Impact of prostate volume on erectile dysfunction and premature ejaculation

Abstract

We evaluated the impact of total prostate volume (TPV) on the international index of erectile function-5 (IIEF) and the premature ejaculation diagnostic tool (PEDT). A cross-sectional study was conducted that included 8336 men who had participated in a health examination. PEDT, IIEF and transrectal ultrasonography were used. A full metabolic work-up and serum testosterone level checks were also performed. The median age of participants was 51.0 years. In total, 40.1% had IIEF scores ≤16. Additionally, 24.7% were classified as demonstrating premature ejaculation (PE) (PEDT > 10). The severity of erectile dysfunction (ED) significantly increased with the TPV (p trend < 0.001). After adjusting for potential confounding factors, the odds ratio (OR) for IIEF scores ≤ 16 significantly increased in the group with TPVs of 30–39 cm³ and the group with TPVs ≥ 40 cm³ compared with the group with TPVs ≤ 19 cm³ (TPV 30–39 cm³, OR: 1.204, 95% confidence interval: 1.034–1.403; TPV ≥ 40 cm³, OR: 1.326: 95% confidence interval: 1.051–1.733) and this relationship was maintained after adjusting for propensity score (TPV ≥ 30 cm³, OR: 1.138: 95% confidence interval: 1.012–1.280). However, neither PEDT nor PE was correlated with TPV. In conclusion, TPV is significantly and independently correlated with IIEF but not with PEDT. Future investigations should explore the temporal relationship between TPV and ED.

• Prostate
• erectile dysfunction
• premature ejaculation
• transrectal ultrasonography
• premature ejaculation diagnostic tool
• international index of erectile function-5

Introduction

Both erectile dysfunction (ED) and premature ejaculation (PE) are highly prevalent in middle-aged and elderly men and could significantly impact their quality of life [1–4]. ED and PE are closely related to each other and each is a risk factor for the other [5]. ED and PE share many comorbidities such as diabetes [1,6], thyroid disease [7] and lower urinary tract symptoms (LUTS) [5].

The prostate is located close to the nerves and blood vessels that supply the penis. The major arterial supply to the corpora cavernosa is derived from the internal pudendal artery, and aberrant branches travel along the anterolateral surface of the prostate [8]. Deep dorsal veins penetrate the urogenital diaphragm, dividing into a superficial branch and the right and left lateral venous plexus. The superficial branch lies outside the anterior prostatic fascia. The lateral venous plexus runs posterolateral to the prostate [8]. The cavernosal nerves run as a plexus of small nerves within a prominent neurovascular bundle on the posterolateral border of the prostate [9]. Because of their anatomical closeness, an enlarged prostate could induce a loss of sexual function by compression of these vessels and nerves. However, data concerning the impact of total prostate volume (TPV) on sexual function (ED and PE) are scant and their results are inconsistent [10,11]. To define the exact role of TPV in ED and PE, we performed this study.

Methods

Subjects

We used a database comprising patients from previous studies [12]. This patient cohort has been described in detail elsewhere [12]. Briefly, the study populations are described below. From August 2011 to November 2013, 8727 men over 40 years of age participated in a urological health checkup. This health screening included anthropometric measurements (blood pressure measurements, waist circumference, height and weight), prostate-specific antigen levels, testosterone levels, a complete blood cell count, basic blood chemistry analyses, a urine analysis and transrectal ultrasonography. The participants were also asked to complete questionnaires concerning urological health, including the International Prostate Symptom Score (IPSS), the Premature Ejaculation Diagnostic Tool (PEDT), the International Index of Erectile Function-5 (IIEF) and the National Institutes of Health-Chronic Prostatitis Symptoms Index. All of the participants provided written informed consent, and data concerning the participants were collected prospectively.

To evaluate the relationship between TPV and ED and PE, data from the TPV, IPSS, IIEF, PEDT, anthropometric measurements, testosterone levels, basic blood chemistry and MetS assessments, as well as other diverse clinical parameters, were used. The Institutional Review Board of our hospital approved this study. (IRB number: 11100176–201502-HR-003).

