Treatment of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Abstract

This article summarizes years of challenging research on erectile dysfunction (ED), a condition that has an important social and cultural relevance. Preclinical and clinical research progress has led to new therapeutic approaches to ED in patients with different comorbidities and particularly in those with low urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals were possible only by combined work of specialists and researchers of different and intertwined medical disciplines. Currently, tadalafil (5?mg/d) is the best choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among options, despite the growing evidence of therapeutic effects. Different regimens of tadalafil may be prescribed based on patient needs, severity of LUTS/BPH – ED profile, and clinical experience. An integrated approach is necessary to choose for a combined therapy with PDE5i and α-blockers following urological and cardiac counseling in terms of outcomes and adverse effects.     

Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Benign prostatic hyperplasia (BPH) is very common in aging men and causes lower urinary tract symptoms (LUTS), which decrease health-related quality of life. A number of evidence suggests that other than ageing, modifiable factors, such as increasing prostate volume, obesity, diet, dyslipidemia, hormonal imbalance, hypertension, metabolic syndrome, alcohol, and smoking, also contribute to the development of BPH and/or LUTS. More recently, erectile dysfunction (ED) has been linked to LUTS/BPH as a part of this syndrome, suggesting that patients with BPH or LUTS easily develop ED, and that LUTS/BPH symptoms often coexist with ED. This article focuses on the epidemiology and risk factors of the combined phenotype LUTS/BPH – ED.     

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

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.     

Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia

Abstract

Purpose: We examined the prevalence of low testosterone (LT) and its relationship with body mass index (BMI) in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), who were enrolled in a clinical trial of drug therapy, the Medical Therapy of Prostatic Symptoms (MTOPS) Study.

Materials and methods: MTOPS enrolled 3047 men, and of these, 1896 had total testosterone (TT) measured at baseline. LT was defined as a single measurement of TT of <300?ng/dL.

Results: The overall prevalence of LT was 25.7%. Prevalence increased with increasing BMI; 14.7% among men who were normal weight (BMI <25?kg/m²) and 24.2% and 39.3% among overweight (BMI 25 to <30?kg/m²), and obese (baseline BMI ≥30?kg/m²) men, respectively.

Conclusions: LT was observed in about one in four MTOPS study participants with baseline TT measurements. The prevalence of LT increased markedly with increasing BMI. Our findings suggest a high prevalence of LT in obese men with LUTS/BPH. Physicians should be alert to the possibility of symptoms of hypogonadism in this population.     

Daily use of sildenafil 50mg at night effectively ameliorates nocturia in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: an exploratory multicenter,double-blind,randomized, placebo-controlled study

Purpose: To compare the efficacy and safety of sildenafil 25?mg qd, 25?mg bid or 50?mg qd – on treating lower urinary tract symptoms with benign prostatic hyperplasia (LUTS/BPH).

Materials and methods: Men aged?>?45 years with LUTS/BPH were randomly assigned to receive sildenafil 25?mg qd (n?=?42), bid (n?=?41), 50?mg qd (n?=?38) or placebo (n?=?41) for 8 weeks. Changes from baseline in International Prostate Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) were assessed at week 4 and week 8.

Results: Sildenafil 25?mg qd (-7.3?±?5.8) and 25?mg bid (-7.0?±?5.7) exhibited significant improvements of I-PSS compared to placebo (-5.2?±?6.4) (p?=?0.020, 0.025, respectively). In particular, voiding domain was more affected than storage domain. Only sildenafil 50?mg qd improved nocturia significantly (versus placebo, p?=?0.027). Quality of life score was improved in all treatment groups. Q_max and PVR did not change significantly in all groups. All regimens were well tolerated.

Conclusions: Sildenafil 25?mg qd, 25?mg bid and 50?mg qd are safe and effective to improve LUTS/BPH in long term, along with coexisting ED. In particular, nocturia is most well-controlled by 50?mg qd.     

Lead exposure is a risk for worsening bone mineral density in middle-aged male workers

Abstract

Objective: Lead exposure linked to osteoporosis in women. However, there is no direct evidence whether lead exposure has effects on bone metabolism in middle-aged male subjects. Therefore, the present study investigated the relationship between bone mineral densitometry measurements, bone markers, endocrine hormones and blood lead levels.

