1. Menopause, Metabolic Syndrome and Obesity Prof Mary Ann Lumsden Prof of Gynaecology and Medical Education February 2013

4. Mortality Rates in Women National Center for Health Statistics. 1999:164-167. Coronary Artery Disease Stroke Lung Cancer Breast Cancer Colon Cancer Endometrial Cancer Age (years) Mortality Rate per 100,000 6500 4500 2500 1600 1200 800 400 0 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

5. 020406080100120140160180200 England & Wales Bangladesh India Pakistan West Africa West Indies China & Hong Kong Standardised Mortality Ratio (SMR) Women Men IHD mortality 2001-2003 (ICD 120-125) by country of birth S Wild, unpublished data

7. Medical Complications of Obesity Phlebitis venous stasis Venous thrombosis Coronary heart disease Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Gall bladder disease Gout Diabetes Osteoarthritis Nonalcoholic fatty liver disease Steatosis/ steatohepatitis cirrhosis Hypertension Dyslipidemia Cataracts Oedema Pancreatitis Idiopathic intracranial hypertension + Loss of vision CANCER breast, uterus, cervix, prostate, kidney colon, esophagus, pancreas, liver Gynecologic abnormalities abnormal menses / infertility polycystic ovarian syndrome gestational diabetes pre-eclampsia Stroke Tiredness Back pain

8. High risk groups Diabetes Metabolic syndrome Obesity Polycystic ovary syndrome Hypertension Premature menopause History of pre-eclampsia

9. Obesity among kuwaitis over 50

10. Body Mass Index Badr et al 2012

12. Fat Distribution

13. Perimenopausal Weight Gain Lovejoy et al 2008

14. Body Fat Changes in the Menopause

15. Body composition menopause *** ***p<0.001 Ley et al. Am J Clin Nutr 1992; 55: 950-54 Android fatGynoid fat

16. Menopause and the Metabolic Syndrome SWAN Study 949 women 9 yr. f-u from pre- to post- menopause Janssen I, et al. Arch Intern Med 2008;168:1568 waist circ. FMP

17. 0.980.94Waist/hip ratio 25.725.9BMI (kg/m2) SA n=1420 European n= 1515 Fat is in the wrong place! (Adapted from McKeigue et al, with permission from authors) Other evidence for increase visceral fat mass Other evidence for increase visceral fat mass

18. 30.0Body mass index (kg/m 2 )30.5 0.70Waist to hip ratio1.20 Female A Pear-shaped body Premenopause Female B Apple-shaped body Postmenopause

19. HRT Some studies suggest that it maintains the ‘gynoid’ fat distribution but this has not been shown conclusively

20. South AsiansWhite Europeansp N4640 Age (y)54.7±8.553.4±6.40.375 BMI25.8±3.124.8±3.10.13 HbA1c (mmol/mol)37.6±4.133.1±3.5<0.001 Fasting Glucose (mmol/l) 5.01±0.64.9±0.50.45 LDL (mmol/l)3.86±0.853.55±0.920.28 HDL (mmol/l)1.38±0.31.7±0.40.006 SBP (mmHg)125.9±14123.5±14.80.48 Waist to Hip Ratio0.84±0.060.79±0.060.006 Metabolic features of a group of healthy European and South Asian women who reside in the UK

21. Fat distribution and ethnicity SAs (ethnicity=1) are more centrally obese for the same BMI than Europeans, but fat distribution in the upper or lower body do not differ P<0.001 mm

22. NEFA, leptin, IL- 6, TNF , resistin release NEFA, leptin, IL- 6, TNF , resistin release Adiponectin release Adiponectin release SKELETALMUSCLE Oxidative capacity Capacity for fatty acid utilisation Evidenced by: - Decreased activities of enzymes regulating oxidative/fatty acid metabolism and increased activities of glycolytic enzymes.  Increased muscle LCACoA concentrations  Reduced fat oxidation at rest and during exercise  Reduced exercise capacity ADIPOSE TISSUE TISSUE INSULINRESISTANCE Effect on muscle metabolism? Innate defect within muscle? Do South Asians metabolize fat less efficiently

