What is Polycystic Ovary Syndrome (PCOS) and its treatment options?

Polycystic Ovary Syndrome (PCOS): Overview and Management

What is PCOS?

PCOS is a common endocrine disorder affecting 8-20% of reproductive-aged women, characterized by at least two of three features: ovulatory dysfunction (oligomenorrhea or amenorrhea), clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound. 1 The syndrome is heterogeneous by nature, with variable presentation ranging from asymptomatic to multiple gynecologic, dermatologic, and metabolic manifestations. 2

Core Diagnostic Features

• Ovulatory dysfunction: Menstrual cycle length >35 days suggests chronic anovulation 3
• Hyperandrogenism: Clinical signs include acne, hirsutism, androgenic alopecia, and clitoromegaly 3
• Polycystic ovaries: Follicle number per ovary (FNPO) ≥20 follicles has 87.64% sensitivity and 93.74% specificity on transvaginal ultrasound with ≥8 MHz transducer 3

Pathophysiology and Associated Risks

Insulin resistance plays a central role in PCOS pathophysiology, affecting 50-70% of women with the syndrome regardless of BMI. 1, 4 This drives compensatory hyperinsulinemia, which contributes to hyperandrogenism through effects on the pituitary, liver, and ovaries. 1

Women with PCOS face substantially elevated cardiometabolic risks:

• Metabolic syndrome occurs twice as frequently compared to the general population 2
• Type 2 diabetes develops four times more frequently than in women without PCOS 2
• Cardiovascular disease risk is increased, with evidence of endothelial dysfunction, subclinical atherosclerosis, elevated coronary artery calcium scores, and increased carotid intima-media thickness 1, 4
• Dyslipidemia is common, including elevated LDL cholesterol, elevated triglycerides, and decreased HDL cholesterol 1

Psychological comorbidities are also prevalent, including depression, anxiety, bipolar disorder, binge eating disorder, poor self-esteem, body image issues, and social isolation. 1, 4

Treatment Approach

First-Line: Lifestyle Modification

Lifestyle management is the first-line treatment in the intervention hierarchy for PCOS, with multicomponent interventions including diet, exercise, and behavioral strategies being central to management. 1 This approach is particularly critical for overweight women seeking pregnancy. 5

• Weight loss of as little as 5% of initial body weight improves metabolic and reproductive abnormalities, including menstrual dysfunction and infertility 1, 3
• Diet and exercise remain the main pillars of weight reduction, though sustainability is challenging 1
• Women with PCOS demonstrate lower overall diet quality, with higher cholesterol intake, lower magnesium and zinc intake, and lower total physical activity levels compared to women without PCOS 1
• Regular exercise and weight control measures should be implemented before initiating drug therapy 1, 3

Pharmacologic Management by Clinical Goal

For Menstrual Irregularities and Anovulation (Not Seeking Pregnancy)

Combination oral contraceptive pills are first-line therapy for long-term management of menstrual irregularities and anovulation in women with PCOS. 1, 3 Benefits include:

• Suppression of ovarian androgen secretion 1
• Increased sex hormone binding globulin levels 1
• Reduction in endometrial cancer risk 1

Medroxyprogesterone acetate (depot or intermittent oral therapy) is an alternative that suppresses circulating androgen and pituitary gonadotropin levels, though optimal progestin type, duration, and frequency for endometrial cancer prevention remain unknown. 1

For Infertility

Clomiphene citrate is first-line treatment for women with PCOS attempting to conceive, with an 80% ovulation rate and 50% conception rate. 3 However, patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses, so start with the lowest recommended dose and shortest treatment duration. 6

Low-dose gonadotropin therapy induces ovulation with lower risk of ovarian hyperstimulation in women who fail clomiphene therapy. 3

Letrozole and metformin may play important roles in ovulation induction based on recent data. 4

For Metabolic Complications

All women with PCOS should be screened for type 2 diabetes and glucose intolerance with a fasting glucose level followed by a two-hour glucose level after a 75-gram glucose load. 1, 3

Metformin is first-line medication for metabolic manifestations such as hyperglycemia and is recommended for patients with cardiometabolic features including abdominal obesity and insulin resistance. 1, 3 Metformin improves insulin sensitivity, glucose tolerance, and ovulation frequency. 1, 3

Screen for dyslipidemia with fasting lipoprotein profile including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in all women with PCOS. 1, 3

For Hirsutism and Hyperandrogenism

Oral contraceptives are first-line therapy for hirsutism in women with PCOS. 3

Combination of an anti-androgen (such as spironolactone or finasteride) and ovarian suppression agent provides better efficacy for treating hirsutism. 3, 4

Mechanical hair removal methods, electrolysis, and laser vaporization are effective for cosmetic management. 3

Monitoring and Long-Term Surveillance

International guidelines recommend comprehensive cardiovascular risk screening for all women with PCOS: 1

• Weight monitoring every 6-12 months 1
• At least annual blood pressure checks 1
• Fasting lipid panel 1
• Glycemic control assessments 1
• Smoking and physical activity assessments 1

Calculate BMI and waist-hip ratio as part of routine assessment. 1, 3

Special Considerations

Ethnic variation exists in PCOS presentation, with East Asian women having the highest prevalence of metabolic syndrome despite lower BMI and less hyperandrogenic features. 1

Health professionals should consider cultural sensitivities and weight-related stigma when addressing lifestyle-based interventions, given the high prevalence of psychological factors including anxiety, depression, and eating disorders in PCOS. 1

Bariatric surgery is emerging as a potential adjunct therapy for patients with PCOS and clinically severe obesity, with improvements in hirsutism, menstrual regularity, and fertility, though existing research is limited and of low quality. 1

Critical Pitfalls to Avoid

Ovarian hyperstimulation syndrome (OHSS) can occur with clomiphene citrate therapy, progressing rapidly within 24 hours to several days into a serious medical disorder with gross ovarian enlargement, ascites, dyspnea, oliguria, and pleural effusion. 6 Early warning signs include abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain. 6

Do not use ultrasound as a primary diagnostic criterion in adolescents <8 years post-menarche due to high false-positive rates from normal multi-follicular ovaries. 7 In adolescents, rely more heavily on clinical and biochemical hyperandrogenism plus menstrual irregularity. 3

Exclude other causes of androgen excess including Cushing's syndrome (buffalo hump, moon facies, hypertension, abdominal striae), androgen-secreting tumors (rapid onset and severe hyperandrogenism), non-classic congenital adrenal hyperplasia, thyroid disease, and prolactin disorders. 1, 3