Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone

Aims: To evaluate the cause of failure of sildenafil citrate (Viagra^®) to restore erections in patients with organic erectile dysfunction (ED) associated with type II diabetes mellitus (DM) and receiving oral antidiabetic drugs. Methods: Diabetic ED patients (n = 120), aged 43-74 years, failing to respond at least three times to 100 mg Viagra were evaluated. After at least 2 weeks' treatment with oral testosterone undecanoate (Andriol^®), 100 mg Viagra was used before coitus. ED was assessed with the International Index of Erectile Function (IIEF). Serum total testosterone, prolactin, thyroid stimulating hormone, lipid profile and prostate-specific antigen (PSA) were determined by standard methods and prostate volume by digital rectal examination. Age-matched diabetic ED patients (n = 100) served as controls for baseline values. Results: Viagra non-responders had, at baseline, significantly lower testosterone and more depressed libido than controls. Andriol restored testosterone to normal levels and increased libido. In 84/120 (70%) Viagra non-responders, combined therapy with Andriol induced satisfactory erections, a significant increase in IIEF scale (question (Q) 3 from 2.0 ± 0.2 to 3.7 ± 0.3, Q4 from 1.9 ± 0.1 to 3.4 ± 0.2, Q12 from 1.0 ± 0.1 to 4.2 ± 0.4) and increased sexual contacts from 0.5 to 3-4 per month. No adverse events were noted, and PSA levels remained below 4 ng/ml. Conclusion: Decreased testosterone levels in patients with ED and type II DM receiving oral antidiabetic agents may be responsible for failure to respond to sildenafil citrate therapy. Combination with oral testosterone undecanoate restores sexual function in these patients.     

The relationship between vitamin D level and erectile dysfunction in patients with type 2 diabetes mellitus

Recent studies have suggested that a relationship could exist between 25-hydroxyvitamin D [25(OH)D] deficiency and erectile dysfunction (ED). The present study evaluated the relationship between 25(OH)D levels and ED in male patients with type 2 diabetes mellitus (DM). The study included 98 patients with type 2?DM aged between 18–80 years. The International Index of Erectile Function (IIEF-5) Questionnaire was administered. The patients were divided into three groups according to IIEF-5 scoring: IIEF-5 score between 5–10, severe ED; IIEF-5 score between 11–20, moderate ED; IIEF-5 score between 21–25, no ED. Biochemical parameters, 25(OH)D and hormonal analysis tests were obtained in all patients. All parameters were compared between these three groups. Of 98 patients included in the study, 32 had severe ED, 45 had moderate ED and 21 had no ED. The mean age was 55.12?±?9.39 years and the mean 25(OH)D level was 13.69?±?8.15?ng/ml. When the three groups were compared, 25(OH)D levels were significantly lower in patients with the IIEF-5 score between 5–10 (p?=?0.020). There was a moderate positive relationship between IIEF-5 score and 25(OH)D level (r?=?0.21, p?=?0.038). The patients with severe ED have considerably lower 25(OH)D levels.     

Association between sarcopenia and erectile dysfunction in males with type II diabetes mellitus

Background: The prevalence rates for both sarcopenia and erectile dysfunction (ED) gradually increase in middle-aged and elderly diabetic male population and they impair physical functioning, sexual functioning, and quality of life. The aim of the present study was to evaluate the sarcopenia in patients with diabetic ED.

Methods: The study included 98 male patients with type II diabetes mellitus (DM) aged 18–80?years. Blood chemistry and hormone levels were obtained. The International Index of Erectile Function (IIEF-5) questionnaire was administered to the patients. The patients were divided into three groups according to the IIEF-5 score; a score of 5–10 points indicated severe ED, a score of 11–20 indicated moderate ED, and a score of 21–25 points indicated no ED. The muscle mass, handgrip strength, timed up and go test, upper mid-arm circumference, calf circumference, and body mass index were obtained. The statistical analysis was performed using MedCalc Statistical Software version 12.7.7. All parameters were compared between the three groups.

