Is there a true association between BPH/LUTS and ED?

Is there a true associationbetween BPH/LUTS and ED? CON

Andrea Salonia, MD, FECSM1,2,3

1Director, URI-Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy2Division of Oncology/Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy3Research Doctorate Program in Urology, Magna Graecia University, Catanzaro, Italy

BPH ED

“…a cause of a disease (ED) is an event, condition (LUTS) or characteristic that preceded the disease that without which it would have never occurred or occurred at a later time…”

Rothman K et al. Philadelphia PA: Lippincot-Raven 1998

BPH & ED

• Simply coexisting/comorbid conditions?

• Shared common risk factors?

• Shared common pathophysiology?

Costabile RA, et al., J Sex Med 2006

Continuum of relationships between medical conditions

Giovannucci E et al. JAMA 1993Bernal-Delgado E et al. Fertil Steril 1998

Hill A. Proc R Soc Med 1965

1EPIDEMIOLOGICAL DATA

Rosen RC, et al. Eur Urol 2003

DAN-PSS-SEXED according to age & LUTS severity

BPH & ED: epidemiological surveys

• Available epidemiological studies in men with LUTS and ⁄ or ED vary with regard to how these disorders are defined, target populations and studydesign

• Most of the reported studies do not specifically measure the joint prevalenceof LUTS and ED, but only describe LUTS symptoms in men with ED or ED symptoms in men with LUTS

• The impact of this type of reporting could be varying prevalence rates basedon the natural distribution of LUTS and ED across the age continuum

Seftel AD et al. Int J Clin Pract 2013

ED prevalence as a function of age - ITALY

Parazzini F. et al. Eur Urol 2000

Random sample from non-randomly selected general practicesQuestion only (type: dissatisfied with ability to achieve and maintain erection sufficient for sexual performance) Response: 82% (n=2010)

50

40

30

20

10

018–29 30–39 40–49 50–59 60–70 >70

Par

tial/c

ompl

ete

ED

(%)

Range di età (anni)

48.3

Patients≤40 years

Patients>40 years

P value*

No. of patients (%) 114 (25.9) 325 (74.1)Age [years; mean (SD)]Range

32.4 (6.0)17-40

57.1 (9.7)41-77

<0.001

CCI [No. (%)]012+

103 (90.4)6 (5.3)5 (4.4)

189 (58.3)62 (19)74 (22.7)

<0.001 (χ2, 39.12)

BMI [kg/m2; mean (SD)]BMI (NIH classification) [No. (%)]

<18.518.5-24.925-29.9≥30

25.1 (4.1)

1 (0.9)63 (56.5)34 (29.6)16 (13)

26.4 (3.7)

0 (0)126 (38.7)157 (48.3)42 (13)

0.0050.002 (χ2, 15.20)

Hypertension [No. (%)] 6 (5.3) 122 (37.5) <0.001 (χ2, 42.40)Hypercholesterolemia [No. (%)] 4 (3.5) 38 (11.7) 0.02 (χ2, 5.64)Hypertriglyceridemia [No. (%)] 0 (0.0) 10 (3.1) 0.12 (χ2, 2.37)MeTs [No. (%)] 2 (1.8) 10 (3.1) 0.57 (χ2, 0.74)

tT [ng/mL; mean (SD)]Hypogonadism (total <3 ng/ml) [No. (%)]

5.3 (2.0)12 (10.3)

4.5 (1.8)54 (16.6)

0.0050.14 (χ2, 2.16)

Capogrosso P, et al. J Sex Med, 10:1833-41, 2013

BPH & ED: Epidemiological Surveys

• Several trials have analysed the association between LUTS and ED

• A CAUSAL ASSOCIATION between LUTS and ED cannot be establishedon the basis of the ever-increasing number of epidemiological studies

Hill A. Proc R Soc Med 1965

Gacci M et al Eur Urol 2011

ASSOCIATION BETWEEN LUTS AND ED

BPH & ED: epidemiological survey cross-sectional studies

Mann CJ. Emerg Med J 2003

• A significant variability exists in many studies looking at a relationship between ED and BPH

• None examining a temporal relationship

• In several studies, the statistical association is either weak or nonexistent

• This variability weakens the argument for causality based on the consistency criterion

Costabile RA, et al., J Sex Med 2006

2COMMON PATHOPHYSIOLOGY

Gacci M et al Eur Urol 2011

BPH & ED: Pathophysiology & Risk Factors

Costabile RA, et al. J Sex Med 2006Andersson KE, et al. NeuroUrol Urodyn 2011

Evidence linking disorders of the prostate and bladder with

LUTS and SD is irrefutable, but

the contribution of metabolic, cardiovascular, and endocrine factors

cannot be discounted

Studies supporting alterations in mechanisms associated with MetS

and cardiovascular disease are critical to our understanding of the

pathways underlying the links between LUTS and sexual dysfunction

3DECREASING RELATIVE RISK WITH CESSATION?

Costabile RA, et al., J Sex Med 2006

• If ED and BPH are correlated, treating one conditionshould improve the other

BPH & ED: decreasing relative risk with cessation?

Wasson JH et al. N Engl J Med 1995

BPH & ED: Decreasing relative risk with cessation?

Leliefeld HHJ et al. BJU Int 2002

BPH & ED: Decreasing relative risk with cessation?

• cohort of #670 patients at baseline and 9 months after either

TURPfinasteride

or watchful waiting (WW)

• Overall, no changes of sexual function were observed in up to 84% of patients, with no significant differences among the three treatment groups

Gacci M et al. BJU Int 2003

For many men sexual functionactually improves with treatment of BPH, possibly via improved QoL

There was a relationship between prostate symptoms and sexual dysfunction, but it was not statistically significant. Patients with slight urinary symptoms had less sexual dysfunction than those with more severe urinary symptoms

Sexual desire and overall satisfaction are relevant only in patients with no severe urinary symptoms, when QoL is preserved

BPH & ED: Decreasing relative risk with cessation?

4DOSE-RESPONSE EFFECT

Porst H et al. J Sex Med 2013

Differences from placebo

Oelke M et al. Eur Urol, 61:917-25, 2012

Oelke M et al. Eur Urol, 61:917-25, 2012

Tadalafil independently (directly) improves signs and

symptoms associated withLUTS/ BPH in men

regardless of ED status

Brock GB et al. J Urol 2014

BPH & ED: Dose-Response Effect

Giuliano F. BJU Int 2006

BPH & ED: Dose-Response Effect

Porst H et al. J Sex Med 2013

• If ED and BPH are correlated, treating one condition should improvethe other (and vice versa)

• IIEF and IPSS measure the condition-related effect on QOL due to amedical condition and are sensitive to treatment effects

• THESE QOL INSTRUMENTS WERE NOT ORIGINALLY DESIGNED TOASSESS PHYSIOLOGICAL CAUSALITY OR ASSOCIATIONS

• The danger of looking only at these QOL instruments is that a variety offactors other than the measured parameters may be influencing thecondition being studied

Costabile RA et al. J Sex Med 2006

BPH & ED: Dose-Response Effect

BPH & ED

Sackett DL et al. BMJ 1996

• Evidence based medicine is not restricted to randomised trials and metaanalyses

• Evidence based medicine is the conscientious, explicit, and judicious use ofcurrent best evidence in making decisions about the care of individualpatients. The practice of evidence based medicine means integratingindividual clinical expertise with the best available external clinicalevidence from systematic research

• While it is tempting to speculate that causality exists between LUTS and ED, further data are required to support this claim