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Keywords:

  • chronic pelvic pain syndrome;
  • erectile dysfunction;
  • penile Doppler ultrasound;
  • psychogenic erectile dysfunction

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

Men presenting with chronic pelvic pain syndrome (CPPS) frequently report concomitant erectile dysfunction (ED), but the underlying cause of ED in this patient population has not been previously studied. This study prospectively investigated the aetiology of ED in men with CPPS. The study population comprised 46 men with penile pain or dysorgasmia, and concomitant ED. All participants completed the NIH-CPSI and international index of erectile function- erectile function domain (IIEF-EFD) questionnaires, and underwent penile duplex Doppler ultrasonography (DUS), following intracavernosal trimix injection, to evaluate erectile hemodynamic parameters. Pearson's correlation between NIH-CPSI and IIEF-EFD scores, and between NIH-CPSI score and the erectile response to trimix injections was investigated. The prevalence of mild, moderate and severe CPPS symptoms was 26, 48 and 26% respectively. The severity of ED was mild, moderate or severe in 15, 61 and 24% of men respectively. NIH-CPSI and IIEF-EFD scores were negatively correlated (r = −0.32, p = 0.002). Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were normal in 96 and 100% of men respectively. The majority of men (78%) required ≥2 trimix injections to attain an adequate erection for DUS. NIH-CPSI scores and the number of trimix injections needed were positively correlated (r = 0.22, p = 0.035). The aetiology of erectile dysfunction in men who present with CPPS and concomitant ED is almost always psychogenic. Penile DUS in this population of men is fraught with the potential for error, and frequently necessitates more than one dose of a vasoactive agent.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

Chronic pelvic pain syndrome (CPPS) is the most frequent and debilitating prostate-related complaint in men, affecting between 4 and 16% of men during their lifetime (Krieger et al., 2003). Symptoms of CPPS include discomfort in the pelvis, genitalia and perineum, as well as pain associated with ejaculation and urination. Under the National Institutes of Health (NIH) classification of prostatitis, CPPS is defined as genitourinary pain in the absence of inflammatory cells or uropathogenic bacteria detected by standard microbiological methods (NIH Category IIIb) (Krieger et al., 1999). As such, CPPS comprises more than 90% of cases of chronic prostatitis.

The aetiology of CPPS is unknown. Proposed theories include undiagnosed genitourinary tract infections, idiopathic neuralgia, abnormal pelvic floor muscle tone, psychological stress and genetic polymorphisms affecting signalling via the androgen receptor (Pontari, 2008). The presence of CPPS, especially when associated with ejaculatory and lower urinary tract symptoms, can, in turn, exacerbate psychological stress and emotional bother, perpetuating an increasingly complex clinical syndrome, and leading to an impaired quality of life (McNaughton Collins et al., 2001).

CPPS negatively impacts several domains of sexual function. Compared to pain-free control subjects, men with CPPS report less frequent sexual desire and sexual activity, and increased ejaculatory difficulties and dysorgasmia (Aubin et al., 2008). In addition, men presenting with CPPS frequently report concomitant erectile dysfunction (ED) (Lee et al., 2008). The underlying cause of ED in men with CPPS has not been previously studied. Such knowledge may influence the treatment of CPPS-associated ED and potentially improve the quality of life of affected patients.

This study was undertaken to define the aetiology of ED in men with CPPS.

Materials and methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

Patient population

The study population was comprised of men who (i) presented to our practice between 2004 and 2006 for the evaluation of penile pain or dysorgasmia, and (ii) complained of concomitant ED. Men with Peyronie's disease were excluded. All patients completed validated questionnaires for the assessment of pelvic pain and erectile function, as described below. Demographic data, comorbidity parameters and prior therapies used for the treatment of CPPS (medications, biofeedback, etc.) were recorded for all patients. In addition, all patients underwent a through history and physical examination, and measurement of serum testosterone levels (prior to 10 AM). Penile duplex Doppler ultrasonography was performed as described below. This study was performed in keeping with the principles of the Declaration of Helsinki, and was approved by the Institutional Review Board of Memorial Sloan-Kettering Cancer Center.

