Comprehensive Management of Polycystic Ovary Syndrome (PCOS)
Foundational Treatment: Lifestyle Modification
Lifestyle modification targeting 5-10% weight loss through diet and exercise is the mandatory first-line treatment for all women with PCOS, regardless of whether they are attempting conception, and must be implemented before or alongside any pharmacological therapy. 1, 2
Weight Loss and Dietary Interventions
Loss of as little as 5% of initial body weight significantly improves metabolic and reproductive abnormalities in PCOS, including ovulation and pregnancy rates. 3, 4
Target an energy deficit of 500-750 kcal/day with total intake of 1,200-1,500 kcal/day, adjusted for individual energy requirements and physical activity levels. 1, 2
Any balanced dietary approach that creates an energy deficit is acceptable—no specific diet type (low-carb, Mediterranean, ketogenic) has proven superior to others in PCOS. 2, 5
Women with PCOS tend to have higher cholesterol intake and lower magnesium and zinc intake compared to women without PCOS, which should be addressed in dietary counseling. 2
Low glycemic index foods, high-fiber diets, omega-3 fatty acids, and anti-inflammatory diets improve insulin sensitivity and hormonal balance. 5
Exercise Recommendations
For weight maintenance and health: 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. 1, 2
For weight loss and prevention of weight 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. 1, 2
Both aerobic and resistance exercise enhance insulin sensitivity, facilitate weight loss, and improve metabolic and reproductive outcomes. 5
Exercise programs show positive effects even without weight loss. 4
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
Treatment Based on Reproductive Goals
For Women NOT Attempting to Conceive
Combined oral contraceptives are the first-line pharmacological treatment for women with PCOS not attempting conception, as they suppress ovarian androgen secretion and increase sex hormone-binding globulin. 1, 2
Hormonal Management
Oral contraceptive pills effectively suppress androgens but are associated with significant increases in circulating triglyceride and HDL cholesterol levels in PCOS patients. 3
However, no evidence suggests that more cardiovascular events occur with oral contraceptive use in women with PCOS compared to the general population. 3
Medroxyprogesterone acetate (depot or intermittent oral therapy) suppresses circulating androgen levels and pituitary gonadotropin levels, though the optimal progestin, duration, and frequency to prevent endometrial cancer in PCOS is unknown. 3
Hirsutism Management
- For hirsutism, consider oral contraceptives, antiandrogen drugs (such as spironolactone), or topical eflornithine hydrochloride cream. 2
Metabolic Management
Metformin improves insulin sensitivity and may have a positive impact on risk factors for diabetes and cardiovascular disease in women with PCOS. 3
In women with PCOS who use metformin, glucose tolerance improves or remains steady over time. 3
The role of insulin-sensitizing agents in primary or secondary prevention of cardiovascular disease in PCOS remains unknown. 3
Anti-obesity medications may be considered for appropriate candidates with BMI ≥25 kg/m². 2
GLP-1 agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement when combined with lifestyle interventions. 1
For Women Attempting to Conceive
Treatment begins with weight control and regular exercise, followed by clomiphene citrate as the first-line pharmacological agent, based on strong evidence showing approximately 80% of PCOS patients ovulate and half of those who ovulate conceive. 3, 1, 4
First-Line: Clomiphene Citrate
Clomiphene citrate is FDA-approved for treatment of ovulatory dysfunction in women desiring pregnancy, with PCOS patients being among those most likely to achieve success. 6
Each course of clomiphene citrate should be started on or about the 5th day of the cycle. 6
Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles). 6
Common pitfall: Do not exceed recommended clomiphene dosage and duration, as this increases risk of ovarian hyperstimulation syndrome. 2
Second-Line: Gonadotropins
If clomiphene treatment fails, use low-dose gonadotropin therapy rather than high-dose, as low-dose treatment induces high rates of monofollicular development with lower risk of ovarian hyperstimulation. 3, 1
Women 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. 6
Role of Metformin in Fertility
Metformin improves ovulation frequency and appears safe during pregnancy, though its effects on early pregnancy outcomes are not fully established. 3, 4
