1. the Link Between Dysfuction - Dr

7/29/2019 1. the Link Between Dysfuction - Dr

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THE LINK BETWEENERECTI LE DYSFUNCTION,

TESTOSTERONE AND METABOLICSYNDROME

PIT I II MK N, PERHIM PUNAN DOKTER UMUM INDONESIA9-11 Maret 2012, Ballroom Pullman HotelNugroho Setiawan, RSUP FATMAWATI


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Testosterone deficiencysyndrome is a proven riskfactor for all the metabolicsyndrome components

All components of metabolicsyndrome are underlying

conditions for erectiledysfunction and T deficiency

Erectiledysfunction

Abdominal obesity represents a vicious circle:abdominal fat tissue reduces testosterone andtestosterone reduces the fat tissues.

Testosteronedeficiencysyndrome

Metabolicsyndrome(abdominal fat, diabetes,obesity, hypertension,dyslipidemia....)


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Metabolic

syndrome

Erectile

dysfunction

Testosteronedeficiency


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Disfungsi Ereksi


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Disfungsi Ereksi (DE) adalahketidakmampuan seorang pria yangmenetap untuk mencapai dan / atau

mempertahankan ereksi untuk sanggama yang memuaskan

Disfungsi Ereksi


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Erection Hardness Score (EHS)

Penis islarger but

not hard

Penis is hardbut not hardenough forpenetration

Penis is hardenough forpenetration

but notcompletelyhard

Penis iscompletely

hard andfully rigid

Severe ED

IIEF 6 - 10

Moderate ED

IIEF 11 - 16

Mild ED

IIEF 17 - 25

No ED

IIEF 26 - 30

Adapted from: Goldstein I , et al. N Engl J Med . 1998;338:1397-140Mullhall J P, et al. Validation of the erection hardness score . J Sex Med. 2007 Nov;4(6):1626-3


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Age and Sexual problem


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Source: MMAS, Decision Resources, Scott-Levin PDDA

Disfungsi Ereksi merupakan

masalah kita bersama

PrevalensiTotal

Pada pria 40-70 th

48% 8% Diagnosa52%

DEDE

92%60%

Diterapi

40%

Tidak

Ya

Tidakterdiagnosa

48% Sedang

19% Berat

33% Ring an

TIDAK


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Psychological Factors Influencing Male Erectile Function

Vascular Male

ErectileFunction

Neural

EndocrineHormones

Structural


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TREATMENT OPTIONS TREATMENT OPTIONS

FIRST LINE : ORAL DRUGS(sildenafil , vardenafil , tadalafil)SEX Therapy

SECOND LINE : VACUM PUMPIntra UrethaINTRACAVERNOSUM INJECTION

THIRD LINE : Prostesis Penis


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cGMP-specific protein kinase

Endothelial

cell

Guanylatecyclase

GTP cGMP

K +

Ca 2+

Decreased Ca 2+

Smooth

musclerelaxation& erection

Nitric

oxide

Smooth muscle cell

PDE5 Inhibitors: Mechanism of Action

5'GMP

PDE5

Cavernousnerve

Sexual st imulation

PDE5 Inhibitor


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Maleable penile prosthesis


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Inflatable penile prosthesis


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New PDE-5 inhibitors

Palit, V. & Eardley, I. Nat. Rev. Urol. 2010


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New Preparation of PDE-5i

Levitra ODT (orodispersible tablet)

Sperling H, Debruyne F, Boermans A, Beneke M, Ulbrich E, Ewald S. J Sex Med. 2010


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A NEW APPROACH TO MENS

HEALTHCAREIn this Event we will introduce a new approach to menshealthcare:

Treat ED and check for T

1.Men presenting with ED often require an immediatesolution to their ED

2. However, men with ED frequently have underlyingconditions which are also linked to testosteronedeficiency

3. In these men, checking testosterone levels may uncovera treatable deficiency

4. This approach has considerable benefits for mensoverall health


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SEKS HORMON ENDOGEN YANG SANGAT PENTING PADAPRIA DAN WANITA

MERUPAKAN HORMON STEROID TERBENTUK DARIKOLESTEROL

BERSIFAT LIPOFILIK DAN MUDAH BERDIFUSI

PADA PRIA 90-95 % DIHASILKAN LEYDIG SEL

DIPRODUKSI 5-7 MG/ HARI PADA PRIA

BERPENGARUH PADA: SEKS ORGAN, TULANG, OTOT,DARAH, J ARINGAN TISSUE, OTAK, KULIT, RAMBUT DANFUNGSI MENTAL

PADA WANITA SANGAT PENTING UNTUK FUNGSI SEKSUALDAN LIBIDO, SERTA PERAN PSIKOLOGIKAL WELL BEING


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ORGAN TUJUAN TESTOSTERON DAN METABOLISMENYA


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TDS

Bone mineral density Muscle mass and strengthObesity

LibidoErectile functionHematopoiesisDepressed mood Cognitive functionGeneral well-being


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Low testosterone

is associated withatherosclerosis


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Svartberg J et al. J Int Med 259: 576-582 (2006)

Cross-Sectional:


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TDS

IN ADULT MEN

Typicaltds


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(Visceral) fat suppressestestosterone production


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Obese men have lower testosterone


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Wu FCW et al. J Clin Endocrin Metab 93(7): 2737-2745 (2008)

European Male Aging Study (EMAS)Relationship between Age, BMI, and Hormones

40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79


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Central obesity: waist circumference in Europids 94 cmAsians: > 90 cm

PLUS any 2 of the following:

raised triglycerides: 1.7 mmol/L ( 150 mg/dL)reduced HDL cholesterol < 1.03 mmol/L ( < 40 mg/dL)raised blood pressure: systolic 130 mm Hg

diastolic 85 mm Hg (or treatment)raised fasting plasma glucose: 5.6 mmol/L ( 100 mg/dL)

(or type 2 diabetes)

The Metabolic Syndrome - A New World Wide Definition: IDF Consensus Group, Berlin 2005

http://www.idf.org/webdata/docs/MetSyndrome_FINAL.pdf


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Prevalence of Metabolic Syndrome in an Urban KoreanPopulation According to Modified NCP ATPI II Criteria

19.7

25.9

34.9

45.5

0

10

20

30

40

50

%

< 40 yr 40-59 yr 50-59 yr 60 and older

Oh J-Y et al. Diabetes Care 27: 2027-2032 (2004)

19.7

25.9

34.9

45.5

0

10

20

30

40

50

%

< 40 yr 40-59 yr 50-59 yr 60 and older


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Fat distributionWAIST CIRCUMFERENCE (WC)

Lowest rib

Iliac crest

Mid axillary line


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BMI and BMI are not the same...waist circumference is more accurate189 cm, 93 kg =BMI 26 190 cm, 94 kg =BMI 26

Waist circumference Waist circumference Testosterone Testosterone

> pembunuh yg tak disadari

Penumpukan lemak di sekitar perut

Kadar lemak yg >Tekanan darah >Gula darah >

Resiko penyakit jantung koroner & DM

Penumpukan lemak di sekitar perut

Kadar lemak yg >Tekanan darah >Gula darah >

Resiko penyakit jantung koroner & DM


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Indikasi untuk Penggantian Testosteron

-TDS-Kadar testosteron pada pagi hari di bawah

normal menengah- TI DAK ADA KONTRA INDIKASI

Nieschlag and Behre, Andrology, 2000, Springer

0

5

10

15

20

25

30

35

40

Hours 8 10 12 14 16 20 24 8

Acc. to Behre et al. 1992 J CEM

n m o l

/ l


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Nugroho Setiawan


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T estosteron

Testosteron total terdiri: T terikat globulin (SHBG) 60% T terikat albumin 38% T bebas 2%

Yang dapat aktif T terikat albumin dan T bebas

Yang aktif oleh enzim dapat dirubahEstradiol (aromatase)Dehidrotestosteron (5 a reduktase)


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Testosterone physiology and aging

Free T

SHBG + T SHBG + T

Free T

aging


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Perubahan hormonal terkait usia

www.get-back-on-track.comNugroho Setiawan


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Mengembalikan kadar testosteron

ke dalam kisaran normal menengah

WHO 1992, Geneva

Target Terapi Testosteron


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Contraindicatedtestosterone treatment:

carcinoma of the prostateor male mammary gland.

