1
A Prospective Study on Association of Prostatic Calcifications with Sexual Dysfunction in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) Zhigang Zhao, MD, PhD,* Xujun Xuan, MD, PhD,† Jingwei Zhang, MD,* Jun He, MD,* and Guohua Zeng, MD, PhD* *Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; †Department of Urology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China DOI: 10.1111/jsm.12534
ABSTRACT
Introduction. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common debilitating condition of unclear etiology. Sexual dysfunction is an important component of the clinical phenotype of CP/CPPS. Patients often have prostatic calcifications, but a link to sexual dysfunction is unknown. Aim. The aim of this study was to evaluate the association of prostatic calcifications with sexual dysfunction in this condition. Methods. A total of 358 males with CP/CPPS were consecutively enrolled, and a prospectively maintained database of these patients was analyzed. Calcifications were diagnosed using ultrasound imaging of the prostate. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Sexual dysfunction was evaluated using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire and 5-item Premature Ejaculation Diagnostic Tool scales. The variables were compared between patients with prostatic calcifications and those without using the Student’s t-test, Wilcoxon unpaired test, or chi-square test. Main Outcome Measure. Logistic regression models were developed to explore a possible association between prostatic calcifications and sexual dysfunction. Results. Measurable calcifications in the prostate were found in 175 (48.9%) of the 358 patients. Patients with calcifications were more likely to have higher white blood cell counts or positive bacteria cultures in their prostatic fluid, longer symptoms duration, and lower scores for the total IIEF-15, IIEF-erectile function, and IIEFintercourse satisfaction domains (P < 0.001 for each). However, the scores for CPSI, premature ejaculation, and IIEF-orgasmic function, IIEF-sexual desire, and IIEF-overall satisfaction domains were identical between men with and without calcifications (P > 0.05 for each). Furthermore, logistic regression analyses revealed that intraprostatic calcification is significantly associated with self-assessed erectile dysfunction (ED) (odds ratio:3.632, 95% confidence interval: 2.405–5.822, P < 0.001). Conclusion. Our results showed that prostatic calcifications are significantly associated with the presence of ED in CP/CPPS males. Zhao Z, Xuan X, Zhang J, He J, and Zeng G. A prospective study on association of prostatic calcifications with sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS). J Sex Med **;**:**–**. Key Words. Prostatic Calcifications; Prostatitis; Chronic Pelvic Pain Syndrome; Sexual Dysfunction
© 2014 International Society for Sexual Medicine
J Sex Med **;**:**–**
2 Introduction
C
hronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common yet poorly understood condition, with significant economic costs and severe impact on the quality of life (QoL) of diagnosed patients [1,2]. The prevalence was estimated between 2.2% and 13.8% [3–5]. It is widely acknowledged that CP/CPPS is associated with significant sexual dysfunction, including erectile dysfunction (ED), decreased sexual desire or frequency of sexual activities, and premature ejaculation (PE) [6–11]. However, the pathogenesis of CP/CPPS-associated sexual dysfunction remains unclear. Prostatic calcifications are common in men and presumed to form by the precipitation of substances within the prostatic secretions and calcification of the corpora amylacea under inflammatory conditions [12,13]. However, the clinical significance of those calcifications with respect to urological diseases and symptoms remains unknown. Some studies have correlated the presence of prostatic calcifications with CP/CPPS-related symptoms [14–16]. One study involved patients with both CP/CPPS and prostatic calculi and found that therapy designed to medically dissolve the prostatic stones resulted in symptomatic improvement in 80% [17]. Their presence in young men is often associated with intraprostatic inflammation [14]. Recently, Shoskes et al. [18] claimed that prostatic calcifications are commonly present in patients with CP/CPPS and significantly correlate with greater intraprostatic inflammation or bacterial colonization, and longer symptoms duration. Several studies have suggested that ED and CP/CPPS may be linked by a shared inflammatory process originating from a prostatic source [19–21]. However, no studies have reported the contribution of prostatic calcifications to sexual dysfunction in this condition. The aims of this prospective study were to compare CP/CPPS patients with prostatic calcifications with those without prostatic calcifications on aspects of their sexual dysfunction and to explore the possible association between intraprostatic calcifications and sexual dysfunction. Materials and Methods
