is there a true association between bph/luts and ed?
TRANSCRIPT
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