What are the biochemical abnormalities in polycystic ovary syndrome (PCOS) and what is the first‑line management?

Biochemical Abnormalities in PCOS and First-Line Management

Multicomponent lifestyle intervention—combining diet, exercise, and behavioral strategies—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 drives the core pathophysiology of the syndrome. 1

Key Biochemical Abnormalities

Hormonal Disturbances

• Hyperandrogenism: Elevated testosterone (>2.5 nmol/L) and androstenedione (>10.0 nmol/L) measured on days 3-6 of the menstrual cycle 1
• Gonadotropin dysregulation: LH/FSH ratio >2, with hypersecretion of LH (>11 IU/L) and relative FSH hypofunction (<7 IU/ml) 1
• Anovulation markers: Low mid-luteal progesterone (<6 nmol/L) indicating chronic anovulation 1

Metabolic Abnormalities

• Insulin resistance: Present irrespective of BMI in all PCOS phenotypes, affecting both lean and overweight women 1, 2
• Hyperinsulinemia: Compensatory response that directly contributes to hyperandrogenism through effects on the pituitary, liver, and ovaries 1, 2
• Glucose dysregulation: Fasting glucose >7.8 mmol/L or glucose/insulin ratio >4 indicating reduced insulin sensitivity 1
• Dyslipidemia: Elevated triglycerides and altered HDL cholesterol patterns 3

Critical understanding: The pathophysiology centers on accelerated pulsatile GnRH secretion, insulin resistance, and downstream metabolic dysregulation, resulting in ovarian theca stromal cell hyperactivity and follicular arrest 1

First-Line Management: Multicomponent Lifestyle Intervention

Dietary Modification

• Energy deficit: Create a daily deficit of 500-750 kcal (target total intake 1,200-1,500 kcal/day) for women with elevated BMI 1, 4
• No superior diet type: Any balanced dietary approach is acceptable; focus on patient preferences and cultural needs while avoiding restrictive or nutritionally unbalanced diets 1, 4
• General principles: Follow healthy eating principles across the life course, with emphasis on reducing sugar-sweetened beverages, fruit juice, and refined carbohydrates 4

Structured Physical Activity

• Minimum target: At least 150 minutes/week of moderate-intensity activity OR 75 minutes/week of vigorous-intensity activity, performed in bouts of at least 10 minutes 1, 4
• Resistance training: Include muscle-strengthening activities involving major muscle groups on 2 non-consecutive days/week 1, 4
• Enhanced weight loss: For those seeking weight loss, increase to at least 250 minutes/week moderate-intensity OR 150 minutes/week vigorous-intensity activity 1, 4
• Daily step goal: Aim for approximately 10,000 steps/day, including at least 30 minutes of structured exercise 4
• Minimize sedentary time: Reduce prolonged sitting, screen time, and overall sedentary behavior 1, 4
• Both aerobic and resistance exercises show benefits in PCOS, improving insulin sensitivity independent of weight loss 1, 4

Behavioral Strategies

• SMART goal-setting: Implement Specific, Measurable, Achievable, Realistic, Timely goals with self-monitoring using fitness tracking devices 1, 4
• Progressive approach: Start with realistic 10-minute activity bouts and progressively increase by 5% weekly 4
• Comprehensive techniques: Include stimulus control, problem-solving, assertiveness training, slower eating, reinforcement of changes, and relapse prevention 1, 4
• Psychological screening: Address anxiety, depression, body image concerns, and disordered eating (particularly binge-eating disorder and night-eating syndrome), as these dramatically reduce adherence to lifestyle interventions 1, 4

Expected Clinical Outcomes

Weight Loss Benefits

• Target: Achievable weight loss of 5-10% in those with excess weight yields significant clinical improvements 1, 4
• Metabolic improvements: Modest 5% weight loss improves insulin sensitivity, restores ovulatory cycles, and enhances fertility 2
• Reproductive benefits: Weight loss reduces circulating androgen concentrations, improves ovulation frequency, and lowers long-term risk of endometrial carcinoma 4

Benefits Independent of Weight Loss

• Insulin sensitivity: Exercise improves insulin sensitivity even without significant weight loss 4
• Quality of life: Healthy lifestyle contributes to health and quality of life benefits even in the absence of measurable weight loss 1, 4

Critical Pitfalls to Avoid

• Do not dismiss lifestyle intervention in lean PCOS patients simply because they have normal BMI—insulin resistance requires management regardless of weight status 1, 4
• Avoid weight-related stigma: Ensure health professional interactions are respectful and patient-centered, as stigma negatively impacts treatment engagement 4
• Do not delay lifestyle intervention: Prevention of weight gain and monitoring should begin from adolescence, as weight gain escalates from this period and central obesity progresses with age 4
• Address psychological barriers early: Failure to identify and manage anxiety, depression, and eating disorders will undermine adherence to all interventions 1, 4

Special Population Considerations

Ethnic-Specific Thresholds

• Lower BMI cutoffs: Apply ethnicity-adjusted BMI and waist circumference thresholds for Asian, Hispanic, and South Asian populations, who are at high cardiometabolic risk at lower thresholds 1, 4

Adolescents

• Activity target: At least 60 minutes/day of moderate-to-vigorous intensity physical activity, including muscle- and bone-strengthening exercises at least 3 times weekly 4
• Early intervention: Begin weight-gain prevention and monitoring from adolescence 4

Age-Related Changes in Lean PCOS

• Improving metabolic profile: In lean women with PCOS who do not gain weight, insulin resistance, androgens, and lipids gradually improve with age 5
• Obesity neutralizes improvement: The age-related improvement in insulin resistance is neutralized in obese patients, emphasizing the critical importance of weight management 6

Monitoring and Follow-Up

• Regular assessment: Monitor weight and waist circumference regularly during both weight-loss and maintenance phases 1, 4
• Structured review: Fortnightly review for the first 3 months with structured dietary and physical activity plans, then regular review for the first 12 months 4

The evidence is unequivocal: Lifestyle management is positioned at the top of the intervention hierarchy in PCOS, with multicomponent intervention as the foundation upon which all other treatments are built. 1