The interplay between premature ejaculation and erectile dysfunction a systematic review and meta-analysis

The interplay between premature ejaculation and erectile dysfunction a systematic review and meta-analysis Giulia Rastrelli MD, PhD Sexual Medicine and Andrology Unit Department of Experimental and Clinical Biomedical Sciences University of Florence 4 February 2016

Premature ejaculation and erectile dysfunction are frequently comorbid 1) One out of three men with erectile dysfunction reports premature ejaculation (Corona et al., J Androl 2006;27:86 93) 2) More than 30% of subjects reporting premature ejaculation complain erectile dysfunction (McMahon et al., J Sex Med 2012;9:454 65) Specific determinants and underlying factors linking ED and PE have yet to be clearly identified Erectile dysfunction Premature ejaculation

Aim To review and meta-analyze all available data regarding the relationship between PE and ED Search terms: premature ejaculation AND erectile dysfunction Search from January 1, 1969 up to April 1, 2015 All trials evaluating the risk of ED in subjects with or without PE were included

Records identified on Medline search N=474 Full-text papers assessed for eligibility N= 40 Records removed from the analysis Reviews N =157 No data on ED in patients with or without PE N=186 Comments or letters N=8 Women - N=14 Animal studies N=6 Adolescents N=7 Specific subpopulations Men with chronic prostatitis /chronic pelvis syndrome N=26 Men with ED N=11 Men with couple infertility N=6 Men with alcohol dependence N=2 Men with opioid dependence N=3 Men with HIV N=2 Men with neurological diseases N=6 Records removed from the analysis Reviews N =5 No data on ED in patients with or without PE N =14 Comments or letters N =1 Men with chronic prostatitis /chronic pelvis syndrome N=2 Studies included in quantitative analysis N=18 Risk of ED in PE n=15* IIEF-5 score in men with or without PE n=3* IELT in men with or without ED n=2

Probability of having erectile dysfunction related to premature ejaculation Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper Relative Rela ratio limit limit p-value weight we El-Sakka et al., 2003 4,92 2,68 9,04 0,00 6,68 Basile_fasolo et al., 2005 7,93 6,99 9,01 0,00 7,66 Laumann et al., 2005 5,62 3,17 9,95 0,00 6,79 Porst et al., 2006 9,30 4,76 18,16 0,00 6,50 El-Sakka et al., 2008 2,13 1,52 2,99 0,00 7,36 Malavige et al., 2008 4,41 2,08 9,37 0,00 6,24 Son et al., 2010 1,49 0,98 2,26 0,06 7,19 Vakalopoulus et al., 2011 3,96 1,76 8,94 0,00 6,04 Tang et al., 2011 2,03 1,15 3,56 0,01 6,81 Lee et al., 2012 11,06 6,59 18,57 0,00 6,94 McMahon et al., 2012 3,28 2,32 4,63 0,00 7,35 Shaeer et al., 2012 2,57 1,72 3,85 0,00 7,22 Shaeer et al., 2013 18,94 2,37 151,55 0,01 2,75 Gao et al., 2013 1,59 1,29 1,95 0,00 7,58 Maseroli et al., 2015 2,69 1,57 4,59 0,00 6,89 Overall 3,83 2,49 5,88 0,00 0,01 0,1 1 10 100 No ED Favours A ED Favours B

Difference in IIEF-5 score in men with or without premature ejaculation Study name Statistics for each study Difference in means and 95% CI Difference Lower Upper Relative R in means limit limit p-value weight El-Sakka et al., 2008-3,90-4,28-3,52 0,00 33,31 Liang et al 2010-5,90-6,09-5,71 0,00 33,45 Gao et al., 2014-0,58-1,04-0,12 0,01 33,23 Overall -3,47-6,43-0,50 0,02-8,00-4,00 0,00 4,00 8,00 Favours PE A Favours No PE B Meta Analysis

Subjects with premature ejaculation more probably report erectile dysfunction

Subjects with premature ejaculation more probably report erectile dysfunction Is there any factor affecting the probability for subjects with premature ejaculation of having also erectile dyfunction?

Odd ratio for ED in PE subjects Influence of age on risk of erectile dysfunction related to premature ejaculation Regression of età on Log odds ratio 3,00 2,70 2,40 S=0.05[0.04;0.06];p<0.0001 I=-0.91[-1.37;-0.44];p=0.0001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00 26,72 30,36 34,00 37,64 41,28 44,92 48,57 52,21 55,85 59,49 63,13 età Age (years)

Odd ratio for ED in PE subjects Influence of education level on risk of erectile dysfunction related to premature ejaculation Regression of education university on Log odds ratio 3,00 2,70 2,40 S=-0.027[-0.033;-0.021];p<0.0001 I=2.341[2.129;2.551];p<0.0001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00 13,32 19,78 26,24 32,70 39,16 45,63 52,09 58,55 65,01 71,47 77,94 Higher education (%) education university

