changes, and relapse prevention to optimize weight management and emotional well-being. 1

Metabolic Screening and Long-Term Management

Screen all women with PCOS for metabolic abnormalities at baseline and regularly thereafter, regardless of weight status, as even lean women with PCOS demonstrate insulin resistance. 2, 3

• Perform oral glucose tolerance testing at baseline and every 1-2 years based on family history of type 2 diabetes and BMI; screen yearly in women with impaired glucose tolerance. 3

• Rates of progression from normal glucose tolerance to impaired glucose tolerance, and subsequently to type 2 diabetes, may reach 5-15% within 3 years. 3

• Assess fasting lipid profile, as young lean PCOS women have lower HDL size, higher VLDL particle number, and higher LDL particle number compared to matched controls. 3

• Screen for mental health conditions including depression, anxiety, and eating disorders, which occur at higher rates in PCOS. 2

Emerging and Adjunctive Therapies

GLP-1 agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement in PCOS, with recent trials demonstrating efficacy when combined with lifestyle interventions. 1, 7

• Inositols, particularly myo-inositol, represent emerging insulin sensitizers with potential benefits. 7

• Statins lower testosterone levels alone or combined with OCPs but have not shown improvement in menses, ovulation, hirsutism, or acne, and their effects on metabolic parameters differ from the general population. 3

Critical Pitfalls to Avoid

• Never neglect metabolic screening in normal-weight PCOS patients, as insulin resistance occurs in both obese and lean women with PCOS. 2, 3

• Always investigate persistent bleeding for pregnancy and/or uterine pathology (transvaginal ultrasound and endometrial biopsy), as chronic anovulation increases risk of endometrial hyperplasia and carcinoma. 3, 6

• Screen and treat hypertension and diabetes prior to conception attempts, as PCOS women have elevated risk for gestational diabetes, pre-eclampsia, and placental abruption. 3

• Do not exceed recommended clomiphene citrate dosage and duration to minimize risks. 2

• Recognize that ethnic groups at high cardiometabolic risk require greater consideration for lifestyle intervention, and ethnic-specific BMI and waist circumference categories should guide treatment intensity. 1