Results: Of 98 patients included in the study, 84 patients had severe sarcopenia, 13 had moderate sarcopenia, while only one patient had normal muscle mass. The mean age was 56.59?±?11.46?years. When patients were divided into three groups according to IIEF-5 score, 38 had severe ED, 39 had moderate ED, and 21 had no ED. There was a significant difference between the three groups in terms of handgrip strength, timed up and go test scores, upper mid-arm circumference, and calf circumference (p?Conclusions: Although muscle mass remains unchanged, muscle strength and physical performance decrease in diabetic ED patients. Diabetic patients with severe and moderate ED have lower muscle strength and physical performance.     

The effect of lifestyle modification and glycemic control on the efficiency of sildenafil citrate in patients with erectile dysfunction due to type-2 diabetes mellitus

Abstract

Objectives: We evaluated the effect of lifestyle modifications and glycemic control on the efficiency of sildenafil citrate in patients with type-2 diabetes (T2DM) and erectile dysfunction (ED).

Methods: Eighty-three men with ED due to T2DM were included in the study. The Group 1 (n?=?41) patients received lifestyle modifications (diet and exercise), and medical treatment for intensive glycemic control. In Group 2 (n?=?42), in addition to the intensive glycemic control, the patients were given sildenafil citrate® 100?mg for 2–3 per weeks. The changes in ED were compared between the two groups after three months of treatment.

Results: The mean age was 54.9?±?9.1 (26–75) years. An increase in the IIEF-5 scores was observed in 23 of 41 patients in Group 1 (44.2%) and 29 of 42 in Group 2 (55.8%). When the changes of the IIEF-5 scores were evaluated, the mean increase was 2.5 in Group 1, and 5.0 in Group 2 (p?=?0.012). The mean IIEF changes according to the duration of diabetes were 4.8 in <5 years, 3.6 in 5–10 years and 1.6 in >10 years (p?=?0.021).

Conclusions: Glycemic control and lifestyle changes are not solely adequate for a better sexual function in ED due to diabetes, and sildenafil citrate should be used additionally.     

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.     

Back to Stir It Up: Erectile Dysfunction in an Evolutionary,Developmental, and Clinical Perspective

In this review, we analyze erectile dysfunction (ED) in the context of sexual selection. We highlight that ED is a specific human male characteristic linked to the loss of the baculum or penile bone and results from a range of physical and psychological factors. We discuss evolutionary interpretations that consider dysfunctional penile erection as an honest signal of a low-quality male. We further emphasize the importance of considering psychosocial context and early attachment dynamics for understanding the etiology of some types of ED. Finally, we suggest that the integration of developmental factors for understanding the emergence of this sexual disorder is instrumental for the calibration of more effective therapies.     

Testosterone/estradiol ratio,is it useful in the diagnosis of erectile dysfunction and low sexual desire?

Erectile dysfunction and low sexual desire are multifactorial diseases. The decrease in testosterone levels is one of the causes, but the effect of estradiol is not well known. Moreover, study has shown that the testosterone/estradiol ratio has more influence over sexuality than does estradiol alone. The aim of the study was to determine whether the balance between testosterone and estradiol has any relation to some aspects of sexual function. It was an ambispective study of 230 patients with urological problems unrelated to sexuality. They underwent a detailed history and hormone study including total, free, bioavailable testosterone and estradiol. They completed the Sexual Health Inventory for Men and questions 11 and 12 of the IIEF15 were used to assess impairment in sexual desire. The T/E ratio was calculated, and the relationship between the different parameters and erectile function and sexual desire were studied by univariate and multivariate analysis. The mean age was 66.32?±?8.17 years. The percentage of patients with erectile dysfunction was 60.9% (7% severe, 14.3% moderate, 12.6% mild to moderate and 27% mild) and decreased sexual desire was 46.5%. Age, free and biodisponible testosteron were the only variables with a positive linear association with erectile dysfunction and decreased sexual desire. Age was the only independent variable for both, erectile dysfunction and sexual desire, in the multiple linear regression. There was no association between a testosterone/estradiol imbalance and an alteration in erectile function and sexual desire. Consequently, in the clinical study of these patients, it is not necessary to request estradiol in the laboratory analyses.     

