Dr.

Sorin Lupu
Specialist Urologie, Sexologie – Clinica Urologie din cadrul
Spitalului Clinic Județean de Urgență Brașov
Noutati si “mici surprize” in etiologia
si epidemiologia Disfunctiei Erectile

SORIN LUPU MD, PhD, FECSM

IOAN SCARNECIU MD, PhD
• Incidenta ED este in crestere evidenta la nivel global
• Din ce in ce mai frecvent la tineri (sub 40 ani !!!)

DE CE ???
• Pana la 87% din pacientii tineri sau adulti cu ED au, pe
langa motivele psihogene, si cauze organice (vasculare,
neurologice, hormonale, fibroproliferative sau induse
medicamentos)

• Florenta: procentul de tineri sub 40 de ani care au cerut

consultatii pentru ED a crescut de la 5% in 2010, la 15% in
2015 (se asteapta date noi!)

• Un studiu efectuat in Elvetia pe un numar de 2500 tineri

cu varste INTRE 18 SI 25 DE ANI: mai mult de 30% dintre
ei aveau diferite grade de ED !!!

Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5,
Issue 4, 508 – 520 (2017)
 Etiologie si factori de risc - Factori
vasculari
(prezenti si la tineri)
• tineri care au efectuat angiografie peniana, fara trauma perineala in
antecedente, la care s-au evidentiat afectari ocluzive arteriale focale
• in special la cei care merg cu bicicleta mai mult de 3 ore pe saptamana –
presiunea perineala determina reducerea presiunii arteriale sistolice la 0 la
nivel cavernos (Sommer et al. Bicycle Riding and Erectile Dysfunction: A Review. The Journal of Sexual Medicine, Volume 7, Issue 7, July 2010, Pages 2346-2358)

• disfunctii endoteliale subclinice: determinate de tensiunea arteriala, nivelurile

de proteina C reactiva, de colesterol, trigliceride, grosimea intima-media
carotidiana (masurata ecografic)
• Boala Peyronie: 8.2% dintre pacienti sunt sub 40 de ani (21% dintre acestia au
ED)
Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Etiologie si factori de risc - Factori endocrini
• Diabet, hipogonadism…..(endocrinopatii)
• Dieta bogata in produse din soia (Daidzein – isoflavona si
fitoestrogen); determina cresterea colagenului si scaderea
continutului de fibre elastice si musculare cavernoase

Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Etiologie si factori de risc - Factori neurologici

• scleroza multipla
• epilepsie
• interventii chirurgicale pentru fractura de femur (prin
neuropraxie)
• interventii sau traumatisme de coloana
Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4,
508 – 520 (2017)
Etiologie si factori de risc - Efecte secundare ale
medicamentelor
• antidepresive
• neuroleptice
• antiepileptice
• finasterid si dutasterid pentru alopecie
• SSRI inhiba si receptorii colinergici si NO sintetaza (apare ED !!!); au si efect
de down-regulare a axului hipotalamo-hipofizo-testicular !!!
• AINS:
• contribuie la aparitia ED mai mult decat s-a crezut !!!
• prostaglandinele care sunt produse sub influenta COX-2 in vasul deferent sunt foarte
importante in mecanismul erectiei (inhibarea acestora are efecte grave asupra
fenomenului erectiei)
Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Etiologie si factori de risc - Afectiuni psihice
• Depresia se asociaza foarte frecvent cu ED; tratamentul cu PDE5i
are efecte net pozitive si in ameliorarea depresiei
• Anxietatea de performanta (un contact sexual esuat deschide larg
“orizontul” pentru ED la indivizii care nu pot manageria corect
situatia); pericol foarte mare la tinerii care au “invatat” dupa tipare
“gresite”
Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Etiologie si factori de risc - Relatia cu partenerul

• Aspect cu o incidenta in crestere marcata!

Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Tratament - Terapie orala cu PDE5i

• Tratamentul cel mai popular

• Rata mare de success
• Usor de utilizat
• Tolerabilitate foarte buna
• First-line therapy
• Este larg acceptat faptul ca nu exista diferente semnificative intre PDE5i in
ceea ce priveste eficacitatea si profilul de siguranta

Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Tratament - Injectii intracavernoase

• singurul aprobat de catre FDA este alprostatil!