TPV, PE, ED and LUTS assessments

The PEDT, IPSS and IIEF were used for the assessments of PE, LUTS and ED, respectively. Males with PEDT scores >10 and between 9 and 10 were classified as having PE and possible PE, respectively [3]. We classified the severity of ED as normal (IIEF >21), mild ED (IIEF > 16 to ≤21), mild to moderate ED (IIEF > 11 to ≤16), moderate ED (IIEF > 7 to ≤11) and severe ED (IIEF ≤ 7). Mild LUTS and moderate to severe LUTS were defined as IPSS <8 and IPSS ≥ 8, respectively.

TPV was calculated using trans-rectal ultrasonography (UltraView 800, BKmedical, Denmark). Prostate size measurements were performed by a single sonographer. The anteroposterior diameter and transverse diameter were measured on the largest transverse image of the prostate, whereas the horizontal distance between the proximal and most distal points of the prostate on a midline sagittal scan was considered the longitudinal diameter [13]. TPV was then estimated assuming a prolate ellipsoid shape using the formula TPV = ([π /6] × [anteroposterior diameter ×  transverse diameter × longitudinal diameter]) [13].

MetS assessment

Two blood pressure (mmHg) measurements, obtained 5 min apart using a mercury sphygmomanometer on the right arm, were averaged. Waist circumference (cm), to the nearest 0.1 cm, was measured midway between the lowest rib and the iliac crest. Body weight (kg) and body height (cm) were also recorded. Serum was collected in the morning (between 7:00 and 9:00 AM) after an overnight fast. The biochemical analyses performed measured fasting serum glucose level, triglyceride level and high-density lipoprotein cholesterol (HDL-C) level. A diagnosis of MetS required the satisfaction of three or more of the NCEP-ATP III criteria [14].

Testosterone assay

Serum testosterone was measured via radioimmunoassay using a kit from Cisbio Bioassays, Inc. (Parc Marcel Boiteux, Codolet). The intra-assay coefficients of variation for all assays were less than 9%, and the inter-assay coefficients of variation were less than 12%. For each assay, all samples from each subject were measured in the same assay run.

Statistical analysis

We excluded 391 men for whom IPSS, IIEF and/or PEDT data were missing, men who had not engaged in sexual intercourse within the previous 6 months, men who had been administered related drugs, including alpha blockers, phosphodiesterase-5 inhibitors, anti-psychotics, or selective serotonin reuptake inhibitors, and men with pyuria. The remaining 8336 subjects were analyzed.

First, we evaluated the relationship of TPV with IIEF and PEDT using Speraman correlation test. Second, we evaluated the relationship between ED severity and the grade of TPV (≤19 cm³, 20–29 cm³,  ≥30 cm³) using the Mantel–Haenszel Extension test (testing for the presence of a trend in case control or cross-sectional studies where a series of increasing or decreasing exposures is being studied). Additionally, the ratio of participants with PE and possible PE according TPV grade was calculated and their trends were analyzed using the Mantel–Haenszel Extension test. Third, unadjusted and adjusted (adjusting for log testosterone, metabolic syndrome, LUTS severity (IPSS < 8, IPSS ≥ 8) and age group (40s, 50s)) ORs for IIEF ≤16 with relation to TPV grade were calculated using logistic regression. Additionally, propensity scores (the propensity score is the probability of treatment or case group assignment conditional on observed baseline characteristics [15]. The propensity score allows one to design and analyze an observational study so that it mimics some of the particular characteristics of a randomized controlled trial [15]) adjusted odds ratio (OR) (adjusting for log testosterone, metabolic syndrome, LUTS severity (IPSS < 8, IPSS ≥ 8), and age group (40s, 50s)) were calculated to confirm the role of TPV ≥ 30 cm³ as a cut-off value to predict IIEF scores ≤16.

Statistical analyses were performed using the Statistical Package for Social Sciences, version 11.0 (SPSS, Chicago, IL). A value of p < (0).05 was considered to be statistically significant.

Results

Patient characteristics

The characteristics of the patient population are shown in Table 1. The median patient age was 51.0 years. The median patient testosterone level was 5.1 ng/mL. The median patient TPV was 23.0 cm³. A total of 574 (6.9%) men had severe ED, 819 (9.8%) men had moderate ED, and 1952 (23.4%) men had mid-moderate ED. Additionally, 2060 men were classified as demonstrating PE (24.7%).

