Introduction:
Urologic chronic pelvic pain syndrome (UCPPS) in males includes patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and/or interstitial cystitis/bladder pain syndrome (IC/BPS).1,2 Historically, these conditions have been poorly understood and lack effective therapies. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Epidemiology and Phenotyping Study was established to address these deficiencies by using an integrated approach to understand the pathophysiology of UCPPS and to examine the interplay between these conditions and other physiologic systems, including sexual function.1 Male sexuality is multi-dimensional and includes libido, erectile function, and orgasm, all of which can be adversely affected by UCPPS.
Sexual dysfunction (SD), including erectile dysfunction (ED), ejaculatory disorders, and suppressed libido, is prevalent among patients with UCPPS and is associated with a diminished quality of life (QoL).3–7 Several mechanisms have been proposed including the influence of associated psychological conditions, endothelial dysfunction, and the destructive effects of the inflammatory response.3,8–12 The current literature is limited by small sample sizes, inconsistent objective evaluations, and lack of control groups.2 As a result, treatments for SD in this patient population are mostly empirical.
To address these deficiencies and to improve the treatment of SD among UCPPS, we used the MAPP I study to perform a cross sectional analysis to compare SD among male patients with UCPPS, other chronic pain conditions, and healthy controls without chronic pain, and to assess the relationship of various psychosocial factors, comorbidities, pain location, and urologic factors with patient-reported measures of ED and ejaculatory disorders in males in all three groups.
Materials and Methods:
Study Participants
Participants were males with UCPPS, other chronic pain conditions (positive controls, PC), and healthy participants (healthy controls, HC) recruited at six clinical sites within the MAPP Research Network.13 Males met CP/CPPS criteria if they reported pain or discomfort in any of the 8 Male Genitourinary Pain Index (MGUPI) domains, with symptoms present for the majority of 3 of the previous 6 months. Males with IC/BPS were eligible if they reported an unpleasant sensation of pain, pressure or discomfort, perceived to be related to the bladder and/or pelvic region, associated with lower urinary tract symptoms for the majority of the time any 3 months in the previous 6 months or for the majority of the time during the most recent 3 months.14 Positive controls (PC) included participants meeting diagnostic criteria for irritable bowel syndrome, chronic fatigue syndrome, or fibromyalgia. Complete eligibility and consent procedures have been described. In MAPP I, the inclusion criteria for UCPPS and PC were not mutually exclusive and therefore participants with symptoms meeting both sets of criteria exist in each of these groups. Healthy controls (HC) consisted of age matched individuals who did not meet criteria for urologic or non-urologic chronic pain. The study protocol, including consent procedures, was approved by each site’s Internal Review Board.
Measures of Sexual Function
Upon study enrollment, all participants underwent a comprehensive health assessment and were asked to complete questionnaires that assessed their overall health, psychosocial state, pain characteristics, and sexual function. Sexual function in male participants was assessed using the International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and University of Washington Ejaculatory Function Scale (EFS).15,16 Decreasing IIEF-EF score and increasing EFS scores were indicative of worsening SD. A composite IIEF-EF score of < 21 was used as a threshold for ED based on literature review.13 EFS was analyzed as a continuous variable.
Measures of Psychosocial Variables
Psychosocial variables were assessed using validated patient-reported questionnaires including the Self Esteem and Relationship (SEAR), Perceived Stress Scale (PSS), Hospital Depression and Anxiety Scale (HADS), International Personality Item Pool (IPIP), Childhood Traumatic Events Scale (CTES), and Current Symptoms Questionnaire (CSQ).17–21 Participants were also asked to identify specific locations of pain on maps of the whole body and of the male genitalia.