• phentolamine plus papaverine: Bi-mix
• phentolamine plus papaverin plus alprostadil: Tri-mix
• dezavantaje: reducere marcata a spontaneitatii; degradare rapida daca nu este
mentinuta la temperatura optima

• Aplicarea de supozitoare sau creme intrauretrale: alprostadil

Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Tratament – Terapie hormonala
• suplimentare cu testosteron (la pacientii cu hipogonadism), tinand seama
de riscuri si beneficii !
• Labilitate emotionala
• Infertilitate
• Policitemie
• Risc crescut de evenimente cardio-vasculare……..
• Clomiphene:
• neaprobat de FDA
• creste GnRH, FSH si LH
• creste productia de testosteron, fara a afecta spermatogeneza si volumul testicular
(la pacientii cu hipogonadism)
• efect secundar: reducerea libidoului
Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Tratament – Altele
• Interventii de revascularizare peniana: la pacientii cu istoric de
traumatisme perineale, pelvine sau peniene
• Montare de proteza peniana
• Terapie cu celule stem (experimental in acest moment)…………

Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Concluzii
• Incidenta in crestere marcata, in special la populatia tanara
• Subdiagnosticata
• Incidenta apreciata la peste 30% in populatia generala
Nguyen Hoang Minh Tue et al. Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk Factors. Sexual Medicine Reviews, Volume 5, Issue 4, 508 – 520 (2017)
 Remember and news
Prevalenta disfunctiei erectile variaza in functie de numerosi factori: locatia unde
s-a desfasurat studiul, metodele de investigatie utilizare, perioada de timp….
ITALIA
46,9% la populatia cu BPH si
42,5% la pupulatia fara BPH !
GERMANIA
42% la populatia cu BPH si
39,1% la pupulatia fara BPH!
FRANTA
41.3% la populatia cu BPH si
39.9% la pupulatia fara BPH !

Irwin GOLDSTEIN et al. Erectile dysfunction prevalence, patient characteristics, and health outcomes globally. The Journal of Sexual Medicine, Volume 14, Issue 5, e298 (2017)
 Remember and news
Prevalenta disfunctiei erectile variaza in functie de numerosi factori: locatia unde
s-a desfasurat studiul, metodele de investigatie utilizare, perioada de timp….

CHINA
41,8% la populatia cu BPH si
41% la pupulatia fara BPH !

BRAZILIA
33.2% la populatia cu BPH si
31.5% la pupulatia fara BPH !

Irwin GOLDSTEIN et al. Erectile dysfunction prevalence, patient characteristics, and health outcomes globally. The Journal of Sexual Medicine, Volume 14, Issue 5, e298 (2017)
 Varsta medie la barbatii cu ED fara BPH

• US: 52.4 ani

• UE: 53.5 ani (UK) – 56.5 ani (Franta)
• Brazilia: 43.8 ani
• China: 45.6 ani

Irwin GOLDSTEIN et al. Erectile dysfunction prevalence, patient characteristics, and health outcomes globally. The Journal of Sexual Medicine, Volume 14, Issue 5, e298 (2017)
 Afectiunile asociate cel mai frecvent cu ED
• DZ: • HTA:
• Germania (18.8%) • Germania (40.9%)
• China (4.4%) • China (17%)
• Dislipidemia: • Depresie (diagnosticata):
• US (34.9%) • UK (21.4%)
• China (7.2%) • China (1.9%)

Irwin GOLDSTEIN et al. Erectile dysfunction prevalence, patient characteristics, and health outcomes globally. The Journal of Sexual Medicine, Volume 14, Issue 5, e298 (2017)
Afectarea pe plan personal si social detereminata de ED – UK
• absenteism de la locul de munca 15%
• impactul general negativ asupra capacitatii de munca 38.8%
• impact asupra intregii activitati 36%

Irwin GOLDSTEIN et al. Erectile dysfunction prevalence, patient characteristics, and health outcomes globally. The Journal of Sexual Medicine, Volume 14, Issue 5, e298 (2017)
 Concluzie
Disfunctia erectila si efectele sale asupra individului si
societatii sunt in crestere (si in populatia tanara),
iar afectarea este substantiala !!!

Irwin GOLDSTEIN et al. Erectile dysfunction prevalence, patient characteristics, and health outcomes globally. The Journal of Sexual Medicine, Volume 14, Issue 5, e298 (2017)
 Umbrella Reviews
• Reprezinta review-uri ale meta-analizelor
sau review-urilor sistematice publicate

• Reprezinta cel mai inalt nivel de sinteza si

evidenta stiintifica disponibil in acest
moment

• Devine cel mai influent instrument in

literatura biomedicala
 Umbrella Review 2019
• A cuprins 98 metaanalize ce au abordat principalele aspect legate
de ED:
• factorii de risc
• etiologia
• tipurile
• modalitatile de tratament (farmacologic, non-farmacologic si
complementar)
• efectele secundare ale tratamentelor
• Total 3.971.122 participanti!