Table 1. Patient characteristics.

Variable	Median (IQR) or number (%)
Age (y)	51.0 (46.0–56.0)
Height (cm)	172.0 (170.0–175.0)
Weight (kg)	74.0 (69.0–80.0)
Systolic blood pressure (mm Hg)	126.0 (115.0–137.0)
Diastolic blood pressure (mm Hg)	82.0 (75.0–90.0)
Waist circumference (cm)	88.0 (84.0–92.0)
Glucose, fasting (mg/dL)	100.0 (94.0–109.0)
Triglyceride (mg/dL)	136.0 (96.0–195.0)
HDL-cholesterol (mg/dL)	43.0 (37.0–50.0)
Testosterone (ng/mL)	5.1 (4.2–6.3)
Total prostate volume (mL)	23.0 (20.0–28.0)
IPSS total	9.0 (5.0–15.0)
IPSS qol	3.0 (1.0–4.0)
IIEF	18.0 (14.0–22.0)
PEDT	7.0 (4.0–10.0)
IIEF
No ED (22–25)	2404 (28.8)
Mild ED (17–21)	2587 (31.0)
Mild-moderate ED (12–16)	1952 (23.4)
Moderate ED (8–11)	819 (9.8)
Severe ED (1–7)	574 (6.9)
PE (PEDT > 10)	2060 (24.7)
TPV
<20 mL	2060 (24.7)
20–29 mL	4752 (57.0)
30–39 mL	1254 (15.0)
≥40 mL	270 (3.2)

IQR, interquartile range; IPSS, International prostate symptom score; qol, Quality of life; IIEF, International Index of Erectile Function-5 questionnaire; PEDT, Premature Ejaculation Diagnostic Tool; ED, Erectile dysfunction; PE, Premature ejaculation.

Relationships between TPV and ED

TPV had significant correlation with IIEF (rho= −0.079; p < 0.001; Speraman correlation test). The severity of ED significantly increased with increases in TPV grade (≤19 cm³, 20–29 cm³, ≥30 cm³) (Table 2). Unadjusted ORs for IIEF ≤16 also increased with increased TPV grade (≤19 cm³, 20–29 cm³, 30–39 cm³, ≥40 cm³) (Table 3). After adjusting for log testosterone, metabolic syndrome, LUTS severity (IPSS < 8, IPSS ≥ 8) and age group (40s, 50s), the OR for IIEF ≤16 was significantly different in 30–39 cm³ and ≥40 cm³ groups compared with the ≤19 cm³ group (Table 3). However, ORs for IIEF ≤16 were not significantly different in the 20–29 cm³ group compared with ≤19 cm³ group (Table 3). According to these results, the cut-off value for predicting IIEF scores ≤16 is a TPV of 30 cm³, and this cut-off value was maintained after adjusting for propensity score (Table 3).

Table 2. Severity of ED according to TPV.

	TPV (mL)
ED severity	≤19	20–29	≥30	p trend
No ED	31.0%	29.5%	23.8%	<0.001
Mild ED	34.1%	30.5%	28.7%
Mild to moderate ED	20.0%	23.4%	28.2%
Moderate ED	8.6%	9.9%	11.2%
Severe ED	6.3%	6.8%	8.1%

No ED, IIEF >21; mild ED, IIEF > 16 to ≤21; mild to moderate ED, IIEF > 11 to ≤16; moderate ED, IIEF > 7 to ≤11; severe ED, IIEF ≤ 7. ED, Erectile dysfunction; IIEF, International Index of Erectile Function-5 questionnaire.

Table 3. OR for ED (IIEF ≤16) according to TPV.

	TPV (mL)
OR for ED	≤19	20–29	30–39	≥40
Unadjusted OR (5–95% CI)	1.000 (reference)	1.246 (1.119–1.387)	1.615 (1.400–1.864)	2.039 (1.579–2.632)
p		<0.001	<0.001	<0.001
Adjusted OR* (5–95% CI)	1.000 (reference)	1.102 (0.984–1.235)	1.204 (1.034–1.403)	1.326 (1.015–1.733)
p		0.093	0.017	0.039
OR for ED	TPV (mL)
		<30	≥30
	Propensity score adjusted OR† (5–95% CI)	1.000 (reference)		1.138 (1.012–1.280)
p			0.031

OR, Odds ratio; ED, Erectile dysfunction.