Material and methods: The present study included lead exposure patients (n: 30) and control subjects (n: 32). We recorded information on patient demographics and risk factors of osteoporosis. Blood lead levels were evaluated using Varian AA 240Z atomic absorption spectrophotometry. Bone mineral density measurements were measured using dual-energy X-ray absorptiometry.

Results: Each lumbar T and Z scores in the lead exposure group were lower than the control group. There were no significant differences in femur neck and femur total T and Z scores between two groups. Blood lead levels were also negatively correlated with lumbar 2-4 T score, total lumbar T score, lumbar 2-4 Z score and total lumbar Z score. Urinary hydroxyproline and urinary deoxypyridinoline levels in the lead exposure group were significantly higher compared to controls. Blood lead levels were strong, positively correlated with urinary deoxypyridinoline. Endocrine hormone levels and 1,25-dihydroxy-vitamin D3 levels were comparable between lead exposure and control group.

Conclusion: Lead exposure in male workers is an important factor for deterioration in bone mineral density. We should be screening blood lead levels and history of lead exposure in male osteoporosis.     

Lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction: from physiology to clinical aspects

Abstract

Erectile dysfunction, prostatic hyperplasia and lower urinary tract symptoms hare important pathogenetic links. Endothelial dysfunction and hormonal alterations represent the main aspects. The present article examines the anatomical, physiological, and pathophysiological characteristics of this association, finalizing the text to an interpretation of the clinical management of these patients based on these functional considerations.     

Efficacy of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review

We conducted a systematic review to evaluate the efficacy and adverse effects of newer drugs used to treat lower urinary tract symptoms (LUTS). The drugs were either Food and Drug Administration (FDA) approved for benign prostatic hyperplasia (BPH) or not FDA approved for BPH but have been evaluated for treatment of BPH since 2008. We searched bibliographic databases through September 2017. We included randomized controlled trials (RCTs) lasting one month or longer published in English. Outcomes of interest were LUTS assessed by validated measures. Efficacy was interpreted using established thresholds indicating clinical significance that identified the minimal detectable difference. Twenty-three unique, generally short-term, RCTs evaluating over 9000 participants were identified. Alpha-blocker silodosin and phosphodiesterase type 5 inhibitor tadalafil were more effective than placebo in improving LUTS (moderate strength evidence) but these drugs had more adverse effects, including abnormal ejaculation (silodosin). Anticholinergics were only effective versus placebo when combined with an alpha-blocker. Evidence was generally low strength or insufficient for other drugs. Evidence was insufficient to assess long-term efficacy, prevention of symptom progression, need for surgical intervention, or long-term adverse effects. Longer trials are needed to assess the effect of these therapies on response rates using established minimal detectable difference thresholds, disease progression, and harms.     

Visceral adiposity index is associated with benign prostatic enlargement in non-diabetic patients: a cross-sectional study

Objective: To evaluate the association between visceral adiposity index (VAI) - a novel indicator for the assessment of visceral adipose tissue and prostate enlargement in non diabetic patients.

Material and methods: Four hundred patients who were admitted to the Urology clinic between January and December 2014 with complaints of BPH(benign prostatic hyperplasia )/LUTS(male lower urinary tract symptoms)were enrolled in this cross-sectional study. Patients were divided into two groups according to their prostate volume and international prostate symptom score (IPSS) value. They were compared in terms of age, body mass index (BMI), VAI, prostate volume, PSA, post micturional residual volume (PMRV), uroflowmetry Q max value, triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and fasting blood sugar (FBS).

Results: Although univariate analyses reveal that age, BMI, waist circumference (WC), FBS, TG, HDL-C level and TG/HDL ratio were correlated with prostate volume, only age [1.125 OR (1.088–1.164), p?=?.00001], BMI [1.119 OR (1.040–1.204), p?=?.003], TG [1.043 OR (1.016–1.071), p?=?.002], HDL-C [0.923 OR (0.860–0.990), p?=?.025] and VAI [1.194 OR (1.110–1.305), p?=?.011] were statistically significant in multivariate analysis. A positive correlation was found between VAI value and prostate volume in the Spearman correlation test (r?=?0.29, p?=?.00001). The calculated area under the curve (AUC) for prostate volumes of 30, 40 and 50?ml were 0.680 (0.621–0.738), 0.625 (0.570–0.681) and 0.590 (0.528–0.652), respectively.