Statistical Analysis
Baseline data among the cohorts were compared by ANOVA for continuous variables and chi-square tests for categorical variables. Separate univariable and multivariable logistic regression models were used to assess associations of psychosocial variables, pain, and other urologic symptoms with ED. All multivariable models, with the exception of childhood trauma, adjusted for age, living with a partner, and cohort (UCPPS, PC, or HC where applicable). Models relating psychosocial variables to ED additionally adjusted for genital pain; models relating pain and urologic variables to ED additionally adjusted for depression and specifically excluded healthy controls due to minimal pain and urologic symptoms in this cohort. The evaluation of the relationship of childhood trauma with ED only adjusted for age and race to avoid adjustment of potential mediating variables. Linear regression was analogously used to evaluate associations with ejaculatory function. Associations were considered statistically significant at p<0.05. Analyses were performed in SAS version 9.3.
Results:
A total of 417 male participants were included, with 191 males with UCPPS, 44 PC, and 182 HC. Table 1 shows cohort characteristics among UCPPS, PCs, and HCs. Of those with UCPPS, 1 man had IC/BPS but not CP/CPPS, 17 were CP/CPPS only, 142 were CP/CPPS and IC/BPS, and 31 were CP/CPPS but undetermined for IC/BPS. Participants with UCPPS reported higher total urologic pain severity, number of genital sites with pain, and urinary symptoms compared to HCs and PCs. UCPPS and PC cohorts both reported significantly decreased self-esteem, as represented by lower mean SEAR self-esteem composite scores, compared to HCs. No differences were observed among all three cohorts with respect to the prevalence of comorbid conditions, such as diabetes mellitus, cardiac history, or BMI.
Table 1.
Patient Demographics
| Characteristic | Stat | UCPPS | Healthy Controls | Positive Controls | p |
|---|---|---|---|---|---|
| Number of participants | N | 191 | 182 | 44 | - |
| Age | Mean (SD) | 46.8 (15.35) | 43.7 (15.09) | 41.1 (12.80) | 0.0082 |
| Race/Ethnicity | White | 162 (84.8%) | 137 (75.3%) | 29 (65.9%) | 0.2597 |
| Black | 9 (4.7%) | 17 (9.3%) | 6 (13.6%) | ||
| Hispanic | 10 (5.2%) | 15 (8.2%) | 4 (9.1%) | ||
| Other | 10 (5.2%) | 13 (7.1%) | 5 (11.4%) | ||
| Employment | Employed | 134 (70.2%) | 122 (67.4%) | 22 (50.0%) | 0.0053 |
| Unemployed | 19 (9.9%) | 37 (20.4%) | 12 (27.3%) | ||
| Retired | 30 (15.7%) | 21 (11.6%) | 1 (2.3%) | ||
| Full-time homemaker | 0 (0%) | 1 (0.6%) | 1 (2.3%) | ||
| Disabled | 8 (4.2%) | 0 (0%) | 8 (18.2%) | ||
| Income | $10K or less | 9 (4.7%) | 15 (8.2%) | 8 (18.2%) | <.0001 |
| >$10K to $25K | 12 (6.3%) | 25 (13.7%) | 9 (20.5%) | ||
| >$25K to $50K | 26 (13.7%) | 44 (24.2%) | 5 (11.4%) | ||