* Adjusted for log testosterone, metabolic syndrome, lower urinary tract symptom severity (IPSS < 8, IPSS ≥ 8), and age group (40s, 50s).

† Adjusted for log testosterone, metabolic syndrome, lower urinary tract symptom severity (IPSS < 8, IPSS ≥ 8), and age group (40s, 50s).

Relationships between TPV and PE

TPV had not significant correlation with IIEF (rho = 0.007; p = 0.513; Speraman correlation test).

Additionally, PE and possible PE were not significantly correlated with increased TPV grades (≤19 cm³, 20–29 cm³, ≥30 cm³) (Table 4).

Table 4. PE ratios according to TPV.

	TPV (mL)
	≤re	20–29	≥9e	p trend
PE	62.9%	63.0%	60.9%	0.356
Possible PE	12.7%	12.3%	13.8%
No PE	24.4%	24.6%	25.3%

PE, PEDT scores >10; possible PE, PEDT ≥ 9 to PEDT ≤ 10; No PE, PEDT < 10; PE, Premature ejaculation; PEDT, premature ejaculatory diagnostic tool.

Discussion

A few studies have demonstrated the impact of TPV on ED, but the effect of TPV has not been consistent across cross-sectional studies. A UK study [10] that enrolled 427 volunteers demonstrated that mean log TPV as assessed by transrectal ultrasound was not significantly different between groups with no ED, intermediate ED and complete ED assessed by a simple questionnaire (no ED: always able to attain a penile erection sufficient for satisfactory sexual activity; complete ED: never able to attain a penile erection sufficient for satisfactory sexual activity; intermediate ED: fell between the two criteria). An Italian retrospective study [11] enrolled 1823 patients attending an outpatient clinic for sexual dysfunction showed that enlarged prostate size as measured by digital rectal examination was significantly associated with the risk of attaining erections that were insufficient for penetration (hazard ratio = 1.115 (1.007–1.234); p = 0.037 for each increment in the score of question 1C of SIEDY) and reduced flaccid acceleration and dynamic peak systolic pressure (hazard ratio = 0.783 (0.697–0.880) and hazard ratio = 0.984 (0.975–0.991); for each increment in acceleration and peak systolic pressure after adjusting for confounders; both p < 0.0001) in older men (age ≥54 years old: stratified according to median age) but not in younger men (age <54 years old). These results are not consistent with our study, which showed that ED is correlated with TPV and that this relationship is maintained after adjusting for age and other potential confounding factors. The UK study [10] did not use systematic and validated questionnaires for ED, and their sample size was relatively small. The population of Italian study [11] was patients complaining of sexual dysfunction, which means these patients likely share similar characteristics. In the Italian study, prostate size was measured by digital rectal exam, which is less accurate than transrectal ultrasound. We believe that these factors may have produced inconsistent results.

Recent studies have reported that the reduction of the prostate by surgery can result in improvements in ED. A randomized control study comparing the effects of holmium laser enucleation of the prostate and transurethral resection of the prostate on sexual function showed marginal improvement in the erectile function domain of the IIEF after surgery in both the transurethral prostate resectioning group (IIEF-erectile function domain: 22.3 at baseline and 24.1 at 24-month follow up) and the holmium laser prostate enucleation group (IIEF-erectile domain: 21.4 at baseline and 23.8 at 24-month follow up) [16]. A prospective study [17] that compared sexual function in randomized patients with BPH to transurethral prostate resectioning, noncontact laser therapy, or conservative management demonstrated that men who underwent transurethral prostate resectioning were significantly more likely to have improved erectile function than those who underwent conservative management (OR 0.37, 95% confidence interval 0.19–0.74). Moreover, a significant improvement in erectile function can be observed after 12 months in patients undergoing plasmakinetic resectioning of the prostate (IIEF score: 8.0 preoperatively to 21.0 at 12 months postoperatively (p < 0.05)) in another prospective study [18]. In our study, the propensity score adjusting for ED was significantly higher for those with large TPVs (≥30 cm³) compared with those with small TPVs (<30 cm³). Considering that the propensity score can suggest causal inference [19], the aforementioned results and our data suggest that enlarged prostates may play a role in the development of ED.

