2ND BIENNIAL MEETING OF THE
MIDDLE EAST SOCIETY FOR SEXUAL
MEDICINE

Metabolic Syndrome in
the Middle East
Tarek Anis, M.D...
What is Metabolic Syndrome
?
What is Metabolic Syndrome ?
The metabolic syndrome refers to a clustering
of various medical conditions, with a number
of...
Evolution of the Metabolic
Syndrome
The Adult Treatment Panel of
the National Cholesterol
Education Program.
World Health
...
Diagnostic Criteria for
Metabolic Syndrome in Men
WHO 1999

World Health Organization

NCEP–ATP III
2001

IDF 2005

The In...
Risks and Associated
Conditions
Cardiovascular disease
Type 2 diabetes mellitus
Non alcoholic fatty liver disease
Polycyst...
Prevalence of Metabolic
Syndrome
Global Prevalence of Metabolic
Syndrome
The age-adjusted prevalence in US and Europe is ≈ 26%
The prevalence is ≈ 20% in A...
Age-Specific Prevalence of the
Metabolic Syndrome

Prevalence %

Prevalence of the Metabolic Syndrome Among 8814 US
Adults...
Prevalence of Metabolic is
Increasing
Two factors appear to account for the global
increase:

Obesity increase
The prevale...
Prevalence of Metabolic Syndrome in the
United States, 1999 to 2010

Beltrá
n-Sá
nchez, et al 2013: Prevalence and Trends ...
Prevalence of Metabolic
Syndrome in the Middle
East
Prevalence of Metabolic
Syndrome in the Middle East
Turkey

33.
higher prevalence in women
9% (39.6%) than in men (28%)

2...
Prevalence of Metabolic
Sydrome in the Middle East
Prevalence is higher than the western countries.
Prevalence is increasi...
Prevalence of Obesity

Source : International Diabetes Federation
Prevalence of Diabetes

Source : International Diabetes Federation
Prevalence of Diabetes
IDF estimates for 2006
6 of the top 10 countries
Prevalence of Diabetes
IDF estimates for 2012
4 of the top 10 countries

6

7

8

9
The top 10 countries for people
with diabetes (20-79 years)

Source IDF 2012
The Association of
Metabolic Syndrome and
Erectile Dysfunction
High prevalence of Erectile
Dysfunction in Men with the Metabolic
Syndrome

26.7%

Men with
Metabolic syndrome

13%

Contr...
(IIEF <21)

prevalence of ED

The Prevalence of ED increases as
the Severity of MetS Increases

Esposito K, Giugliano F, M...
Men with Metabolic Syndrome
Have Reduced IIEF-EF Score

IIEF-EF Score

268 patients, 89 (33%) with metabolic syndrome

Dem...
The relationship between
Metabolic Syndrome and severity
of ED

Incidence of ED

393 urological patients, 39.9% met MetS c...
Prevalence of
metabolic syndrome

Prevalence of Metabolic
Syndrome in Men with Organic
ED

Bansal TC, Guay AT, Jacobson J,...
Prevalence of
metabolic syndrome

The Relationship between Severity of
ED and the Prevalence of Metabolic
Syndrome

Sexual...
The Relationship between Severity of ED
and the Prevalence of MetS in men with
low Testosterone

García-Cruz E, Leibar-Tam...
Metabolic Syndrome
Impairs Female Sexual
Dysfunction
Sexual Dysfunction among
Postmenopausal Women
Percentage of women with sexual dysfunction (FSFI score <23)

103 women with...
Prevalence of pathological scores

Female Sexual Function Index
Domains

Martelli et. al., Prevalence of sexual dysfunctio...
Women with Metabolic
Syndrome Have Reduced FSFI
Score

FSFI score

120 women with metabolic syndrome and 80
matched contro...
Female Sexual Function Index

FSFI Decrease with increase of
Metabolic Syndrome Severity

Esposito K, Ciotola M, Marfella ...
The Pathogenesis of ED in
Metabolic Syndrome
The Pathogenesis of ED in
Metabolic Syndrome
Food intake ↑

Gene

Activity ↓

Visceral obesity

↓ Androgen

Insulin resist...
Men with Metabolic Syndrome
Have Impaired Endothelial
Function
Endothelial function score

blood pressure and platelet agg...
Men with Metabolic Syndrome
Have Impaired Endothelial
Function
Endothelium-dependent vasodilation

Endothelium-dependent
v...
Men with Metabolic Syndrome
Have Impaired Endothelial
Function
Endothelium-dependent vasodilation
Change of forearm blood ...
Metabolic Syndrome and
Hypogonadism
Testosterone and Metabolic
Syndrome
A systematic review
was performed
including all
prospective and crosssectional studies...
Incidence of Hypogonadism
in Metabolic Syndrome
Patients
1,134 men
with sexual
dysfunction

Metabolic syndrome

No metabol...
803 patients
with sexual
dysfunction

mean and 95% confidence interval

Total Testosterone (nM)

Relationship Between Tota...
Number of Metabolic syndrome
Components

Relative Risk for Hypogonadism
According to the Number of MetS
Components
1
2
3
4...
Odds ratio for hypogonadism in
metabolic syndrome patients
Elevated BP

♦
♦
♦

Elevated Fasting Glucose
Elevated Waist cir...
Metabolic Syndrome and
Hypogonadism

Adopted from Jones T. 2007 : Testosterone Associations with Erectile Dysfunction, Dia...
Androgens Maintain Penile Tissues
Structure and Function
Androgens maintain vascular endothelial structure and
function
An...
Testosterone Restores PDE5 Inhibitors
Responsiveness in Hypogonadal Patients
with Erectile Dysfunction
Authors

