Aging and sexual health: getting to the problem

Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis. This review aims to identify the mechanisms of ED in the penile aging process in experimental and clinical data. It also highlights areas that are in need of more research. The search strategies yielded total records screened from PubMed. Clarification of the molecular mechanisms that accompanies corpus cavernosum aging and aging-associated ED will aid new perspectives in the development of novel mechanism-based therapeutic approaches. Age is not a limiting factor for ED medical management, and it is never too late to treat. Hypogonadism should be managed regardless of age, and synergistic effects have been found during testosterone (T) replacement therapy when used along with oral phosphodiesterase-5 (PDE-5) inhibitors. Therefore, the clinical management of ED related to aging can be done by therapeutic interventions that include PDE-5 inhibitors, and other pharmacological treatments.     

The relationship of salivary testosterone and male sexual dysfunction in opioid-associated androgen deficiency (OPIAD)

Background: Opioids are an effective treatment for chronic non-malignant pain (CNP). Long-term use risks and side effects such as opioid-induced androgen deficiency (OPIAD) exist. This could be measured by saliva testosterone (Sal-T).

Objectives: To evaluate OPIAD in long-term opioid use in CNP patients.

Methods: A cross-sectional study included CNP male outpatients under opioid treatment. Total-Testosterone (Total-T), Free-Testosterone (Free-T), Bio-Testosterone (Bio-T) and Sal-T were measured. Correlations were calculated by Spearman’s rho (SPSS 20).

Results: From 2012 to 2014, 134 from 249 (54%) consecutive male outpatients reported erectile dysfunction (ED), 37% of them related to opioids and 19% evidenced OPIAD. A total of 120 subjects (94 cases and 26 matched-controls) were included. A significantly lower luteinizing hormone, Total-T and Free-T were found, as well as, a significant correlation between Sal-T and Total-T (r?=?0.234, p?=?0.039), Bio-T (r?=?0.241, p?=?0.039), IIEF (r?=?0.363, p?=?0.003) and HAD-anxiety (r =??0.414, p?=?0.012) in OPIAD patients. Sal-T levels were significantly lower in patients with severe–moderate ED versus mild ED (p?=?0.045) and in patients with severe ED versus moderate–mild ED (p?=?0.036).

Conclusions: These data demonstrate the high prevalence of ED in long-term use of opioids, part of this is associated to OPIAD, which can be tested by Sal-T as a non-invasive approach.     

Effects of testosterone supplementation on prevention of age-related penile remodeling

Abstract

Erectile dysfunction develops among 46.2% of men between 40 and 70 years. Studies demonstrated substitution on detrusor muscle by collagen due testosterone deprivation. It is clear the correlation among aging and oxidative stress, accelerating apoptosis process in many tissues. This study aims to demonstrate the collagen substitution over the muscle fibers on muscle structure of rat’s penis and the effects of testosterone supplementation. Sixteen senescent Wistar rats were divided into two groups: treatment (receiving standard supplementation testosterone dose) and control (receiving equivalent saline solution). Testosterone was dosed on D0 and D56 of study. All penises were prepared with picrosirius colored histology; stereology was applied to determine the volumetric density of collagen fibers (Vv). Analysis of variance demonstrated testosterone group’s replacement therapy to be effective, while the androgenic decline continued by the time of experiment in control group (p?<?0.05). Testosterone group had Vv of 20.6%, lower than control group (47.8%); t-test (p?<?0.001). Pearson’s correlation demonstrated an inverse correlation between the Vv and testosterone’s levels (p?<?0.001). This is a pioneer study on demonstration of structural alterations over the cavernous corpora muscle caused by deprivation of testosterone on elderly rat. These finding implicate that the testosterone levels can influence, not only the libido, but also the erectile function.     

Association between hand-grip strength and erectile dysfunction in older men

Abstract

Objectives: To evaluate the association between handgrip strength and erectile dysfunction (ED) in community-dwelling older men.

