Sexual dysfunction in male LUTS

M. GacciDepartment of Urology, University of Florence

Roma, 25-26 June, 2015

Cross-sectionalpopulation-basedstudy of 4800men (40–79 yr ofage)UK, Netherlands,France, Korea

currently having ED

consulted a doctor for this reason Boyle P, BJU Int 2003

Moderate-to-severe LUTS can adversely affect important areas of personal relationships

3Measured through questionnaire-based survey: EP in American Men Survey

Lack ofphysical intimacy

Anger orconflict

Avoidanceor withdrawal

A feeling ofdistance or

isolation

Lack ofcommunication

Pro

po

rtio

n o

f m

en w

ith

en

larg

ed p

rost

ate

and

th

eir

spo

use

s re

po

rtin

g sp

ecif

ic

rela

tio

nsh

ip c

on

cern

s

Men with mild symptoms (n=216)

Men with moderate-to-severe symptoms (n=203)

Spouses of men with enlarged prostate (n=77)

Roehrborn C, Prostate Can Prost. Dis. 2006

20–70% of men have ED44–90% of men have LUTS

GENERAL population based studies

58–82 % of men with LUTS have ED8–26% of men with ED have LUTS

BPH /ED population based studies

Gacci M et al; Eur Urol 2011; ;60(4):809-25

% o

f m

en w

ho

hav

e er

ecti

on

s

50-59 years 60-69 years

0

10

20

30

40

50

60

70

80

90

100 No, I cannot get an erection Net reduction in stiffness

50-59 years 60-69 years 70-79 years

Age cohort

LUTS severity

34 800 surveys were mailed out, 14 254 were completed and returned, and 12 815 analyzed

US and six European countries

50% of men 50–59 yearswith moderate LUTS haveerectile dysfunction

Sexual dysfunction isstrongly related to bothage and severity of BPHsymptoms

Adapted from Rosen R at al; Eur Urol. 2003; 44(6):637-49

Adapted from Rosen R at al; Eur Urol. 2003; 44(6):637-49

Hammarsten J et al; Prostate Can & Pros Dis, 1998; 1(3):157-162

MetS & Prostate…

Multicenter, cross-sectional, study in 2238 men with T deficiency (1094 subjects with MetS)

Garcia Cruz E et al; J Sex Med 2013; 10(10):2529-38

MetS & ED

Gacci M. at al; Prostate Can Prost Dis 2013; 16(1):101-6

271 consecutive men treated with OP in two tertiary referral centers for LUTS/BPH.

MetS & LUTS

60cc 45mm

Gacci M. at al; Prostate Can Prost Dis 2013; 16(1):101-6

271 consecutive men treated with OP in two tertiary referral centers for LUTS/BPH.

MetS & LUTS

Vignozzi L, Gacci M; Prostate. 2013 Sep;73(13):1391-402

A multi-center cohort of BPH patients (n = 244) + effects of MetS insults on (hBPH)

MetS, LUTS and Inflammation

Infl

amm

ato

rySc

ore

3

4

5

6

7

8

9

Placebo PDE5-I Placebo PDE5-I

without MetS With MetS

44 Pts treated with OP/TURP for persistent severe LUTS, refractory to medical treatment

MetS, LUTS & ED: Inflammation

Vignozzi L, Gacci M; Prostate 2013; 73(8):789-800

CDU: Color doppler ultrasound Lotti et al: Asian j Urol 2014

30-26 25-22 <22(192) (30) (17)

IIEF erectile function score

Age-Adj.r= 0.162 p<0.02

IPSS

to

tals

core

171 infertile subjects, mean age 36.5±8.3 years

Lotti A, Andrology, 2013

0

(76)

1

(47)

2

(26)

3

(16)

≥4

(6)

Number of MetS components

Pro

sta

te v

olu

me (

ml)

p for trend at ANOVA < 0.0001

Prostate volume (ml)

0.7 0.9 1.1 1.31

Waist

(≥102 cm)

Glycemia

(≥6.1 mmol/L)/t

HDL

(<1.03 mmol/L)/t

Triglycerides

(≥1.7 mmol/L)/t

Blood Pressure

(≥130/85 mmHg)/t

171 infertile subjects, mean age 36.5±8.3 years

Lotti A, Andrology, 2013

Corona G et al et al; J Sex Med 2010; 7(4 Pt 1):1362-80

Cross-sectional multicenter survey on 3369 community-dwelling men (mean age 60y)

Adapted from Gacci M et al. Eur Urol 2011; 60: 809-825

CVD

BPH /LUTSED

MetS & ED

Liu , Int J Impot Res 2014

MetS & ED

Liu , Int J Impot Res 2014Overall RR: 1,60 (1,27-2,02)

MetS & BPE

Gacci M, Corona G, BJU Int 2015

Total prostate volume mean differences (mL) 1.80 (> 30mL: 2.13)

Gacci M, Corona G, BJU Int 2015

MetS & BPE

AGE

Waist

HDL-C

MetS & BPE

Gacci M, Corona G, BJU Int 2015

Pe

aksy

sto

licve

loci

ty(c

m/s

ec)

Corona G, Asian Journal of Andrology (2014) 16, 581–591

Increased WC is associated to more severe ED and worst PCDU parameters

A multi-center cohort of BPH patients (n = 378) , 238 with MetS

Gacci M et al, BJU Int 2015

0

5

10

15

20

25

PRE POST

IPSS

TO

TAL

WC < 102 cm WC ≥ 102 cm

0

2

4

6

8

10

PRE POST

IPSS

irri

tati

veWC < 102 cm WC ≥ 102 cm

A multi-center cohort of BPH patients (n = 378) , 238 with MetS

Gacci M et al, BJU Int 2015

Wang C et al; Diabetes Care 2011;34(7):1669-75

Ferrario C, J Clin Hypert , 2002Ferrario C, J Clin Hypert , 2002

Tacklind J, Cochrane Library, 2012

Tacklind J, Cochrane Library, 2012

Larson TR, Urology. 2003 Apr;61(4):692-8.

