Impact of metabolic syndrome on erectile dysfunction and lower urinary tract symptoms in benign prostatic hyperplasia patients

Abstract

Introduction. The aim of this study was to investigate the relationship among metabolic syndrome (MetS), erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).

Methods. Our study included 106 patients with BPH, 33 (31.1%) of whom had MetS. Blood pressures, waist circumferences, serum levels of fasting blood glucose, high density lipoprotein and triglyceride of patients were recorded. Erectile functions of the patients were evaluated by International Index of Erectile Function (IIEF). Patients were divided into two groups according to IIEF scores, namely ‘mild/no ED’ and ‘moderate/severe ED’. IIEF scores of ED groups were between 17 and 30 and 6–16 in turn. LUTS severities were assessed by International Prostate Symptom Score (IPSS) and classified as mild (IPSS 0–7), moderate (IPSS 8–19) and severe (IPSS 20–35).

Results. There was a significant difference between ED groups concerning MetS presence (p = 0.032). MetS presence was not found to be associated with the severity of LUTS (p = 0.144). There was no correlation between ED groups regarding LUTS severity (p = 0.303).

Conclusion. Results of the present study showed a correlation between MetS presence and ED. In the light of our results, MetS seems to play an important role in the etiopathogenesis of ED in patients with BPH.

Keywords:

• Metabolic syndrome
• erectile dysfunction
• lower urinary tract symptoms
• benign prostatic hyperplasia

Introduction

In our daily urological practice, we frequently see that our patients with benign prostatic hyperplasia (BPH) have also symptoms associated with erectile dysfunction (ED) and metabolic syndrome (MetS) components besides lower urinary tract symptoms (LUTS). This combination of symptoms is remarkable and studies investigating the relationship among these clinical conditions are growing.

MetS is a common health problem and a significant cause of morbidity and mortality becoming increasingly important in recent years. At least three of the following five factors to constitute the diagnosis of MetS are required: central obesity (waist circumference (WC) ≥ 102 cm), blood pressure ≥ 130/85 mmHg, fasting blood glucose (FBG) ≥ 110 mg/dl, elevated triglyceride ≥ 150 mg/dl and reduced high density lipoprotein (HDL)-cholesterol <40 mg/dl [1]. The studies based on the clinical observation that diabetic and obese men seemed to have larger prostate glands than men without these conditions have strengthened the theories claiming that ‘BPH is a component of the MetS’ or ‘MetS plays an important role in BPH aetiology’ [2,3]. Further increase observed in prostate growth in BPH patients with MetS also supports the link between MetS and BPH [4].

In men aged ≥50 years, LUTS are common and usually caused by BPH [5]. In the same age group of men, it has shown a significant association between LUTS and ED in large-scale epidemiological studies [5–7]. However, a few studies have disclaimed this association [8–10]. The relationship between these conditions still remains to be illuminated in many ways.

Recently, MetS is thought to have an important role in both LUTS and ED aetiologies. A strong association has been found between the presence of MetS and ED [11,12], and LUTS probability has been shown to be increased in men who have three or more components of MetS [13]. Further studies are needed to understand the exact relationship among ED, LUTS/BPH and MetS. The aim of this study was to investigate the possible association among these clinical conditions in our cohort of patients with BPH.

Methods

Between January and October 2009, 106 patients over 50 years of age admitted to our clinic with BPH-related LUTS were included in the study. The patients who were taking medications likely to alter lower urinary system function (α-blockers, phosphodiesterase-5 (PDE5) inhibitors and 5-α-reductase inhibitors) and those with other conditions leading to LUTS such as neurogenic bladder, prostate cancer, bladder cancer, bladder stone, urethral stricture, etc. were excluded from the study.

All patients provided written informed consent. Patients underwent physical examination including blood pressure, weight, height, hip and WC measurements and digital rectal exam. Blood samples were drawn from overnight-fasting patients and serum levels of prostate specific antigen (PSA), FBG, HDL, low density lipoprotein (LDL), total-cholesterol and triglyceride were recorded. Maximum urine flow rates (Q_max) were measured by uroflowmetry (MMSUD 2000, MMS, Holland). Prostate and post-void urine volumes were calculated with the use of ultrasound device (Hitachi EUB-400 with 6.5 MHz biplanar trans-rectal and 3.5 MHz abdominal probes).