Assessment of pelvic pain

The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) is a validated scoring system that assesses pain, urinary symptoms and quality of life (QOL)/impact. All patients enrolled in the study completed the NIH-CPSI at the initial visit. The questionnaire contains nine questions covering the three domains of pain, urinary symptoms and QOL/impact. Patient symptoms in each domain are assigned points for a total of 43 points (pain = 21 points, urinary symptoms = 10 points and QOL/impact = 12 points). Based on the NIH-CPSI scoring system, the severity of CPPS was classified as mild (0–14 points), moderate (15–29 points) or severe (≥30 points).

Assessment of erectile function

The International Index of Erectile Function (IIEF) is a validated questionnaire which evaluates five aspects of sexual function over the preceding 4-week period: erectile function, orgasm, sexual desire, intercourse satisfaction and overall satisfaction (Rosen et al., 1997). All patients enrolled in the study completed the IIEF at the initial visit. The questionnaire consists of a total of 15 items, with each item scored on a scale of 0–5, for a maximum score of 75. Six of the 15 items pertain to ED (questions 1–5 and 15), representing the IIEF erectile function domain (EFD), with a score ranging from 0 to 30. Erectile function can be further stratified as mild (1–10), moderate (11–16) or severe (17–30). An EFD score <26 was a strict inclusion criterion for enrolment in this study.

Duplex Doppler ultrasonography

Five units (0.05 mL) of trimix (30 mg papaverine/10 μg alprostadil/1 mg phentolamine/1 mL) was administered to the study patients to induce an erection. Erection quality was assessed 10 min following trimix administration. Patients who failed to achieve an erection rigid enough for sexual penetration were re-dosed with 10 units (0.1 mL) of Trimix at 10-min intervals until a sufficient erection was achieved. Patients who were unable to achieve a sufficient erection despite a total of 25 units (0.25 mL) of trimix, over three intracavernosal injections, were excluded from the final analysis. Following trimix administration, all study patients underwent duplex penile Doppler ultrasound (DUS) examination (MicroMaxx; SonoSite Inc., Bothell, WA, USA) to assess intracavernosal blood flow. Peak systolic velocity (PSV) >30 cm/sec and end-diastolic velocity (EDV) <5 cm/sec were used as cut-offs for normal erectile hemodynamic parameters.

Statistics

All statistical analyses were performed using spss for Windows (spss 16; spss Inc., Chicago IL, USA). A Pearson correlation was sought between the NIH-CPSI and IIEF-EFD scores. The correlation between the NIH-CPSI score and the erectile response to intracavernosal trimix injections was also investigated.

Main outcome measures

The primary outcome measures included NIH-CPSI and IIEF-EFD scores for each of the study participants, along with erectile hemodynamic parameters. The number of trimix injections required to attain a sufficient erection was a secondary outcome measure.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

Patient population

The study population consisted of 46 patients who met all the inclusion criteria. Mean age was 32 ± 9 years. Fifty percent of the men were partnered. Vascular risk factors (VRF) related to ED included hypertension (13%), dyslipidaemia (15%) and cigarette smoking (25%). Fifty five percent of men had no VRF. Mean serum total testosterone level was 495 ± 125 ng/dL. Of note, all study patients had a serum testosterone level >300 ng/dL.

CPPS/ED symptoms

The mean (median) duration of CPPS symptoms was 9 ± 12 (13) months, while the mean (median) duration of ED was 7 ± 16 (12) months. In 96% of men, the onset of ED post-dated the onset of CPPS symptoms. The mean NIH-CPSI score was 16 ± 4.5. Mild CPPS symptoms occurred in 12 men (26%), moderate symptoms in 22 men (48%) and severe symptoms in 12 men (26%). With respect to CPPS symptoms, 76% of men reported penile pain, while 50% reported ejaculatory pain. Prior treatment strategies used by the study patients for the treatment of CPPS included alpha-adrenergic blockers (83%), amitriptyline (33%), gabapentin (20) and biofeedback (65%) and other strategies (65%), such as nutriceuticals, acupuncture and non-pharmacologic alternative therapies.