| >$50K to $100K | 61 (32.1%) | 57 (31.3%) | 6 (13.6%) | ||
| >$100K | 68 (35.8%) | 24 (13.2%) | 12 (27.3%) | ||
| Prefer NTA | 14 (7.4%) | 17 (9.3%) | 4 (9.1%) | ||
| Education | < High School | ||||
| High School or GED | 14 (7.3%) | 17 (9.3%) | 2 (4.5%) | 0.1641 | |
| Some College | 42 (22.0%) | 59 (32.4%) | 14 (31.8%) | ||
| College/Univ Grad | 77 (40.3%) | 51 (28.0%) | 14 (31.8%) | ||
| Professional/Grad Degree | 58 (30.4%) | 55 (30.2%) | 14 (31.8%) | ||
| Lives with Spouse or Partner | Yes | 115 (60.2%) | 81 (44.5%) | 11 (25.0%) | 0.0005 |
| Diabetes | Yes | 3 (1.6%) | 4 (2.2%) | 2 (4.5%) | 0.3269 |
| Cardiac History | Yes | 66 (34.6%) | 40 (22.0%) | 11 (25.0%) | 0.1292 |
| BMI | Mean (SD) | 26.6 (3.90) | 26.7 (4.52) | 26.1 (4.22) | 0.8593 |
| Antidepressant Use - Any | Yes | 42 (22.0%) | 6 (3.3%) | 10 (22.7%) | <.0001 |
| SSRIs | Yes | 11 (5.8%) | 4 (2.2%) | 5 (11.4%) | 0.0412 |
| SNRIs | Yes | 1 (0.5%) | 2 ( 1.1%) | 2 (4.5%) | 0.1921 |
| Tricyclics | Yes | 33 (17.3%) | 0 (0%) | 4 (9.1%) | 0.4615 |
| Duration of Symptoms | Mean (SD) | 7.8 (10.71) | 17.8 (6.15) | 0.0612 | |
| Pain Severity | Mean (SD) | 14.0 (5.44) | 0.3 (1.12) | 3.2 (4.61) | <.0001 |
| Urinary Severity | Mean (SD) | 11.4 (6.22) | 3.0 (3.10) | 6.7 (5.33) | <.0001 |
| Non-Pelvic Regions with Pain | 0 | 57 (29.8%) | 104 (57.1%) | 9 (20.5%) | <.0001 |
| 1 – 2 | 72 (37.7%) | 60 (33.0%) | 13 (29.5%) | ||
| 3 – 7 | 62 (32.5%) | 18 (9.9%) | 22 (50.0%) | ||
| Number of Genital Sites with Pain | Mean (SD) | 1.8 (0.91) | 0.0 (0.19) | 0.3 (0.61) | <.0001 |
| SEAR Self Esteem | Mean (SD) | 72.0 (24.87) | 90.4 (14.63) | 75.6 (24.01) | <.0001 |
| SEAR Self Esteem Missing | Yes | 7 (3.7%) | 12 (6.6%) | 1 (2.3%) | 0.2927 |
| Sear Sexual Relationship | Mean (SD) | 63.3 (28.00) | 82.4 (20.20) | 67.9 (30.04) | 0.0002 |
Table 2 shows self-reported erectile function among participants in all three cohorts. Males with UCPPS reported significantly lower mean IIEF-EF scores than both PC and healthy subjects and were 5 times more likely to have ED than HC (19.7% UCPPS, 4.2% HC, 12.5% PC, p = 0.0034). While many participants in the study reported little or no ED, patients with UCPPS were significantly more likely to have ED than PCs and HCs, although this may somewhat be explained by men with UCPPS being older and more likely to live with a partner.
Table 2.
Sexual Function
| Male | |||||
|---|---|---|---|---|---|
| Characteristic | Statistic | UCPPS | Healthy Controls | Positive Controls | p |
| N | 191 | 182 | 44 | - | |
| IIEF [EF] | Mean (SD) | 24.7 (6.44) | 28.5 (3.46) | 26.2 (6.15) | < 0.001 |
| IIEF [EF] < 21 | n(%) | 30 (19.7%) | 6 (4.2%) | 4 (12.5%) | 0.003 |
| IIEF [EF] Inactive | n(%) | 37 (19.6%) | 39 (21.4%) | 11 (25.6%) | 0.5347 |
| IIEF [EF] Missing | n (%) | 2 (1.0%) | 0 (0%) | 1 (2.3%) | 0.64 |