No. of
sub...
Obesity: New Aspects

For a long time adipose tissue was considered to
be an inactive reserve depot of fat.
It is now reco...
Adipocytokine
Adipocytokine is a general
term for a bioactive product
produced by adipose tissue.
They include
- Inflammat...
Adipocytokine
They include inflammatory mediators (IL-6, IL-8),
angiogenic proteins (VEGF), and metabolic regulators
(adip...
Adipocytokines
The production by the liver of C reactive
protein is triggered by various proinflammatory cytokines derived...
Sex Differences in Fat
Distribution
Adult men and women differ in their fat distribution

Breast
Hips
Thighs

abdominal
re...
Sex Differences in Fat
Distribution
Since regional localization of body fat is
considered to be a secondary sex characteri...
Sex Differences in Fat
Distribution
The ovarian production of estrogens and
progesterone at puberty induces an increase in...
The paradoxical relationships of
testosterone and fat distribution in
adulthood and aging
Adult onset hypogonadism in men ...
Hormonal Fat Regulation
lipoprotein
lipase

Lipase
β-adrenergic
receptors

α2-adrenergic
receptors

Catecholamines
Testost...
Androgen and Metabolic
Control
Androgen deprivation treatment of men with prostate
cancer increases fat mass, reduces insu...
Hormonal Fat Regulation
The activity of lipoprotein lipase, the enzyme responsible for the
accumulation of triglycerides i...
Stress and Obesity
The pattern of fat distribution in the metabolic syndrome
shows similarities with the clinical manifest...
12 weeks
Control Diet

long-acting
GnRH analog

High Fat Diet
(0.5% cholesterol + 4% peanut oil)

High Fat Diet + T
(pharm...
Testosterone Ameliorates Metabolic
Profile in an Animal Model of Metabolic
Syndrome
HFD rabbits showed all the features of...
Testosterone Ameliorates Erectile
Responsiveness to PDE5 Inhibitors in an
Animal Model of Metabolic Syndrome
HFD also indu...
EFS-induced CC
Relaxation (%)

Testosterone Ameliorates Erectile
Responsiveness to PDE5 Inhibitors in an
Animal Model of M...
Response to PDE5
Inhibitors in ED Patients
with Metabolic Syndrome
Response to sildenafil in ED
Patients with Metabolic Syndrome
Suetomi et al, evaluated the response to sildenafil
in ED pa...
Response to sildenafil in
Metabolic Syndrome Patients

Metabolic syndrome1

Other ED patients2

1. Suetomi et al., 2008. N...
Response rate

Response rate of sildenafil
according to MetS components

*
*
MetS component

Suetomi et al., 2008. Negativ...
IIEF-EF score

IIEF Score Before and After
Sildenafil Treatment

Suetomi et al., 2008. Negative impact of metabolic syndro...
Response rate to 50 mg

Response Rate of Sildenafil

IDF for Japanese men
Suetomi T, Kawai K, Hinotsu S, Joraku A, Oikawa ...
The Odds Ratios for Sildenafil
Non-response
◆

Age > 60

◆

Severe ED

◆

Pelvic surgery

3.3

◆

Metabolic syndrome
0.1

...
Vardenafil for the Treatment of ED
in Men with Metabolic Syndrome
A 12 weeks double-blind, randomized, placebocontrolled s...
IIEF-EF scores

Vardenafil for the Treatment of
ED in Men with Metabolic
Syndrome

n=75

n=70

Schneider et al. Efficacy a...
(successful penetration)

SEP2

Vardenafil for the Treatment of ED in
Men with Metabolic Syndrome

Schneider et al. Effica...
(successful Intercourae)

SEP3

Vardenafil for the Treatment of ED in
Men with Metabolic Syndrome

Schneider et al. Effica...
Management of metabolic
syndrome
Management is aimed primarily at reducing longer-term
risk of cardiovascular diseases and...
Onset of effects of testosterone and
time span until maximum effects
Sexual interest and desire
Sexual thoughts and fantas...
Conclusions
Conclusions
About 25% of men world wide have metabolic
syndrome. The prevalence is higher in the Middle
East
Metabolic syn...
Conclusions
Men with erectile dysfunction should be thoroughly
investigated for metabolic syndrome components
Early detect...
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Metabolic syndrome and erectile dysfunction