Our common future: a rapidly growing and rapidly aging humankind

Abstract

Physical inactivity, diabetes, hypertension, dyslipidemia, smoking and obesity were associated with imbalance in oxidative stress, leading to endothelial dysfunction. Such dysfunction is present in both cardiovascular disease (CVD) and erectile dysfunction (ED). ED is the persistent inability to achieve or sustain an erection sufficient for satisfactory sexual performance and is one of the first manifestations of endothelial damage in men with CVD risk factors. The purpose of this article is to review the results of studies involving physical activity, CVD, endothelial dysfunction and ED in order to verify its applicability for improving the health and quality of life of men with such disorders. There is consistent evidence that endothelial damage is intimately linked to ED, and this manifestation seems to be associated with the appearance CVDs. On the other hand, physical activity has been pointed out as an important clinical strategy in the prevention and treatment of CVDs and ED mainly associated with improvement of endothelial function. However, further experimental and clinical prospective investigations are needed to test the role of physical exercises in the modulation of endothelial function and their implications on erectile function and the appearance of CVDs.     

Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome

Metabolic syndrome (MetS) is a diagnostic category, based on a cluster of risk factors (hyperglycemia/diabetes, abdominal obesity, hypertriglyceridaemia, low HDL cholesterol and hypertension), which identifies subjects at high risk for forthcoming type 2 diabetes mellitus and cardiovascular (CV) diseases. Recently, a close association between MetS, erectile dysfunction (ED) and male hypogonadism has been reported. In patients with MetS, hypogonadism can exacerbate sexual dysfunction and arteriogenic ED because of its typical symptoms, such as decreased sexual desire and mood disturbances. On the other hand, hypogonadism per se has been associated with an increased risk of CV and overall mortality. Obesity and in particular central obesity is nowadays considered the most important determinant of MetS-induced hypogonadism whereas hypertension and diabetes play a major role in ED associated with MetS. This review analyses the current literature regarding the relationship between ED, MetS and hypogonadism emphasising the epidemiological and psychopathological aspects and stressing the concept that ED subjects are ‘lucky’, because ED offers a unique chance to undergo medical examination and therefore to improve not only their sexual but, most importantly, their overall health.     

Testosterone therapy in erectile dysfunction

Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel®; Schering AG, Germany/AndroGel®; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (&lt;?400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.     

Impact of prostate volume on erectile dysfunction and premature ejaculation

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?3 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.     

Factors associated with phosphodiesterase type 5 inhibitor treatment satisfactions: results of patient interrogation

Introduction. Phosphodiesterase type 5 (PDE5) inhibitor therapy is an efficacious means of treatment for erectile dysfunction (ED). PDE5 inhibitors supply penile erection by inhibiting the hydrolysis of cGMP and therefore relaxing the corpus cavernosum. In this study, retrospective evaluation of those patients who were admitted to our clinic with the complaint of ED and who were recommended on PDE5 inhibitor treatment in terms of follow-up results and patient satisfaction were aimed.

Method. The patients were called by phone and after informing about the study and taking the informed consent, patient satisfaction with the treatment, purposes of withdrawal, treatment alterations and partner satisfaction were investigated.

Results. Interviews were made with 345 patients, who accepted to enroll in the study and the mean patient age was 56 ± 11.2 years. Of the patients 66.4% were learned to be satisfied with the treatment. It was determined that 10.7% of the patients have never used the medication and 50% could not continue because of high drug cost. It was recognised that 50.2% of the patients who are not satisfied with the treatment tried another PDE5 inhibitor. The success rate of the treatment was found to be higher in the followed-up group than those losses to follow-up.

Conclusion. Therapy with PDE5 inhibitors is an effective means of ED treatment. The importance of doctor-patient communication should be considered, and the patient should be advised for adaptation to follow-up program. High drug cost is a significant predictor of patient compliance to treatment continuation.     