| IIEF Q1: Erection during sexual activity | Mean (SD) | 3.8 (1.61) | 4.2 (1.71) | 3.7 (1.90) | 0.82 |
| IIEF Q2: Erections hard enough | Mean (SD) | 3.7 (1.70) | 4.2 (1.64) | 3.7 (1.94) | 0.40 |
| IIEF Q3: Able to penetrate | Mean (SD) | 3.5 (1.97) | 3.8 (2.04) | 3.2 (2.21) | 0.86 |
| IIEF Q4: Maintain erection | Mean (SD) | 3.4 (1.95) | 3.7 (2.05) | 3.3 (2.16) | 0.77 |
| IIEF Q5: How difficult to maintain to completion | Mean (SD) | 3.3 (1.97) | 3.8 (2.05) | 3.3 (2.16) | 0.52 |
| IIEF Q6: Confidence to get and keep erection | Mean (SD) | 3.6 (1.31) | 4.4 (0.99) | 3.8 (1.37) | 0.002 |
| EFS [MSFS] | Mean (SD) | 2.7 (2.20) | 0.6 (0.92) | 2.0 (2.04) | <.0001 |
| EFS [MSFS] Missing | n(%) | 2 (1.0%) | 4 (2.2%) | 4 (9.1%) | 0.02 |
| EFS Q1: Pain with ejaculation | Mean (SD) | 1.0 (1.11) | 0.0 (0.13) | 0.2 (0.66) | <.0001 |
| EFS Q2: Premature ejaculation | Mean (SD) | 0.7 (1.14) | 0.3 (0.73) | 0.6 (0.89) | 0.007 |
| EFS Q3: Difficulty in reaching ejaculation | Mean (SD) | 1.0 (1.21) | 0.3 (0.56) | 1.1 (1.42) | 0.03 |
Ejaculatory dysfunction was worse in patients with UCPPS followed by PC and then HC, who showed little indication of ejaculatory dysfunction. Patients with UCPPS also reported significantly more pain with ejaculation compared to PCs and HCs. (1.0(1.1) UCPPS, 0.2(0.7) PC, 0 (0.1) HC, p ≤0.0001). UCPPS patients also reported lower quality of sexual relationships as represented by decreased sexual relationship scores on the SEAR questionnaire (63.3 UCPPS, 82.4 HC, 67.9 PC, p = 0.0002).
Table 3 shows the relationship of psychosocial variables, comorbid conditions, and pain characteristics with ED. Adjusting for cohort, urologic pain severity, increasing number of genital sites with pain, and other urologic specific conditions were not associated with ED. Psychosocial factors such as depression, higher perceived stress, and self-report of childhood sexual trauma were predictive of ED in univariable and multivariable analysis. Comorbid conditions including cardiovascular disease and increasing BMI were found to be positively associated with ED in univariable analysis; cardiovascular disease was not associated with ED after adjustment. Diabetes mellitus was strongly associated with ED. Predictors of ED were not differentially associated with SD across cohorts.
Table 3.
Univariable and Multivariable Analysis of Factors Associated with IIEF-EF <21
| Unadjusted | Adjusted | ||||
|---|---|---|---|---|---|
| Variable | OR(95% CI) | p | OR(95% CI) | p | Adjusted Cohort interaction p-value |
| SEAR Total1 | 0.93 (0.91–0.95) | p<.0001* | 0.92 (0.90–0.95) | p<.0001* | 0.2863 |
| SEAR Sexual Relationship1 | 0.92 (0.90–0.94) | p<.0001* | 0.91 (0.88–0.94) | p<.0001* | 0.5081 |
| SEAR Confidence1 | 0.95 (0.94–0.97) | p<.0001* | 0.95 (0.94–0.97) | p<.0001* | 0.3461 |
| Sear Self Esteem1 | 0.96 (0.95–0.97) | p<.0001* | 0.96 (0.95–0.98) | p<.0001* | 0.7096 |