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  • Hanefeld and Leonhardt in 1981 were the first to coin the term “Metabolic Syndrome”
    Since that report was published in the German language and behind the “iron curtain” it remained unnoticed by many scientists and clinicians until later
  • WHO Criteria #1 plus 2 of the other 4
    NCEP ≥ 3 of 5 criteria
    Criteria #2 plus 2 of the other 4
    The definitions of MetS have provided clear criteria by which subjects can be evaluated by physicians, however, not all clinical studies have used the same definition, making comparisons among such studies difficult
    Diabetes FBS &gt; 126, hypertension Sys BP &gt; 140/90
  • Age-Specific Prevalence of the Metabolic Syndrome Among 8814 US Adults Aged at Least 20 Years, by Sex, National Health and Nutrition Examination Survey III, 1988-1994
    6.7% among participants aged 20 through 29 years to 43.5% and 42.0% for participants aged 60
    through 69 years and aged at least 70 years
  • 100 Men with metabolic syndrome were recruited among those attending the outpatient department for metabolic diseases of the teaching hospital in Italy
    Men with the metabolic syndrome were matched with men of the control group for age and BMI.
  • Erectile dysfunction prevalence (IIEF &lt;21) increased as the number of components of the metabolic
    syndrome increased
  • A total of 268 patients were included in this study. 89 patients (33%) constituted the metabolic syndrome by NCEP chriteria
  • 393 male patients aged 40 to 70 years, who were admitted to
    the urology clinics of four different institutions. Of the 393 patients, 157 (39.9%) had MS
  • Bansal et al determined the incidence of metabolic syndrome in 154 men with organic ED
    Metabolic syndrome was present in 43% of ED population as opposed to 24% in a matched patient
    population
  • Sexual Health Inventory for Men
  • Sexual function was assessed using the Female Sexual Function Index (FSFI), a recognized 19-item questionnaire. The maximum score for this scale is 36. Sexual function was considered good if the score was 30 or above, intermediate if between 23 and 29, and poor if below 23.
  • Female Sexual Function Index is a validated 19-item self-report measure of female sexual function. The 19 items are assigned to six separate domains of female sexual function. Four domains are related to the four major categories of sexual dysfunction: desire disorder, arousal disorder, orgasmic disorder, and sexual pain disorder. The fifth domain assesses the quality of vaginal lubrication, whether the sixth domain is related to global sexual and relationship satisfaction: it is viewed as the &apos;quality of life&apos; domain of the scale. Each domain is scored on a scale of zero or 1-6, with higher score indicating better function. The full FSFI scale score, which could be 36 at the highest, was obtained by adding the six domain scores. We considered the functional results to be good when the FSFI score was 30 or more, intermediate between 23 and 29, and poor below 23.
  • A total of 268 patients were included in this study. 89 patients (33%) constituted the metabolic syndrome by NCEP chriteria
  • 100 Men with metabolic syndrome 50 controls
    Men with the metabolic syndrome were matched with men of the control group for age and BMI.
    Endothelial function was assessed with the L-arginine test, a score in which the blood pressure and platelet aggregation responses to L-Arginine (3 g i.v.) were summed. This gives a score ranging from 0 points, indicating maximal impairment of endothelial function, to 10 points, indicating normal function of the endothelium
  • 100 Men with metabolic syndrome 50 controls
    Men with the metabolic syndrome were matched with men of the control group for age and BMI.
    Endothelial function was assessed with the L-arginine test, a score in which the blood pressure and platelet aggregation responses to L-Arginine (3 g i.v.) were summed. This gives a score ranging from 0 points, indicating maximal impairment of endothelial function, to 10 points, indicating normal function of the endothelium
  • 100 Men with metabolic syndrome 50 controls
    Men with the metabolic syndrome were matched with men of the control group for age and BMI.
    Endothelial function was assessed with the L-arginine test, a score in which the blood pressure and platelet aggregation responses to L-Arginine (3 g i.v.) were summed. This gives a score ranging from 0 points, indicating maximal impairment of endothelial function, to 10 points, indicating normal function of the endothelium
  • A consecutive series of 1,134 (mean age 52.1 13 years) male patients with sexual dysfunction was
    studied
    Incidence of metabolic syndrome 29%
    total testosterone &lt; 10.4 nmol/L,
  • Corona et al studied 803 patients with sexual dysfunction. 236 patients (29.4%) diagnosed as having a MS by NCEP
    Relationship between total testosterone (TT) and the number of MS components
  • Corona et al studied 803 patients with sexual dysfunction. 236 patients (29.4%) diagnosed as having a MS by NCEP
    Relative risk for hypogonadism (TT &lt; 8 nM) accordingly with the number of MS components
  • Corona et al studied 803 patients with sexual dysfunction. 236 patients (29.4%) diagnosed as having a MS by NCEP. Odds ratio (95% CI) for hypogonadism (TT &lt; 8 nM) as detected by logistic regression analysis, considering MS components as putative predictors
  • Increasing abdominal obesity leads to increased activity of the enzyme aromatase, present in adipose tissue, which converts testosterone to oestrogen. The resulting low testosterone level increases lipoprotein lipase enzyme activity and triglyceride uptake leading to increased obesity and insulin resistance. This in turn causes further androgen deficiency and visceral fat deposition. Estradiol inhibits gonadotrophin release from the pituitary. Furthermore, testosterone levels are also lowered as a result of leptin resistance at the hypothalamic-pituitary level and the inhibitory effect of leptin on the testicular axis. Pro-inflammatory adipocytokines such as tumor necrosis a (TNF-a) and interleukin 6 (IL-6) could also potentially inhibit the pituitary axis resulting in low testosterone levels. Increased cortisol secretion affecting T production via the hypothalamic pituitary access
  • Vascular endothelial growth factor (VEGF)
  • Vascular endothelial growth factor (VEGF)
  • Male New Zealand White rabbits. After 1 week of standard rabbit diet, animals were randomly assigned to control or treatment group. The control group continued to receive a standard diet (control) while the treatment group was fed HFD, constituted by 0.5% cholesterol and 4% peanut oil (HFD rabbit) for 12 weeks. A first subset of HFD rabbits was supplemented with a pharmacological dose of T (30 mg/kg weekly i.m.) A second subset of control rabbits was treated for the last 8 weeks with the long-acting GnRH analog, in order to induce a hypogonadotropic hypogonadism
  • only 50 mg available in Japan
    Questions 3 (Q3, ability to achieve an erection) and 4 (Q4, ability to maintain an erection) of IIEF
  • 50 mg dose
    8 doses
    asian IDF
    Q3 and Q4 of IIEF score ≥4
  • a logistic regression analysis considering independent risk factors for nonresponse to sildenafil. The adjusted odds ratio for the risk was 7.47 for severe ED, 8.83 for presence of history of pelvic surgery, and 3.30 for presence of MS. Interestingly, this study showed that MS was a more significant risk factor than age
  • Metabolic syndrome and erectile dysfunction

