Menopause and Metabolic Syndrome - PowerPoint Presentation

1. Menopause and Metabolic SyndromeProf. Sunila Khandelwal

2. Metabolic Syndrome An Epidemic and increasing worldwideMet S is a rising disease entity, still remains under diagnosed.1.5‑2 times more common in women than in men.May develop in women in their menopausal transition years .More common over the age of 55 years with significant rise in risk factors during postmenopausal phase.Higher in Asian than Caucasian women, resulting in an enormous health, social and economic burden which is threatening to overwhelm the health care systems. LejskovaM etal,Climacteric 2011;13:83-91

3. Highlight the prevalence of MetS.Identify reasons and the key metabolic issues based on recent research.Discuss updated guidelines and preventive strategies. Focus on aggressive early therapy for achieving targets.Clinicians should increase their awareness of the metabolic derangements associated with the syndrome, Consider them when weighing MHT options and also while considering management of individual parameters of syndrome. Learning objective

4. What are the key metabolic issues in women?Why should we focus on aggressive early therapy?How should we achieve targets?Challenge is to understand its pathogenesis and to identify effective measures to prevent it either at the population level or at the individual level in any of the country / region.

5. Menopause & Metabolic SyndromeCharacterized by clustering of metabolic conditions, Menopause itself contributes to the development of this syndrome

6. Adverse metabolic changes occurring at menopause transition as a consequence of declining of ovarian sex steroids, increases the risk of CVD and stroke 3 times, DM type II 5 times LINKED METABOLIC ABNORMALITIES RESULTING CLINICAL CONDITIONImpaired glucose handling/insulin resistanceAtherogenic dyslipidaemia Endothelial dysfunctionProthrombotic stateHemodynamic changesProinflammatory stateExcess ovarian testosterone productionSleep-disordered breathingType 2 diabetesEssential hypertensionPolycystic ovary syndrome (PCOS)Non-alcoholic fatty liver diseaseCardiovascular Disease (Myocardial Infraction (MI), peripheral vascular disease (PVD), Stroke) Cancer (Breast, Colorectal, Liver)Obstructive Sleep apnoea

7. Criteria for diagnosisDifferent criteria have been proposed by different agencies:World Health OrganizationInternational Diabetes Federation (IDF) American Heart AssociationThe International Atherosclerosis Society and the International Association for the Study of Obesity.National Cholesterol Education Project, Adult Treatment Panel (NCEP-ATP III)The result is that waist circumference has been dropped, and the presence of any three risk factors from the five is sufficient to make the diagnosis of metabolic syndrome. The limits for waist circumference are, for the present, determined by national or regional thresholds. World Health Federation and all other international associations proposed a harmonized definition (H_MS)Alberti et al,Climacteric 2010;13:192-200Alberti et al,Circulation 2009;120:1640-45.

8. The Metabolic Syndrome :WHO criteriaAlberti k etal, Lancet2005:366;1059-62

9. Alberti et al. Climacteric 2010;13:192-200

10. Menopause results in adverse changes in several metabolic risk factors for CHD and diabetes: Loss of ovarian function at the menopause is associated with adverse changes in the lipid profile. Elevated levels of LDL cholesterol lead to increased risk of deposition of cholesterol in the sub-endothelial space, where the particles become more prone to oxidative damage. Oxidised LDL attracts macrophages and leads to the production of foam cells, the start of the atherogenic process.Triglycerides are also related to hyperinsulinemia and insulin resistance.

11. Influence of the Menopause on MetabolismCarr MC.J Clin Endocrinol Metab 88:2404-11, 2003

12. Central (android) fat distribution Fat accumulation around the trunk and abdominal cavity, is associated with an adverse lipid profile, particularly hypertriglyceridaemia and low levels of HDL cholesterol,insulin resistance and increased risk of CHD.In contrast, lower body (gyncoid) fat distribution, Fat accumulates particularly around the hips, thighs and buttocks, does not appear to be related to increased risk of CHD Patterns of Body Fat Distribution