| Perceived Stress Scale1 | 1.05 (1.00–1.09) | p=0.0388 | 1.05 (1.00–1.11) | p=0.0668 | 0.2540 |
| HADS Depression1 | 1.16 (1.08–1.25) | p<.0001* | 1.14 (1.05 – 1.25) | p=0.0032* | 0.5476 |
| HADS Anxiety1 | 1.06 (0.99–1.14) | p=0.1006 | 1.03 (0.95–1.13) | p=0.4596 | 0.1495 |
| IPIP – Neuroticism1 | 1.02 (1.00–1.04) | p=0.0549 | 1.02 (1.00–1.05) | p=0.0680 | 0.0982 |
| IPIP – Extraversion1 | 0.98 (0.96–1.01) | p=0.2073 | 0.99 (0.96–1.02) | p=0.4786 | 0.0853 |
| IPIP – Openness1 | 0.98 (0.95–1.01) | p=0.1662 | 0.98 (0.95–1.02) | p=0.3336 | 0.9522 |
| IPIP – Agreeableness1 | 1.03 (0.99–1.06) | p=0.1230 | 1.03 (0.99–1.07) | p=0.1887 | 0.8162 |
| IPIP – Conscientiousness1 | 0.99 (0.97–1.02) | p=0.6866 | 0.99 (0.96–1.01) | p=0.3241 | 0.3277 |
| CSQ: catastrophizing1 | 1.04 (1.00–1.08) | p=0.0659 | 1.01 (0.96–1.06) | p=0.4296 | 0.0807 |
| CSQ: decrease pain1 | 0.86 (0.72–1.03) | p=0.1076 | 0.91 (0.73–1.14) | p=0.1933 | 0.2822 |
| CSQ: control pain1 | 0.91 (0.77–1.09) | p=0.3093 | 0.91 (0.74–1.13) | p=0.4064 | 0.0912 |
| Diabetes1 | 11.55 (1.87–71.43) | p=0.0085* | 13.87 (1.82–105.86) | p=0.0058* | 0.9996 |
| Cardiac History1 | 2.23 (1.12–4.45) | p=0.0225* | 1.13 (0.51–2.54) | p=0.7629 | 0.6474 |
| BMI1 | 1.10 (1.02–1.18) | p=0.0126* | 1.10 (1.01–1.19) | p=0.0312 | 0.5936 |
| Pain Severity 2 | 1.05 (0.99– 1.12) | P= 0.0761 | 1.04 (0.96–1.13) | p=.3063 | 0.2063 |
| Urinary Severity 2 | 1.03 (0.97–1.09) | p=0.3896 | 0.99 (0.92–1.07) | p=0.8096 | 0.2063 |
| Pain Beyond Pelvic Region 2 | 1.48 (0.62–3.52) | p=0.3717 | 1.48 (0.56–3.96) | p=0.4315 | 0.9649 |
| Number of Body Sites with Pain 2 | 1.03 (0.98 – 1.09) | p=0.2608 | 1.06 (.98–1.15) | p=0.1412 | 0.1541 |
| Number of Genital Sites with Pain Ordinal 2 | 1.61 (0.83–3.11) | P=0.1581 | 1.99 (0.79–4.97) | P=0.1421 | 0.6635 |
| Number of Genital Sites with Pain 2 | 1.20 (0.84–1.72) | p=0.3177 | 1.30 (0.80–2.13) | p=0.2905 | 0.5836 |
| Genital Sites with Pain Y/N 2 | 1.07 (0.40–2.83 | p=0.0011* | 0.58 (0.12–2.87) | p=0.4999 | 0.1356 |
| Childhood Sexual Trauma3 | 3.31 (1.28–8.57) | p=0.0138* | 3.60 (1.24–10.47) | p=0.0186* | |
Adjusted for age, living with a partner, cohort, and any pain in genital area
Adjusted for age, living with a partner, cohort and depression, excluding Healthy Controls
Adjusted for age, race and cohort
Table 4 shows the association of psychosocial factors, comorbid conditions, and pain characteristics with ejaculatory dysfunction. Increased depression, anxiety, urinary symptom severity, pain in the genitalia, perceived stress, pain catastrophizing, and history of childhood sexual trauma were associated with greater ejaculatory dysfunction. Conversely, higher total SEAR score and higher scores within the Sexual Relationship, Confidence, Self Esteem subdomains of the SEAR questionnaire were associated with lower ejaculatory dysfunction.
Table 4.