    1. 1. 2ND BIENNIAL MEETING OF THE MIDDLE EAST SOCIETY FOR SEXUAL MEDICINE Metabolic Syndrome in the Middle East Tarek Anis, M.D. Prof. of Andrology, Cairo University
    2. 2. What is Metabolic Syndrome ?
    3. 3. What is Metabolic Syndrome ? The metabolic syndrome refers to a clustering of various medical conditions, with a number of pathological components, that contribute to the development of cardiovascular diseases and diabetes. These pathological components include blood glucose abnormality, dyslipidemia, visceral fat accumulation and elevated blood pressure
    4. 4. Evolution of the Metabolic Syndrome The Adult Treatment Panel of the National Cholesterol Education Program. World Health (NCEP ATPIII) Organisation (WHO) The International Diabetes Federation (IDF) 3 1 1998 1999 2000 2 The European Group for the Study of Insulin Resistance (EGIR) 2001 5 2002 2003 2004 4 The American Association of Clinical Endocrinologists (AACE) 2005 6 The American Heart Association (AHA/NHLBI) Hanefeld and Leonhardt in 1981 were the first to use the term “Metabolic Syndrome”
    5. 5. Diagnostic Criteria for Metabolic Syndrome in Men WHO 1999 World Health Organization NCEP–ATP III 2001 IDF 2005 The International Diabetes Federation The National Cholesterol Education Program Glucose abnormality Obesity FBS ≥ 110 mg/dL Type 2 DM 0.90 Waist/Hip ratio > WC ≥ 102 cm WC ≥ 94 cm BMI ≥ 30 kg/m2 Type 2 DM FBS > 100 mg/dL Central obesity (ethnic specific values)* Europids ≥94cm - Asians >90cm ≥ 150 mg/dL ≥ 150 mg/dL < 35 mg/dL < 40 mg/dL < 35 mg/dL BP ≥ 140/90 mmHg BP ≥ 130/85 mmHg Systolic BP ≥ 130 mmHg ↑ Triglyceride ↓ HDL Cholesterol ↑ Blood Pressure FBS > 110 mg/dL ↑ insulin or IR Type 2 DM or HTN on Rx or HTN on Rx If BMI is >30 kg/m², central obesity can be assumed and waist circumference does not ≥ 150 mg/dL or on specific treatment Diastolic BP ≥ 85 mmHg or HTN to be need on Rx measured Traish AM, Guay A, Feeley R, Saad F. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl 2009 Jan-Feb; 30 (1): 10-22.
    6. 6. Risks and Associated Conditions Cardiovascular disease Type 2 diabetes mellitus Non alcoholic fatty liver disease Polycystic ovarian syndrome Obstructive sleep apnea Hypogonadism and erectile dysfunction Grundy S. 2008 : Metabolic Syndrome Pandemic. Arterioscler. Thromb. Vasc. Biol 28;629-636
    7. 7. Prevalence of Metabolic Syndrome
    8. 8. Global Prevalence of Metabolic Syndrome The age-adjusted prevalence in US and Europe is ≈ 26% The prevalence is ≈ 20% in Africa and Asia The prevalence of the syndrome is strongly related to age. At the age of 20 years ≈ 7% and at the age of 60 ≈ 40% Men and women are affected about equally The prevalence is increasing 1- Grundy et al. 2008 : Metabolic Syndrome Pandemic. Arterioscler. Thromb. Vasc. Biol. 28;629-636 2- Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among U.S. Adults. Diabetes Care. 2004;27:2444 –2449. 3- Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Sabico SLB, et al. (2010) Decreasing Prevalence of the Full Metabolic Syndrome but a Persistently High Prevalence of Dyslipidemia among Adult Arabs. PLoS ONE 5(8): e12159. doi:10.1371/journal.pone.0012159
    9. 9. Age-Specific Prevalence of the Metabolic Syndrome Prevalence % Prevalence of the Metabolic Syndrome Among 8814 US Adults Ford et al, 2002 : Prevalence of the Metabolic Syndrome Among US Adults. Findings From the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:356-359
    10. 10. Prevalence of Metabolic is Increasing Two factors appear to account for the global increase: Obesity increase The prevalence of obesity in the US increased from 22.5% to 32% between 1994 and 2007. Ageing of the population The prevalence of the MetS increases with age increase. This effect can be explained largely by agerelated rises of blood pressure and blood glucose Grundy S. 2008 : Metabolic Syndrome Pandemic. Arterioscler. Thromb. Vasc. Biol 28;629-636
    11. 11. Prevalence of Metabolic Syndrome in the United States, 1999 to 2010 Beltrá n-Sá nchez, et al 2013: Prevalence and Trends of Metabolic Syndrome in the Adult U.S. Population, 1999– 2010, J Am Coll Cardiol. 62(8):697-703
    12. 12. Prevalence of Metabolic Syndrome in the Middle East
    13. 13. Prevalence of Metabolic Syndrome in the Middle East Turkey 33. higher prevalence in women 9% (39.6%) than in men (28%) 2108 men and 2151 women Tunisia 45. higher prevalence in women 5% than in men 1244 men and 2191 women 39. higher prevalence in women 3% (42%) than in men (37.2%) 17,293 (30–70 years) Jordan 36. higher prevalence in women 3% (40.9%) than in men (28.7%) 1121 northern Jordanians U.A.E 40. 5% 4097 men and women Kozan et al, 2007 2007 Bouguerra et al, Saudi Arabia 2005 Al-Nozha et al, Khader et al, 2007 Malik & Razig , 2008 46. Qatar Sliem HA, Ahmed S, Nemr N, El-Sherif I. : Metabolic syndrome in the Middle East., Indian136 adultsMetab. J Endocrinol Ismael, 2012 3% males (42.4%) 2012 Jan;16(1):67-71 higher in females (50%) than in
    14. 14. Prevalence of Metabolic Sydrome in the Middle East Prevalence is higher than the western countries. Prevalence is increasing. Female prevalence is higher than the male prevalence Physical and cultural barriers to physical activity Climatic conditions of extreme heat in the summer Limited exercise facilities devoted solely for women Lack of physical education or an emphasis on its importance in schools Absence of women's participation in organised sports Sliem HA, Ahmed S, Nemr N, El-Sherif I. : Metabolic syndrome in the Middle East., Indian J Endocrinol Metab. 2012 Jan;16(1):67-71