Singh DV, J Sex Med,2013

Singh DV, J Sex Med,2013

Mean Prostate Volume: 50 mL Casabè A, J Urol 2014

Mean Prostate Volume: 50 mL

IPSS IIEF

Casabè A, J Urol 2014

Eur Urol 2011 Curr Bladde Dys Rep 2013

Porst H. Eur Urol. 2011160 men (pla) vs. 160 men (tad) 5 mg once daily for 12 wk

-4 0 12 16 24 38 51 64

Me

an

IP

SS

10

15

20

25

Weeks.

Ru

n-i

n p

lace

bo

Bas

ale

Estensione in aperto

427 402

-2,2 (5,3)

-2,5 (5,1)

0,2 (5,4)

-0,2 (5,8)

0,8 (6,4)

Endpoint n=416 (LOCF)

In aperto fino a variazione endpointmedia (DS)

351

Placebo

Tad 2,5

Tad 20,0

Tad 10,0

Tad 5,0

Tad 5,0

Tad 5,0

Tad 5,0

Tad 5,0

Tad 5,0

Donatucci BJU Int 2011

Tota

l IP

SS

299 men (69.9%) completed the 1-year, open-label extension period

Placebo Tadalafil Overall

(N=92)

2,5 mg

(N=96)

5 mg

(N=83)

10 mg

(N=85)

20 mg

(N=71) (N=427)

IPSS total (n) 89 95 82 81 69 416

Change: Week 0 - E -4,1±6,8 -5,7±5,4 -5,0±7,2 -5,7±6,4 -4,6±7,7 -5,0±6,7

Change: Week 12 – E -2,2±5,3 -2,5±5,1 0,2±5,4 -0,2±5,8 0,8±6,4 -0,9±5,7

IPSS irritative(n) 89 95 82 81 69 416

Change: Week 0 – E -1,6±3,2 -2,1±2,6 -2,1±3,1 -1,9±2,7 -1,8±3,3 -1,9±3,0

Change: Week 12 – E -0,9±2,4 -1,0±2,7 -0,0±2,4 0,2±2,7 0,3±2,8 -0,3±2,6

IPSS obstructive (n) 89 95 82 81 69 416

Change: Week 0 - E -2,5±4,2 -3,6±3,6 -3,0±4,8 -3,8±4,3 -2,8±4,9 -3,1±4,4

Change: Week 12 - E -1,3±3,6 -1,6±3,1 0,2±3,4 -0,5±3,6 0,4±4,2 -0,6±3,6

Donatucci BJU Int 2011

Gacci M et al, Eur Urol 2012

Gacci M et al, Research & Rep 2013

IPSS

Mean difference in IPSS: -2,8 (ALL) - 1,6 to - 4,1 (TADALAFIL)

Reduction of both irritative (storage) an obstructive (voiding) LUTS

Timing: 4 weeks (3/4) – 12 weeks (1/4): (lasting 12 months)

Dose dependent

PDE5-Is alone: +5,5 IIEF

PDE5-Is + α-blocker: +3,6 IIEF

IIEF

Mean difference in IIEF: + 5,5 (ALL) + 4,0

to 6,9 (TADALAFIL)

International Index of Erectile Function - Orgasmic Function

IIEF-Question 9 (IIEF-Q9)(ejaculatory frequency)

IIEF-Question 10 (IIEFQ10)(orgasmic frequency)

Giuliano F; J Sex Med 2013

BPH + ED Placebo (N = 105), Tadalafil 5 mg (N = 106), Tamsulosin 0.4 mg (N = 99)

Gacci M & Maggi M, j Sex Med, 2014

Alpha blocker vs. Placebo 5 ARI vs. Placebo

OR 7.03 OR 2.90

Gacci M & Maggi M, j Sex Med, 2014

Combination Vs. Alpha blocker Combination Vs. 5 ARI

OR: 4,7 - 3,3 Gacci M & Maggi M, j Sex Med, 2014

Finucane MM et al., Lancet. 2011;377:557-67

Trends in age-standardised BMI between 1980 and 2008 in adults 20 yr or older

TAKE HOME MESSAGE: Epidemiology

LUTS /BPE

Adapted from Gandaglia G et al; Eur Urol 2013; E-Pub ahead of print

TAKE HOME MESSAGE: Pathophysiology

Kirby M et al; Int J Clin Prat 2013; 67(7):606-18

TAKE HOME MESSAGE: Co-Diagnosis

TAKE HOME MESSAGE: Treatments

Five-pin «Italian» billiardPool «American» billiard

LUTS

EDAge

Comorbidities

Drug