Erectile function

The mean IIEF-EFD score was 15 ± 5. The severity of ED was mild in 15% of men, moderate in 61% and severe in the remaining 24% of men. A negative correlation was noted between NIH-CPSI and IIEF-EFD scores (Pearson's r = −0.32, p = 0.002). Mean PSV was 46 ± 12 cm/sec, mean EDV was 1.5 ± 1.5 cm/sec and calculated mean resistive index was 0.94 ± 0.1. Only 2/46 patients (4%) had an abnormal PSV (28 and 26.5 cm/sec respectively). Both these patients required intracavernosal phenylephrine for post-procedure detumescence. No patients had an abnormal EDV. Seventy-eight percent of patients required ≥2 injections of trimix to attain an erection sufficient for the performance of the Doppler ultrasound study. A positive correlation was noted between NIH-CPSI score and the number of trimix injections required to attain a sufficient erection (Pearson's r = 0.22, p = 0.035).

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

A number of studies have reported a high prevalence of ED among patients with CPPS, ranging from 15 to 50% in different series (Liang et al., 2004; Bartoletti et al., 2007; Lee et al., 2008). Men with CPPS who have both erectile and ejaculatory dysfunction report a worse quality of life than CPPS patients without sexual dysfunction (Lee et al., 2008). The aetiology of ED in men with CPPS has not been specifically or objectively investigated to date. The NIH-CPSI contains only one question pertaining to sexual dysfunction, which assesses pain during ejaculation, and not ED per se. Psychogenic ED is a diagnosis of exclusion and should only be diagnosed after taking a thorough history, performing a physical examination and performing appropriate testing. The basic adjunctive testing includes laboratory testing and a vascular assessment most often performed using penile duplex Doppler ultrasonography.

The IIEF, although widely used in the diagnosis of ED, has previously been shown to be inaccurate in distinguishing between organic and psychogenic ED in up to one-fifth of men studied (Deveci et al., 2008). To our knowledge, this is the first study that uses an objective tool, namely, penile duplex DUS, to evaluate the aetiology of concomitant ED in men with CPPS.

The results of our study confirm the presence of normal erectile hemodynamic parameters in almost all men presenting with symptoms of CPPS. Only 2 of 46 men (4%) had abnormal erectile hemodynamic parameters (PSV <30 cm/sec). Interestingly, both these patients obtained an erection just rigid enough for penetration (6/10). Both men also required intracavernosal phenylephrine for reversal of erection after the DUS study, suggesting that their inability to generate adequate arterial inflow may have been adrenaline-mediated, rather than owing to true underlying cavernosal artery insufficiency.

The prevalence of vascular comorbidities varied from 0 to 2 in this cohort of men, with the majority having no VRF, and approximately one-third having a single VRF. Besides the two above-mentioned patients, each of whom had vascular comorbidities, the presence or absence of vascular comorbidities was not associated with abnormal DUS findings in the study population. Notably, the onset of ED succeeded the onset of CPPS in virtually all men. These observations, coupled with serum total testosterone levels >300 ng/dL in the study population (Bhasin et al., 2010), further supports the finding that the underlying cause of ED in the study population was primarily psychogenic (adrenaline-mediated), not organic.

Adrenaline (epinephrine) is the primary neurotransmitter of the sympathetic nervous system, and plays a key role in the systemic fight-or-flight response. It is well established that penile erection is a vascular event controlled by the central nervous system, with sympathetic pathways being anti-erectile (Giuliano & Rampin, 2004). Elevated serum epinephrine levels are negatively correlated with IIEF scores (Trussell et al., 2010). The use of intracavernosal epinephrine for the treatment of priapism has also been reported (Roberts et al., 2009). The latter is certainly not surprising, as other sympathomimetic agents, such as phenylephrine, have long been considered the first-line pharmacologic therapy for the treatment of priapism.