    15. 15. Prevalence of Obesity Source : International Diabetes Federation
    16. 16. Prevalence of Diabetes Source : International Diabetes Federation
    17. 17. Prevalence of Diabetes IDF estimates for 2006 6 of the top 10 countries
    18. 18. Prevalence of Diabetes IDF estimates for 2012 4 of the top 10 countries 6 7 8 9
    19. 19. The top 10 countries for people with diabetes (20-79 years) Source IDF 2012
    20. 20. The Association of Metabolic Syndrome and Erectile Dysfunction
    21. 21. High prevalence of Erectile Dysfunction in Men with the Metabolic Syndrome 26.7% Men with Metabolic syndrome 13% Control Group matched for age and BMI Esposito K, Giugliano F, Martedi E, Feola G, Marfella R, D’Armiento M, Giugliano D. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005;28:1201–3
    22. 22. (IIEF <21) prevalence of ED The Prevalence of ED increases as the Severity of MetS Increases Esposito K, Giugliano F, Martedi E, Feola G, Marfella R, D’Armiento M, Giugliano D. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005;28:1201–3
    23. 23. Men with Metabolic Syndrome Have Reduced IIEF-EF Score IIEF-EF Score 268 patients, 89 (33%) with metabolic syndrome Demir T. Prevalence of erectile dysfunction in patients with metabolic syndrome. Int J Urol 2006; 13:385–8.
    24. 24. The relationship between Metabolic Syndrome and severity of ED Incidence of ED 393 urological patients, 39.9% met MetS criteria Bal et al 2007. Prevalence of Metabolic Syndrome and Its Association with Erectile Dysfunction Among Urologic Patients: Metabolic Backgrounds of Erectile Dysfunction. Urology , Volume 69 , Issue 2 , Pages 356 - 360
    25. 25. Prevalence of metabolic syndrome Prevalence of Metabolic Syndrome in Men with Organic ED Bansal TC, Guay AT, Jacobson J, Woods BO, Nesto RW. Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. J Sex Med. 2005; 2: 96-103
    26. 26. Prevalence of metabolic syndrome The Relationship between Severity of ED and the Prevalence of Metabolic Syndrome Sexual Health Inventory for Men Bansal TC, Guay AT, Jacobson J, Woods BO, Nesto RW. Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. J Sex Med. 2005; 2: 96-103
    27. 27. The Relationship between Severity of ED and the Prevalence of MetS in men with low Testosterone García-Cruz E, Leibar-Tamayo A, Romero J, Piqueras M, Luque P, Cardeñ osa O, and Alcaraz A. Metabolic syndrome in men with low testosterone levels: Relationship with cardiovascular risk factors and comorbidities and with erectile dysfunction. J Sex Med 2013;10:2529–2538
    28. 28. Metabolic Syndrome Impairs Female Sexual Dysfunction
    29. 29. Sexual Dysfunction among Postmenopausal Women Percentage of women with sexual dysfunction (FSFI score <23) 103 women with the metabolic syndrome 105 matched control women Martelli V, Valisella S, Moscatiello S, Matteucci C, Lantadilla C, Costantino A, Pelusi G, Marchesini G, and Meriggiola MC. Prevalence of sexual dysfunction among postmenopausal women with and without metabolic syndrome. J Sex Med 2012;9:434–441.
    30. 30. Prevalence of pathological scores Female Sexual Function Index Domains Martelli et. al., Prevalence of sexual dysfunction among postmenopausal women with and without metabolic syndrome J Sex Med 2012;9:434–441.
    31. 31. Women with Metabolic Syndrome Have Reduced FSFI Score FSFI score 120 women with metabolic syndrome and 80 matched control Esposito K, Ciotola M, Marfella R, Di Tommaso D, Cobellis L, Giugliano D. The metabolic syndrome: a cause of sexual dysfunction in women. Int J Impot Res 2005 May-Jun; 17 (3): 224-6.
    32. 32. Female Sexual Function Index FSFI Decrease with increase of Metabolic Syndrome Severity Esposito K, Ciotola M, Marfella R, Di Tommaso D, Cobellis L, Giugliano D. The metabolic syndrome: a cause of sexual dysfunction in women. Int J Impot Res 2005 May-Jun; 17 (3): 224-6.
    33. 33. The Pathogenesis of ED in Metabolic Syndrome
    34. 34. The Pathogenesis of ED in Metabolic Syndrome Food intake ↑ Gene Activity ↓ Visceral obesity ↓ Androgen Insulin resistance Sodium retention ↑Sympathetic activity Oxidative Stress Aging Atherosclerosis Suetomi et al. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450
    35. 35. Men with Metabolic Syndrome Have Impaired Endothelial Function Endothelial function score blood pressure and platelet aggregation responses to L-Arginine (3 g i.v.) n = 100 n = 50 Esposito K, Giugliano F, Martedi E, Feola G, Marfella R, D’Armiento M, Giugliano D. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005;28:1201–3
    36. 36. Men with Metabolic Syndrome Have Impaired Endothelial Function Endothelium-dependent vasodilation Endothelium-dependent vasodilation Change of forearm blood flow in response to infusion of 50g/min of acetylcholine Lind L, Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Atherosclerosis. 2008 Feb;196(2):795-802
    37. 37. Men with Metabolic Syndrome Have Impaired Endothelial Function Endothelium-dependent vasodilation Change of forearm blood flow in response to infusion of 50g/min of acetylcholine Lind L, Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Atherosclerosis. 2008 Feb;196(2):795-802
    38. 38. Metabolic Syndrome and Hypogonadism