Univariable and Multivariable Analysis of Factors Associated with Ejaculatory Dysfunction
| Unadjusted | Adjusted | ||||
|---|---|---|---|---|---|
| Variable | OR(95% CI) | p | OR(95% CI) | p | Adjusted Cohort interaction p-value |
| SEAR Total4 | −0.052 (−0.060, −0.045) | p<.0001* | −0.040 (−0.049, −0.034) | p<.0001* | <.0001 |
| SEAR Sexual Relationship4 | −0.042 (−0.049, −0.036) | p<.0001* | −0.033 (−0.040, −0.028) | p<.0001* | <.0001 |
| SEAR Confidence4 | −0.050 (−0.058, −0.042) | p<.0001* | −0.036 (−0.044, −0.029) | p<.0001* | 0.0024 |
| SEAR Self Esteem4 | −0.047 (−0.054, −0.039) | p<.0001 | −0.034 (−0.042, −0.027) | p<.0001 | 0.0672 |
| Perceived Stress Scale4 | 0.098 (0.074, 0.123) | p<.0001* | 0.061 (0.036, 0.085) | p<.0001* | 0.0538 |
| HADS Depression4 | 0.250 (0.207, 0.294) | p<.0001* | 0.171 (0.127, 0.215) | p<.0001* | 0.0012 |
| HADS Anxiety4 | 0.189 (0.149, 0.229) | p<.0001* | 0.112 (0.069, 0.154) | p<.0001* | 0.3717 |
| IPIP – Neuroticism4 | 0.041 (0.030, 0.052) | p<.0001* | 0.026 (0.015, 0.036) | p<.0001* | 0.0461 |
| IPIP – Extraversion4 | −0.022 (−0.036, −0.008) | p=0.0017* | −0.011 (−0.023, 0.002) | p=0.888 | 0.0916 |
| IPIP – Openness4 | −0.014 (−0.030, 0.001) | p=0.0737 | −0.010 (−0.023, 0.004) | p=0.1761 | 0.2074 |
| IPIP – Agreeableness4 | −0.015 (−0.034, 0.004) | p=0.1208 | −0.008 (−0.024, 0.008) | p=0.3304 | 0.4828 |
| IPIP – Conscientiousn ess4 | −0.027 (−0.042, −0.013) | p=0.0002* | −0.024 (−0.037, −0.011) | p=0.0004 | 0.2845 |
| CSQ: catastrophizing4 | 0.128 (0.107, 0.150) | p<.0001* | 0.086 (0.062, 0.109) | p<.0001* | 0.6305 |
| CSQ: decrease pain4 | −0.220 (−0.330, −0.110) | p<.0001* | −0.017 (−0.121, 0.087) | p=0.7433 | 0.1688 |
| CSQ: control pain4 | −0.116 (−0.223, −0.010) | p=0.0320* | −0.023 (−0.116, 0.071) | p=0.6321 | 0.0009 |
| Diabetes4 | 0.175 (−1.165, 1.515) | p=0.7972 | 0.290 (−0.861, 1.442) | p=0.6204 | 0.7858 |
| Cardiac History4 | 0.902 (0.474, 1.329) | p=<.0001 | 0.676 (0.258, 1.095) | p=0.0016 | 0.9052 |
| BMI4 | 0.005 (−0.042, 0.052) | p=0.8280 | 0.003 (−0.038, 0.044) | p=0.8797 | 0.5894 |
| Pain Severity 5 | 0.122 (0.082, 0.163) | p<.0001* | 0.109 (0.058, 0.161) | p<.0001* | 0.1568 |
| Urinary Severity 5 | 0.113 (0.071, 0.156) | p<.0001* | 0.086 (0.041, 0.130) | p<.0002* | 0.1357 |
| Pain Beyond Pelvic 5 | 0.443 (−0.194, 1.080) | p=0.1718 | 0.180 (−0.422, 0.783) | p=0.5565 | 0.6678 |
| Number of Body Sites with Pain 5 | 0.049 (−0.001, 0.099) | p=0.0563 | -0.025 (−0.028, 0.078) | p=0.3568 | 0.9258 |
| Number of Genital Sites with Pain [Ordinal] 5 | 1.020 (0.538, 1.501) | p<.0001* | 0.986 (0.409, 1.563) | p=0.0009* | 0.0199 |
| Number of Genital Sites with Pain 5 | 0.548 (0.281, 0.816) | p<.0001* | 0.512 (0.204, 0.819) | p=0.0012 | 0.0031 |
| Genital Site with Pain5 Y/N | 1.244 (0.517, 1.972) | p=0.0009* | 1.598 (0.531, 2.665) | p=0.0035 | 0.2699 |
| Childhood Sexual Trauma3 | 1.135 (0.409, 1.861) | p=0.0023* | 0.875 (0.253, 1.498) | p=0.0060 | 0.0041 |
Adjusted for age, living with a partner, cohort, and any pain in genital area
Adjusted for age, living with a partner, cohort and depression (excluding Healthy Controls)
Adjusted for age, race, and cohort
Several factors were differentially associated with worse ejaculatory dysfunction in UCPPS participants than PCs or HCs, including self-esteem and relationship variables, depression, and history of childhood sexual trauma(Table 4). SEAR Total, SEAR Sexual Relationship, and SEAR Confidence were more strongly inversely related with ejaculatory function among UCPPS and PC than HC. The association of depression with ejaculatory dysfunction was 3x greater among UCPPS participants than PC and HC. The ability to control pain was inversely associated with ejaculatory dysfunction in UCPPS participants but not PC. In fact, in PC a non-significant trend