Menopause, Metabolic Syndrome and ObesityProf Mary Ann LumsdenProf of Gynaecology and Medical EducationFebruary 2013

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+

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S Wild, unpublished data

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

High risk groups

DiabetesMetabolic syndromeObesityPolycystic ovary syndromeHypertensionPremature menopauseHistory of pre-eclampsia

Obesity among kuwaitis over 50

Body Mass Index

Badr et al 2012

Fat Distribution

Perimenopausal Weight Gain

Lovejoy et al 2008

Body Fat Changes in the Menopause

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

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

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

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

HRT

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

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

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

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

Why do women put on Weight?

Eat more?Less Exercise?Altered metabolism?Combination of the above?

Food plentiful –hard to resist

Healthy Food and Exercise – or not!

Metabolic Syndrome

Metabolic Syndrome and BMI

MS Components by gender

Al Zenki et al 2012

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

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

Hot Flushing and Cardiovascular Disease

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

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

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

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

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

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

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

Obesity, Cardiovascular Disease and the Menopause

A problem for all and particularly middle aged women.