Conclusion: Our study revealed a positive correlation between VAI and prostate volume. Our results are needed to be tested with well-designed randomized prospective cohort studies.     

Effects of dutasteride on lower urinary tract symptoms: a prospective analysis based on changes in testosterone/dihydrotestosterone levels and total prostatic volume reduction

This study analyzed the effects of dutasteride on lower urinary tract symptoms based on the association between changes in the total testosterone (TT)/dihydrotestosterone (DHT) levels and total prostate volume (TPV) reduction. Sixty participants diagnosed with benign prostatic hyperplasia were given 0.5?mg of dutasteride daily for 52 weeks. Measures of TT and DHT levels, TPV and uroflowmetry were obtained before and after dutasteride treatment. Forty-three patients demonstrated a TPV reduction of ≥5% (Group 1), whereas the remaining 17 patients demonstrated a TPV reduction of <5% (Group 2). DHT suppression and DHT/TT ratio at baseline were significantly higher in Group 1 than Group 2. International Prostate Symptom Scores (IPSS) and uroflowmetry were significantly improved in both groups. In Group 2, nine patients demonstrated some improvement in IPSS (Group 2A), whereas eight did not (Group 2B). The rate of TT increase and improvement in voiding symptoms were significantly higher in Group 2A than Group 2B. Dutasteride-induced TPV reduction is dependent on individual 5-α reductase inhibitor activity. Some patients demonstrating smaller dutasteride-induced TPV reduction may experience an improvement in voiding symptoms owing to an increased level of testosterone.     

An association between bone mineral density and anabolic hormones in middle-aged and elderly men with prediabetes

Introduction: Prediabetes (PD) leads to reduced testosterone (T) in males, but the association between the anabolic hormones and bone mineral density (BMD) remains unknown.

Objectives: We investigated an association between the anabolic hormones and BMD in middle-aged and elderly men with PD.

Methods: We investigated 84 prediabetic and 56 control men. Total T (TT), calculated free T (cFT), and dehydroepiandrosterone sulfate (DHEAS) were measured, and BMD was assessed using DXA methods.

Results: Patients with PD had lower TT (p?p?<?.005), and DHEAS (p?<?.02) than control group. BMD values of the lower lumbar spine (p?<?.02) and total body (p?<?.05) in prediabetic men were lower than in control group. Lumbar spine BMD correlated with TT (r?=?0.376), cFT (r?=?0.235), and HbA1c (r?=??0.368); femoral neck BMD correlated with TT (r?=?0.412) and cFT (r?=?0.421). The high lumbar spine and femur neck BMD was associated with high TT, cFT, and low HbA1c, while the high total body BMD with high TT, cFT, and low HbA1c.

Conclusion: The anabolic hormones significantly affect BMD in male with PD, and screening for low BMD is necessary in these patients.     

Bone mineral density in men with and without the metabolic syndrome

The objective of this study was to measure bone mineral density (BMD) in middle-aged men with and without the metabolic syndrome according to the International diabetes federation (IDF) definition from 2005. We studied 80 men (mean age: 51.9 ± 9.0 y, mean body mass index (BMI): 32.0 ± 1.7 kg/m²) with and 92 men without the metabolic syndrome (mean age: 52.6 ± 15.1 y, mean BMI: 24.9 ± 2.8 kg/m²). Height (cm), weight (kg), waist circumference (cm) and blood pressure were measured. Fasting plasma glucose (FPG) and blood lipids were determined. BMD at the lumbar spine and total hip was measured by dual X-ray absorptiometry on a Hologic QDR 4500 bone densitometer. In men around 59.3% had a waist circumference > 94 cm (abdominal obesity). Among them 58.7% showed abnormal BP values. Around 30.7% had FPG ≥ 5.6 mmol/L and 22.7% had low high density lipoprotein (HDL)-cholesterol and 36.6% had hypertriglyceridemia. In men with the metabolic syndrome, mean lumbar spine BMD was 0.986 ± 0.210 g/cm² and total hip BMD – 1.012 ± 0.209 g/cm². The corresponding values in men without this syndrome were 0.934 ± 0.179 g/cm² and 0.894 ± 0.189 g/cm², respectively. The inter-group BMD difference reached statistical significance only at the hip (p = 0.039). Respectively, the prevalence of osteoporosis at the central sites was significantly higher in men without the metabolic syndrome (MS) (13.2 versus 20.8%, p = 0.03). Our data confirmed the trend for higher BMD in the studied men with the metabolic syndrome.     

