menopause, metabolic syndrome and obesity
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Menopause, Metabolic Syndrome and Obesity. Prof Mary Ann Lumsden Prof of Gynaecology and Medical Education February 2013. Mortality Rates in Women. 6500. Coronary Artery Disease Stroke Lung Cancer Breast Cancer Colon Cancer Endometrial Cancer. 4500. 2500. 1600. - PowerPoint PPT PresentationTRANSCRIPT
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Menopause, Metabolic Syndrome and ObesityProf Mary Ann LumsdenProf of Gynaecology and Medical EducationFebruary 2013
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Mortality Rates in Women
National Center for Health Statistics. 1999:164-167.
Coronary Artery DiseaseStrokeLung CancerBreast CancerColon CancerEndometrial Cancer
Age (years)
Mor
talit
y R
ate
per 1
00,0
00
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+
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0 20 40 60 80 100 120 140 160 180 200
England & Wales
Bangladesh
India
Pakistan
West Africa
West Indies
China & Hong Kong
Standardised Mortality Ratio (SMR)
WomenMen
IHD mortality 2001-2003 (ICD 120-125) by country of birth
S Wild, unpublished data
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Medical Complications of Obesity
Phlebitisvenous stasisVenous thrombosis
Coronary heart disease
Pulmonary diseaseabnormal functionobstructive sleep apneahypoventilation syndrome
Gall bladder disease
Gout
Diabetes
Osteoarthritis
Nonalcoholic fatty liver diseaseSteatosis/ steatohepatitiscirrhosis Hypertension
Dyslipidemia
Cataracts
Oedema
Pancreatitis
Idiopathic intracranial hypertension + Loss of vision
CANCERbreast, uterus, cervix, prostate, kidneycolon, esophagus, pancreas, liver
Gynecologic abnormalitiesabnormal menses / infertilitypolycystic ovarian syndromegestational diabetespre-eclampsia
Stroke Tiredness
Back pain
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High risk groups
DiabetesMetabolic syndromeObesityPolycystic ovary syndromeHypertensionPremature menopauseHistory of pre-eclampsia
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Obesity among kuwaitis over 50
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Body Mass Index
Badr et al 2012
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Fat Distribution
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Perimenopausal Weight Gain
Lovejoy et al 2008
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Body Fat Changes in the Menopause
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Body composition
30
40
50
60
pre post
%
30
40
50
60
pre post
%
menopause menopause
*** ***
***p<0.001
Ley et al. Am J Clin Nutr 1992; 55: 950-54
Android fat Gynoid fat
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Menopause and the Metabolic SyndromeSWAN Study
949 women9 yr. f-u from pre- to
post- menopause
Janssen I, et al. Arch Intern Med 2008;168:1568
waist circ.
FMP
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0.980.94Waist/hip ratio25.725.9BMI (kg/m2)
SAn=1420
Europeann=1515
Fat is in the wrong place!
(Adapted from McKeigue et al, with permission from authors)
• Other evidence for increase visceral fat mass
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30.0 Body mass index (kg/m2) 30.5
0.70 Waist to hip ratio 1.20
Female APear-shaped body
Premenopause
Female BApple-shaped body
Postmenopause
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HRT
Some studies suggest that it maintains the ‘gynoid’ fat distribution but this has not been shown conclusively
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South Asians White Europeans p
N 46 40
Age (y) 54.7±8.5 53.4±6.4 0.375
BMI 25.8±3.1 24.8±3.1 0.13
HbA1c (mmol/mol) 37.6±4.1 33.1±3.5 <0.001
Fasting Glucose (mmol/l)
5.01±0.6 4.9±0.5 0.45
LDL (mmol/l) 3.86±0.85 3.55±0.92 0.28
HDL (mmol/l) 1.38±0.3 1.7±0.4 0.006
SBP (mmHg) 125.9±14 123.5±14.8 0.48
Waist to Hip Ratio 0.84±0.06 0.79±0.06 0.006
Metabolic features of a group of healthy European and South Asian women who reside in the UK
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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
mm
mm
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NEFA, leptin, IL-6, TNFa, resistin release
Adiponectin release
SKELETAL MUSCLE
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
INSULINRESISTANCE
Effect on muscle
metabolism?
Innate defect within muscle?
Do South Asians metabolize fat less efficiently
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Why do women put on Weight?
Eat more?Less Exercise?Altered metabolism?Combination of the above?
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Food plentiful –hard to resist
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Healthy Food and Exercise – or not!
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Metabolic Syndrome
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Metabolic Syndrome and BMI
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MS Components by gender
Al Zenki et al 2012
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17.4 17.6
32.7
47.1
0
10
20
30
40
50
60
NCEP-ATPIII WHO
Metabolic syndrome definitions
Age
sta
ndar
dise
d pr
eval
ence
(%) European
South Asian
Overall prevalence of metabolic syndrome in South Asians
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IL-6 CRP
ALT TG,HDL
IR Skeletal muscle
GenesFA
PAI-1
+ve
leptinadiponectin
EnvironmentAging
Centralobesity
Steroids, Ang II Hypertension
Fat cells release many things
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Hot Flushing and Cardiovascular Disease
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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
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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
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SWAN Study
Study of Women’s Health Across the Nation (SWAN) Study3302 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 calcificationHeart participants were Caucasian or African-American
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NON-FLUSHERS FLUSHERSNumber 229 263Age 50.0 (2.8) 50.7 (2.9)
Postmenopausal 18.6% 39.7%
BMI kg/m2 28.6 (6.1) 29.8 (6.2)
HDL mg/dl 56.4 ((14.4) 58.1 (13.9)
LDL mg/dl 116.1 (32 .0) 122.3 (32.3)
Aortic Calcification Score **0 86 (35%) 52 (23.7)
>0 - <10 61 (24.7) 60 (27.3)
>10% 41 (16.6) 58 (26.4)
FSH mIU/ml 39.8 (35.6) 48.3 (69.5)
SWAN Study, Cardiovascular Risk and Flushing
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NON-FLUSHERS FLUSHERSNumber 229 263
Age 50.0 (2.8) 50.7 (2.9)
Postmenopausal 18.6% 39.7%
BMI kg/m2 28.6 (6.1) 29.8 (6.2)
HDL mg/dl 56.4 ((14.4) 58.1 (13.9)
LDL mg/dl 116.1 (32 .0) 122.3 (32.3)
Aortic Calcification Score **
0 86 (35%) 52 (23.7)
>0 - <10 61 (24.7) 60 (27.3)
>10% 41 (16.6) 58 (26.4)
FSH mIU/ml 39.8 (35.6) 48.3 (69.5)
SWAN Study, Cardiovascular Risk and Flushing
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Cardiovascular Risk Factors in women who flush : Lipids
p= 0.91Adjusted p= 0.97
p<0.001Adjusted p<0.001
p= 0.01Adjusted p= 0.01
p= 0.29Adjusted p= 0.29
p= 0.83Adjusted p= 0.97
p= 0.23Adjusted p= 0.29
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Cardiovascular Risk Factors in women who flush: Inflammatory markers
p= 0.59Adjusted p= 0.67
p= 0.07Adjusted p= 0.18
p= 0.38Adjusted p= 0.48
p= 0.68Adjusted p= 0.69
p= 0.02Adjusted p= 0.05
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Obesity, Cardiovascular Disease and the Menopause
A problem for all and particularly middle aged women.