Intracavernous injection as an option for aging men with erectile dysfunction

Sexuality remains a vital aspect of life in spite of aging. Advances in impotence research and increased knowledge of the pathophysiology of erection have completely changed the treatment of erectile dysfunction. Before oral therapy, intracavernous injection was considered as the first-line therapy for impotent patients. However, the new simple oral treatment raises the question as to whether intracavernous injection therapy is still a useful tool for treatment of aging men with erectile dysfunction. The efficacy and safety of oral therapy and intracavernous injection are reviewed.     

Erectile dysfunction is a marker for obstructive sleep apnea

Purpose: To investigate the prevalence of erectile dysfunction (ED) in patients with obstructive sleep apnea (OSA) with and without any other comorbidities.

Methods: The patient group was newly diagnosed as having OSA (apnea–hypopnea index [AHI]?>?5/h) using a polysomnographic examination. A group of subjects with simple snoring were included into the control group. Clinically relevant comorbidities were systematically assessed in face-to-face interviews. All patients were asked to complete the 15-item International Index of Erectile Function (IIEF-15) questionnaire for the evaluation of ED. The patients with OSA and ED were evaluated according to these comorbidities.

Results: Of the 94 patients, 39 patients were excluded because of severe diseases. OSA was observed in 38 (69.1%) of the 55 patients. ED was seen in 24 (63.2%) patients with OSA, and in 8 (47.1%) patients without OSA (p?>?0.05). There were no statistical differences between the groups’ ages, IIEF scores, and body mass index (BMI) scores. There were statistically significant differences between the groups’ AHI scores (p?p?Conclusion: The rate of ED was higher in patients with OSA who had no other comorbidities. Therefore, ED can be a sensitive marker of OSA.     

Erectile dysfunction is strongly linked with decreased libido in diabetic men

Erectile dysfunction frequently occurs with diabetes mellitus. A survey of diabetic men was conducted by anonymous questionnaire to investigate the associations of erectile dysfunction with various predictive factors. A total of 112 diabetic males without an obvious history of erectile dysfunction were available for analyses. The mean age and duration of diabetes were 53.7?±?12.2 years and 10.2?±?8.6 years (mean?±?standard deviation), respectively. The questionnaire included questions on the presence or absence of smoking, hypertension, libido and subjective symptoms of diabetic neuropathy that may be associated with erectile dysfunction. Analysis of the answers to the questionnaire revealed that 40% of the patients complained of erectile dysfunction (erection ‘always insufficient’). Erectile dysfunction was significantly correlated with age (p?=?0.005), but not with duration of diabetes (p?=?0.25), adjusted for age. Erectile dysfunction was also associated with sensory neuropathy and reduced libido, independently of age. The logistic regression analysis revealed that erectile dysfunction was positively associated with reduced libido and age. The odds ratio of erectile dysfunction for reduced compared to unreduced libido was 18.21, suggesting that psychogenic factors have a marked influence on erectile dysfunction. It is concluded that the presence of erectile dysfunction should be considered when symptoms related to diabetic neuropathy are observed; psychological approaches, such as sexual counseling, could be applied for the treatment of erectile dysfunction.     

Efficacy and safety of mirodenafil for patients with erectile dysfunction: a meta-analysis of three multicenter,randomized, double-blind,placebo-controlled clinical trials

Abstract

Aim: To systematically review evidence on the efficacy and safety of mirodenafil treatment in erectile dysfunction (ED) from randomised controlled trials.

Methods: We searched PubMed, Embase and the Cochrane Library database up to March 2013. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.0. Outcome measures assessed were the International Index of Erectile Function (IIEF), erectile function domain (EFD) score (primary), the Sexual Encounter Profile questions 2 and 3, and the response to the Global Assessment Questionnaire and adverse effects (secondary).

Results: A total of 374 participants from three randomized controlled trials were identified in this meta-analysis. After 12 weeks treatment, mirodenafil was found to be more effective than placebo, and tolerability was good. The pooled results showed that the IIEF EFD score for 100?mg mirodenafil group was higher than placebo group (MD?=?8.13, 95%CI: 6.64–9.61, p?<?0.00001) and the mirodenafil group was also higher than placebo group in the changes from baseline for the IIEF EFD score (MD?=?7.32, 95%CI: 5.56–9.07, p?<?0.00001), respectively. The most common drug-related adverse events were flushing and headache (mirodenafil versus placebo: 15.8% versus 3.2%, 3.1% versus 0%; respectively).