13. ObesityObesity is an independent predictor of CHD and diabetes. During menopausal transition: Redistribution of body fat towards an android distribution. This has been shown to be a more important risk factor than just obesity itself in womenLey et al. Am J Clin Nutr. 1992;55:950-4

14. Obesity Epidemiological data suggest that 60% of postmenopausal women tend to gain weight, with a shift towards visceral fat distribution.Why do women put on Weight ?Eat more ?Less Exercise ?Altered metabolism ?Combination of the above ?Obesity et al. Endoc. J 2002;49(4):503-9

15. National Health and Nutrition Examination Survey (NHANES)Non-Hispanic black and Mexican American women aged 25 years or older have the highest rates of obesity class 1 (26.02% and 24.16%, respectively) compared with 75.58% of non-Hispanic black women. Compared with western, obesity is less prevalent in most Asian countries. South- Eastern Asia- Singapore (6.7%), Thailand (8.8%), and Malaysia (7.6%). Eastern Asia – Japan (3.3%), China (3.7%) and the Republic of Korea (3.0%).Globally, the burden of disease is 44% due to DM, 23% to IHD, and 7–41% for cancers, particularly breast cancer; these are attributable to overweight and obesity.Obesity has become a world-wide epidemic.40% of adult women world-wide are overweight (BMI >25 kg/m2), 15% are obese (BMI >30 kg/m2). In the European Region 25%,Eastern Mediterranean Region 24% and in Americas 30%, over 50% of women are overweight and in all three regions roughly half of overweight women are obese. A gender concern? Incidence and prevalence of Obesity in womenGlobal status report on noncommunicable diseases 2014. Geneva: World Health Organization; 2014. http://www.apps.who.int/iris/bitstream/ 03 March 2016Yang L , Colditz GA. JAMA Intern Med 2015

16.  Visceral FatAdipocyteAdipocyteAdipocyte Free Fatty AcidsDegradation of apolipoprotein B by the liver TG Small dense LDL and HDL particles InflammationInsulin Resistance TNF – a IL - 6 Adiponectin*Adiponectin secretion Hepatic Lipase activityThe role of increased visceral fat in promoting insulin resistance, inflammation and dyslipidemia

17. Menopause is an independent risk factor for the metabolic syndromeMenopause is associated with an estrogen deficiency-related decrease in insulin sensitivity over time after menopause, with a reduction in glucose tolerance, and hyperinsulinemia. Postmenopausal women have a higher lipase activity in gluteal and abdominal adipose tissue, indicating a predisposition to fat deposition. Lipolysis response is lower in postmenopausal women. These differences predispose to the accumulation of fat stores. Widespread consensus that lifestyle changes focused on improving dietary intake and increased daily physical activities are the cornerstones in both prevention and treatment of obesity and the metabolic syndrome. Even a modest weight loss over 3 years of 5.6 kg through lifestyle intervention reduces the risk of developing type 2 DM by 58% in those overweight with impaired glucose tolerance.

18. The adverse lifestyle-related disease underpinned by insulin resistance, adiposity changes and metabolic changes that result in CVD.Castelo-Branco. Cardiovascular risk in climacteric women: focus on diet. CLIMACTERIC, 2016

19. Risk factors for CVD in WomenHypertension1/3rd > 20 yrsDyslipidaemiaApprox.50% have total Chol > 200 mgPre Diabetes Mellitus¼ of all womenObesity> 1/3rd - BMI > 30Sedentary lifestyle> 2/3rds Smoking> 1/5th with rising prevalenceRosamond W, Flegal K, Furie K, et al. American Heart Association Statistics Committee 2008;117:e1-121

20. HypertensionMenopause is associated with increased hypertension and a deterioration in vascular function. There is a reduction in arterial compliance, as measured by an increase in carotid arterial waveform pulsatility index. Endothelial-dependent vasodilation is also reduced in postmenopausal women.Alterations in coagulation factors have also been described at the menopause. Serum fibrinogen, factor VII activity, antithrombin and PAI-1, highly predictive of IHD, are significantly increased

21. HyperinsulinemiaMetabolism of glucose and insulin is adversely affected by the menopause. Although there is no immediate change in circulating insulin concentrations, this masks a decrease in pancreatic insulin secretion and insulin elimination. Postmenopausal women become increasingly insulin resistant as a result of decreased insulin sensitivity, which results in hyperinsulinemia, thus results in the development of metabolic syndrome. risk 3 times v/s men =  risk x 2 times for CHD  risk 2 times for MIDM usually presents as a cluster of risk factors (Metabolic Syndrome).