23. Why do women put on Weight? Eat more? Less Exercise? Altered metabolism? Combination of the above?

24. Food plentiful –hard to resist

25. Healthy Food and Exercise – or not!

26. Metabolic Syndrome

27. Metabolic Syndrome and BMI

28. MS Components by gender Al Zenki et al 2012

29. 17.4 17.6 32.7 47.1 0 10 20 30 40 50 60 NCEP-ATPIIIWHO Metabolic syndrome definitions Age standardised prevalence (%) European South Asian Overall prevalence of metabolic syndrome in South Asians

30.  IL-6  CRP  ALT  TG,  HDL IRSkeletalmuscle Genes  FA  PAI-1 +ve  leptin  adiponectin EnvironmentAging Centralobesity Steroids, Ang II Hypertension Fat cells release many things

31. Hot Flushing and Cardiovascular Disease

32. Flushing and cardiovascular disease In WHI, incident CHD concentrated among older women reporting VSM. Oestrogen withdrawal has significant impact on blood vessel structure and function. Oestrogen improves endothelial function. Oestrogen use is associated with fewer calcified plaques in the coronary arteries. Calcitonin gene-related peptide is released during flushing but not during exercise or sweating. Obesity and smoking are risk factors for heart disease and flushing

33. Vasomotor Symptoms and CVD Rancho Brando Study (Svartberg et al 2009) HR 0.72(0.55-0.94) in favour of flushing. Gast et al over 10,000 Dutch Women (HR 1.33 (1.06-1.69). Largely explained by cholesterol levels Hot Flushing and Cardiovascular Disease

34. SWAN Study Study of Women’s Health Across the Nation (SWAN) Study 3302 participants across 7 sites (42-52 years of age). 588 women in ‘Heart’ Study. 491 gave information on flushing (assessed according to number of days on which flushes occurred in previous 14 days) 374 had USS to assess flow-mediated dilatation (FMD) or assessment of coronary artery calcification Heart participants were Caucasian or African-American

35. NON-FLUSHERSFLUSHERS Number229263 Age50.0 (2.8)50.7 (2.9) Postmenopausal18.6%39.7% BMI kg/m228.6 (6.1)29.8 (6.2) HDL mg/dl56.4 ((14.4)58.1 (13.9) LDL mg/dl116.1 (32.0)122.3 (32.3) Aortic Calcification Score ** 086 (35%)52 (23.7) >0 - <1061 (24.7)60 (27.3) >10%41 (16.6)58 (26.4) FSH mIU/ml39.8 (35.6)48.3 (69.5) SWAN Study, Cardiovascular Risk and Flushing

36. NON-FLUSHERSFLUSHERS Number229263 Age50.0 (2.8)50.7 (2.9) Postmenopausal18.6%39.7% BMI kg/m228.6 (6.1)29.8 (6.2) HDL mg/dl56.4 ((14.4)58.1 (13.9) LDL mg/dl116.1 (32.0)122.3 (32.3) Aortic Calcification Score ** 086 (35%)52 (23.7) >0 - <1061 (24.7)60 (27.3) >10%41 (16.6)58 (26.4) FSH mIU/ml39.8 (35.6)48.3 (69.5) SWAN Study, Cardiovascular Risk and Flushing

37. Cardiovascular Risk Factors in women who flush : Lipids p= 0.91 Adjusted p= 0.97 p<0.001 Adjusted p<0.001 p= 0.01 Adjusted p= 0.01 p= 0.29 Adjusted p= 0.29 p= 0.83 Adjusted p= 0.97 p= 0.23 Adjusted p= 0.29

38. Cardiovascular Risk Factors in women who flush: Inflammatory markers p= 0.59 Adjusted p= 0.67 p= 0.07 Adjusted p= 0.18 p= 0.38 Adjusted p= 0.48 p= 0.68 Adjusted p= 0.69 p= 0.02 Adjusted p= 0.05

39. Obesity, Cardiovascular Disease and the Menopause A problem for all and particularly middle aged women.