Criteria proposed for clinical diagnosis of MetS were provided by the report of US National Cholesterol Education Program, Adult Treatment Panel III [1].

Erectile functions and LUTS of the patients were evaluated by culturally and linguistically validated versions of International Index of Erectile Function (IIEF) and International Prostate Symptom Score (IPSS). LUTS severities were classified as mild (IPSS 0–7), moderate (IPSS 8–19) and severe (IPSS 20–35). The erectile function domain of IIEF consisted of six questions (1–5 and 15) was used in our study. The patients with mild ED and without ED (IIEF score 17–30) were included in ‘mild/no ED’ group and the ones with moderate and severe ED (IIEF score 6–16) were contained in ‘moderate/severe ED’ group.

Statistical analysis

Statistical Package for Social Sciences, version 13.0 (SPSS, Chicago, IL) software program was used for the analysis of data. Pearson's χ² and Mann–Whitney U tests were applied and p values ≤0.05 were considered as significant.

Results

Age, laboratory and questionnaire data of total 106 patients with BPH are shown in Table I.

Table I. Patient characteristics.

Variable	Mean	SD
Age (year)	60.41	6.75
Serum PSA level (ng/ml)	2.32	2.68
Serum FBG level (mg/dl)	102.19	48.49
Serum total cholesterol level (mg/dl)	193.40	38.37
Serum HDL-cholesterol level (mg/dl)	40.07	10.76
Serum triglyceride level (mg/dl)	154.38	108.16
Prostate volume (ml)	38.71	25.60
Post-void urine volume (ml)	98.69	107.93
Qmax (ml/sn)	14.37	7.79
IIEF	18.58	6.64
IPSS	10.76	5.31

SD, standard deviation; PSA, prostate specific antigen; FBG, fasting blood glucose; HDL, high density lipoprotein; Q_max, maximum urine flow rate; IIEF, international index of erectile function; IPSS, international prostate symptom score.

The mean levels of our patients' somatometric parameters were as follows; height was 169.01± 6.69 cm, waist circumference 99.77 ± 10.52 cm and weight 79.23 ± 12.68 kg.

When we looked over the presence of five criteria of MetS; of our total 106 patients, 65 (61.3%) had reduced HDL-cholesterol, 48 (45.3%) had central obesity, 40 (37.7%) had elevated triglyceride, 24 (22.6%) had HT and 22 (20.8%) had DM. Thirty-three (31.1%) of 106 patients met the three of five criteria and regarded as MetS. Distribution of MetS criteria in 33 MetS patients was similar to entire group of patients; 29 of 33 patients (87.9%) had reduced HDL-cholesterol, 27 (81.8%) had central obesity, 24 (72.7%) had elevated triglyceride, 15 (45.5%) had HT and 15 (45.5%) had DM.

Of 106 BPH patients in the study, 11 (10.4%) had no ED (IIEF score ≥ 26) while the rest of the patients (95/106, 89.6%) had different severities of ED, being mild (IIEF score 17–25) in 62 (58.5%), moderate (IIEF score 11–16) in 25 (23.6%) and severe (IIEF score 6–10) in 8 (7.5%). We evaluated our ED patients according to common risk factors for ED; such as cigarette, alcohol, previous pelvic surgery, neurological diseases, trauma and chronic use of drugs. Eventually, no difference was found between BPH patients with/without ED regarding these risk factors (p > 0.05).

There was no significant correlation between mild/no ED group and moderate/severe ED group in regard to LUTS severity (p = 0.303) (Table II).

Table II. Association between ED and LUTS severities.