22. Oral intakeFFAFFAFFAL I v e rLower extraction of insulinHyperinsulinemiaLow synthesis of SHBG in the LiverHigh free testosteroneHypertensionDiabetesC A DHigh TriglyceridesAbdominal Fat DepotsHigh % of type II bMuscle Fibre.Impaired oxidationof fat.Central Obesity & Disrupt Glycemic Control

23. Possible causes of Metabolic changes at menopauseGeneticEnvironmentLife style changes & lack of exerciseDecreasing levels of estrogen.Androgen dominance: Altered A:E ratio Recent studies…..MeshVR etal ,Climacteric 2008:11;509-17

24. Korean study:2008In a cross sectional longitudinal study spanning 9 yrs, 1002 women,618 premenopausal and 384 postmenopausal, at Anam Hospital in Seoul enrolled for the study for annual Health check up. Conclusions:Postmenopausal status is an independent risk factor for the metabolic syndrome and all of its individual components : hypertension, diabetes, impaired lipids .Risk for the metabolic syndrome increased up to 14 years since menopause. Joong Coo et al, Menopause. 2008;15:524-529

25. Cardiovascular Health StudyHigher Serum Testosterone Concentration in Older Women is Associated with Insulin Resistance, Metabolic Syndrome, and Cardiovascular Disease 344 women aged 65–98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to examine the associations between total and free T and IR, MetS, and CHD. Conclusions: Higher levels of T are associated with IR, MetS, and CHD in elderly women. Whether T is a marker or mediator of cardiovascular disease in this population merits further investigation. Shrita M. Patel, Sarah J. Ratcliffe et al The Journal of Clinical Endocrinology & Metabolism 2008 ; 94(12) 4776-4784

26. SWAN StudyLongitudinal, 9-year study of 949 participants, of 5 ethnicities at 7 geographic sites investigated the natural history of the menopausal transition ,and they were eligible for this study if theyreached menopause during the study; had never taken hormone therapy, anddid not have diabetes mellitus or the Met S at baseline.Results: by Final Menstrual period-Odds of developing the MetS per year in perimenopause were 1.45 (95% confidence interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval, 1.18-1.30). These odds were significantly different (P<.001). An increase in bioavailable testosterone or a decrease in sex hormone-binding globulin levels increased the odds. Janson et al. Archives of Internal Medicine, 2008; 168 (14):1568-75

27. SWAN STUDYConclusions: 13.7% of the women had new-onset MBS. Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife womenThe interaction between T and E2 during the menopausal transition, rather than the individual change of each over time, is a factor in the determination of risk of developing metabolic syndrome during the menopausal transition. This relationship was independent of ethnicity and other factors associated with prevalent metabolic syndrome before the onset of the menopausal transition. Torréns, et aL Menopause: 2009;16:(2)257-264

28. SWAN Study:2017 Longitudinal Analysis of Changes in Weight and Waist Circumference in Relation to Incident Vasomotor Symptoms10 follow-up visits for 1,546 participants, reported no VMS at baseline were modelled for time to first symptomatic visit in relation to concurrent BMI and waist circumference and change in weight and waist circumference during early and late menopause using discrete survival analyses, adjusting for covariates.Ellen B. Gold et al. Menopause. 2017;24(1):9-26Conclusions: Concurrent BMI and waist circumference were positively related to incident VMS in early menopause and negatively related in late menopause. Maintaining healthy weight in early menopause may help prevent VMS.