Methods: This cross-sectional study included 1771 participants of the Dong-gu Study. Handgrip strength was measured with a handheld dynamometer. ED was assessed with the Korean version of the International Index of Erectile Function (IIEF). ED was categorized as none to mild (IIEF-EF scores of 13–30) and moderate to severe (IIEF-EF scores of 0–12). Multivariable logistic regression was conducted with adjustment for potential confounders.

Results: The proportion of men with moderate to severe ED was 48.8%. The age-adjusted ED score increased with increasing quartile of handgrip strength (11.0, 12.4, 13.4, and 14.0 in the lowest, second, third, and highest quartiles, respectively). After adjustment for potential confounders, greater handgrip strength was associated with a lower risk of ED (odds ratio (OR): 0.82 per 5?kg; 95% confidence interval (CI): 0.74–0.90). In addition, a high level of moderate to vigorous physical activity was associated with a lower risk of ED (OR: 0.75; 95% CI: 0.61–0.93).

Conclusion: In this study, aging men with greater handgrip strength had a lower risk of ED. This result suggests that reduced physical functioning may contribute to ED.     

Increased visceral adiposity index associated with sexual dysfunction in men

Objective: Visceral adipose index (VAI) is a novel parameter for the evaluation of visceral obesity. As we know that obesity is a risk factor for erectile dysfunction (ED). So, in this study, we compared the VAI levels between the men with ED and without ED.

Materials and method: A total of 177 men were included in the study. Ninety-five men with ED and 82 men without ED (control). All men were evaluated for ED by Index of Erectile Function-5 items (IIEF-5). VAI levels were calculated using body mass index, high density lipoprotein and tryglyceride levels.

Results: Mean age was 53.5 (38–69) in men who have ED and 53.1 (34–69) in control. The men with ED had higher body mass index (BMI), triglyceride (TG) levels, higher waist circumference (WC) and lower high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level was 5.18?±?2.50 in study group and 3.47?±?1.76 in control goup, respectively. VAI levels were statistically higher in men with ED (p?Discussion: The simplicity of WC and BMI measurement and TG and HDL assessment, make VAI an easily applicable index for the evaluation of visceral fat dysfunction. VAI can be useful index for the evaluation and calculation of erectile dysfunction risk.     

The impact of irritative lower urinary tract symptoms on erectile dysfunction in aging Taiwanese males

Objective.?This study assessed the possible associations between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging Taiwanese males and investigated the impact of various aspects of LUTS on ED.

Methods.?A free health screening for aging males (≥40 years old) was conducted in Kaohsiung Medical University Hospital. All the subjects had completed clinical data and answered questionnaires. ED and LUTS were assessed by validated symptom scales: the International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS).

Results.?A total of 339 eligible patients enrolled in this study with a mean age of 60.1 years old. In multiple logistic regression analysis, age and IPSS (p?<?0.001 and p?=?0.013, respectively) were significantly associated with ED after controlling other comorbidities. In a further age-adjusted multiple regression analysis, our results showed that irritative symptoms (p?=?0.042) have a more significant association with ED than the obstructive symptoms (p?=?0.101).

Conclusions.?Our results indicate that age and LUTS are the two most independent risk factors for ED. Aging Taiwanese males with LUTS are at increasing risk for ED, especially for those with significant irritative symptoms.     

Levels of uric acid in erectile dysfunction of different aetiology

Erectile dysfunction is a common disease characterized by endothelial dysfunction. The aetiology of ED is often multifactorial but evidence is being accumulated in favor of the proper function of the vascular endothelium that is essential to achieving and maintaining penile erection. Uric acid itself causes endothelial dysfunction via decreased nitric oxide production. This study aims to evaluate the serum uric acid (SUA) levels in 180 ED patients, diagnosed with the International Index of Erectile Function-5 (IIEF-5) and 30 non-ED control. Serum uric acid was analyzed with a commercially available kit using ModularEVO (Roche, Monza, Italy). Within-assay and between-assay variations were 3.0% and 6.0%, respectively. Out of the ED patients, 85 were classified as arteriogenic (A-ED) and 95 as non-arteriogenic (NA-ED) with penile-echo-color-Doppler. Uric acid levels (median and range in mg/dL) in A-ED patients (5.8, 4.3–7.5) were significantly higher (p?p?相似文献   

Increased prevalence of erectile dysfunction (ED): Results of the second epidemiological study on sexual activity and prevalence of ED in Thai males

Objective.?The aim of this study is to investigate changes in sexual activity and the prevalence of erectile dysfunction (ED) in Thai males. In addition, the treatment-seeking behaviour of Thai patients suffering from ED is also investigated.