Nugroho Setiawan


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40-49 50-59 60-69 70-79

%CaP

Total T

CaP Prevalence Increases as T Levels De


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Morgentaler A and Rhoden, Urology (2006)

Lower levels of total testosterone or free testosteroneare associated with an increased risk of cancer.

Risk of cancer doubled for men with TT < 250 ng/dl


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Pemeriksaan fisik

Tensi, nadi, berat badan, lingkar pinggang

Pemeriksaan colok dubur

Pertumbuhan organ seks dan tanda sekssekunder

Nugroho Setiawan


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Laboratory examination

TESTOSTERONEPSA

Optional:Hemoglobin, hematokrit

HbA1CLipid profilSHBG, estradiol, LH


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Testosterone preparations

1940

1954

1977

1992

1995

1998

20042004

2002

2004

Testosterone


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Sediaan Testosteron diIndonesia yang disetujui POMTestosterone Undecanoat capsul 40mgMesterolone tablet 25 mgTestosterone Propionat 30mg,

Testosterone Phenylpropionat 60mg,Testosterone isocaproate 60 mg,Testosterone decanoat 100mg AmpulTestosterone Undecanoat 1000 mg

ampulTestosterone gel


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Pemilihan preparat Testosteron- Sudah di setujui BPOM RI- Aman, minimal side effects , tidak toxic

tidak melalui liver / portal systemLevels within the normal range of physiological

- Comfortable ?????- Pemilihan diserahkan pada pasien dengan

menerangkan effectifitas, keamanan, carapemberian , perkiraan harga obat, resiko sideeffect, dll.

- Pemberian testosteron harus dibawah tanggung jawab dokter


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403530

25201510

5

0

6055

5045

0 2 4 6 8 10 12 14Weeks

T o t a l t e s

t o s t e r o n e n m o l

/ l

Nieschla and Behre, Androlo , 2000, S rin er

Normal range

Testosterone enanthate Testosterone undecanoate (Nebido)


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h b l d d


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Men with metabolic syndrome and testosterone deficiency receive testosterone

treatment

Improves every single factor of the metabolicsyndromeNormalisation of testosterone level about 8-9 months:

- Reduced fat mass(viseral/abdomen>> than subcutaneous / WC )

- Improves muscle mass (glucose metabolised)

Improves every single factor of the metabolicsyndromeNormalisation of testosterone level about 8-9 months:

- Reduced fat mass(viseral/abdomen>> than subcutaneous / WC )

- Improves muscle mass (glucose metabolised)

M i h b li d d


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Men with metabolic syndrome and testosterone deficiency receive testosterone

treatment Normalisation of testosterone level about

8-9 months:- Reduced glucose, insulin, HbA1c, improved

insulin sensitivity (with diet and exercisereduced HbA1c 1,2% without any anti diabeticmedication)

- Improves lipid patern (inhibit lipoprotein lipase),LDL cholesterol and triglycerides are reduced,HDL cholesterol increases.

- Reduction in both systoic and diastolic bloodressure.

Normalisation of testosterone level about8-9 months:- Reduced glucose, insulin, HbA1c, improved

insulin sensitivity (with diet and exercisereduced HbA1c 1,2% without any anti diabeticmedication)

- Improves lipid patern (inhibit lipoprotein lipase),LDL cholesterol and triglycerides are reduced,HDL cholesterol increases.

- Reduction in both systoic and diastolic bloodressure.