Metformin reduces insulin levels, which subsequently decreases ovarian androgen production. 4
The combination of clomiphene with metformin and lifestyle changes may be superior to clomiphene alone. 7
At present, the FDA has not labeled any insulin-sensitizing agent for the treatment of PCOS. 3
Surgical Options
- The benefit and role of laparoscopic ovarian drilling by laser or diathermy are undetermined in women with PCOS. 3
Preconception Counseling
- All women with PCOS attempting pregnancy must receive preconception counseling about increased pregnancy risks and undergo metabolic screening before conception: fasting glucose, 2-hour glucose tolerance test, and lipid profile. 4
Pregnancy Management
Women with PCOS who become pregnant 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
Diagnostic Evaluation
Laboratory Assessment
Laboratory evaluation should include androgen levels (total and free testosterone), gonadotropins (LH, FSH), fasting glucose, 2-hour glucose tolerance test, and lipid profile. 1, 4
Calculate body mass index and waist-hip ratio to assess metabolic risk. 1
Ethnic-specific BMI and waist circumference categories should guide treatment intensity, as ethnic groups at high cardiometabolic risk require greater consideration for lifestyle intervention. 1, 2
Exclusion of Other Conditions
Pelvic examination is necessary prior to the first and each subsequent course of clomiphene citrate treatment to exclude ovarian cysts (except in polycystic ovary syndrome). 6
If abnormal vaginal bleeding is present, carefully evaluate to ensure neoplastic lesions are not present. 6
Endometrial biopsy should always be performed prior to clomiphene citrate therapy in older women, as the incidence of endometriosis and endometrial carcinoma increases with age. 6
Exclude other impediments to pregnancy including thyroid disorders, adrenal disorders, hyperprolactinemia, and male factor infertility. 6
Long-Term Monitoring and Complications
Metabolic Screening
Regular screening for metabolic abnormalities is essential, as women with PCOS have abnormal glucose tolerance and diabetes mellitus in 31-35% and 7.5-10% respectively—a risk 2-3 times higher than normal. 2, 7, 8
Screen regularly for type 2 diabetes mellitus and cardiovascular disease throughout the patient's lifespan. 1, 2
Women with PCOS are at increased risk for hepatic steatosis, metabolic syndrome, hypertension, dyslipidemia, vascular thrombosis, cerebrovascular accidents, and possibly cardiovascular events. 8
Women with PCOS are at increased risk for endometrial atypia or carcinoma, and possibly ovarian malignancy. 8
Mental Health Assessment
Assess mental health regularly, as women with PCOS have higher rates of depression, anxiety, and eating disorders. 1, 2
Management should include education modules to improve awareness, adherence, and effectiveness of conventional treatment and to manage mental health issues related to PCOS. 5
Ovarian Hyperstimulation Syndrome (OHSS)
OHSS may progress rapidly (within 24 hours to several days) and become a serious medical disorder, with early warning signs including abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain. 6
Severe cases can include gross ovarian enlargement, gastrointestinal symptoms, ascites, dyspnea, oliguria, pleural effusion, pericardial effusion, hypotension, renal failure, pulmonary edema, ovarian hemorrhage, deep venous thrombosis, ovarian torsion, and acute respiratory distress. 6
Death due to hypovolemic shock, hemoconcentration, or thromboembolism has occurred. 6
Monitor for OHSS during fertility treatments, especially in PCOS patients who are unusually sensitive to gonadotropins. 2, 6
If ovarian enlargement occurs, do not give additional clomiphene citrate therapy until the ovaries have returned to pretreatment size, and reduce the dosage or duration of the next course. 6
Common Pitfalls to Avoid
Do not neglect lifestyle interventions in normal-weight PCOS patients, as overall health benefits of lifestyle changes extend beyond weight loss. 2
Do not neglect metabolic screening even in normal-weight PCOS patients. 1
Do not exceed recommended clomiphene dosage and duration. 2
Exercise caution when using clomiphene citrate in patients with uterine fibroids due to potential for further enlargement. 6
Do not use clomiphene citrate in pregnant patients, patients with ovarian cysts (except polycystic ovary syndrome), patients with abnormal vaginal bleeding, or patients with abnormal liver function. 6
If visual symptoms occur during clomiphene citrate therapy (blurring, scotomata, phosphenes), discontinue treatment immediately and perform complete ophthalmological evaluation. 6