Materials and methods.?In a cross sectional study using a standardized questionnaire with a multi-stage stratified random sampling, 2,269 men aged 40–70 were interviewed. The questionnaire was designed to investigate the effects of socioeconomic factors, medical conditions and unhealthy lifestyles on the development of ED. Furthermore, the questionnaire was designed to characterize the treatment-seeking behaviour of Thai patients suffering from ED.

Results.?Compared to the first report dated the year 2000, the prevalence of ED has increased from 37.5% to 42.18%. In terms of socioeconomic factors, the highest prevalence of ED was observed among unemployed men (78.51%). Prostatism and/or prostatitis (Odd ratios (OR) = 2.02) and long histories of smoking (more than 30 years, OR = 2.36) were identified as statistically significant risk factors for ED, with p-values of <0.001. It is important to notice that 38.78% of the ED patients wanted to discuss their problem with spouses or partners. Three quarters of the ED patients (74.54%) preferred oral medication as therapy.

Conclusions.?The epidemiology of ED in Thailand is changing. An increased prevalence of ED does require further epidemiological studies on a regular basis in order to better understand the etiology of ED and look for measures (such as education) to counter the disease.     

Erectile dysfunction,loss of libido and low sexual frequency increase the risk of cardiovascular disease in men with low testosterone

Introduction: Testosterone deficiency increases the cardiovascular disease (CVD) risk.

Aim: To evaluate the effect of erectile dysfunction (ED), sexual frequency and hypogonadal symptoms on CVD risk.

Methods: A total of 395 hypogonadal men aged 45–74 years were surveyed using the Androgen Deficiency in the Aging Male and the International Index of Erectile Function.

Main outcome measures: The 10-year CVD risk was measured with the Framingham Risk Score. Logistic regression was performed to obtain the odds ratios of sexual function and hypogonadal symptoms for a 10-year CVD risk ≥20% (high risk).

Results: The mean age was 56.1?±?6.7 years. The mean 10-year CVD risk of the whole cohort was 18.1%?±?11.4%, while 131 subjects (33.2%) were classified as high risk. Logistic regression revealed that ED severity was associated with CVD risk [OR?=?2.37 (CI 1.24–4.51) for mild-to-moderate ED, OR?=?4.39 (1.78–8.43) for moderate ED and OR?=?12.81 (4.65–26.11) for severe ED]. Compared to sexual frequency <1 per month, sexual frequency?≥4 decreased the risk of high CVD risk [OR?=?0.35 (0.23–0.780)]. Loss of libido [OR?=?2.95 (1.91–4.12)] and less strong erection [OR?=?3.87 (CI 2.11–4.95)] increased the risk of high CVD risk. All remained significant after adjustment for age and testosterone.

Conclusions: ED, decreased sexual frequency and loss of libido predict a high 10-year CVD risk in hypogonadal men.     

Endothelial progenitor cells and erectile dysfunction: a brief review on diagnostic significance and summary of our experience

Abstract

The article provides a brief review of the literature concerning the diagnostic use of endothelial progenitor cells in patients with erectile dysfunction. In particular, patients with arterial erectile dysfunction could benefit from the use of this diagnostic marker, which in clinical practice can be used together with more conventional methods such as the penile Doppler. It is very important to acquire diagnostic tools for the diagnosis of sub clinical form of endothelial dysfunction in these patients, in particular when the erectile dysfunction is associated with cardiovascular risk factors.     

Comprehensive evaluation of androgen replacement therapy in aging Japanese men with late-onset hypogonadism

Abstract

Objective: This study assessed the efficacy and safety of testosterone replacement therapy (TRT) in aging Japanese men with late-onset hypogonadism (LOH).