The effects of daily alendronate,daily calcitonin and alendronate every other day on bone mineral density in osteoporotic men

Objectives. Biphosphonates have been widely used in the treatment of osteoporosis, but there is not enough data on their use in men. The aim of this study is to investigate the effects of twelve months' treatment with daily 10 mg alendronate, every other day 10 mg alendronate and daily 200 IU calcitonin on bone mineral density (BMD) in men with osteoporosis.

Materials and methods. 46 men with osteoporosis were randomly allocated to three groups: 15 patients in the first group received daily 10 mg alendronate and calcium (1000 mg/day), 14 patients in the second group used every other day 10 mg alendronate and calcium and 17 patients in the third group were given intranasal salmon calcitonin and calcium. At the baseline, sixth and twelfth months, BMD was measured at lumbar spine (L_2–4), femoral neck and Ward's triangle zone by means of dual energy X-ray absorptiometry (LUNAR).

Results. In daily and every other day alendronate and calcitonin groups there was a significant increase in BMD at lumbar spine (p = 0.004, p = 0.001, p = 0.04), but no difference at the femoral neck (p > 0.05) at the end of twelve months. When the groups were compared with each other, no significant differences in BMD levels at lumbar spine, femoral neck and Ward's triangle were found (p > 0.05).     

Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia

Objectives: To investigate the predictive values of free prostate-specific antigen (fPSA), total PSA (tPSA) and age on the prostate volume.

Methods: The data of 2148 patients with lower urinary tract symptoms were analyzed retrospectively. The patients who had transrectal ultrasonography guided 10 core biopsies owing to the findings obtained on digital rectal examination and presence of high PSA levels (PSA?=?2.5–10?ng/dl), and proven to have BPH histopathologically were included in the study. Age, tPSA, fPSA and the prostate volumes (PV) of the patients were noted.

Results: One thousand patients that fulfilled the inclusion criteria were included in the study. The PV of the patients were significantly correlated with age, tPSA and fPSA (p?r?=?0.307, p?r?=?0.382, p?r?=?0.296, respectively). On linear regression model, fPSA was found as a stronger predictive for PV (AUC?=?0.75, p?p?p?=?0.013).

Conclusions: Although tPSA is an important prognostic factor for predicting PV, the predictive value of fPSA is higher. PV can easily be predicted by using age, and serum tPSA and fPSA levels.     

Impact of metabolic status on the association of serum vitamin D with hypogonadism and lower urinary tract symptoms/benign prostatic hyperplasia

Objective: The objective of this study is to investigate the impact of metabolic status on associations of serum vitamin D with hypogonadism and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH).

Patients and methods: A total of 612 men underwent physical examination, biochemical/hormonal blood testing, and transrectal prostate ultrasound. Moreover, the subjects filled out standard questionnaires for identification and grading of LUTS and hypogonadism symptoms. Parameters were statistically compared with independent t-tests and correlation analyses.

Results: Vitamin D levels positively correlated with total testosterone (TT) but not with prostate volume or International Prostate Symptom Score (IPSS). Patients with metabolic syndrome had significantly lower vitamin D levels, which were not correlated with TT, prostate volume, or IPSS. However, vitamin D was positively correlated with TT, and negatively correlated with prostate volume and quality-of-life IPSS in subjects without metabolic syndrome.

Conclusion: The clinical usefulness of vitamin D for treatment of hypogonadism or LUTS/BPH varies according to metabolic status.     

Effects of oral testosterone undecanoate therapy on bone mineral density and body composition in 322 aging men with symptomatic testosterone deficiency: a 1-year,randomized, placebo-controlled,dose-ranging study

Abstract

Objective: We investigated the effects of oral testosterone undecanoate (TU) on bone mineral density (BMD), lean body mass (LBM) and body fat mass (BFM) in aging men with symptomatic testosterone deficiency (TD).