Patients Population and Study Design The patient population included 358 consecutive male patients with a diagnosis of CP/CPPS, who were prospectively evaluated in the urology and andrology clinic of our hospital from November J Sex Med **;**:**–**
Zhao et al. 2009 to July 2013 by one urologist (Z. Zhao). All patients were diagnosed according to the National Institutes of Health (NIH) criteria [22]. In brief, the patients had primarily urological pain complaints, as well as voiding complaints and sexual dysfunction. The presence of leukocytes in their expressed prostatic secretions (EPSs), postprostate massage urine specimen (voided bladder urine-3 [VB3]), or semen was categorized as the inflammatory subtype of CP/CPPS (Type IIIA), and no evidence of inflammation on EPSs, VB3, or semen was categorized as the noninflammatory subtype of CP/CPPS (Type IIIB). Each patient was assessed by a focused physical examination that included pre-massage urine and EPSs or postmassage urine analysis and culture, a digital rectal examination of the prostate and the pelvic floor muscles, and transabdominal ultrasonic imaging of the prostate at the first visit. During the same visit, each patient filled out all questionnaires himself at the urologist office and was also interviewed for their sociodemographic and medical history, including age, smoking habits, diabetes, hypertension, and cardiovascular disease. Comorbidities were evaluated as absent or present. Patients who smoked in the last 5 years were considered smokers to evaluate the chronic effects of smoke on the disease. In addition, anthropometric measurements, including the height and weight, were determined and body mass index (BMI) was calculated for each patient. Patients who received any form of erectile aid supplementation (such as phosphodiesterase type 5 inhibitors) or had acute urinary tract infections or infections localized to the prostate (i.e., acute or chronic bacterial prostatitis), positive cultures for Chlamydia trachomatis or Neisseria gonorrhoea, previous surgery or radiation therapy of the lower urinary tract organs, postoperative pain, pain from another source in the genitourinary tract (e.g., renal calculi), a history or evidence of genitourinary tumor, neurologic diseases affecting the bladder, as well as suicidal ideation or psychosis were excluded. The protocol was approved by the Ethics Review Board of Guangzhou Medical University, and each patient provided the written informed consent to undergo this study.
Measurements and Definitions Prostatic calcifications and prostate volume were measured during the transabdominal ultrasonography, which was done by one urologist who was blinded to the clinical data. The discrete small echoes distributed diffusely throughout the pros-
Prostatic Calcifications and Sexual Dysfunction in CP/CPPS tate or larger, more echogenic foci that caused acoustic shadowing were considered prostatic calcifications in this study. According to the presence of prostatic calcifications, we divided the cohort into the calcification group and no calcification group, and resumed the analysis. Each patient had their symptom measured by using the NIH Chronic Prostatitis Symptom Index (CPSI), a nine-item validated questionnaire with high test–retest reliability and good psychometric properties, reported as the total score (0–43 points) and the subscores for pain (0–21 points), urinary (0–10 points), and QoL (0–12 points) [23]. Sexual function was assessed by using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire [24–26] to evaluate ED, orgasmic function (OF), and sexual desire (SD), plus the validated 5-item Premature Ejaculation Diagnostic Tool (PEDT) to evaluate PE [27]. The erectile function (EF) domain consisted of questions 1 to 5 and question 15 for the global EF assessment. The scoring of the IIEF-EF domain allowed classification of each patient as having no (score 25–30), mild (score 19–24), mild to moderate (score 13–18), moderate (score 7–12), or severe (score 0.05 for each). Although the mean NIH-CPSI total and all its three subdomains scores were higher in the calcification group than in the no calcification group, the differences were not statistically significant (P > 0.05 for each). Compared with patients without prostatic calcifications, those with prostatic calcifications usually had symptoms for significantly longer (median 47 vs. 15 months, P < 0.001). Using a definition of EPS inflammation of at least 10 white blood cells (WBCs) per high power field (hpf), 107 (29.9%) were classified as category IIIa (inflammatory) and 251 (70.1%) were category IIIb diseases. The calcification group had slightly higher WBC counts/hpf in their EPSs (median 5.2 vs. 1.0, P < 0.001) and was more likely to have category IIIa disease (P < 0.001). Also, cultures of the EPSs were more likely to be positive in men with calcifications, whether for uropathogens (gram negative, such as Escherichia coli or Klebsiella sp. or Enterococcus) or non-uropathogens (other gram-positive bacteria such as Staphylococcus epidermidis (P < 0.001 for each). J Sex Med **;**:**–**