Compression of blood flow due to an enlarged prostate is one possible explanation for the relationship between TPV and ED. A twin study [20] enrolled 130 men who has IPSS > 8 and TPV measured by transrectal ultrasonography >18 cm³ reported a positive correlation between the periurethral artery RI and the TPV; a greater resistive index was associated with a larger TPV. They also found that the capsular artery resistive index was correlated with the transitional zone volume [20]. They explained this relationship as a result of the enlarged prostate compressing blood vessels and leading to increased vascular resistance [20]. The aforementioned results concern vessels leading to the urethra or prostate. However, these results suggest that an enlarged prostate could induce the compression of vessels and ischemia. The previously described Italian retrospective study demonstrated that enlarged prostate size measured through a digital rectal exam was associated with a higher risk of arteriogenic ED (dynamic PSV thresholds (<25 and 35 cm s⁻¹)) [11]. Additionally, reduced peak systolic velocity of the cavernous artery is associated with LUTS, which is related to prostate size in patients with ED [21]. Taken together, compression by an enlarged prostate of vessels supplying the penis can cause chronic ischemia, which can result in ED. Compression of the erectile nerves by an enlarged prostate is another possible explanation [18]. Zhang et al. [18] reported a significant improvement in erectile function after prostate surgery, explaining that surgery relieves the oppression of the erectile nerves by an enlarged prostate and thereby improves the local microenvironment. Further experimental and clinical data are needed to explain the relationship between prostate size and erectile function.

The data from a number of pre-clinical and clinical studies clearly showed that treatment with 5α-reductase inhibitors diminished ED [22]. However, erectile function is restored in some patients and the reason is unclear [23]. According to our results and previous researches concerning prostate surgery and improving erectile function, prostate size reduction induced by 5α-reductase inhibitors could be a possible explanation for restoring ED during 5α-reductase inhibitors therapy. Follow up study would be needed to confirm our theory.

In this study, the cut-off value for predicting ED was a TPV of 30 cm³ after adjusting for confounding factors. A recent analysis of the ability of digital rectal examination to identify a gland larger than 30 cm³ reported that digital rectal examination had a high sensitivity (94.3%) and a low negative likelihood ratio (0.08%) [24]. Therefore, digital rectal examination is clinically very important for the identification of ED as well as for prostate cancer screening. Detailed digital rectal examination is warranted during regular heath checkups as well as in urologic clinics. (The data used in this study are derived from health checkups.)

In this study, PE was not found to be correlated with prostate size. The etiology of PE is thought to be a disorder of the central nervous system rather than the peripheral nervous system. Serotonin is the neurotransmitter of greatest interest in the control of ejaculation, and has the most robust associated data in animal and human models [25]. Therefore, it is postulated that the local effect of an enlarged prostate on the nerves supplying the penis does not induce PE. Further research is needed to confirm a relationship between prostate size and PE.

In this study, the proportion of ED (defined by IIEF-5 < 22) was 71.2%. This result is similar to the other results from middle age group. In a population-based study [26] from china, the prevalence of mild, moderate and severe ED (classified by IIEF-5) was 28.06%, 10.26% and 39.54%, respectively. The total prevalence of ED among all subjects aged 40–69 years was 77.85%. Another cross-sectional study in Qatar has demonstrated that ED (defined by IIEF-5 < 22) was present in 58% in 40s and 69% in 50s [27].

Several limitations of the present study warrant mention. First, we used the PEDT to assess PE. PEDT is a 5-item questionnaire that uses the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) [28], although the PEDT showed relatively high sensitivity (89.3%) [29] and a recent study demonstrated that the PEDT showed a high level of agreement with intravaginal ejaculation latency time [29,30]. Second, as this study included data from a single institution and was conducted using a single occupational cluster, it may include selection bias. Nevertheless, we believe that the results of this study are highly relevant, as this is the largest study to date evaluating the relationship between TPV, ED and PE.

In conclusion, TPV is significantly and independently correlated with IIEF but not with PEDT. According to our results, an enlarged prostate may play a role in the development of ED. Future investigations should explore the temporal relationship between TPV and ED. The confirmation of associations in a prospective longitudinal data set would be informative.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.