    39. 39. Testosterone and Metabolic Syndrome A systematic review was performed including all prospective and crosssectional studies, comparing T levels in subjects with or without MetS 13 properly performed studies were identified Corona G, Monami M, Rastrelli G, Aversa A, Tishova Y, Saad F, Lenzi A, Forti G, Mannucci E, Maggi M. Testosterone and metabolic syndrome: a meta-analysis study. J Sex Med 2011; 8 (1): 272-83
    40. 40. Incidence of Hypogonadism in Metabolic Syndrome Patients 1,134 men with sexual dysfunction Metabolic syndrome No metabolic syndrome Corona G, Mannucci E, Petrone L, Balercia G, Paggi F, Fisher AD, Lotti F, Chiarini V, Fedele D, Forti G, Maggi M. NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction. J Sex Med 2007; 4 (4 Pt 1): 1038-45.
    41. 41. 803 patients with sexual dysfunction mean and 95% confidence interval Total Testosterone (nM) Relationship Between Total Testosterone and the Number of Metabolic Syndrome Components (29.4%) diagnosed as having a MS Number of Metabolic syndrome Components Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A, Balercia G, Chiarini V, Forti G, Maggi M. Psychobiologic Correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol. 2006; 50: 595-604
    42. 42. Number of Metabolic syndrome Components Relative Risk for Hypogonadism According to the Number of MetS Components 1 2 3 4-5 ♦ ♦ 803 patients with sexual dysfunction ♦ ♦ Relative risk for hypogonadism Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A, Balercia G, Chiarini V, Forti G, Maggi M. Psychobiologic Correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol. 2006; 50: 595-604
    43. 43. Odds ratio for hypogonadism in metabolic syndrome patients Elevated BP ♦ ♦ ♦ Elevated Fasting Glucose Elevated Waist circumference Reduced HDL-C Elevated Triglycerides ♦ ♦ Odds ratio for hypogonadism Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A, Balercia G, Chiarini V, Forti G, Maggi M. Psychobiologic Correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol. 2006; 50: 595-604
    44. 44. Metabolic Syndrome and Hypogonadism Adopted from Jones T. 2007 : Testosterone Associations with Erectile Dysfunction, Diabetes, and the Metabolic Syndrome. European Urology Supplements. Volume 6, Issue 16, 847-857
    45. 45. Androgens Maintain Penile Tissues Structure and Function Androgens maintain vascular endothelial structure and function Androgens maintain tunica albuginea structural integrity and connective tissue matrix fibro-elastic properties Androgens regulate differentiation of pluripotent precursor cells into trabecular smooth muscle, and maintain smooth muscle structure and function Androgens maintain penile cavernosal and dorsal nerves structure and function Traish,AM, 2008. Androgens Play a Pivotal Role in Maintaining Penile Tissue Architecture and Erection: A Mini Review. Published-Ahead-of-Print on September 18, 2008 by Journal of Andrology
    46. 46. Testosterone Restores PDE5 Inhibitors Responsiveness in Hypogonadal Patients with Erectile Dysfunction Authors No. of subjects Hypogona dism Sildenafil response at baseline Overall efficacy Aversa et al. 20 No Failure 80% Kalinchenko et al. 120 Yes Failure 70% Shabsigh et al. 75 Yes Failure 70% Chatterjee et al. 12 Yes Not evaluated 100% Shamloul et al. 40 PADAM Failure Improve d Greenstein et al. 49 Yes Not evaluated 63% Hwang et al. 32 Yes Failure 57% Adopted from Greco EA, Spera G, Aversa A: Combining testosterone and PDE5 inhibitors in erectile dysfunction: Rosenthal et basic rationale and clinical evidences. Eur Urol. 2006 Nov;50(5):940-7 24 Yes Failure 92% al.
    47. 47. Obesity: New Aspects For a long time adipose tissue was considered to be an inactive reserve depot of fat. It is now recognized that adipose tissue is an active tissue, directly involved in the control of body weight and energy balance via the secretion of a large number of molecules with regulatory potential (adipokines)
    48. 48. Adipocytokine Adipocytokine is a general term for a bioactive product produced by adipose tissue. They include - Inflammatory mediators (IL6, IL-8) - Angiogenic proteins (VEGF) - Metabolic regulators (adiponectin; leptin) Gooren L., Obesity: new aspects. Journal of Men's Health. Volume 5, Issue 3, September 2008, Pages 249-256
    49. 49. Adipocytokine They include inflammatory mediators (IL-6, IL-8), angiogenic proteins (VEGF), and metabolic regulators (adiponectin; leptin). Not all white adipose tissue is metabolically equivalent. Visceral adipose tissue, due in part to its association with the hepatic portal venous system, appears to be a critical regulator of glucose and fat metabolism. Subcutaneous adipose tissue appears to be the principal source of leptin and adiponectin
    50. 50. Adipocytokines The production by the liver of C reactive protein is triggered by various proinflammatory cytokines derived from numerous sources, such as macrophages, monocytes, and adipose tissue. Several large population studies have indicated that biomarkers of inflammation predict an increased risk for cardiovascular diseases including ED. Gooren L., Obesity: new aspects. Journal of Men's Health. Volume 5, Issue 3, September 2008, Pages 249-256
    51. 51. Sex Differences in Fat Distribution Adult men and women differ in their fat distribution Breast Hips Thighs abdominal region (both subcutaneous and visceral) Men generally have a larger visceral fat depot than (premenopausal) women