of greater ejaculatory dysfunction with increasing ability to control pain was noted. Comparing UCPPS and PC participants, the association of the number of genital sites with pain with ejaculatory dysfunction was 4x greater among PC than UCPPS. The association of childhood sexual trauma with ejaculatory dysfunction appeared to be driven by UCPPS, for whom among those experiencing trauma, EFS scores were nearly 1.8 higher than those not having experience childhood sexual trauma. There was actually no association of childhood sexual trauma with ejaculatory dysfunction in HC and PC.
Discussion:
Our study adds to the literature that examines the association between SD and UCPPS in males using patient-reported measures and comparing to healthy controls and patients with other pain conditions. The results suggest that SD is more common in male patients with UCPPS than healthy males or males with other chronic pain conditions and manifests as erectile and ejaculatory dysfunction.
Sexual dysfunction, and particularly, erectile dysfunction is caused by an interplay of factors, including general health, comorbid conditions, age, and psychological well-being.22,23 Not surprisingly, we found that a similar diverse array of factors, including diabetes, cardiovascular disease, and stress were all significantly associated with ED in our study population. What was noteworthy in our analysis was that urologic symptoms commonly experienced by patients with UCPPS, such as genital pain and urinary symptom severity were not predictive of ED but predictive of ejaculatory dysfunction. While the relationship between ejaculatory dysfunction and UCPPS is not surprising given the genital focused location of pain, it appears that the diagnosis of UCPPS is driving ED rather than specific urologic symptoms. As such, what is inherently different about patients with UCPPS and their associated symptoms that makes them more susceptible to ED than PC and HC requires further investigation. While the underlying culprit may simply be having pain or anticipating pain in the genitals during sexual activity, this is not established and there could be other less understood factors at play.
Recently, momentum has shifted towards attributing SD in patients with UCPPS to the elevated inflammatory state observed among patients with chronic pelvic pain conditions. Studies have suggested that inflammation within the prostate and genitalia, perhaps evidenced by the presence of intraprostatic calcifications, can cause local tissue injury that can damage vascular integrity, smooth muscle function, and impair release of erection-promoting neurotransmitters including nitric oxide and cyclooxygenase-2.24–26 Additionally, others have proposed that inflammation may also lead to local destruction of the neurovascular bundle which lies in close proximity to the prostate.27 Supporting this premise are the findings of Zhao et al that suggest intraprostatic calcifications seen on prostate biopsy are sensitive markers for chronic inflammation and patient-reported SD.10 While these explanations are germane to patients with chronic prostatitis, the pro-inflammatory state of patients with IC and other pain conditions also makes them susceptible to the above mechanisms.20 It is also important to acknowledge the potential influence of pain management and opioids in these patients. While opioid intake was not characterized in this study, the known disruption of the hormonal axis by opioids could contribute to SD in study participants. While the local tissue damage caused by inflammation can potentially explain SD in patients in UCPPS, the effect of psychosocial variables and central nervous system changes associated with chronic pain conditions on ED and ejaculatory dysfunction must also be considered.