Erectile hemodynamics assessment using duplex Doppler ultrasound is most accurate in the setting of an erection that is rigid enough for penetration (Schwartz et al., 1989; Mulhall et al., 2006). DUS in the flaccid or semi-erect state may lead to falsely low PSVs, suggesting arteriogenic insufficiency, or falsely elevated EDVs, suggesting venous leak. In this study, trimix re-dosing was often required for the study subjects to attain a penetration-hardness erection. Investigators performing DUS in men with CPPS should be mindful of this observation.

Although DUS provides a direct measurement of penile arteriogenic function through the measurement of PSV, it is only capable of providing an indirect measurement of the venocclusive mechanism through the measurement of EDV. The accuracy of DUS is dependent on complete penile smooth muscle relaxation. Excessive sympathetic discharge, or an anxiety-induced high adrenaline state, has the potential to prevent smooth muscle relaxation in response to intracavernosal vasoactive agent injection, leading to a false diagnosis of arteriogenic ED or venous leak in up to 50% of cases (Aversa et al., 1996; Aversa & Sarteschi, 2007; Teloken et al., 2011). The propensity for false diagnoses is most likely in younger men without significant cardiovascular risk factors (Teloken et al., 2011). Vasoactive agent re-dosing is one means of minimizing this effect.

NIH-CPSI and IIEF-EFD scores were correlated (= −0.32). This finding suggests that the severity of CPPS symptoms may predict the prevalence of ED in affected men, that is, men with a higher NIH-CPSI score being more likely to report concomitant ED. A higher CPPS score may also be reflective of more severe ED. Interestingly, a small, but positive correlation was noted between the patients' NIH-CPSI score and the number of trimix injections they required to attain a penetration-hardness erection. This observation again points to the significant psychological impact of CPPS on sexual function, as well as the importance of using an objective tool, such as DUS, to determine the cause of ED in men with CPPS.

Chung et al. investigated the magnitude of the association between ED and CPPS, and reported an odds ratio of previous CPPS of 3.62 among men with ED, compared with controls (Chung et al., 2012). Given the strength of this association, it is reasonable to recommend that men with CPPS be screened for the presence of concomitant ED. Diagnosis of the aetiology of ED, and its treatment, may significantly improve the morbidity, reduced quality of life and healthcare costs associated with CPPS.

The advantages of this study include its prospective design and use of validated questionnaires for CPPS and ED, coupled with an objective assessment of penile hemodynamic parameters to identify the underlying aetiology of concomitant ED in men with CPPS. The most important limitation of this study is that of selection bias. Patients enrolled in the study were identified on the basis of specific complaints of penile pain or dysorgasmia, in an outpatient setting focused on male sexual health. The majority of patients had already sought previous treatment for CPPS, further indicating that this was a selected sub-population of men with CPPS. It is possible that in a larger and more diverse group of men with CPPS, DUS may have demonstrated a greater frequency of alternative aetiologies of ED. Nevertheless, the fact that the majority of men with CPPS and concomitant ED have a psychogenic aetiology of ED remains obvious from our results, and unlikely to be negated by a larger sample size.

Conclusion

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

The aetiology of erectile dysfunction in men who present with CPPS and concomitant ED is almost always psychogenic. Penile duplex Doppler ultrasonography in this population of men is fraught with the potential for error; accurate assessment of erectile hemodynamic parameters frequently necessitates more than one dose of a vasoactive agent prior to DUS.

Disclosures

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

None of the authors have any competing financial interests in relation to this study.

Author contributions

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References

AM – Data analysis and manuscript preparation, DSS – Study design and data analysis, KO – Study design and data accrual, JPM – Study design, data analysis and manuscript editing

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosures
  10. Author contributions
  11. References