Metabolic syndrome PCOS: what a physician should know

1. Metabolic syndrome & PCOS:what a physician should know Sanjay Kalra Bharti Hospital Karnal

2. The MetS pandemic: OBESE INDIA

3. No one can eat just one!

4. Definition : WHO Diabetes/IGT/IFG or ? insulin sensitivity Any 2 of Central obesity/obesity Hypertension > 140/90 Dyslipidemia Insulin resistance microalbuminuria

5. Definition: AACE(2003) IGT or IFG BMI > 25 Family history Ethnicity Focus on insulin resistance Clinical judgement

6. Definition : AHA-NHLBI Hypertension BP > 130/85 Obesity WC > 40” in men, 35” in women Lipids HDL < 40 in men, 50 in women TG > 150 Diabetes FBG < 100

7. etiology Obesity/overweight Central obesity Waist:hip ratio Waist circumference Insulin resistance IFG/IGT/DM No simple markers Cutaneous markers

8. Effects of obesity EFRMD =excessive fat-related metabolic diseases Non-metabolic diseases

9. Effects of obesity Cardiovascular Hypertension Stroke Diabetes Endocrine Hyperlipidemia Gout Gall bladder disease Musculoskeletal Behavioural/ psychological Sleep disorders Eating disorders Cancers Financial Social

10. Secondary MetS HAART Hyperalimentation Age

11. Why is MetS important ? MetS prevalence? MetS is a risk factor Allows risk stratification/assessment 80% USA episodes can be prevented

12. Why is MetS important ? RR 4x for new-onset diabetes in Framingham study Accounts for 25% of all new CVDs in Framingham study Accounts for 50% of 1st MI in INTERHEART study

13. Years of life lost BMI > 25 nonsmoking women lose 3.3 yrs BMI > 25 nonsmoking men lose 3.1 yrs BMI > 30 nonsmoking women lose 7.1 yrs BMI > 25 nonsmoking men lose 5.8 yrs (Peeters et al, 2003)

14. linkages CHD NASH CA breast, endometrium, pancreas, colon PCOS

15. CHD 10 to 20% risk of CHD in Framingham cohort 26% prevalence of MetS in acute MI patients MetS is NOT a CHD equivalent

16. NASH Mitochondrial dysfunction Oxidative stress Biochemical, USG diagnosis May use metformin, TZDs if OT/PT are upto 2x normal If in doubt, use insulin

17. NASH Asymptomatic Upper abdominal fullness Cirrhosis 20% Hepatocellular carcinoma UDCA long-term Rosiglitazone

18. malignancies IGF-1 receptor mediated IGF-1 mediated Endocrine organs Breast Endometrium Colon Pancreas Liver

19. definition : PCOS Ovulatory disorder Hyper androgenism hyper androgenemia se testosterone > 80 Exclusion of adrenal/pituitary pathology

20. Polycystic-appearing ovaries USG diagnosis 8 or more subcapsular cysts < 10 mm diameter Increased ovarian stroma Absence of clinical features

21. treatment Aim to reduce risk of CHD Aim to ? life expectancy ?quality of life ?fertility status Prevent avoidable morbidity

22. strategies Modify root causes Physical activity diet Directly treat metabolic derangements Lipids Blood pressure Prothrombotic state Insulin resistance

23. treatment Lifestyle modification Diet Exercise Stress management Tobacco cessation

24. Limitations of lifestyle measures Difficult to implement High intrusion index (Phelan, Wadden,2002) More difficult to maintain Time consuming Limited efficacy (PiSunyer, 2003)

25. Use these drugs for their specific indications Glucose-lowering effect Metformin Glitazones Antihypertensive effect ACE (I) ARBs

26. Use these drugs for their risk-reducing capacity Statins Fibrates Aspirin Be aggressive in lowering LDL metS without CVD/DM : < 100 metS with CVD/DM : < 70

27. Proven pharmacotherapy vs. unproven therapies: COST A unit drug (one tablet) sells for Rs 5 A unit of weight loss (one inch) sells for Rs.2000

28. rimonabant New kid on the block peripheral and central effects 60% success in ?wt by >5% at 1y 40% success in ?wt by >10% at 1y 6.5 cm ?in waist circ at 1y 20% ?in HDL 7% ? in TGs

29. Mechanism of action

30. Effect on smoking cessation STRATUS US Compared with placebo, rimonabant (20 mg): Doubled the odds of quitting smoking Markedly reduced post-cessation weight gain Was well tolerated

31. Recommendations: NIH, NHLBI,NAASO Advise pharmacotherapy to all obese persons (BMI >30) Advise pharmacotherapy to all overweight persons (BMI > 27) with comorbid conditions Southward trend seen in targets for glucose, BP, lipids will soon be evident in obesity management.

32. Why treat PCOS ? Infertility Acnehirsutism Obesity Menstrual disturbances

33. Anti-androgens ? synthesis ? binding ? conversion of precursors ? action at target tissue

34. Anti-androgens Spironolactone 50 to 200 mg A/E hyperkalemia, hypotension, menstrual irregularities Finasteride 5 mg Flutamide 250 mg; very potent Hepatic dysfunction

35. Anti-androgens O C s with non-androgenic progesterone component Cyproterone 50 mg/d alone or with E in reverse sequential method 2 mg/d with E in continuous combined manner

36. Corticosteroids Dexamethasone 0.5 mg/d Prednisolone 5 – 10 mg h.s Suppress adrenal production of androgens Monitored by DHEA-S levels Aim < 70ug%

37. monitoring Clinical features Acne 1 to 2 mths Hirsutism 6 to 12 mths Serum testosterone Aim < 80 ng% Ultrasonongraphic appearance Reduction in ovarian volume

38. Induction of ovulation Clomiphene Letrozole FSH hMG GnRH agonists

39. Metabolic dysfunction Metformin Maximal tolerated dose A/E GI effects; hypoglycemia Rimonabant 20 mg/d before breakfast Glitazones In lean PCOS Hyponidd (d-chiro inositol)

40. Lifestyle modification Diet Weight reduction/maintenance Physical activity Weight reduction Insulin sensitivity

41. counselling A chronic disease Lifestyle modification necessary Drugs may be needed Treatment changes according to the need Early marriage Early conception

42. Is MetS an artificial entity ? To drive drug consumption ? To drive pharma profits ? To fill medicine OPDs ? Prevention vs. cure Primary prevention vs. secondary prevention

43. Polio Primary prevention: vaccine Secondary prevention: limit disability Which one is better ?

44. Primary prevention

45. Secondary prevention

46. Thank you