4 Table 1
Zhao et al. Demographic and clinical characteristics of the patient cohort
Characteristics Age (years) Mean ± SD (range) BMI (kg/m2) Mean ± SD (range) Prostate volume (mL) Mean ± SD (range) Comorbidity, n (%) Diabetes Cardiovascular disease Hypertension Smoking (smokers or ex-smokers) NIH-CPSI scores, mean ± SD (range) Total score Pain subscore Voiding subscore QoL subscore Duration of symptoms (month) Mean ± SD (range) CP/CPPS diagnosis, n (%) Inflammatory (Type IIIa) Noninflammatory (Type IIIb) WBC in EPS, counts/hpf Mean ± SD (range) EPS cultures, n (%) No growth Gram-positive bacteria Gram-negative bacteria Pelvic muscle tenderness, n (%)
All patients (n = 358)
Calcification group (n = 175)
No calcification group (n = 183)
P value*
45.5 ± 10.3 (20–68)
45.3 ± 9.6 (20–68)
45.8 ± 10.1 (22–67)
0.874
24.6 ± 2.2 (17.9–32.2)
24.8 ± 2.1 (20.4–30.7)
24.6 ± 2.2 (17.9–32.2)
0.910
26.5 ± 8.5 (22.8–36.4)
26.4 ± 8.4 (24.5–32.0)
26.0 ± 8.2 (22.8–36.4)
0.781
27 (7.5) 35 (9.8) 82 (22.9) 97 (27.1) 24.45 ± 7.13 (6–42) 10.52 ± 3.06 (0–21) 4.38 ± 2.41 (0–8) 8.60 ± 2.52 (1–12) 26.4 ± 7.2 (3–182)
12 (6.9) 18 (10.3) 43 (24.6) 45 (25.7) 25.04 ± 7.62 (10–42) 10.52 ± 3.10 (0–21) 4.60 ± 2.48 (1–8) 9.09 ± 2.60 (1–12) 49.5 ± 10.8 (10–182)
15 (8.2) 17 (9.3) 39 (21.3) 52 (28.4)
0.144 0.203 0.117 0.114
24.77 ± 7.20 (6–42) 10.24 ± 3.00 (0–20) 4.37 ± 2.40 (0–8) 8.82 ± 2.52 (2–12)
0.085 0.126 0.105 0.060
16.3 ± 5.6 (3–104)
A Prospective Study on Association of Prostatic Calcifications with Sexual Dysfunction in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) Zhigang Zhao, MD, PhD,* Xujun Xuan, MD, PhD,† Jingwei Zhang, MD,* Jun He, MD,* and Guohua Zeng, MD, PhD* *Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; †Department of Urology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China DOI: 10.1111/jsm.12534
ABSTRACT
Introduction. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common debilitating condition of unclear etiology. Sexual dysfunction is an important component of the clinical phenotype of CP/CPPS. Patients often have prostatic calcifications, but a link to sexual dysfunction is unknown. Aim. The aim of this study was to evaluate the association of prostatic calcifications with sexual dysfunction in this condition. Methods. A total of 358 males with CP/CPPS were consecutively enrolled, and a prospectively maintained database of these patients was analyzed. Calcifications were diagnosed using ultrasound imaging of the prostate. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Sexual dysfunction was evaluated using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire and 5-item Premature Ejaculation Diagnostic Tool scales. The variables were compared between patients with prostatic calcifications and those without using the Student’s t-test, Wilcoxon unpaired test, or chi-square test. Main Outcome Measure. Logistic regression models were developed to explore a possible association between prostatic calcifications and sexual dysfunction. Results. Measurable calcifications in the prostate were found in 175 (48.9%) of the 358 patients. Patients with calcifications were more likely to have higher white blood cell counts or positive bacteria cultures in their prostatic fluid, longer symptoms duration, and lower scores for the total IIEF-15, IIEF-erectile function, and IIEFintercourse satisfaction domains (P < 0.001 for each). However, the scores for CPSI, premature ejaculation, and IIEF-orgasmic function, IIEF-sexual desire, and IIEF-overall satisfaction domains were identical between men with and without calcifications (P > 0.05 for each). Furthermore, logistic regression analyses revealed that intraprostatic calcification is significantly associated with self-assessed erectile dysfunction (ED) (odds ratio:3.632, 95% confidence interval: 2.405–5.822, P < 0.001). Conclusion. Our results showed that prostatic calcifications are significantly associated with the presence of ED in CP/CPPS males. Zhao Z, Xuan X, Zhang J, He J, and Zeng G. A prospective study on association of prostatic calcifications with sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS). J Sex Med **;**:**–**. Key Words. Prostatic Calcifications; Prostatitis; Chronic Pelvic Pain Syndrome; Sexual Dysfunction