Odd ratio for ED in PE subjects Influence of relationship on risk of erectile dysfunction related to premature ejaculation Regression of stable relationship on Log odds ratio 3,00 2,70 2,40 Log odds ratio 2,10 1,80 1,50 1,20 0,90 S=-0.03[-0.04;-0.02];p<0.0001 I=3.60[2.91;4.29];p<0.0001 0,60 0,30 0,00 23,05 30,91 38,77 46,63 54,49 62,35 70,21 78,07 85,93 93,79 101,65 stable relationship Stable relationship (%)

Subjects with premature ejaculation more probably report erectile dysfunction Risk of erectile dysfunction related to premature ejaculation is higher in men: Older With lower education With unstable couple relationship

Odd ratio for ED in PE subjects Influence of anxiety on risk of erectile dysfunction related to premature ejaculation Regression of anxiety on Log odds ratio 3,00 2,70 S=0.05[0.03;0.07];p<0.0001 I=0.44[0.17;0.71];p=0.001 2,40 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00 3,20 6,56 9,92 13,28 16,64 20,00 23,36 26,72 30,08 33,44 36,80 Anxiety symptoms (%) anxiety

Odd ratio for ED in PE subjects Influence of depression on risk of erectile dysfunction related to premature ejaculation Regression of depression on Log odds ratio 3,00 2,70 2,40 S=0.05[0.04;0.07];p<0.0001 I=0.48[0.27;0.69];p<0.0001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00-0,21 3,52 7,25 10,99 14,72 18,45 22,18 25,91 29,65 33,38 37,11 Depressive symptoms (%) depression

Subjects with premature ejaculation more probably report erectile dysfunction Risk of erectile dysfunction related to premature ejaculation is higher in men: Older With lower education With unstable couple relationship With severer anxiety and depressive symptoms

Odd ratio for ED in PE subjects Influence of diabetes mellitus on risk of erectile dysfunction related to premature ejaculation Regression of dm on Log odds ratio 3,00 2,70 2,40 S=-0.006[-0.001;-0.003];p<0.001 I=1.585[1.501;1.668];p<0.0001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00-5,60 5,92 17,44 28,96 40,48 52,00 63,52 75,04 86,56 98,08 109,60 Diabetes mellitus dm (%)

Odd ratio for ED in PE subjects Influence of hypertension on risk of erectile dysfunction related to premature ejaculation Regression of hypetension on Log odds ratio 3,00 2,70 2,40 S=-0.04[-0.05;-0.03];p<0.0001 I=2.32[2.03;2.60];p<0.0001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 Age adjusted β -0.302;p<0.0001 0,00 4,76 8,77 12,78 16,78 20,79 24,80 28,81 32,82 36,82 40,83 44,84 Hypertension hypetension (%)

Odd ratio for ED in PE subjects Influence of dyslipidemia on risk of erectile dysfunction related to premature ejaculation Regression of dislipidemia on Log odds ratio 3,00 2,70 2,40 S=-0.05[-0.06;-0.04];p<0.0001 I=2.35[2.17;2.53];p<0.0001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00 2,80 6,52 10,24 13,96 17,68 21,40 25,12 28,84 32,56 36,28 40,00 Dyslipidemia dislipidemia (%)

Subjects with premature ejaculation more probably report erectile dysfunction Risk of erectile dysfunction related to premature ejaculation is higher in men: Older With lower education With unstable couple relationship With severer anxiety and depressive symptoms With better metabolic profile

Odd ratio for ED in PE subjects Influence of history of PE on risk of erectile dysfunction related to premature ejaculation 3,00 2,70 2,40 Regression of acquired PE on Log odds ratio S=0.016[0.013;0.019];p<0.0001 I=0.632[0.461;0.803];p=0.001 Log odds ratio 2,10 1,80 1,50 1,20 0,90 0,60 0,30 0,00 10,65 20,39 30,14 39,89 49,64 59,39 69,13 78,88 88,63 98,38 108,12 Acquired acquired PE (%)

Subjects with premature ejaculation more probably report erectile dysfunction Risk of erectile dysfucntion related to premature ejaculation is higher in men: Older With lower education With unstable couple relationship With severer anxiety and depressive symptoms With better metabolic profile With acquired premature ejaculation

Conclusions ED and PE cannot be considered as distinctly separate entities They should be not categorized in rigid diagnostic figures, but should be seen in a dimensional perspective Older men, with lower level of education, without stable relationship and with depressive or anxiety symptoms more frequently experience both ED and PE Their simultaneous presence is less dependent on organic factors Understanding this dimensional perspective might help sexual health care professionals in providing the most appropriate therapeutic approach

Acknowledgements Giovanni Corona Valentina Boddi Sarah Cipriani Alessandra D. Fisher Francesco Lotti Elisa Maseroli Edoardo Mannucci Linda Vignozzi Prof. Mario Maggi