Methods: This study included 50 (median age: 57.7 years) Japanese men with LOH, who were consecutively enrolled and treated with TRT for at least six months at our institution. We evaluated the following measurements before and after six months of treatment with TRT as follows: blood tests, prostate volume, residual urine volume, self-ratings for International Index of Erectile Function 5 (IIEF-5), International Prostate Symptom Score (IPSS), Self-Rating Depression Scale (SDS), Aging Male Symptom (AMS) and the Medical Outcomes Study 8-item Short-Form health survey (SF-8).

Results: Following six months of TRT, the levels of testosterone, red blood cells, hemoglobin and hematocrit were significantly increased from baseline, while total cholesterol level was significantly decreased from baseline. Furthermore, TRT led to a significant increase in IIEF-5 score and a significant decrease in IPSS score. Of 30 men who were diagnosed with depression at baseline, only 11 men (36.7%) were still suffering from depression after TRT, and SDS scores were significantly decreased from baseline at month six. Treatment with TRT led to a significant decrease in all scores of the AMS scale as well as a significant improvement in all scores of the SF-8 survey, with the exception of the bodily pain score.

Conclusion: These findings suggest that TRT is an effective and safe treatment for aging Japanese men with LOH. TRT improved depressive symptoms as well as health-related quality of life.     

Research of stroke combined hyperlipidemia-induced erectile dysfunction in rat model

Abstract

Objective: The study was aimed to evaluate the influences of erectile dysfunction (ED) in a rat model of stroke combined with hyperlipidemia (HLP).

Methods: Male Sprague–Dawley rats were divided into control and hyperlipidemia (HLP) groups. HLP model was constructed by feeding with high-fat and cholesterol diets. Serum levels of total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), and non-HDL were identified to check the model was success. Stroke model was established by FeCl₃. ICP/MAP value was detected to evaluate the erectile function of rats. Serum level of lipoproteins and the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) were detected by ELISA. Hematoxylin–eosin (HE) staining of corpus cavernosum and measurement of penis length were utilized to assessment erectile function. Western blot was used.

Results: TC, TG, LDL, and non-HDL-C in serum were up-regulated, while HDL level was attenuated. After treatment, the serum lipid level recovered. From the ICP/MAP values, the erectile function of both two treatment groups recovered. The expression of PDE5A was up-regulated, while the levels of eNOS and cGMP were suppressed after surgery. The length of penis was decreased, and corpus cavernosum was damaged following HLP and stroke. However, the erectile function was recovered after treatment.

Conclusion: Stroke combined HLP caused ED through NO-cGMP-PDE5 pathway.     

Effect of cigarette smoking on sexual functions,psychological factors,and disease activity in male patients with ankylosing spondylitis

Objective: This study aims to investigate the effect of smoking on sexual functions in AS patients.

Patients and methods: A total of 67 male AS patients with a median age of 34 years (range: 18–57) reporting sexual activity at least for the past 4 weeks period were included. Patients were divided into smokers (Group 1, n?=?47) and non-smokers (Group 2, n?=?20). Fagerström test for nicotine dependence, smoking history, exhaled carbon monoxide test were recorded for smoking AS patients. Visual analogue scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL), International Index of Erectile Function (IIEF), Beck Depression Inventory (BDI) were filled for both groups.

Results: There was no significant difference between smokers and non-smokers in all evaluation parameters. BASMI scores were significantly lower in the mild dependency subgroup as compared to those with moderate or severe dependency (p?=?.005 and p?=?.007, respectively). Total IIEF score and IIEF categories correlated significantly with BASDAI, BASFI, BASMI, ASQoL, pain, fatigue, and cumulative smoking. BDI showed an inverse correlation with the IIEF score and IIEF category (p?r?=?–0.520, p?r?=?–0.508, respectively).

Conclusions: Sexual function in AS patients is associated with the pain, fatigue, disease activity, functional status, quality of life, depression as well as the cumulative exposure to smoking, and that sexual functions tend to decline with increasing degree of cigarette dependency.     