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TestosteroneAs a vasodilator by

Increase of endothelial nitric oxideproduction and decrese of endothelin 1.As anticoagulatory effects by

Reducing fibrinogen andplasminogen activator inhibitor 1PAI-1

As a vasodilator byIncrease of endothelial nitric oxideproduction and decrese of endothelin 1.As anticoagulatory effects by

Reducing fibrinogen andplasminogen activator inhibitor 1PAI-1


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International multicenter Post

Authorization Surveillance Study on theuse of Nebido to assess tolerability andtreatment outcomes in daily clinical

practice

IPASS-NEBIDO


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IPASS

Patients received up to 5 TU injduring an observation parameters of:

- Erectile function- Libido- Vigour/ vitality- Mood and- Ability to concentrate


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NEBIDOContaining 4 ml solution for injectioncontains 1000 mg Testosterone undecanoate


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Tracking statusCountry N Australia 164Austria 120Bulgaria 22Colombia 123Czech Republic 5Germany 68Hong Kong 14Indonesia 20Italy 148Kazakhstan 12Republic of Korea 95Macedonia 55Malaysia 21

Mexico 8Moldova 48Philippines 19Romania 80Russian Federation 122Saudi Arabia 40Singapore 31

Taiwan 15 Thailand 38UK 66Ukraine 20

Total 1354

164

120 22

123

5 68

14

20

148

12

95 55

21

8

48

19

80

122

40

31

15

38

66 20

N is equal to either n=enrolled or n=returned, whichever is greater.In this status, the n of CRFs considers that all enrolled patients started therapy and are being documented. L ikely, the truen of cases is smaller.

circle areas proportional to n patients in center/country


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Recommended treatment regimen for TU 1000 mg


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Patient demographics and baseline characteristics

Parameter

Age (years ) 49.2 13.9

Weight (kg) 86.8 17.6

Waist circumference (cm) 99.5 15.25

Previous androgen therapy n=641 (54%)injections: 37.4%, gels: 44.9%, capsules: 17.5%

Comorbidities Diabetes: 14.0%

Hypertension: 26.1%

Dyslipidemia: 22.2%

ED: 64.7%

Zitzmann M et al. Mens Health World Congress 2010.


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Summary of key safety data

Adverse events

Most common ADRs: hematocrit increased, PSAincreased and injection site pain (all


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Summary of key results of final analysis

1493 Patients enrolled (1500 planned)

1438 valid patients (safety population) 55 patients excluded due to retrospective documentation or

violation of study entry criteria

1123 (78.1%) patients completed study

First patient first visit: 30 October 2006Last patient last visit: 14 July 2010Data base lock: 1 September 2010Report final: 24 September 2010

6333 injections documented

Mean age: 49.2 years

54 % of patients were previously treated with androgens


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Change from Baseline in Sexual Desire after 90 days of Testosterone Treatment in 274 Hypogonadal Men According to Achieved Testosterone Levels (Threshold 600 ng/dL?)

Seftel AD et al. J Androl 25(6): 963-972 (2004)

0

0.5

1

1.5

2

0-300 (n=121) 300-599 (n=125) 600+ (n=28)

Chang e in daily desire score

p=0.25

p=0.0003

p


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Body Mass Index in 183 Hypogonadal Men after a total of 2,135 Injections of Nebido (maximal Treatment Duration 11 years)

k g x m - 2

p = 0.03

15

20

25

30

35

40

Baseline Nadir levelsat 5th injection(40 - 44 th week)

Mean nadir levelsafter 572 th injection

Zitzmann M and Saad F,Abstract Book of the 3rd Japan-Asean Mens Health & Aging Conference: 41 (2008)


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Waist Circumference in 130 Hypogonadal Men after at least 8 Injections (total of 923 Injections) of Nebido

c m

p = 0.001

80

85

90

95

100

105

110

115

120


Mean nadir levelsafter 8 th injection



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LDL-Cholesterol in 183 Hypogonadal Men after a total of 2,135 Injections of Nebido (maximal Treatment Duration 11 years)

m

g / d L

p < 0.001

100

110120130140

150160170180

190


Mean nadir levelsafter 8th injection(max. 572 th week)



