This presentation discuss the relationship of metabolic syndrome and erectile dysfunction

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. What is Metabolic Syndrome
?

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. 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. 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. 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. Prevalence of Metabolic
Syndrome

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. 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. 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. 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. Prevalence of Metabolic
Syndrome in the Middle
East

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. 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. Prevalence of Obesity
Source : International Diabetes Federation

16. Prevalence of Diabetes
Source : International Diabetes Federation

17. Prevalence of Diabetes
IDF estimates for 2006
6 of the top 10 countries

18. Prevalence of Diabetes
IDF estimates for 2012
4 of the top 10 countries
6
7
8
9

19. The top 10 countries for people
with diabetes (20-79 years)
Source IDF 2012

20. The Association of
Metabolic Syndrome and
Erectile Dysfunction

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. (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. 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. 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. 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. 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. 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. Metabolic Syndrome
Impairs Female Sexual
Dysfunction

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. 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. 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. 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. The Pathogenesis of ED in
Metabolic Syndrome

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. 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. 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. 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. Metabolic Syndrome and
Hypogonadism

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Response to PDE5
Inhibitors in ED Patients
with Metabolic Syndrome

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. 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. 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. 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. 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. 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. 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. 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. (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. (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. 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. 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. Conclusions

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. 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.