The impact of physical health and socioeconomic factors on sexual activity in middle-aged and elderly Taiwanese men

Sexual activity in older people has become a topic of growing interest. The aim of this study is to investigate the effect of physical health and socioeconomic factors on the sexual activity of middle-aged and elderly Taiwanese men. From August 2007 to April 2008, 744 men older than 40 years were enrolled from a free health screening in Kaohsiung, Taiwan. All participants received detailed physical examination and answered questionnaires that collected demographic and lifestyle information, and medical history as well as answered items from the International Prostate Symptoms Score and five-item version of the International Index of Erectile Function (IIEF-5). Overall, 100 (13.4%) participants reported to be sexually inactive in previous 6 months. Older age, lower education levels, loss of a partner, erectile dysfunction, and increased number of comorbidities were found to be independent predictors for sexual inactivity. In conclusion, most middle-aged and elderly Taiwanese men remain sexually active. In addition to erectile dysfunction and loss of a partner, lower education levels and increased number of comorbidities were found to be predictors for sexual inactivity. Further research would need to elucidate whether improvement of those factors could help to preserve sexual activity.     

Original immunophenotype of blood endothelial progenitor cells and microparticles in patients with isolated arterial erectile dysfunction and late onset hypogonadism: effects of androgen replacement therapy

Objective.?Blood endothelial progenitor cells (EPCs) and endothelial microparticles (EMPs) have been proposed as markers of endothelial dysfunction. Aim of this study was to evaluate an original immunophenotype of EPCs and EMPs in patients with isolated arterial erectile dysfunction (ED) and late onset hypogonadism (LOH) before and after androgen replacement therapy.

Materials and methods.?Fifty patients (50–64 years) with ED and LOH were selected. EPC (CD45_neg/CD34_pos/CD144_pos) and EMP (CD45_neg/CD34_neg/CD144_pos) blood concentrations were evaluated by flow cytometry. Thirty patients received androgen replacement therapy (Tostrex® ProStrakan) for 6 months (group A), other 20 patients not received androgen therapy for the contraindications in their clinical history (group B).

Results.?After 6 months, group B showed IIEF-5 score, peak systolic velocity and acceleration time significantly worse than group A; in addition EPCs and EMPs were significantly higher in group B compared to group A.

Conclusions.?Patients with isolated arterial ED and LOH not treated with androgen therapy showed worst vascular parameters measured by penile Doppler and higher EPCs and EMPs compared to treated hypogonadal patients, hence, LOH appears to be an additional vascular risk factor, and these markers may be considered as predictors of cavernous artery disease. Finally, androgen therapy improves endothelial dysfunction.     

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.     

The impact of metabolic syndrome on serum total testosterone level in patients with erectile dysfunction

Abstract

Objectives: To determine the association between metabolic syndrome (MetS) and serum testosterone levels (TT) in patients with erectile dysfunction (ED).

Methods: This study included 280 ED patients above 40-years-of-age. Participants were divided into two groups according to 2005 criteria of International Diabetes Federation. The severity of ED was determined according to the International Index of Erectile Function-EF (IIEF-EF score; 0–10 severe ED, 11–25 mild to moderate ED). The severity of ED, serum TT levels and other MetS components were compared between the groups.

Results: The mean age of the patients was 55.7?±?8.2 years. One hundred eighteen patients (%42.1) had MetS. Sixty-eight patients with MetS (57.6%) and 71 patients without MetS (43.8%) had severe ED (p?=?0.031). A total of 46 (16.4%) patients had hypogonadism. Hypogonadism was seen more prevalent in patients with MetS (22.9% vs. 11.7%, p?=?0.013). Logistic regression analyses for ED risk factors demonstrated that abnormal FBG increased the relative risk of severe ED up to 10.7-fold (p?<?0.001) but not presence of hypogonadism (p?=?0.706).

Conclusion: Metabolic syndrome was seen in almost half of the patients with ED. ED was more severe among MetS patients. Hypogonadism alone is a not risk factor for severe 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.