Menopause, Metabolic Syndrome and Obesity

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

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

5. Women Men IHD mortality 2001-2003 (ICD 120-125) by country of birth China & Hong Kong West Indies West Africa Pakistan India Bangladesh England & Wales 0 20 40 60 80 100 120 140 160 180 200 Standardised Mortality Ratio (SMR) S Wild, unpublished data

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

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

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

17. Fat is in the wrong place! European n=1515 SA n=1420 BMI (kg/m2) 25.9 25.7 Waist/hip ratio 0.94 0.98 • Other evidence for increase visceral fat mass (Adapted from McKeigue et al, with permission from authors)

18. 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. Metabolic features of a group of healthy European and South Asian women who reside in the UK

21. Fat distribution and ethnicity P<0.001 mm mm 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 mm

22. Do South Asians metabolize fat less efficiently ADIPOSE TISSUE SKELETAL MUSCLE Effect on muscle metabolism? NEFA, leptin, IL-6, TNFa, resistin release Adiponectin release Oxidative capacity Capacity for fatty acid utilisation INSULIN RESISTANCE Innate defect within muscle? • 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

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

30. Fat cells release many things Hypertension Steroids, Ang II leptin adiponectin IR Skeletal muscle Genes Central obesity FA ALT TG,HDL Environment Aging IL-6 CRP +ve PAI-1

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 Hot Flushing and Cardiovascular Disease • 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

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. SWAN Study, Cardiovascular Risk and Flushing

36. SWAN Study, Cardiovascular Risk and Flushing

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

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

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