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019
PREVALENTA ED

• Sub 30 ani ≈ 20%

• 30 – 39 ani ≈ 25%
• 40 – 49 ani ≈ 40%
• 50 – 59 ani ≈ 60%
• 60 – 69 ani ≈ 80%
• Peste 70 ani ≈ 90%

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – factori de risc
STILUL DE VIATA
• FUMATUL (actual sau in trecut): • Nivel moderat sau ridicat de
asociere liniara dependenta de ACTIVITATE FIZICA SI REGIM
doza (numar mare de tigari – ALIMENTAR SANATOS: reducere a
risc mare de DE) riscului de ED

• Consumul de ALCOOL: asociere • Folosirea de opioide: factor de risc

curbiliniara (consumul moderat pentru ED
de alcool SCADE riscul de DE;
consumul redus sau consumul
mare de alcool CRESTE riscul de
DE)

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – factori de risc

FACTORI GENETICI

identificati 4 markeri genetici implicati in aparitia ED

cel mai frecvent polimorfisme genetice la nivelul eNOS (nitric oxid

sintetaza endoteliala)

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – factori de risc
Conditii medicale care sunt asociate cu risc crescut pentru aparitia ED

• Diabet
• Obezitate
• Depresie
• Apneea obstructiva de somn
• Spondilita anchilozanta
• Prostatita cronica / Sd. Dureros pelvin cronic
• Psoriazis
• Guta
• Periodontita cronica (marker al unei sanatati generale precare)
• Infectia HIV
• Afectiunile cardio-vasculare
• Afectiuni hematologice (cu afectarea volumului plachetar)

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – Tratamentul
TESTOSTERONUL
• are efect clar in imbunatatirea functiei sexuale comparative cu
placebo
• risc crescut de eritrocitoza (policitemie)

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – Tratamentul
STATINELE
• sunt superioare placebo pentru imbunatatirea erectiei

• in combinatie cu PDE5i sunt superioare la pacientii cu hipercolesterolemie !

• par a avea rol pozitiv la pacientii neresponsivi la PDE5i

• pot determina reducerea nivelului de testosteron (agravand ED) !

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – Tratamentul

TOTI INHIBITORII DE PDE5 SUNT SUPERIORI COMPARATIV CU PLACEBO !

• Eficacitate comparabila intre toti PDE5i aflati pe piata

• Efect superior in asociere cu psihoterapia sau alfa-blocantele!

• Efecte secundare tip cefalee, dispepsie, congestia fetei (dar nu efecte secundare
severe)

• Unii PDE5i au efecte secundare mai frecvente si mai neplacute cand sunt comparati cu
altii (sildenafil)

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – Tratamentul

Tratamentele non-farmacologice, psihoterapia, activitatea fizica regulata, low intensity

ESWT (extracorporeal shock wave therapy)

Rezultate inconstante, dar mai eficiente decat “asteptarea”!

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 Umbrella Review 2019 – Tratamentul
Cel mai eficient tratament comportamental: ACTIVITATEA FIZICA SUSTINUTA
datorita efectelor fiziologice substantiale
• creste nivelul de testosteron
• creste expresia oxid-nitric sintetazei
• imbunatateste functia endoteliala

Allen Mark S. et al. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. The Journal of Sexual Medicine, Volume 16, Issue 4, 531 – 541 (2019)
 INHIBITORII PDE5

FIRST LINE THERAPY for ED

(EAU, AUA, ESSM, ISSM……)
 METAANALIZA CE A CUPRINS 162.936 PACIENTI CU ED

• In ciuda eficientei, rata de discontinuare a tratamentului cu PDE5i de prima

generatie este de 4% pe luna si aprox. 50% pe an
• In special la persoanele tinere
• Motive: lipsa de eficacitate, efecte secundare, probleme legate de partener

Corona G, Rastrelli G, Burri A, et al. First-generation phosphodiesterase type 5 inhibitors dropout: a comprehensive review and meta-analysis. Andrology-US 2016; 4(6):1002-1009.
FIRST-GENERATION vs. SECOND-GENERATION PDE5i

