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

Treatment Options for Polycystic Ovary Syndrome (PCOS)

Lifestyle modification targeting 5-10% weight loss through multicomponent intervention (diet, exercise, and behavioral strategies) is the mandatory first-line treatment for all women with PCOS, regardless of BMI or reproductive goals, before considering any pharmacological therapy. 1, 2

First-Line Treatment: Lifestyle Modification

Lifestyle intervention is positioned at the top of the treatment hierarchy in PCOS management and must be implemented before or alongside any pharmacological approach. 1

Dietary Intervention

• Create an energy deficit of 500-750 kcal/day, with total intake of 1,200-1,500 kcal/day, adjusted for individual energy requirements, body weight, and physical activity levels. 2
• No specific diet is superior—any balanced dietary approach that creates an energy deficit is acceptable, including low glycemic index foods, Mediterranean diet, high-fiber diets, or omega-3 rich diets. 1, 3
• Avoid overly restrictive or nutritionally unbalanced diets; tailor to food preferences while following general healthy eating principles. 2

Exercise Prescription

• For weight maintenance: Perform at least 150 minutes/week of moderate-intensity activity OR 75 minutes/week of vigorous activity, PLUS muscle-strengthening activities on 2 non-consecutive days/week. 2
• For weight loss and prevention of regain: Perform at least 250 minutes/week of moderate-intensity activity OR 150 minutes/week of vigorous activity, PLUS muscle strengthening on 2 non-consecutive days/week. 2
• Both aerobic and resistance exercise enhance insulin sensitivity and improve metabolic and reproductive outcomes, even without weight loss. 4, 3

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. 2

Treatment Based on Reproductive Goals

For Women NOT Attempting to Conceive

Combined oral contraceptives (COCs) are first-line pharmacological treatment for women with PCOS not attempting pregnancy, as they suppress ovarian androgen secretion and increase sex hormone binding globulin. 2, 5

• COCs address irregular menses, hirsutism, and acne effectively. 5
• Antiandrogens (such as spironolactone) combined with ovarian suppression agents are effective for treating hirsutism. 6
• For hirsutism, multiple laser hair removal treatments are typically needed alongside medical management directed at reducing androgen levels. 6

For Women Attempting to Conceive

Start with weight loss and exercise first—modest weight loss of just 5% of initial body weight significantly improves ovulation and pregnancy rates. 4

Clomiphene citrate is the first-line pharmacological treatment for ovulation induction, with approximately 80% of PCOS patients ovulating and half of those who ovulate conceiving. 2, 4, 7

• Clomiphene should be started on or about the 5th day of the cycle. 7
• Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles). 7
• 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 increased sensitivity to gonadotropin. 7

If clomiphene fails, low-dose gonadotropin therapy is recommended due to lower risk of ovarian hyperstimulation. 2

Metformin improves insulin sensitivity and ovulation frequency and appears safe during pregnancy, though its effects on early pregnancy outcomes are not fully established. 4

Preconception and Pregnancy Management

• All women with PCOS attempting pregnancy require preconception counseling about increased pregnancy risks and screening for metabolic abnormalities: fasting glucose, 2-hour glucose tolerance test, and lipid profile. 4
• Once pregnant, women with PCOS require closer monitoring throughout pregnancy, with regular monitoring of blood pressure, kidney function, and proteinuria. 4
• Prescribe low-dose aspirin from week 12 to week 36 to reduce preeclampsia risk. 4

Management of Metabolic Aspects

Screen all PCOS patients for metabolic abnormalities at diagnosis, including fasting glucose, 2-hour glucose tolerance test, and lipid profile, regardless of BMI. 2, 5

Metformin is first-line medication for metabolic manifestations such as hyperglycemia, as it improves insulin sensitivity and reduces risk factors for diabetes and cardiovascular disease. 2, 5

• Metformin reduces insulin levels, which subsequently decreases ovarian androgen production, and improves or maintains glucose tolerance over time. 4

Emerging Anti-Obesity Pharmacological Agents

GLP-1 receptor agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement in PCOS when combined with lifestyle interventions. 1, 2

• Liraglutide at 3-mg dose has been shown to optimize weight loss. 1
• Semaglutide is the most potent long-acting GLP-1 RA but has limited data in PCOS populations. 1
• GLP-1 RAs should be delivered with lifestyle co-interventions, particularly resistance training, to preserve lean body mass. 1
• Longer-acting GLP-1 RA medications have advantages with improved adherence, glycemic effects, and tolerance. 1

Orlistat has shown benefits for weight reduction and reduction in HOMA-IR, insulin, and testosterone when used with lifestyle or COCPs, but has high adverse events. 1

Long-Term Monitoring

Regular screening for metabolic abnormalities is essential, as metabolic syndrome is twice as common in PCOS patients, and they are four times more likely to develop type 2 diabetes mellitus. 5

Mental health assessment is mandatory, as women with PCOS have higher rates of depression, anxiety, and eating disorders. 2

Endometrial biopsy should be performed prior to clomiphene citrate therapy in women of increasing age due to increased incidence of endometriosis and endometrial carcinoma. 7

Critical Safety Considerations

Ovarian Hyperstimulation Syndrome (OHSS)

• OHSS can occur with clomiphene citrate therapy and may progress rapidly (within 24 hours to several days) to become a serious medical disorder. 7
• Early warning signs include abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain. 7
• If ovarian enlargement occurs, additional clomiphene citrate therapy should not be given until the ovaries have returned to pretreatment size. 7

Visual Symptoms

• Patients with any visual symptoms (blurring, scotomata, phosphenes) should discontinue clomiphene treatment immediately and have a complete ophthalmological evaluation. 7

Multidisciplinary Approach

PCOS management requires coordination among multiple specialists: endocrinologists, gynecologists, primary care providers, dietitians, exercise physiologists, psychologists, and dermatologists. 8, 9, 10

• Multidisciplinary PCOS clinics have demonstrated increased weight loss, high patient satisfaction, and high retention compared to single-care providers. 8
• The involvement of a dietitian in clinical practice is fundamental but remains sporadic despite evidence supporting its necessity. 10