LUTS severity	Mild/No ED (IIEF 17–30)	Moderate/Severe ED (IIEF 6–16)	Total	p Value
Mild (IPSS 0–7)	78.8% (n = 26)	21.2% (n = 7)	100% (n = 33)	0.303
Moderate (IPSS 8–19)	65.1% (n = 43)	34.9% (n = 23)	100% (n = 66)
Severe (IPSS 20–35)	57.1% (n = 4)	42.9% (n = 3)	100% (n = 7)

LUTS, lower urinary tract symptoms; ED, erectile dysfunction; IPSS, international prostate symptom score; IIEF, international index of erectile function.

There was no statistically significant difference between BPH patients with and without ED concerning mean serum PSA level, prostate volume, Q_max, post-void urine volume (p > 0.05). Mean age of moderate/severe ED group was significantly higher than mild/no ED group (p = 0.019).

The presence of MetS was cross-tabulated with ED severity. There was a significant difference between mild/no ED and moderate/severe ED groups with regard to MetS presence (p = 0.032) (Table III).

Table III. Association between MetS presence and ED–LUTS severities.

	MetS (+)	MetS (−)	Total	p Value
ED severity
Mild/No ED (IIEF 17–30)	24.7% (n = 18)	75.3% (n = 55)	100% (n = 73)	0.032
Moderate/Severe ED (IIEF 6–16)	45.4% (n = 15)	54.6% (n = 18)	100% (n = 33)
LUTS severity
Mild (IPSS 0–7)	42.4% (n = 14)	57.6% (n = 19)	100% (n = 33)	0.144
Moderate (IPSS 8–19)	24.2% (n = 16)	75.8% (n = 50)	100% (n = 66)
Severe (IPSS 20–35)	42.9% (n = 3)	57.1% (n = 4)	100% (n = 7)

MetS, metabolic syndrome; ED, erectile dysfunction; LUTS, lower urinary tract symptoms; IPSS, international prostate symptom score; IIEF, international index of erectile function.

The presence of MetS was also cross-tabulated with LUTS severity. MetS presence was not found to be associated with the severity of LUTS (p = 0.144) (Table III).

No difference was observed between BPH patients with and without MetS with reference to mean age, serum PSA level, prostate volume, Q_max and post-void urine volume (p > 0.05).

Discussion

In the present study, we investigated whether the presence of MetS, ED and LUTS correlate with each other in patients with BPH some of whom also have ED and/or MetS besides LUTS. The relationship between MetS and LUTS has been mainly attributed to insulin resistance and secondary hyperinsulinemia [14] and hyperinsulinemia has been shown to cause autonomic nervous system over-activity [15]. Both ED and BPH were found to share autonomic over-activity aetiologically in rat studies [16,17]. As a component of MetS, obesity is another condition resulting in increased sympathetic tone [18].

One of the findings of our study elicited that main diagnostic criteria of BPH, including mean age, serum PSA level, prostate volume were not different with regard to the presence of MetS. Taking into consideration prostate volume in particular, our finding was not consistent with that of Hammarsten et al. They found significant differences in prostate volumes and annual BPH grow rates between the patients with a component of MetS and the ones without. Eventually, they suggested that BPH was a component of MetS [2,3]. They evaluated the components of MetS one by one for a risk factor analysis of BPH. However, we merely assessed the relationship between BPH and MetS, not the relationship between BPH and one of the components of MetS. In another study, Ozden et al. have found a correlation between MetS and annual prostatic growth rate in patients with BPH but they have not observed the same correlation concerning total prostate and transitional zone volumes [4]. The reason for prostate volumes in patients with and without MetS were not different, might be connected to the differences in hormonal profile of patients or prostatic growth rate. We neither measured androgen levels nor prostatic growth rate of our patients. Another responsible factor for our result might be linked to the prostate gland volumes measured with ultrasound did not truly reflect the volume of BPH.

