What is Polycystic Ovary Syndrome (PCOS) and how is it managed?

Polycystic Ovary Syndrome (PCOS): Comprehensive Overview

Definition and Diagnosis

PCOS is the most common endocrine disorder affecting 8-13% of reproductive-age women, diagnosed by the Rotterdam criteria requiring two of three features: oligo/anovulation, polycystic ovaries on imaging, and clinical or biochemical hyperandrogenism. 1

Clinical Presentation

• Menstrual irregularities: Oligomenorrhea or amenorrhea due to chronic anovulation 1, 2
• Hyperandrogenism signs: Hirsutism, acne, androgenic alopecia, and balding 1, 2
• Infertility: PCOS accounts for 80% of anovulatory infertility cases 3
• Metabolic features: Obesity, acanthosis nigricans (indicating insulin resistance), and abdominal adiposity 1

Essential History Components

• Onset and duration of androgen excess symptoms 1
• Menstrual history and medication use, including exogenous androgens 1
• Lifestyle factors: Diet, exercise, alcohol use, and smoking 1
• Family history of cardiovascular disease and diabetes 1

Physical Examination Findings

• Androgen excess signs: Acne, balding, clitoromegaly, and abnormal body hair distribution 1
• Insulin resistance markers: Obesity, acanthosis nigricans (consider associated insulinoma or gastric adenocarcinoma if present) 1
• Ovarian enlargement on pelvic examination 1

Pathophysiology

Insulin resistance is central to PCOS pathophysiology and occurs irrespective of BMI, affecting both lean and overweight women. 1, 4

• Hyperinsulinemia drives hyperandrogenism through effects on the pituitary, liver, and ovaries 1
• Obesity exacerbates insulin resistance and worsens all PCOS symptoms 1
• Insulin resistance affects 50-70% of women with PCOS 2

Differential Diagnosis

Before confirming PCOS, exclude other causes of androgen excess through targeted screening. 1

Conditions to Rule Out:

• Cushing's syndrome: Screen if buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, or proximal myopathies present 1
• Androgen-secreting tumors of ovary or adrenal gland 1
• Nonclassic congenital adrenal hyperplasia (late-onset) 1
• Thyroid disease and prolactin disorders 1
• Primary ovarian failure and primary hypothalamic amenorrhea 1
• Acromegaly and genetic defects in insulin action 1

Diagnostic Laboratory Testing

Required Screening Tests:

• TSH level to exclude thyroid disease 1
• Prolactin level to exclude hyperprolactinemia 1
• Total testosterone or bioavailable/free testosterone to assess ovarian hyperandrogenism 1
• Fasting glucose followed by 2-hour glucose after 75-gram oral glucose load to screen for type 2 diabetes and glucose intolerance 1, 5
• Fasting lipid profile: Total cholesterol, LDL, HDL, and triglycerides 1, 5
• BMI and waist-hip ratio calculation 1, 5

Long-Term Health Risks

Metabolic Complications:

• Type 2 diabetes: All women with PCOS require screening due to demonstrated increased risk 1, 5
• Dyslipidemia: Elevated LDL cholesterol, elevated triglycerides, and decreased HDL cholesterol 1
• Metabolic syndrome affects a significant proportion of PCOS patients 2
• Insulin resistance with decreased sex hormone binding globulin 1

Cardiovascular Risk:

• Increased coronary artery calcium scores and carotid intima-media thickness 2
• Hypertension occurs more frequently 2
• Cardiovascular disease risk factors cluster in PCOS patients 1

Reproductive Complications:

• Endometrial cancer risk increased due to obesity, chronic anovulation, and hyperinsulinemia 1
• Infertility from chronic anovulation 2, 3

Psychological Comorbidities:

• Depression, anxiety, bipolar disorder, and binge eating disorder occur more frequently 2

Management Strategy

First-Line Treatment: Multicomponent Lifestyle Intervention

Lifestyle management is the first-line treatment in the intervention hierarchy for all women with PCOS, regardless of body weight, because insulin resistance affects both lean and overweight women. 1, 4

Dietary Management:

• Energy deficit of 30% or 500-750 kcal/day for women with excess weight, considering individual energy requirements, body weight, and physical activity 5, 4
• Target 5-10% weight loss in those with excess weight, as this yields significant clinical improvements in metabolic and reproductive abnormalities 5, 4, 2
• No specific diet is recommended over others; focus on sustainable caloric deficit 1

Exercise Prescription:

• At least 150 minutes/week of moderate-intensity physical activity or 75 minutes/week of vigorous-intensity activity or equivalent combination 5, 4
• Muscle-strengthening activities on 2 non-consecutive days per week 5, 4
• Exercise improves insulin sensitivity and metabolic outcomes 1

Behavioral Strategies:

• SMART goal setting and self-monitoring to enable achievement of realistic lifestyle goals 4
• Behavioral interventions: Goal-setting, self-monitoring, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 4

Before initiating drug therapy, regular exercise and weight control measures should be tried. 1, 5

Pharmacological Management

For Women NOT Attempting Conception:

Combined oral contraceptive pills (COCs) are the first-line pharmacological treatment for menstrual irregularities and hyperandrogenism. 1, 5, 4

• COCs suppress androgen secretion by the ovaries and increase sex hormone binding globulin 1
• COCs reduce endometrial cancer risk, though the extent of this effect in PCOS is unknown 1

Alternative hormonal therapy:

• Medroxyprogesterone acetate (depot or intermittent oral) suppresses circulating androgen and pituitary gonadotropin levels 1
• The optimal progestin, duration, and frequency for endometrial cancer prevention in PCOS is unknown 1

Insulin-Sensitizing Agents:

Metformin should be considered for women with PCOS who have cardiometabolic features such as abdominal obesity and insulin resistance. 5, 4

• Metformin (biguanide) tends to decrease weight and improves insulin sensitivity 1
• Thiazolidinediones (pioglitazone, rosiglitazone) tend to increase weight; troglitazone was removed from market due to hepatotoxicity 1
• Improvements in insulin sensitivity are associated with decreased circulating androgens, better glucose tolerance, and improved metabolic outcomes 1
• FDA has not labeled any insulin-sensitizing agent specifically for PCOS treatment 1
• Interventions to improve insulin sensitivity improve ovulation frequency 1

For Hyperandrogenism:

• Spironolactone and finasteride treat symptoms of androgen excess 2

For Infertility:

• Clomiphene citrate for ovulation induction 2, 3
• Letrozole and metformin may play important roles in ovulation induction 2, 3
• Laparoscopic ovarian drilling as an option 2
• Gonadotropins and assisted reproductive technology for refractory cases 2

Monitoring and Follow-Up

Regular Assessments:

• BMI and waist circumference at each visit 5, 4
• Fasting lipoprotein profile including total cholesterol, LDL, HDL, and triglycerides 5
• Menstrual regularity to assess treatment success 5
• Glucose tolerance screening given increased diabetes risk 1, 5

Critical Clinical Pitfalls

A common pitfall is neglecting lifestyle interventions in normal-weight PCOS patients; overall health benefits of lifestyle changes are important regardless of weight status because insulin resistance occurs independent of BMI. 1, 5, 4

• Do not delay lifestyle intervention while pursuing pharmacological treatment 1
• Screen for endometrial cancer risk in women with chronic anovulation and amenorrhea 1
• Consider malignancy (particularly gastric adenocarcinoma) or insulinoma in women with acanthosis nigricans 1
• Address psychological comorbidities as depression and anxiety are more common 2
• Monitor cardiovascular risk factors aggressively given increased long-term cardiovascular disease risk 1, 2