    52. 52. Sex Differences in Fat Distribution Since regional localization of body fat is considered to be a secondary sex characteristic, it is likely that sex steroids are involved in the male and female patterns of fat deposition Until puberty, boys and girls do not differ very much in the amount of body fat and its regional distribution
    53. 53. Sex Differences in Fat Distribution The ovarian production of estrogens and progesterone at puberty induces an increase in total body fat as well as selective fat deposition in the breast and gluteo-femoral region. Adolescent boys lose subcutaneous fat but accumulate fat in the abdominal region, which in most boys is not very visible at that stage of development but is clearly demonstrable using imaging techniques. Roemmich JN, Clark PA, Mai V, Berr SS, Weltman A, Veldhuis JD, et al. Alterations in growth and body composition during puberty: III. Influence of maturation, gender, body composition, fat distribution, aerobic fitness, and energy expenditure on nocturnal growth hormone release. J Clin Endocrinol Metab 1998;83(5): 1440–7.
    54. 54. The paradoxical relationships of testosterone and fat distribution in adulthood and aging Adult onset hypogonadism in men is associated with increase of visceral fat. While androgens induce visceral fat accumulation at puberty, once fat has been stored in the visceral depot it does not need continued androgen stimulation, in contrast to the maintenance of bone and muscle mass, which are lower in men with adult onset hypogonadism than in eugonadal controls. Katznelson L, Rosenthal DI, Rosol MS, Anderson EJ, Hayden DL, Schoenfeld DA, et al. Using quantitative CT to assess adipose distribution in adultmen with acquired hypogonadism. Am J Roentgenol 1998;170(2): 423–7. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996;81(12):4358–65.
    55. 55. Hormonal Fat Regulation lipoprotein lipase Lipase β-adrenergic receptors α2-adrenergic receptors Catecholamines Testosterone Insulin estrogens/ progesterone Louis Gooren. Obesity: new aspects. Journal of Men's Health. Volume 5, Issue 3, September 2008, Pages 249-256
    56. 56. Androgen and Metabolic Control Androgen deprivation treatment of men with prostate cancer increases fat mass, reduces insulin sensitivity and impairs lipid profiles increasing cardiovascular risk or considerably worsens the metabolic control of men with diabetes mellitus Lower endogenous androgens predict central adiposity in men, and androgen level is inversely correlated with levels of blood pressure, fasting plasma glucose, triglycerides and BMI, but positively correlated with HDL Rosmond R, Wallerius S, Wanger P, Martin L, Holm G, Bjorntorp P. A 5-year follow-up study of disease incidence in men with an abnormal hormone pattern. J Intern Med 2003;254(4):386–90. Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middleaged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997;146(8):609–17.
    57. 57. Hormonal Fat Regulation The activity of lipoprotein lipase, the enzyme responsible for the accumulation of triglycerides in the fat cell, is higher in the gluteo-femoral region than in the abdominal area. Conversely, lipolysis is regulated by hormone-sensitive lipase, which is regulated by several hormones and by the sympathetic nervous system. The visceral fat depot constitutes a quickly available source of calories and energy. By its close anatomical proximity to the liver it delivers fatty acids through the portal system. The latter may have served a useful function in evolution, suiting the needs of men for quick physical action and employment in manual labor. Louis Gooren. Obesity: new aspects. Journal of Men's Health. Volume 5, Issue 3, September 2008, Pages 249-256
    58. 58. Stress and Obesity The pattern of fat distribution in the metabolic syndrome shows similarities with the clinical manifestation of increased blood cortisol Elevated glucocorticoid exposure might be a factor in the pathogenesis of obesity in general and in abdominal/visceral obesity in particular The hormonal correlates of stress (an overactivity of the hypothalamo–pituitary–adrenal-axis) being associated with a low secretion of sex steroids and growth hormone. Deficiencies of the latter two hormones are characterized by an accumulation of visceral fat. Louis Gooren. Obesity: new aspects. Journal of Men's Health. Volume 5, Issue 3, September 2008, Pages 249-256
    59. 59. 12 weeks Control Diet long-acting GnRH analog High Fat Diet (0.5% cholesterol + 4% peanut oil) High Fat Diet + T (pharmacological dose) Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, Mannucci E, Maggi M. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med 2009; 6 (12): 3274-88.
    60. 60. Testosterone Ameliorates Metabolic Profile in an Animal Model of Metabolic Syndrome HFD rabbits showed all the features of MetS. HFD induced hypogonadotropic hypogonadism is characterized by a reduction of plasma T, FSH, LH levels, testis and and seminal vesicles weight. Such changes were similar to that induced by GnRH analog administration. Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, Mannucci E, Maggi M. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med 2009; 6 (12): 3274-88.