Presence of MetS was not correlated with Q_max, post-void urine volume and IPSS of the patients in our study. This result might be based on the lack of difference in prostate volumes between the patients with and without MetS. As an alternative explanation, BPH-related LUTS may not be associated with MetS. However, we are unable to make a definitive comment due to our relatively small sample size. Consistent with our study, Park et al. have not found any relationship between LUTS and MetS in elderly Korean male patients [19]. In other studies, Temml et al. have demonstrated that LUTS and mean IPSS did not significantly differ with regard to the existence of MetS in either sex [20]. Kupelian et al. have observed that the association between LUTS and MetS primarily existed only in younger men but not in men over 60 [21]. Along with our study, the abovementioned three reports question the supposed relationship between MetS and LUTS.

When we compared the ED prevalence, we found a significant difference between mild/no ED and moderate/severe ED groups regarding MetS presence. This result might be interpreted that the presence of MetS was important for the etiopathogenesis of ED in patients with BPH. In a clinical setting, if a BPH patient had an additional MetS diagnosis, probability of the presence of ED was higher than the one who had not MetS. Treatment choice and lifestyle changes for ED could be directed to aetiologic MetS component. It can be thought conversely; the presence of ED may serve as a predictor of MetS in a patient with BPH. This scenario is important for early diagnosis and treatment of MetS in patients otherwise considered at low risk for MetS.

In our study cohort consisting of patients with BPH, ED prevalence was higher than in general population of our country (89.6% and 69.2%, respectively) [22]. And the mean age of BPH patients with ED was significantly higher than the ones without. BPH and ED are worsening conditions with age and our result is compatible with that information [23,24].

The association among LUTS, ED and MetS was also investigated in the study of Demir et al. [12]. Study population of that report was patients who were over the age of 40 and were presenting with LUTS. They pointed out the role of MetS in both ED and LUTS aetiologies. Our result suggesting a meaningful relationship between MetS and ED is consistent with that study. However, we have found no significant association between LUTS and MetS and between LUTS and ED like they did. This may be due to the higher age of our patients which was over 50 and including patients who had LUTS only secondary to BPH. The conditions leading to LUTS other than BPH were excluded from our study.

The link between LUTS and ED was shown in several epidemiological studies [25–28]. In the review of McVary [7] and a Multi-National Survey of the Aging Male (MSAM-7) study [5] have also supported the association between LUTS and ED. In the systematic review of McVary, LUTS and ED were found to be strongly linked but there were not any proven casual relationship. Results of the studies supporting the existence of biological plausibility between LUTS and ED summarised by McVary under four main theories; nitric oxide synthase/nitric oxide theory, pelvic atherosclerosis, Rho-kinase activation/endothelin pathway, autonomic hyperactivity and MetS hypothesis [6]. Using sildenafil in patients with both ED and LUTS, McVary et al. achieved significant improvement comparable to that gained with α1-blockers and 5α-reductase inhibitors in LUTS secondary to BPH. However, there was no improvement in Q_max [29]. A benefit in LUTS after PDE5-inhibitors treatment has also shown in large clinical trials [30]. All the studies discussed above have found a relationship between ED and LUTS but the exact pathophysiological mechanism still remains unclear. Nevertheless, there are also a few studies disapproving the findings of studies mentioned above. They did not observe any meaningful association between LUTS and ED [8–10]. Our results have seemed to support their findings. We also did not observe any significant correlation between ED presence and LUTS severity (mild, moderate and severe). Mean serum PSA level, prostate volume, Q_max and post-void urine volume of our BPH patients were also not different with regard to ED presence. The expected association between LUTS and ED might be null when LUTS are only secondary to BPH. Further studies in selected large patient population are needed to understand the genuine causal link between BPH-related LUTS and ED.

Conclusions

Our results showed a significant correlation between MetS presence and ED. However, we did not find any significant association either between MetS and LUTS or between ED and LUTS.

It has largely been acknowledged that BPH, ED and MetS are diseases whose prevalences are increasing with age. However, it is obvious that the age is not the only factor bringing all of these three or two clinical conditions together. It can be thought that these diseases share similar pathophysiological and aetiological factors. If studies questioning the relationship among mentioned clinical conditions increases then there would be a better understood exact mechanism. Although the relationship between MetS and ED has been well accepted so far, many aspects of these clinical conditions still need to be enlightened.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.