© 2014 International Society for Sexual Medicine
J Sex Med **;**:**–**
2 Introduction
C
hronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common yet poorly understood condition, with significant economic costs and severe impact on the quality of life (QoL) of diagnosed patients [1,2]. The prevalence was estimated between 2.2% and 13.8% [3–5]. It is widely acknowledged that CP/CPPS is associated with significant sexual dysfunction, including erectile dysfunction (ED), decreased sexual desire or frequency of sexual activities, and premature ejaculation (PE) [6–11]. However, the pathogenesis of CP/CPPS-associated sexual dysfunction remains unclear. Prostatic calcifications are common in men and presumed to form by the precipitation of substances within the prostatic secretions and calcification of the corpora amylacea under inflammatory conditions [12,13]. However, the clinical significance of those calcifications with respect to urological diseases and symptoms remains unknown. Some studies have correlated the presence of prostatic calcifications with CP/CPPS-related symptoms [14–16]. One study involved patients with both CP/CPPS and prostatic calculi and found that therapy designed to medically dissolve the prostatic stones resulted in symptomatic improvement in 80% [17]. Their presence in young men is often associated with intraprostatic inflammation [14]. Recently, Shoskes et al. [18] claimed that prostatic calcifications are commonly present in patients with CP/CPPS and significantly correlate with greater intraprostatic inflammation or bacterial colonization, and longer symptoms duration. Several studies have suggested that ED and CP/CPPS may be linked by a shared inflammatory process originating from a prostatic source [19–21]. However, no studies have reported the contribution of prostatic calcifications to sexual dysfunction in this condition. The aims of this prospective study were to compare CP/CPPS patients with prostatic calcifications with those without prostatic calcifications on aspects of their sexual dysfunction and to explore the possible association between intraprostatic calcifications and sexual dysfunction. Materials and Methods
Patients Population and Study Design The patient population included 358 consecutive male patients with a diagnosis of CP/CPPS, who were prospectively evaluated in the urology and andrology clinic of our hospital from November J Sex Med **;**:**–**
Zhao et al. 2009 to July 2013 by one urologist (Z. Zhao). All patients were diagnosed according to the National Institutes of Health (NIH) criteria [22]. In brief, the patients had primarily urological pain complaints, as well as voiding complaints and sexual dysfunction. The presence of leukocytes in their expressed prostatic secretions (EPSs), postprostate massage urine specimen (voided bladder urine-3 [VB3]), or semen was categorized as the inflammatory subtype of CP/CPPS (Type IIIA), and no evidence of inflammation on EPSs, VB3, or semen was categorized as the noninflammatory subtype of CP/CPPS (Type IIIB). Each patient was assessed by a focused physical examination that included pre-massage urine and EPSs or postmassage urine analysis and culture, a digital rectal examination of the prostate and the pelvic floor muscles, and transabdominal ultrasonic imaging of the prostate at the first visit. During the same visit, each patient filled out all questionnaires himself at the urologist office and was also interviewed for their sociodemographic and medical history, including age, smoking habits, diabetes, hypertension, and cardiovascular disease. Comorbidities were evaluated as absent or present. Patients who smoked in the last 5 years were considered smokers to evaluate the chronic effects of smoke on the disease. In addition, anthropometric measurements, including the height and weight, were determined and body mass index (BMI) was calculated for each patient. Patients who received any form of erectile aid supplementation (such as phosphodiesterase type 5 inhibitors) or had acute urinary tract infections or infections localized to the prostate (i.e., acute or chronic bacterial prostatitis), positive cultures for Chlamydia trachomatis or Neisseria gonorrhoea, previous surgery or radiation therapy of the lower urinary tract organs, postoperative pain, pain from another source in the genitourinary tract (e.g., renal calculi), a history or evidence of genitourinary tumor, neurologic diseases affecting the bladder, as well as suicidal ideation or psychosis were excluded. The protocol was approved by the Ethics Review Board of Guangzhou Medical University, and each patient provided the written informed consent to undergo this study.
