Introduction: Phosphodiesterase type 5 inhibitors (PDE5-i) are used for the oral treatment of erectile dysfunction (ED). Since the launch of sildenafil more than 15 years ago, new molecules have become available. At present, in addition to tadalafil and vardenafil, there are three other drugs, udenafil, avanafil and mirodenafil, marketed in some countries which appear to be promising. Areas covered: The clinical pharmacological differences in dosage and side effects of all PDE5-i are evaluated. Expert opinion: All PDE5-i are equally effective and safe for the treatment of ED. On-demand use of any PDE5-i is also safe for patients with comorbid conditions. Tadalafil seems to be the preferred drug by patients and physicians, probably due to its peculiar pharmacological profile that makes sexual intercourse more spontaneous for the patients. Preliminary data suggest that the use of vardenafil may also be beneficial in cases of ED associated with premature ejaculation. Daily treatment is another option in men with ED and documented vascular or prostate disease. In geriatric or in difficult-to-treat populations, the evaluation of testosterone plasma levels will help to predict the efficacy of any PDE5-i. Remarkably, when such drugs are withdrawn for any reason, ED most often continues to occur because of the presence of an underlying disease.

The pharmacological treatment of erectile dysfunction (ED) is mainly represented by the administration of inhibitors of phosphodiesterase-5 (PDE5). However, in the clinical practice many patients do not benefit from such a treatment, hence the scientific interest extends to other therapeutic strategies; in particular, to the vascular regenerative therapy. This review describes the main acquisitions related to this approach represented by the mesenchymal stem cell or adipose tissue stem cell transplantation and endothelial nitric oxide synthase or vascular endothelial growth factor gene therapy. Moreover, there are other two aspects of wide interest represented by the potential vascular regenerative effects exerted by the PDE5 inhibitors and the therapeutic strategies for a category of patients who more frequently do not respond to the conventional treatment for ED, the patients with diabetes mellitus.

INTRODUCTION:

Obesity and inactivity are associated with erectile dysfunction and hypogonadism.

AIM:

To compare the effects of low volume (LV) and high volume (HV) of moderate-intensity exercise on sexual function, testosterone, lower urinary tract symptoms (LUTS), endothelial function, and quality of life (QoL) in obese men.

MAIN OUTCOME MEASURES:

Weight, waist circumference (WC), body composition, International Index of Erectile Function 5-item (IIEF-5), International Prostate Symptom Scale (IPSS) (for LUTS), and 36-item Short Form Survey version 2 Instrument (SF-36) (for QoL) scores, plasma testosterone, sex-hormone binding globulin, glucose, insulin and lipids, and endothelial function (by Reactive Hyperaemia Index [RHI] using finger plethysmography) were measured at baseline and 24 weeks.

METHODS:

Ninety abdominally obese (body mass index > 27.5 kg/m(2) , WC > 90 cm), sedentary (exercise ∼80 minutes/week) Asian men (mean age 43.6 years, range 30-60) were prescribed a diet to reduce daily intake by ∼400 kcal below calculated requirement and randomized to perform moderate-intensity exercise of LV (<150 minutes/week) or HV (200-300 minutes/week) (n = 45 each) for 24 weeks. Seventy-five men (83.3%) completed the study.

RESULTS:

Weekly exercise volume was significantly greater in the HV (236 ± 9 minutes) than the LV (105 ± 9 minutes) group. The HV group had significantly greater increases in IIEF-5 score (2.6 ± 0.5 points) and testosterone (2.06 ± 0.46 nmol/L) and reductions in weight (-5.9 ± 0.7 kg, -6.2%), WC (-4.9 ± 0.8 cm, -4.9%), and fat mass (-4.7 ± 1.0 kg, -14.5%) than the LV group (-2.9 ± 0.7 kg, -3.0%; -2.7 ± 0.7 cm, -2.5%; -1.1 ± 0.8 kg, -3.2%; 0.79 ± 0.46 nmol/L; and 1.8 ± 0.5 points). Improvements in IPSS and SF-36 scores, and RHI, were similar.

CONCLUSIONS:

Moderate-intensity HV aerobic exercise > 200 minutes/week produces greater improvements in sexual function, testosterone, weight, WC, and fat mass than smaller exercise volume. Khoo J, Tian H-H, Tan B, Chew K, Ng C-S, Leong D, Teo RC-C, and Chen RY-T. Comparing effects of low- and high-volume moderate-intensity exercise on sexual function and testosterone in obese men. J Sex Med **;**:**-**.

The relationship between testosterone, well-being and mood is poorly understood. We investigated the effect of testosterone supplementation on mood, well-being, and self-reported health in men with erectile dysfunction (ED) and low serum testosterone levels. This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov registration number NCT00512707), in which 140 men, 40-70 years, with ED and low serum testosterone levels were first optimized on sildenafil alone for 3-7 weeks and then randomized to receive either sildenafil plus testosterone gel (n = 70) or sildenafil plus placebo (n = 70) gel for 14 weeks. Using multiple imputations and generalized linear regression, we compared psychological changes in well-being, evaluated by the Psychological General Well-Being Index, and mood, evaluated by Derogatis Affects Balance Scale. Mood and well-being scores were similar between the two groups at baseline and did not substantially change during the administration of sildenafil or after randomization to testosterone. Our findings show that the addition of testosterone to sildenafil in men with ED and low serum testosterone levels was not associated with improvement in either well-being or mood.