    61. 61. Testosterone Ameliorates Erectile Responsiveness to PDE5 Inhibitors in an Animal Model of Metabolic Syndrome HFD also induced penile alterations, - Reduction of cavernosal smooth muscle relaxation induced by electrical field stimulation - Reduced response to Sildenafil. T administration prevented almost all penile alterations observed in HFD rabbits. T treatment dramatically reduced visceral obesity. Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, Mannucci E, Maggi M. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med 2009; 6 (12): 3274-88.
    62. 62. EFS-induced CC Relaxation (%) Testosterone Ameliorates Erectile Responsiveness to PDE5 Inhibitors in an Animal Model of Metabolic Syndrome Sildenafil (nM) Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, Mannucci E, Maggi M. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med 2009; 6 (12): 3274-88.
    63. 63. Response to PDE5 Inhibitors in ED Patients with Metabolic Syndrome
    64. 64. Response to sildenafil in ED Patients with Metabolic Syndrome Suetomi et al, evaluated the response to sildenafil in ED patients with metabolic syndrome The study included 133 ED patients 25 patients met the criteria for MetS using the IDF criteria for Japanese men (cut-point for WC = 90 cm) Patients received 50 mg sildenafil on demand Response was evaluated after usage of 8 doses or more, using IIEF score Suetomi et al, 2008. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450
    65. 65. Response to sildenafil in Metabolic Syndrome Patients Metabolic syndrome1 Other ED patients2 1. Suetomi et al., 2008. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450 2. Kobayashi et al. 2006. Outcome analysis of sildenafil citrate for erectile dysfunction of Japanese patients. Int J Impot Res 2006;18:302–5
    66. 66. Response rate Response rate of sildenafil according to MetS components * * MetS component Suetomi et al., 2008. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450
    67. 67. IIEF-EF score IIEF Score Before and After Sildenafil Treatment Suetomi et al., 2008. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450
    68. 68. Response rate to 50 mg Response Rate of Sildenafil IDF for Japanese men Suetomi T, Kawai K, Hinotsu S, Joraku A, Oikawa T, Sekido N, Miyanaga N, Shimazui T, and Akaza H. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450
    69. 69. The Odds Ratios for Sildenafil Non-response ◆ Age > 60 ◆ Severe ED ◆ Pelvic surgery 3.3 ◆ Metabolic syndrome 0.1 1 10 100 The Odds Ratios for Sildenafil Non-response Suetomi et al., 2008. Negative impact of metabolic syndrome on the responsiveness to sildenafil in Japanese men. J Sex Med 2008;5:1443–1450
    70. 70. Vardenafil for the Treatment of ED in Men with Metabolic Syndrome A 12 weeks double-blind, randomized, placebocontrolled study including 145 men with ED and metabolic syndrome. Two groups (Vardenafil N=75; placebo, N=70). Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks, depending on efficacy and tolerability. Schneider et al. Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial. J Sex Med DOI: 10.1111/j.1743-6109.2011.02383.x
    71. 71. IIEF-EF scores Vardenafil for the Treatment of ED in Men with Metabolic Syndrome n=75 n=70 Schneider et al. Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial. J Sex Med DOI: 10.1111/j.1743-6109.2011.02383.x
    72. 72. (successful penetration) SEP2 Vardenafil for the Treatment of ED in Men with Metabolic Syndrome Schneider et al. Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial. J Sex Med DOI: 10.1111/j.1743-6109.2011.02383.x
    73. 73. (successful Intercourae) SEP3 Vardenafil for the Treatment of ED in Men with Metabolic Syndrome Schneider et al. Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial. J Sex Med DOI: 10.1111/j.1743-6109.2011.02383.x
    74. 74. Management of metabolic syndrome Management is aimed primarily at reducing longer-term risk of cardiovascular diseases and diabetes. Current guidelines recommend initial focus on intensive therapeutic lifestyle interventions (such as increased physical activity, dietary modification and modest weight reduction) that address many of the metabolic risk factors including insulin resistance. Cardiovascular risk should also be assessed to guide clinical management of individual risk factors. If necessary, pharmacological agents should be used to achieve recommended therapeutic targets Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365: 1415-1428.
    75. 75. Onset of effects of testosterone and time span until maximum effects Sexual interest and desire Sexual thoughts and fantasy Erectile function Morning erections Satisfaction with sex life Number of erections / week Sexual activity/ejaculations Saad F et al. Eur J Endocrinol 2011;165:675-685
    76. 76. Conclusions
    77. 77. Conclusions About 25% of men world wide have metabolic syndrome. The prevalence is higher in the Middle East Metabolic syndrome impairs erectile function through impaired endothelial function and increased incidence of hypogonadism. Metabolic Syndrome has a negative impact on the efficacy of PDE5 inhibitors. Metabolic syndrome impairs all domains of female sexual function
    78. 78. Conclusions Men with erectile dysfunction should be thoroughly investigated for metabolic syndrome components Early detection of metabolic syndrome in patients with ED may be a gateway to the reduction of cardiovascular diseases and diabetes in younger men with increased risk, who present for treatment of ED alone.

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