29. Oopherectomy and metabolic syndromeSurgical menopause may increase the risk of CVDs The aim of this study was to determine the risk of metabolic syndrome in women who had undergone risk-reducing salpingo-oophorectomy (RRSO) because of increased risk of hereditary breast ovarian cancer (HBOC). A higher incidence (36.5%) was found in these patients after 5yrs of follow up.Michelsen TM et al. Eur J Cancer. 2009 Jan;45(1):82-9

30. Bilateral oophorectomy before menopause associated with increased risk for metabolic syndrome A study from Norway examined 263 women (mean age, 56.3 years) who had bilateral oophorectomy before natural menopause. Each woman was matched with 789 controls (mean age, 56.4 years) who had intact uterus and ovaries. Using the IDF definition, 47% of women who had bilateral oophorectomy had metabolic syndrome compared with 36% of women who had natural menopause (P=.001). The numbers were also greater for women with early oophorectomy using the ATP III definition — 35% vs. 25% (P=.002). Dørum A et al. Gynecol Oncol. 2008;109:377-383.

31. Low dose HRT and Metabolic syndromeHormonal Therapy (HT) in normal PM women, generally decreases abdominal fat, but the effect of transdermal estrogen is preferable to oral therapy. In women with MetS, oral therapy was found to increase leptin and the leptin/adiponectin ratio, while transdermal therapy showed no changes. HT improves insulin resistance in Postmenopausal women, although the data are mixed. Oral therapy is found to worsen parameters of insulin resistance, while transdermal therapy had minimal effects overall. Fenkci S, et al. Hum Reprod. 2003;18:866-870

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33. Met S and Menopausal SymptomsFrequency & severity of symptoms (40-65 yrs.) in MetS screening program – MRS, HADS questionnaire showed higher total score correlated positively with abdominal perimeter, intake of psychotropic drug and correlated inversely with female education.Gynecol Endocrino 2014Collins et al. Eur. Heart J 2007;28:2028-40Screening for CV risk in Perimenopause

34. Menopause Symptoms and CV Risk FactorsGerrie-Cor et al. Hypertension 2008;51:1492-8

35. Raikkonen et al. Diabetes Care 2007;30:872-7

36. Treatment goalsTreatment of risk factors should be prioritized Primary Goal is to reduce risk for CVD and to prevent Type 2 DM .Therapeutic Lifestyle Change: commonest clinical feature is excess body fat. Physical activity and diet modifications are indicated for the long-term treatment of MetS First-line therapy directed towards major risk factors. Pharmacotherapy of dyslipidemia is indicated in high-risk groups.

37. NCEP/ATP III GuidelinesClinical Management of Metabolic SyndromeManaging underlying causeWeight control strategies enhances LDL lowering and reduces all other risk factorsPhysical activity increases HDL, reduces VLDL, and lowers LDLMedications :sibuteramine / orlistatAggressive dietary interventionsManaging lipid and non-lipid risk factorsTreat HTN (ACE inhibitor are drug of choice(beta blocker cause weight gain and thiazides alter IR)Aspirin in high risk patientsMetformin for diabetic prevention.Treat the elevated LDL first, then address elevated TG’s and low HDL

38. Targeted Area Goal CHD and CHD risk equivalent (10-yr risk for CHD >20%) <100 mg/dL Multiple (2+) risk factors and 10-yr risk < 20% <130 mg/dL Institute weight control -10% from baseline Institute physical activity 30 to 60 min/d for 3 to 7 d/wk Monitor treatment of hypertension <130/85 mm Hg ATP III Guidelines for treatment of Metabolic syndromeTreat LDL Cholesterol First

39. Dyslipidemia Management For patients with LDL > 130 mg/dL, treat with a statin first, then assess HDL and TG levels to determine if a fibrate or niacin* is needed.For patients with LDL < 130 mg/dL, a fibrate or niacin* is first line therapy when HDL is < 40 mg/dL, then reassess the LDL level to determine if a statin is needed.*Niacin should be used with caution in these patients because of its negative effect on insulin sensitivity and blood glucose levels.Targeted Area Goal Goal of NON-HDL cholesterol for patients with triglyceride >200 mg/dL and <499 mg/dLHigh CHD risk: <130 mg/dLIntermediate CHD risk: <160 mg/dLLow CHD risk: <190 mg/dL Treat elevated triglycerides and low HDL cholesterolATP III Guidelines for Treatment of Met S

