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

Treatment of Polycystic Ovary Syndrome (PCOS)

Lifestyle modification targeting 5-10% weight loss through diet and exercise is the mandatory first-line treatment for all women with PCOS, regardless of body weight, because insulin resistance affects both lean and overweight patients and contributes to hyperandrogenism, ovulatory dysfunction, and metabolic complications. 1, 2

First-Line Treatment: Lifestyle Intervention (All Patients)

Weight loss of even 5% improves metabolic and reproductive abnormalities in PCOS. 3, 1 This is non-negotiable and must be implemented before or alongside any pharmacological therapy, even in normal-weight women, because insulin resistance is present irrespective of BMI. 2, 4

Dietary Approach

• Target an energy deficit of 500-750 kcal/day (total intake 1,200-1,500 kcal/day), adjusted for individual energy requirements and activity levels. 1, 2
• No specific diet type (low-carb, Mediterranean, DASH) is superior—any balanced approach creating an energy deficit is acceptable. 1, 4
• Follow general healthy eating principles tailored to food preferences; avoid overly restrictive or nutritionally unbalanced diets. 1, 4
• Address common nutritional deficiencies: women with PCOS have higher cholesterol intake and lower magnesium and zinc intake compared to women without PCOS. 1

Exercise Prescription

• For weight maintenance: minimum 150 minutes/week of moderate-intensity activity OR 75 minutes/week of vigorous-intensity activity, plus muscle-strengthening exercises twice weekly. 1, 2
• For weight loss: minimum 250 minutes/week of moderate-intensity activity OR 150 minutes/week of vigorous-intensity activity, plus muscle-strengthening exercises twice weekly. 1, 2
• Both aerobic and resistance training show benefits; exercise improves insulin sensitivity even without significant weight loss. 1, 4
• Activity should be performed in bouts of at least 10 minutes (approximately 1,000 steps), aiming for at least 30 minutes daily on most days. 4

Behavioral Strategies

• Implement SMART goal-setting (specific, measurable, achievable, realistic, timely) and self-monitoring. 1, 4
• Include stimulus control, problem-solving, assertiveness training, slower eating, reinforcement of changes, and relapse prevention. 1, 4
• Address psychological factors including anxiety, depression, body image concerns, and disordered eating, as women with PCOS have higher rates of these conditions. 1, 4

Second-Line Treatment: Pharmacological Management

Treatment selection depends on the patient's primary concern and reproductive goals. The following algorithm should guide pharmacological therapy:

For Patients NOT Attempting to Conceive

Combined oral contraceptives (COCs) are first-line pharmacological therapy because they suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne. 3, 1, 2

Metabolic Management

• Add metformin (500-2000 mg daily) when insulin resistance or glucose intolerance is documented, lifestyle modifications alone are insufficient, or the patient has obesity or elevated cardiovascular risk factors. 2
• Metformin improves glucose tolerance and may positively impact risk factors for diabetes and cardiovascular disease, though its role in primary or secondary prevention of cardiovascular disease remains unknown. 3, 2
• Consider thiazolidinediones as an alternative insulin-sensitizing agent, though evidence is more limited. 3

Hirsutism Management

• For hirsutism, combine an antiandrogen (spironolactone, flutamide, or finasteride) with an ovarian suppression agent (oral contraceptive), as combined medical interventions are most effective. 3
• The only FDA-approved topical agent for hirsutism is eflornithine hydrochloride cream, though additional benefits or risks in PCOS are unknown. 3
• Mechanical hair removal (plucking, shaving, waxing), electrolysis, and laser vaporization are adjunctive; multiple treatments are typically needed, and concomitant medical management to reduce androgen levels is usually necessary. 3

For Patients Attempting to Conceive

Begin with weight control and regular exercise, then proceed to clomiphene citrate as first-line ovulation induction because approximately 80% of women with PCOS ovulate and half of those conceive with this agent. 3, 5

Clomiphene Citrate Protocol (FDA-Approved)

• Start with 50 mg daily for 5 days, beginning on or about day 5 of the cycle. 5
• A low dosage is particularly recommended for patients with polycystic ovary syndrome due to unusual sensitivity to pituitary gonadotropin and risk of ovarian hyperstimulation syndrome. 5
• If ovulation does not occur after the first course, increase to 100 mg daily for 5 days (maximum recommended dose). 5
• Courses may be repeated as early as 30 days after the previous one, after excluding pregnancy. 5
• If ovulation does not occur after three courses at 100 mg, discontinue clomiphene and reevaluate the patient. 5
• If three ovulatory responses occur without pregnancy, further clomiphene treatment is not recommended. 5
• Long-term cyclic therapy should not exceed approximately six total cycles (including three ovulatory cycles). 5

Critical Pitfall: Patients with polycystic ovary syndrome are unusually sensitive to gonadotropins and may have an exaggerated response to usual doses of clomiphene citrate, increasing risk of ovarian hyperstimulation syndrome. 5

Second-Line Ovulation Induction

• If clomiphene 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
• While metformin and thiazolidinediones improve ovulation frequency, their effects on early pregnancy are not well-documented; metformin appears safe but documentation is poor for thiazolidinediones. 3
• The benefit and role of laparoscopic ovarian drilling (by laser or diathermy) are undetermined. 3

Emerging Therapies

GLP-1 receptor agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement when combined with lifestyle interventions and appear superior to placebo for anthropometric outcomes. 2, 4 These agents may be considered for appropriate candidates with BMI ≥25 kg/m². 1

Mandatory Metabolic Screening and Monitoring

All patients with PCOS require comprehensive metabolic surveillance regardless of weight: 2

• Screen for type 2 diabetes with fasting glucose 2
• Obtain fasting lipid profile 2
• Calculate BMI and waist-hip ratio using ethnic-specific cutoffs (Asian, Hispanic, South Asian populations require lower thresholds) 2, 4
• Repeat screening at least annually 2
• Metabolic syndrome is twice as common in PCOS patients, and they are four times more likely to develop type 2 diabetes mellitus compared to the general population 6

Critical Pitfall: Do not neglect metabolic screening in normal-weight PCOS patients—insulin resistance and cardiovascular risk factors require monitoring regardless of BMI. 2, 4

Special Considerations by Ethnicity

Ethnic groups at high cardiometabolic risk (Asian, Hispanic, South Asian) require greater consideration for lifestyle intervention and should use ethnic-specific BMI and waist circumference categories to guide treatment intensity. 1, 2, 4

Common Pitfalls to Avoid

• Never dismiss lifestyle intervention in lean PCOS patients—insulin resistance requires management regardless of weight. 2, 4
• Do not exceed recommended clomiphene dosage (100 mg/day) or duration (5 days per cycle, maximum 6 total cycles) due to risk of ovarian hyperstimulation syndrome, especially in PCOS patients. 5
• Do not delay evidence-based treatment while pursuing unproven complementary therapies such as evening primrose oil or other herbal supplements, which are not supported by international evidence-based guidelines. 4
• Ensure health professional interactions are respectful and patient-centered, avoiding weight-related stigma, as psychological factors require active management to optimize engagement with treatment. 1, 4