Metabolic Dysfunction in PCOS

PCOS Overview & Metabolic Nexus - Syndrome's Shadow

Polycystic Ovary Syndrome (PCOS): complex endocrine disorder. Rotterdam criteria for diagnosis. Linked to metabolic dysfunction.

• Rotterdam Criteria (≥2 of 3):
  • Oligo/anovulation
  • Hyperandrogenism (clin/biochem)
  • PCOM on USG (≥12 follicles 2-9mm / ovarian vol >10ml)
• Metabolic Impact:
  • Insulin Resistance (IR) pivotal
  • Dyslipidemia (↑TG, ↓HDL)
  • ↑Risk: T2DM, NAFLD, CVD

⭐ Acanthosis nigricans (marker of IR) seen in up to 75% of PCOS women.

Insulin Resistance Pathophysiology - Sugar's Siege

• Peripheral insulin resistance (IR) in muscle/fat impairs glucose uptake ("Sugar's Siege").
• Pancreas compensates: chronic hyperinsulinemia.
• Excess insulin acts as a "rogue hormone":
  • Ovary: Stimulates theca cells (with LH) → ↑ androgen synthesis (CYP17).
  • Liver: ↓ Sex Hormone-Binding Globulin (SHBG) → ↑ free, active androgens.

⭐ Hyperinsulinemia in PCOS directly stimulates ovarian theca cell androgen production and suppresses hepatic SHBG, significantly increasing bioavailable androgens.

Dyslipidemia & NAFLD in PCOS - Fatty Fallout

• PCOS Dyslipidemia:
  • Hallmark: ↑ Triglycerides (TG), ↓ HDL-C, ↑ LDL-C (small, dense particles).
  • Driven by insulin resistance.
  • 📌 PCOS Lipids: ↑TG, ↓HDL ("Pathetic Cholesterol, Oh So sad").
• Non-Alcoholic Fatty Liver Disease (NAFLD):
  • Common co-morbidity; prevalence 30-70%.
  • Spectrum: Steatosis → NASH → Cirrhosis.
  • Screening: Liver Function Tests (LFTs), Ultrasound.
  • Management: Lifestyle changes (weight loss, diet).

⭐ Insulin resistance is the central pathophysiological link between PCOS, dyslipidemia, and NAFLD.

Glucose Dysregulation & CVD Risks - Sweet & Sour Sequelae

• Core: Insulin Resistance (IR) drives metabolic disturbances.
• Screening: 2-hour OGTT (75g glucose) for all at diagnosis.
  • Repeat every 1-3 years (normal), annually (if IGT).
• Progression: IGT → T2DM (risk ↑ 2-7x).
• CVD Risks:
  • Dyslipidemia: ↑Triglycerides, ↓HDL, ↑LDL.
  • Hypertension.
  • Metabolic Syndrome common.
  • Endothelial dysfunction.

⭐ Women with PCOS should be screened for T2DM with a 75g OGTT, not solely HbA1c or FPG, due to higher sensitivity for IGT/T2DM in this population.

Management of Metabolic Dysfunction - Countering Chaos

• Lifestyle Modification: First-line.
  • Diet: Low Glycemic Index (GI), calorie-restricted.
  • Exercise: ≥ 150 min/week moderate-intensity.
  • Weight loss: 5-10% target; improves metabolic & ovulatory function.
• Pharmacotherapy:
  • Metformin: For Impaired Glucose Tolerance (IGT)/Type 2 Diabetes Mellitus (T2DM). Dose: 500mg up to 1g BD.
    • Improves insulin sensitivity, aids weight loss.
  • Statins: For dyslipidemia if lifestyle modification fails.
  • GLP-1 Agonists: Aid weight loss, glycemic control.
  • Orlistat: For BMI ≥ 30 kg/m² (or ≥ 27 kg/m² + comorbidities).
• Bariatric Surgery: Consider for BMI ≥ 40 kg/m² (or ≥ 35 kg/m² + comorbidities) if other methods fail.

⭐ Metformin is first-line for insulin resistance in PCOS, improving metabolic & reproductive outcomes even in euglycemic women anovulatory women for ovulation induction assistance when other factors are addressed like lifestyle changes etc..

High-Yield Points - ⚡ Biggest Takeaways

• Insulin Resistance (IR) is central to PCOS metabolic dysfunction, causing hyperinsulinemia.
• IR drives hyperandrogenism via ↑ ovarian androgen synthesis & ↓ Sex Hormone-Binding Globulin (SHBG).
• Screen for Type 2 Diabetes Mellitus (T2DM) with an Oral Glucose Tolerance Test (OGTT).
• Dyslipidemia (↑ Triglycerides, ↑ LDL, ↓ HDL) is frequently observed.
• PCOS increases risk of Metabolic Syndrome and Non-alcoholic Fatty Liver Disease (NAFLD).
• Long-term complications include ↑ risk of Cardiovascular Disease (CVD) and endometrial hyperplasia due to chronic anovulation and unopposed estrogen (though this point might be slightly outside pure 'metabolic' dysfunction, it's a key long-term PCOS risk often linked).