1st generation: sildenafil, tadalafil & vardenafil

2nd generation: udenafil, avanafil & mirodenafil

1. Wayne J. G. Hellstrom, Laura M. Douglass, Mary K. Powers. How Does

Avanafil Compare for Erectile Dysfunction? - Medscape - Aug 14, 2012.
2. B.P. Jiann , Urological Science 27 (2016) 66-70
3. Corona G, et al. EAU Congress, London 2017
PDE5i pot fi folositi cu succes remarcabil si reactii secundare
minime in tratarea efectiva a insuficientei cardiace sau macar
a anumitor tipuri de insuficienta cardiaca
(studii pilot pe oi, la doze similare cu cele folosite la oameni)

Michael Lawless, Jessica L. Caldwell, Emma J. Radcliffe, Charlotte E. R. Smith, George W. P. Madders, David C. Hutchings, Lori S. Woods, Stephanie J. Church, Richard D. Unwin, Graeme J.
Kirkwood, Lorenz K. Becker, Charles M. Pearman, Rebecca F. Taylor, David A. Eisner, Katharine M. Dibb, Andrew. W. Trafford. Phosphodiesterase 5 inhibition improves contractile function
and restores transverse tubule loss and catecholamine responsiveness in heart failure. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-019-42592-1
 PDE5i au efect protector evident impotriva
- infarctului miocardic
- toxicitatii cardiace cauzate de doxorubicin
- cardiomiopatiei diabetice
- hipertrofiei cardiace
- distrofia musculară Duchenne (afecțiune neuromusculară progresivă, debilitantă)
- amelioreaza fenomenele sindromului Raynaud
- tratament eficient ca adjuvant pentru eliminarea calculilor ureterali distali
- posibil efecte antitumorale !

Anindita Das, David Durrant, Fadi N. Salloum, Lei Xi, Rakesh C. Kukreja, PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer. Pharmacology &
Therapeutics, Volume 147, March 2015, Pages 12-21
Effects of the Phosphodiesterase-5 (PDE-5) Inhibitors, Avanafil and Zaprinast, on
Bone Remodeling and Oxidative Damage in a Rat Model of Glucocorticoid-
Induced Osteoporosis
Zübeyir Huyut, Nuri Bakan, Serkan Yıldırım, Hamit Hakan ALP (Department of Biochemistry, Medical Faculty,
Yuzuncu Yıl University, Van, Turkey)
Med Sci Monit Basic Res 2018; 24:47-58

CONCLUSIONS: In the GIOP (glucocorticoid-induced osteoporosis) rat model,

markers of oxidative stress and bone atrophy were significantly reduced by
treatment with the PDE-5 inhibitors, zaprinast and avanafil.
Effects of a micronutrient supplementation combined with a
phosphodiesterase type 5 inhibitor on sperm quantitative and qualitative
parameters, percentage of mature spermatozoa and sperm capacity to undergo
hyperactivation: A randomised controlled trial.
Tsounapi P, Honda M, Dimitriadis F, Koukos S, Hikita K, Zachariou A, Sofikitis N, Takenaka A
Andrologia. 2018 Oct;50(8):e13071. doi: 10.1111/and.13071. Epub 2018 Jul 10.

We suggest that MS or MS plus avanafil combined administration or avanafil

alone improves sperm membrane permeability with an overall result
improvement in sperm motility, outcome of HOST (hypoosmotic swelling test)
and increase in the percentage of hyperactivated spermatozoa.
• DE este problema majora de sanatate, ce are implicatii asupra
• increderii de sine
• asupra relatiilor de cuplu
• a celor sociale
• cu afectarea marcata a calitatii vietii
• Disfunctia erectila are un impact extrem de important asupra sanatatii fizice si
mentale ale persoanei afectate, determinand
• cresterea riscului de tulburari psihice si
• reducerea activitatii sexuale.

CONFORM MULTOR STUDII, ACELEASI AFECTARI POT FI REGASITE SI LA PARTENERA

PACIENTULUI !
• Toate studiile din ultima perioada sustin ca ED devine o
problema foarte importanta in populatia tanara !!!

• Oferiti sfaturi si recomandari legate de schimbarea stilului

de viata, alaturi de tratamentul sau combinatiile de
tratament specifice ED.
• SA NU UITAM CA TREBUIE SA TRATAM CUPLUL, NU PENISUL!

• NU EXISTA NICI O PROBLEMA SEXUALA PANA NU INTREBAM !