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HDL-Cholesterol in 183 Hypogonadal Men after a total o f 2,135 Injections of Nebido (maximal Treatment Duration 11 years)

m g /

d L

20

253035404550556065

70

p = 0.003


Mean nadir levelsafter 8th injection(max. 572 th week)


R i S li d Di li Bl d P ( H ) i 183


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Resting Systolic and Diastolic Blood Pressure (mm Hg) in 183Hypogonadal Men after a total of 2,135 Injections of

Nebido (maximal Treatment Duration 11 years)

Baseline 5th injection(40 - 44th week)

8th injection(max. 572 thweek)

m m / H g

p =0.003

100,0

110,0

120,0

130,0

140,0

150,0

160,0

Baseline 5th injection(40 - 44th week)

8th injection(max. 572 thweek)

p =0.001

60,0

70,0

80,0

90,0

100,0

110,0

Zitzmann M and Saad F, Abstract Book of the 3rd Japan-Asean Mens Health & Aging Conference: 41 (2008)


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Double-Blind Study by Svartberg:Reduction of fat mass by 5.7 kg, increase of muscle mass by 4.2 kg after 1 year treatmentwith Nebido


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Observational Study by Haider:Improvement of metabolic syndrome and liver

function (non-alcoholic liver steatosis) after1 year treatment with Nebido


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Median Value of Blood Glucose and Mean Total Cholesterol, LDL,HDL, and Triglycerides over the Study Period

54

56

58

60

62

H D L ( m m o l

/ L )

H D L ( m m o l

/ L )

200

220

240

260

280

300

T r i g l y c e r i d e a n

d C

h o l e s t e r o l

( m m o l

/ L )

T r i g l y c e r i d e a n

d C

h o l e s t e r o l

( m m o l

/ L )

100

110

120

130

140

G l u c o s e a n

d L D L ( m m o l

/ L )

G l u c o s e a n

d L D L ( m m o l

/ L )

begin 3 mths 6 mths 9 mths 12 mths Time

GlucoseLDL

TriglycerideCholesterolHDL

Haider A et al. Experimental Clin Endocrinol Diab, accepted (2009)


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Study by Kurbatov:Improvement of erectile function in

hypogonadal ED patients after treatment withNebido for an average of 30 weeks.9 out of 17 patients with venous leakage fullyrecovered their erectile function.


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Pilot Study by Kalinchenko:Improvement of the diabetic foot after a single

injection of Nebido


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77-year-old man, type 2 diabetes, phlegmon of left foot,osteomyelitis of the left calcaneus, critical ischemia of the leftleg before and 25 days after a single injection of Nebido

Kalinchenko S et al. Cardiovasc Diabetol 8: 19: 1-6 (2009)


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Study by Corona:Increased arterial stiffness is associated with

arteriogenic ED and hypogonadism.


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ED patients who did not respond to PDE

5 inhibitors alone, experiencedsignificant improvement in erectilefunction when treated with testosteroneand PDE 5 inhibitor.

Testosterone and Erectile Function:

Aversa A, et al. Clin Endocrinol (Oxf )2000;53:517522.Aversa A, et al., Clin Endo 2003;58:632638.Shabsigh R, et al., J Urol 004;172:658663.Shabsigh R. J Sex Med 2005;2:785792.Hwang TI-S, et al., Intl. J . Impotence. Res.2006; 18: 400-404. Yassin AA et al., J Sex Med 2006;3:727735 Yassin A Saad F Diede H. Andrologia38:61-68 (2006)


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Clinical Outcomes

www.get-back-on-track.comNugroho Setiawan


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MENINGKATKAN KUALITAS HIDUP

Nugroho Setiawan


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Clinical Symptomatology

Usual appearance of young men


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Nugroho Setiawan


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Documents

1. the Link Between Dysfuction - Dr