40. Diet for prevention of MetSMediterranean diet and CHD Diet has been shown to modulate inflammation. Adherence to the Mediterranean diet is associated with lower levels of inflammation and has been suggested to have a beneficial effect on mortality from all causes, primary and secondary prevention of chronic diseases, mainly CVD and cancer, as well as obesity and type 2 diabetes. Has beneficial effects on total cholesterol, LDL cholesterol, BP and MI and protects against the development of CHD in patients with HTN, hypercholesterolemia and MetS.Is comparable with other interventions such as aspirin, statins, physical activity, and even anti hypertensives such as angiotensin converting enzyme inhibitors or beta-blockers in terms of reducing the risk of CVD morbidity and mortality. For this reason, nutritional strategies to prevent CVD in this population should be a primary objective for health-care providers.Martinez-Gonzalez MA et al Nutr Metab Cardio Dis 2011;21:237-44

41. The Mediterranean diet is considered particularly healthy in terms of reduced CVD and Metabolic risk in contrast with the Western diet.Basic Components of the Mediterranean and Western DietsKastoriniCM, Nutr Metab Cardiovasc 2010;20:563-51

42. Prevention Diet Mediterranen (PREDIMED) StudyA randomized, controlled trial comparing a low-fat diet to the Mediterranean diet supplemented with either olive oil or nuts. This flagship study is one of the largest randomized trials focusing on primary CVD prevention and clearly places the Mediterranean diet at the forefront of preventive cardiovascular medicine. The underlying mechanisms are multiple, and its components have been found to reduce CVD risk by mechanisms including reduction of surrogates of CVD such as BP, lipids, endothelial dysfunction, glucose, BMI and waist circumference, as well as by providing increased nitric oxide bioavailability, antioxidant properties, and anti-inflammatory effects.Estruch R. et al. PREDIMED study investigators. N Engl J Med 2013;368:1279-90

43. Effective Dietary InterventionsReduce caloriesReduce saturated and trans fatsReduce sodiumReduce simple sugarsIncrease whole grainsIncrease fruits and vegetablesEat fish 1-2 times per weekUse monounsaturated or polyunsaturated oilsOlive, Canola, and PeanutSafflower, Sunflower or Sesame seed, Corn, or Soy Reduce alcohol consumptionGrowing number of US- style fast food restaurants in many developing countries of world , means that the MetS will probably emerge every where. US experience serves as a warning to others ! Millen et al. Am J Clin Nutr 2000;62:623-32

44. International Approach to EatingMarie-Pierre St-Onge et al. Circulation. 2017;135:00–00

45. Effects of ExercisePhysical activity level is negatively associated with fasting insulin level.Regular moderate exercise promotes alterations of lipolytic enzymes and a significant increase in plasma HDL.Should include components that improve cardio-respiratory fitness, muscular strength and endurance.

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47. Caloric Expenditure by ActivityActivityCal/hrSleep45Sitting81Standing140Golf240Housework240Walking297Gardening324ActivityCal/hrYoga360Dancing370Biking441Tennis549Swimming603Jogging675Numbers are estimated for a 150 lb. person, and will vary depending on weight, body composition, and level of intensity. www.cancer.org

48. BMI categoryClinical Practice Guidelines on Menopause. Journal of Mid-life Health. 2013; 4(2):77-106

49. Managing Menopausal Symptoms in Women With Metabolic SyndromeMHT may be considered to relieve vasomotor and other symptoms of menopause in women with metabolic syndromeDoes not interfere with glycemic control in women with type 2 diabetes, does not increase BP in normotensive womenTransdermal estrogen treatment has a protective effect against the risk factors of metabolic syndrome (homocysteine, ADMA, HDL Cholesterol) in surgically menopausal patients who have undergone surgery in the early menopausal period.Transdermal HT should be regarded as first-line treatment in women at risk of developing diabetes (including those with Metabolic syndrome). S. Kilic,, N. Yilmaz et al. Climacteric 2010;13:55-62.