Conclusion: This meta-analysis suggested that mirodenafil is effective and well-tolerated therapy for ED.     

Androgen deficiency in the adult male

Introduction. The purpose of this study was to investigate the association between severity of lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and metabolic syndrome.

Methods. Our study population included a consecutive series of 190 patients with LUTS (International Prostate Symptom Score-IPSS >7) with or without manifestations of the metabolic syndrome. The diagnoses of diabetes mellitus and hypertension were obtained from the patient's medical history. Data on blood pressure, waist measure, body height and weight were collected and body mass index were calculated. Patients were assessed based on the International Index of Erectile Function (IIEF) for ED and IPSS and IPSS-Quality of Life for LUTS. Blood samples were drawn from fasting patients to determine, fasting blood glucose (FBG), triglycerides, HDL-cholesterol and serum total testosterone levels.

Results. In severe LUTS patient group, IIEF erectile function domain scores were significantly lower than moderate LUTS patient group (p < 0.05). Multiple logistic regression analysis confirmed that presence of ED was the most predictor of severe LUTS. The prevalence of metabolic syndrome was higher in patients with severe LUTS (26%vs. 46%, p = 0.009). The severe form of the LUTS was significantly correlated with waist circumference >102 cm (p < 0.05), blood pressure ≥130/85 mmHg (p < 0.05) and FBG >110 mg/dl (p < 0.01).

Conclusion. Obesity, high plasma level of FBG and hypertension constitute risk factors for the development of severe LUTS. Metabolic syndrome may play a key role in the pathogenesis in both ED and LUTS. Presence of ED is the most predictor of severe LUTS.     

Sex life after 65: How does erectile dysfunction affect ageing and elderly men?

Introduction. We report the findings pertinent to the ageing and elderly participants of a population-based study of erectile dysfunction (ED).

Method. We examined the sociodemographic characteristics, self-reported morbidities and responses to the 5-item International Index of Erectile Function (IIEF-5) of participants aged ≥65 years and ≥80 years.

Results. Most (73%) participants were married or had partners. Among the participants aged ≥65 years, the prevalence of ED (IIEF-5 scores <22) was 67% and of severe ED (IIEF-5 scores <8) 48%. About 32% were sexually active, and 11% had regular sexual intercourse. Cardiovascular disease (CVD) was reported in 37% and diabetes mellitus (DM) in 13%, with odds of ED at 3.91 and 4.68, respectively. Among those aged ≥80 years, the prevalence of ED was 68% and of severe ED 57%. About 12% were sexually active, and 3% had regular sexual intercourse. CVD was reported in 44% and DM in 11%, with corresponding odds of ED at 2.55 and 2.90.

Conclusions. Most ageing and elderly men are in a relationship and many are sexually active. ED is prevalent and severe. Morbidities are common and significantly associated with ED, impairing the sex lives of affected men.     

Testosterone and erectile physiology

The role of testosterone deficiency in sexual dysfunction is an important aspect of aging, because it affects such a large proportion of men over 50 years old. A number of age-related factors can cause sexual dysfunction (in particular erectile dysfunction) and testosterone deficiency, such as chronic illness and multiple medications, and the causative link between hypogonadism and erectile dysfunction is still debated. However, studies in castrated animals have proven that addition of testosterone, and its conversion to dihydrotestosterone, can restore erectile function. It appears that testosterone achieves this by peripheral mechanisms (endothelial dependent and independent) and central mechanisms. Testosterone replacement therapy is therefore effective for erectile dysfunction in men with hypogonadism, with success rates of 35–40%. Testosterone supplementation is also important in men who fail on phosphodiesterase type-5 inhibitors, because a minimum plasma concentration of testosterone is required for the successful restoration of erectile function with these agents. Testosterone gels are now the preferred formulation for testosterone supplementation and they can be highly beneficial in a proportion of men with erectile dysfunction.