Measurements and Definitions Prostatic calcifications and prostate volume were measured during the transabdominal ultrasonography, which was done by one urologist who was blinded to the clinical data. The discrete small echoes distributed diffusely throughout the pros-
Prostatic Calcifications and Sexual Dysfunction in CP/CPPS tate or larger, more echogenic foci that caused acoustic shadowing were considered prostatic calcifications in this study. According to the presence of prostatic calcifications, we divided the cohort into the calcification group and no calcification group, and resumed the analysis. Each patient had their symptom measured by using the NIH Chronic Prostatitis Symptom Index (CPSI), a nine-item validated questionnaire with high test–retest reliability and good psychometric properties, reported as the total score (0–43 points) and the subscores for pain (0–21 points), urinary (0–10 points), and QoL (0–12 points) [23]. Sexual function was assessed by using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire [24–26] to evaluate ED, orgasmic function (OF), and sexual desire (SD), plus the validated 5-item Premature Ejaculation Diagnostic Tool (PEDT) to evaluate PE [27]. The erectile function (EF) domain consisted of questions 1 to 5 and question 15 for the global EF assessment. The scoring of the IIEF-EF domain allowed classification of each patient as having no (score 25–30), mild (score 19–24), mild to moderate (score 13–18), moderate (score 7–12), or severe (score 0.05 for each). Although the mean NIH-CPSI total and all its three subdomains scores were higher in the calcification group than in the no calcification group, the differences were not statistically significant (P > 0.05 for each). Compared with patients without prostatic calcifications, those with prostatic calcifications usually had symptoms for significantly longer (median 47 vs. 15 months, P < 0.001). Using a definition of EPS inflammation of at least 10 white blood cells (WBCs) per high power field (hpf), 107 (29.9%) were classified as category IIIa (inflammatory) and 251 (70.1%) were category IIIb diseases. The calcification group had slightly higher WBC counts/hpf in their EPSs (median 5.2 vs. 1.0, P < 0.001) and was more likely to have category IIIa disease (P < 0.001). Also, cultures of the EPSs were more likely to be positive in men with calcifications, whether for uropathogens (gram negative, such as Escherichia coli or Klebsiella sp. or Enterococcus) or non-uropathogens (other gram-positive bacteria such as Staphylococcus epidermidis (P < 0.001 for each). J Sex Med **;**:**–**
4 Table 1
Zhao et al. Demographic and clinical characteristics of the patient cohort
Characteristics Age (years) Mean ± SD (range) BMI (kg/m2) Mean ± SD (range) Prostate volume (mL) Mean ± SD (range) Comorbidity, n (%) Diabetes Cardiovascular disease Hypertension Smoking (smokers or ex-smokers) NIH-CPSI scores, mean ± SD (range) Total score Pain subscore Voiding subscore QoL subscore Duration of symptoms (month) Mean ± SD (range) CP/CPPS diagnosis, n (%) Inflammatory (Type IIIa) Noninflammatory (Type IIIb) WBC in EPS, counts/hpf Mean ± SD (range) EPS cultures, n (%) No growth Gram-positive bacteria Gram-negative bacteria Pelvic muscle tenderness, n (%)
All patients (n = 358)
Calcification group (n = 175)
No calcification group (n = 183)
P value*
45.5 ± 10.3 (20–68)
45.3 ± 9.6 (20–68)
45.8 ± 10.1 (22–67)
0.874
24.6 ± 2.2 (17.9–32.2)
24.8 ± 2.1 (20.4–30.7)
24.6 ± 2.2 (17.9–32.2)
0.910
26.5 ± 8.5 (22.8–36.4)
26.4 ± 8.4 (24.5–32.0)
26.0 ± 8.2 (22.8–36.4)
0.781
27 (7.5) 35 (9.8) 82 (22.9) 97 (27.1) 24.45 ± 7.13 (6–42) 10.52 ± 3.06 (0–21) 4.38 ± 2.41 (0–8) 8.60 ± 2.52 (1–12) 26.4 ± 7.2 (3–182)
12 (6.9) 18 (10.3) 43 (24.6) 45 (25.7) 25.04 ± 7.62 (10–42) 10.52 ± 3.10 (0–21) 4.60 ± 2.48 (1–8) 9.09 ± 2.60 (1–12) 49.5 ± 10.8 (10–182)
15 (8.2) 17 (9.3) 39 (21.3) 52 (28.4)
0.144 0.203 0.117 0.114
24.77 ± 7.20 (6–42) 10.24 ± 3.00 (0–20) 4.37 ± 2.40 (0–8) 8.82 ± 2.52 (2–12)
0.085 0.126 0.105 0.060
16.3 ± 5.6 (3–104)
