TESTOSTERONE &

CARDIOVASCULAR MORTALITY

ANY LINK ?

Claude SCHULMAN

University of Brussels

FOIU 2018

Financial and Other Disclosures

• I have the following financial interests or relationships to disclose:

• Disclosure code :

• No financial relationships

Skin

Hair growth,

balding, sebum

production

Liver

Synthesis of

serum proteins

Male sexual organs

Penile growth,

spermatogenesis,

prostate growth and

function

Brain Libido, Mood

Muscle

Increase in strength

and volume

Kidney

Stimulation of

erythropoietin

production

Bone marrow

Stimulation of

stem cells

Bone

Accelerated linear

growth, closure of

epiphyses

The Role of Testosterone

Morley JE, et al. Metab. 2000;49:

1239-1242.

AACE Hypogonadism Task Force

Endocrine Pract. 2002;8:439-456

Low T and General Practice (HIM Study )

Prevalence Odds Ratio

Obesity 52.4% 2.38

Diabetes 50% 2.09

Hypertension 42.4% 1.84

Hyperlipidaemia 40.4% 1.47

Osteoporosis 44.4% 1.41

Prostatic disease

41.3% 1.29

Mulligan et al. Int J Clin Pract. 2006 n =2162 men > 45 years

Hazard-Ratio for Mortality 10-Years follow-up Study

High T (Median 507 ng/dL) vs low T (Median 171 ng/dL)

Laughlin et al. JCEM 2007

Testosterone as a Predictor of

Mortality, CVD death, and Cancer

Death

The Massachusetts Male Ageing Study

Araujo AB, et al: Total Testosterone as a Predictor of Mortality in Men.

The Endocrine Society 2005 Annual Meeting, San Diego, CA, June 4-7.

Testosterone as a Predictor of

Mortality, CVD death, and Cancer

Death

• 3,518 men were followed for 17 years

– Age adjusted HR’s* for men with Total T< 200 ng/dL

vs. men with Total T of 410-509 ng/dL

• 1.93 or two fold for all Mortalities (p=.03)

• 3.30 or three fold for Cancer Death (p=.03)

• 1.93 or two fold for CVD death (p=.28)

* Hazard Ratio Araujo AB, et al: Total Testosterone as a Predictor of Mortality in Men.

The Endocrine Society 2005 Annual Meeting, San Diego, CA, June 4-7.

Copyright ©2008 The Endocrine Society

Laughlin, G. A. et al. J Clin Endocrinol Metab 2008;93:68-75

. All-cause mortality according to deciles of total testosterone adjusting for age, BMI, waist to hip ratio, current smoking, alcohol use, and exercise

General life expectancy and testosterone levels

Shores et al. Arch Int Med 2006; 166: 1660

Cu

mu

lati

ve

Su

rviv

al

≥ 8,7 nmol/l (n=452) < 8,7 nmol/l (n=160)

858 Men (Age ≥ 40 Years; ø 60 Y.)

Total testosterone at 2 assessments

0,5

0,6

0,7

0,9

1,0

0,8

0 2 4 6 8 10

Years

S w e d e n S w e d e n

M a lm oM a lm o

U .K .U .K .

M a n c h e s te rM a n c h e s te r

B e lg iu mB e lg iu m

L e u v e nL e u v e n

S p a inS p a in

S a n t ia g oS a n t ia g o

E s to n ia E s to n ia

T a r tuT a r tu

P o la n d P o la n d

L o d zL o d z

H u n g a r y H u n g a r y

S z e g e dS z e g e d

I ta ly I ta ly

F lo r e n c eF lo r e n c e

EE u ro p e a nu ro p e a n MM a lea le AA g e in gg e in g SS tu d ytu d y

F ra n c eF ra n c e

G e rm a n yG e rm a n y

R u s s iaR u s s ia

Waist circumference and testosterone levels

Svartberg et al. Eur J Epidemiol 2004; 19: 657-663 (Tromsø-Study)

Limit of lower normal

0

4

8

12

16

20

24

p < 0,001

<94 94 - 101,9 ≥102

Waist circumference (cm)

To

tal

testo

ste

ron

e (

nm

ol/

l)

n=666 n=536 n=346

14,7

12,7

11,0

1.584 men (Age 25-84 years)

TESTOSTERONE DEFICIENCY

&

ADIPOSE TISSUE

TESTOSTERONE OBESITY

(-)

(-)

ADIPOSE TISSUE & TESTOSTERONE

Caprio et al, TEM, 2001

TDS & OBESITY

ADIPOSE

TISSUE

TESTOSTERONE

LIPOPROTEINE LIPASE

ACTIVITY

UPTAKE

TRIGLICERIDES

ADIPOCYTES

The hypogonadal-obesity cycle (Cohen PG, 1999)

INS

UL

INE

RE

SIS

TA

NC

E

LEPTIN

The Metabolic Syndrome

Obesity Diabetes Hypertension Dyslipidemia

The deadly 4

Metabolic Syndrome Number of risk factors

Muller M et al, JCEM 2005

Corona , Eur Urol 2009

Metabolic Syndrome

• There is a strong association between

low levels of testosterone ( TDS ) and

– the different components of the metabolic

syndrome

– with the metabolic syndrome both in cross-

sectional and prospective studies.

• Men with metabolic syndrome have an

increased risk of developing

hypogonadism

Change life style + further

interventions

Endothelial dysfunction

DM Type 2

A pathway to endothelial dysfunction

and vascular morbidity

Lifestyle lack of physical activity

overnutrition smoking stress

MetS

TDS

Change life style

Substitution

Cardiovascular Events

Myocardial infarction

Stroke

THE CONVENTIONAL VIEWS PROTECT US

FROM THE PAINFUL JOB OF THINKING

J. K. GALBRAITH Nobel Prize in Economics

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