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Metabolic Dysfunction in PCOS

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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 PCOS Phenotypes and Metabolic Risk

⭐ 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). Metabolic dysfunction in PCOS and NAFLD

⭐ 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).

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What conditions is Metformin primarily used to treat?

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In polycystic ovarian syndrome, excess androgen (from theca cells) is converted to _____ in adipose tissue, which inhibits FSH secretion from anterior pituitary

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In polycystic ovarian syndrome, excess androgen (from theca cells) is converted to _____ in adipose tissue, which inhibits FSH secretion from anterior pituitary

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