Methods: Three hundred twenty-two men ≥50 years with TD symptoms and calculated free testosterone <0.26?nmol/L participated in a multicenter, double-blind, placebo-controlled trial. Patients were randomized to placebo, oral TU 80?mg/d, oral TU 160?mg/d, or oral TU 240?mg/d, administered as divided doses with normal meals. BMD of the hip and lumbar spine were evaluated by dual energy X-ray absorptiometry (DEXA), and body composition (LBM and BFM) by whole body DEXA.

Results: Oral TU significantly increased BMD at Month 12 at the lumbar spine (240?mg/d), total hip (240?mg/d), and trochanter and intertrochanter (160 and 240?mg/d) compared with placebo. Oral TU significantly increased LBM at Months 6 and 12 for all oral TU groups compared with placebo. BFM significantly decreased at Month 6 (all oral TU groups) and Month 12 (160?mg/d) compared with placebo. The effects on BMD and body composition showed a clear dose response.

Conclusions: Treatment with oral TU led to improvement in BMD, LBM and BFM in aging men with symptomatic TD.     

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective.?The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone.

Design.?Randomized, double-blind, placebo-controlled study.

Participants.?Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels.

Results:?Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm²) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD.

Conclusions.?Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.     

Prevalence of low testosterone in aging men with benign prostatic hyperplasia: data from the Proscar Long-term Efficacy and Safety Study (PLESS)

Abstract

Objectives: We examined the prevalence of low testosterone (LT) in the subset of men in the Proscar Long-term Efficacy and Safety Study (PLESS) who had serum total testosterone (TT) measured at baseline.

Methods: PLESS enrolled 3040 men with benign prostatic hyperplasia (BPH). Of these men, 299 had TT and body mass index (BMI) measurements at baseline. Patients were classified as having LT if their baseline TT was <300?ng/dl.

Results: Of the 299 PLESS patients with baseline TT and BMI measurements, 65 (21.7%) had LT. The prevalence of LT increased with increasing BMI, occurring in 8/78 (10.3%) normal weight patients (baseline BMI <25?kg/m²), 35/160 (21.9%) overweight patients (baseline BMI ≥25–<30?kg/m²), and 22/61 (36.1%) obese patients (baseline BMI ≥30?kg/m²).

Conclusions: LT was observed in more than one in five PLESS patients with baseline TT and BMI measurements. The prevalence of LT increased with increasing BMI – more than one in three obese PLESS patients with baseline TT measurements had LT.     

Bone mineral density at distal forearm in men over 40 years of age in Mae Chaem district,Chiang Mai Province,Thailand: a pilot study

Objective: To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand.

Methods: The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men.

Results: The BMD was highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The average T-score at the distal forearm was also highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The BMD decreased as a function of age-group (p?p?p?>?.05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density.

Conclusions: We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.     

Use of the International Prostate Symptom Score (IPSS) in Chinese male patients with benign prostatic hyperplasia

Purpose: To test the psychometric properties of the International Prostate Symptom Score (Hong Kong Chinese version 2) (IPSS) in Chinese male patients with benign prostatic hyperplasia (BPH) under secondary care.

Methods: A prospective longitudinal study was done by interviewing subjects at baseline, at 2 week after baseline for assessing test–retest reliability and at 26 week after baseline for assessing responsiveness. All subjects were interviewed to complete a structured questionnaire including IPSS, Short Form-12 Health Survey version 2 (SF-12v2) and Depression Anxiety Stress Scale (DASS).

Results: The IPSS HRQOL score had weak correlations with SF-12v2 summary and DASS domain scores. For reliability analysis, Cronbach’s alpha coefficient was 0.90 for the seven symptom-related items. The intraclass correlation coefficients of the IPSS total symptom score and HRQOL score were 0.90 and 0.86, respectively. For sensitivity, statistically significant differences were detected between the subjects with BPH and those without for IPSS total symptom score (effect size?=?0.68) but not the IPSS HRQOL score. The areas under ROC curves for the IPSS total symptom and HRQOL scores were 0.67 and 0.60, respectively.

Conclusions: The IPSS was valid, reliable instrument in Chinese patients with BPH. The IPSS total symptom score, but not the HRQOL score, is sensitive in differentiating subgroups.