50. Updated 2013 International Menopause Society recommendations on MHT and preventive strategies for midlife healthClimacteric 2013;16:316-337.MHT has the potential for improving the cardiovascular risk profile through its beneficial effects on vascular function, cholesterol levels and glucose metabolism.Cardio protective if started around the time of menopause (often referred to as the ‘window of opportunity’ concept).MHT also reduces the risk of diabetes and, through improving insulin action in women with insulin resistance.It has positive effects on other related risk factors for cardiovascular disease such as the lipid profile and metabolic syndrome.

51. World Menopause Month International Campaigns !!!Excess weight can lead to an increased risk of heart disease, hypertension, diabetes, sleep apnoea, cancer, osteoarthritis and mental health problems.For further information visit www.imsociety.orgStay fit and reduce your risk of excess weight after the menopauseDo what makes your heart healthyInternational Menopause Society, PO Box 751, Cornwall TR2 4WD Tel: +44 01726 884 221 Email: leetomkinsims@btinternet.comHeart Health Matters While menopause is a perfectly natural occurrence, hormonal changes and other changes can lead to heart disease. Reduce your risk factors; a happy heart is a healthy heart.For further information visit www.imsociety.org

52. Prevention of Diseases after Menopause (WMM-2014)Obesity and Diabetes Approximately 14% of the global population is obeseCentral adiposity is associated with IR and DMAfter menopause body composition changes resulting in central adiposity (android)Prevention and treatment of Obesity include:Exercise, caloric restriction,Complementary/alternate approaches.Pharmacotherapy and bariatric surgery may have a role in selective cases MHT reduces central adiposity, IR and onset of Diabetes, does not cause weight gain.

53. The Metabolic syndrome Prevention RecommendationsEncourage combination of exercise, dietary interventions & behavioral therapy to prevent MetS in menopausal woman Gold Standard for weight loss program Assess the risk of CADAddress modifiable risk factorsDyslipidaemiaHypertensionSmokingDiabetesObesity Lack of exercisePsychological stressesKeep tabs onCholesterol levelsSearch for secondary cause hypothyroidismBlood pressure lifestyle DepressionGet checkedTreat if appropriate Consider preventative medicationGlobal Health Observatory . Obesity . Geneva: World Health Organization , 2014 . Available at: http://www.who.mt/gho/ncd/risk_factors/obesityMHT: A meta-analysis of pooled data from 107 trials concluded that HRT reduced IR, abdominal obesity, new-onset diabetes, lipids, blood pressure, adhesion molecules, and procoagulant factors in women without diabetes and reduced fasting glucose and IR in women with diabetes. The effects were diminished by the addition of progestin (Grade A).

54. Lifestyle ModificationMind body therapies :Yoga (4000 years ago originated in India) successfully used for prevention and management of HTN, DM and other conditions associated with aging. It may represent a promising intervention even in western countries to reduce the risk Met S.Tai Chi Chuan and Qigong (Traditional practice in Chinese medicines for more than 2500 yrs.) group practice of these ancient disciplines strongly associated with decrease CVD risk – a source of social support (Studies from China, Korea, Japan, Sweden and USA).

55. Key PrinciplesSpread the word of awareness mainly among the high risk groups (those with family history obesity, diabetes of premature CVD; personal history of PCOS a POF) through appropriate media.Care should be started as early as the prenatal and intrauterine life through adequate nutrition (micro and macro nutrients).Lifestyle modifications starting from early Childhood, extending into adolescence and then adulthood forms an extremely important preventive measure. - Regular physical activity, restriction of sedentary habits &well balanced diet, (Carbs – 55-65%; complex carbohydrates; restricted total and mono-saturated fats and adequate monounsaturated fats.) - Mind body therapies have been evidenced to reduce IR, However further stronger studies are warranted.Maintenance of an ideal BMI between 18 to 22.9 kg/m2 and waist circumference less than 80 cm for women.Intervention with insulin sensitizers and other metabolic modulator drugs.