It has been well established that psychological well-being is inextricably linked to sexual performance and satisfaction and conditions such as depression and anxiety are independently associated with SD.28,29 Because psychopathology and stressors are commonplace in patients with UCPPS, SD is to be anticipated.30 Each stage of the male sexual response, including desire and arousal, can be suppressed by psychiatric disorders. 31 This is partly explained by the increased basal secretion of epinephrine, seen in patients with stress, anxiety, and depression, that impairs blood flow by counteracting the vasodilation crucial for erectile function. SD can also cause depression, stress, and other psychological disturbances and as a result, patients with UCPPS may find themselves in a vicious cycle that leads to worsening SD, stress, and depression. As such, effectively treating patients with UCPPS should involve collaboration with mental health professionals to comprehensively address concomitant psychological dysfunction to minimize the basal adrenergic response.
Our study also shows the association between chronic pelvic pain and ejaculatory dysfunction. Patients with UCPPS reported higher EFS scores than HCs and PCs, and in particular, ejaculatory pain. As others have described, the mechanism of ejaculatory dysfunction in these patients is due to alteration in the sensation and modulation of the ejaculatory reflex due to local inflammation as well as the influence of performance anxiety.32,33 One of the common symptoms of UCPPS is ejaculatory pain, and it has been proposed that the anticipation of ejaculatory pain may lead to performance anxiety, which then contributes to another form of dysfunction: premature ejaculation.34 As with ED, the relationship between psychological factors and ejaculatory function has been widely discussed and our analysis found that similar factors, such as depression, anxiety, and history of childhood sexual trauma were associated with ejaculatory dysfunction. 35,36 In contrast to ED, we found that urinary symptoms and genital specific-pain were predictive of ejaculatory dysfunction. While confirming previously established associations, our study was not able to assess the influence of alpha blocker use which may also causes of ejaculatory dysfunction. Regardless of its cause, ejaculatory dysfunction is a source of frustration in male patients with UCPPS and must be addressed in a way that considers the many social and mental issues contributing to ejaculatory dysfunction in these patients.
The results of our study confirm previously reported relationships between UCPPS and SD. It is likely that a complex interplay of extrinsic stressors, local pelvic inflammation, and intrinsic psychological disturbance contributes to SD in patients with UCPPS. It is also clear that the location of pain is very influential, as genital pain was highly associated with SD, whereas pain beyond the pelvis was not. While our study corroborates many previously reported associations between UCPPS and SD, the MAPP protocol did not allow for assessment of hypertonia which has been previously shown to be associated with CPPS and sexual function.37–39 While we were not able to confirm these conclusions, we agree that a significant number of patients with UCPPS likely have hypertonia contributing to their SD. Factoring in the results of our study and recognizing the role of hypertonic/pelvic floor muscle dysfunction, we believe a comprehensive, multidisciplinary strategy is required to adequately address each contributing factor, including specifically alleviating genital pain, that integrates traditional therapy as well as other more holistic approaches.40,41
Our study is strengthened by its inclusion of HCs and PCs and use of validated, patient-reported questionnaires. This study is not without limitations. Because only one participant had IC/BPS as a sole diagnosis, we were not able to examine the isolated influence of IC/BPS on SD. In addition, our study did not examine the utilization of treatments for pelvic pain and SD including the use of erectogenic medications, alpha blockers, or opioids. Lastly, because assessment of hypertonia was not included in the MAPP protocol, we were unable to account for it in our analyses. Future studies should be focused on the utility of using a multidisciplinary approach to treating SD in patients with UCPPS.
Conclusions:
When compared to HCs and patients with other chronic pain conditions (PCs), males with UCPPS have a higher incidence of erectile and ejaculatory dysfunction. Risk factors including medical comorbidities and psychological variables, were independently found to predict worsening erectile function whereas genital pain and urologic symptoms were predictive of ejaculatory dysfunction.
Acknowledgments
Funding for the MAPP Research Network was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316.)
Footnotes
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