56. Summary Midlife body changesWeight gain at midlife is often attributed to hormonal changes at menopause. However, both sectional and longitudinal studies have consistently shown this not to be the case.The steady weight gain, of about 0.5 kg per year, seen in women at midlife is associated with age and environmental factors, not menopause.Variables associated with a greater likelihood of obesity in women at midlife include urbanization, lower level of education, inactivity, higher parity, family history of obesity and marriage at earlier age.Disruption of the circadian rhythm by shift work and sleep deprivation also contributes to weight gain.The relationship between depression and midlife weight gain is bidirection. R.J. Baber, et al. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016.

57. Contd.. summaryThe change in the hormonal milleu at menopause is associated with significant increases in waist circumference and central abdominal fat.Increased waist circumference occurs in relation to FMP & significant increases in central abdominal fat have been seen in longitudinal studies of Caucasian and Asian women.Total mass, percentage fat mass, truncal fat mass and visceral fat also increase in non-obese women across the menopausal transition.The redistribution of fat to the abdomen results in a transition from a gyncoid to an android pattern of fat distribution.Studies using a range of radiological modalities have shown that postmenopausal women have greater amounts of intra-abdominal fat compared to premenopausal women.Waist circumference represents both subcutaneous and visceral adipose tissue, depot size and correlates closely with cardiovascular disease risk. In women, it is also closely associated with dyslipidemia.Animal models shows that estrogen depletion favors central abdominal fat accumulation and that this is ameliorated by estrogen therapy.

58. Governing principles for managing midlife body changesPrimary approach to minimize weight gain at midlife is caloric restriction and maintenance of physical activity.Management of factors associated with weight gain, such as depression requires pharmacotherapy, medications associated with weight gain commonly used e.g. clozapine, imipramine, and amitriptyline should be avoided.More RCTs show a reduction in central adiposity with estrogen therapy. In a subsample of participants in the WHI E+P study, the E + P intervention at 3 yrs. significantly helped to maintain lean body mass and prevented a shift toward android fat distribution.Effects of exogenous estrogen are generally favourable in terms of body composition;however, Oral estrogen has been associated with a small but significant increase in fat mass and a decrease in lean mass, whereas lean body mass and fat mass are unaffected by TD estradiol. Neither route appears to alter visceral fat mass.The different effects of oral v/s TD estrogen may related to the effects of route of administration on growth factors and substrate oxidation. R.J. Baber, et al. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016.

59. Modifiable unmet ChallengesCurrent evidence suggests that features of MS present before menopause:IR , small dense particle LDL and elevated PAI during perimenopause, may be the carriers for genetic predisposition i.e. masked by the effect of estrogen and unmasked by Menopause. This subset of women requires targeted management to prevent future cardiovascular risk. Source : Bjorn CarlssonClassical risk factorsNovel risk factorsMajor unmet clinical needMetabolic syndrome LDL-C BP SmokingHDL-CInsulin Glu PAI-1 TGAbdominal obesity TNF  IL-6T2DMCardiovascular Disease

60. Key success factorsLifestyle change in adults at risk of diabetes / CVDAddress psychosocial issues firstIncreases effectivenessTargeted strategies for prevention of weight gain: diet/physical activity (e.g. pedometers, time management, self talk)Incorporate established behaviour change technique (more effective than advice/education)Mobilise social supportClear plan for maintenance support Stage of journey to Success :Engage  Educate  Behaviour Change  Support

61. Metabolic syndrome often complicates the many physiologic consequences of menopause and growing into a significant public health problem. Challenges Clinicians to adopt strategies for managing Menopause that do not exacerbate this metabolic dysfunction and if possible improve. More research is needed to understand the gene-environment interaction for the observed discrepancy between Asians and Caucasians.Screening at menopause, is an ideal opportunity ……For the physician to look for factors that may in future lead to a full blown metabolic syndromeTo discuss a woman’s risk profile, ensure accurate risk perception focus on prevention of weight gain .To develop a long-term effective community based preventative health plan by encouraging combination of exercise, dietary modifications , behavioural therapy and pharmacological interventions with appropriate use of MHT Conclusions