We have previously reported that infertile patients with diabetes mellitus (DM) have a particular ultrasound features of the seminal vesicles (SV) characterized by higher fundus-to-body ratio and lower pre- and post-ejaculatory difference in body antero-posterior diameter (APD). Based on these premises the aim of the present study was to investigate possible ultrasound SV changes in infertile patients with DM and diabetic neuropathy (DN), after prolonged administration of tadalafil (TAD) (a specific phosphodiesterase-5 inhibitor). To accomplish this, 20 infertile patients with symptomatic DN and erectile dysfunction were selected and arbitrarily divided into two groups which were assigned to: daily administration of 5 mg TAD for 3 months (Group A) (n = 10) and administration of placebo (Group B) (n = 10). All patients underwent to scrotal and prostate-vesicular transrectal ultrasound evaluation and semen analysis (Laboratory Manual for the Examination and Processing of Human Semen, WHO, 2010) before and after treatment. The following SV US parameters were recorded: (i) body APD; (ii) fundus APD; (iii) parietal thickness of the right and left SVs; and (iv) number of polycyclic areas within both SVs. We then calculated the following parameters: (i) fundus/body (F/B) ratio; (ii) difference of the parietal thickness between the right and the left SV and (iii) pre- and post-ejaculatory APD difference. In addition, we also evaluated the SV ejection fraction. Group A patients showed a significant reduction in F/B ratio and higher pre- and post-ejaculatory body SV APD difference compared with baseline or Group B after 3 months. These patients showed also a significant increase in SV ejection fraction and a significant improvement of the total sperm count, progressive motility, seminal levels of fructose, leucocytes and ejaculate volume. In conclusion, these results suggest that infertile DM patients with DN and erectile dysfunction had an improvement of ultrasound features suggestive of diabetic neuropathy after daily treatment with low doses of TAD.

Nowadays, erectile dysfunction (ED) is considered an increasingly important clinical condition in men with heart failure (HF) which might influence the therapeutic approach to these patients. Since there is cogent evidence that ED is a "sentinel marker" of acute cardiovascular events especially in men younger than 65 years old or in those affected by type 2 diabetes mellitus, it deserves an early diagnosis and an appropriate treatment. In NYHA III-IV class HF patients, sexual activity could lead to acute cardiovascular events and this should be taken into account when approaching ED patients. Moreover, it is well known that some classes of drugs, normally employed in the treatment of HF patients (e.g.thiazide diuretics, spironolactone and ß-blockers), might worsen or even contribute to ED development. However, growing evidence suggests that PDF 5 inhibitors (vardenafil, tadalafil and sildenafil) seem to better satisfy the needs of NYHA HF I- II class men suffering from ED. In fact, they show a few side effects, while improving both cardiopulmonary parameters and quality of life. Therefore, the aim of this review is to sum up the most recent evidences regarding the management of ED in men suffering from HF.

The low pharmacological response to phosphodiesterase type 5 inhibitors represents an expression of higher endothelial damage in certain categories of patients with erectile dysfunction and high cardiovascular risk. The present study evaluated this objective in type 2 diabetic patients with erectile dysfunction, classified as "non responders" to Sildenafil.Eighteen "responder" and twelve "non responder" type 2 diabetic patients were evaluated, relatively to different levels of endothelial damage, through the diagnostic use of a new immunophenotype of circulating endothelial progenitor cells (CD45neg/CD34pos/CD144pos) and endothelial microparticles (CD45neg/CD144pos/Annexin Vpos), recently developed and published by our group."Non responder" patients showed a significant higher severity [8.0±3.0 (International Index of Erectile Function-abbreviated version with 5 questions) vs 14.0±3.0] and duration (10.0±2.0 vs 7.0±2.0 years) of erectile dysfunction, higher level of penile arterial insufficiency (peak systolic velocity=13.0±16.0 vs 28.0±26.0cm/s; acceleration time=153±148 vs 125±128 mm/s) and finally a significant higher level of endothelial apoptosis [0.15±0.13 vs 0.05±.0.03% (serum concentrations of endothelial microparticles)] associated with higher serum concentrations of circulating late immunophenotype of endothelial progenitor cells (0.40±0.35 vs 0.12±.0.10%).The results of this study corroborate the clinical value of the low clinical response to phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction in the patients with high cardiovascular risk profile, such as diabetics. In addition, the markers used in this study confirm their potential application in clinical practice as useful indicators of endothelial alteration. However, in the future we will have to assess a larger number of patients and for a longer period of observation in order to better understand the causal and temporal relations.

Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done.

To investigate the relationship of erectile dysfunction (ED) with blood vessel-, nerve- and androgen-related factors in young and middle-aged men with type 2 diabetes mellitus (T2DM) in order to provide some clinical evidence for early prevention and treatment of ED.We divided 53 male T2DM patients under 50 years into an ED group (IIEF-5 score < or = 21, n = 28) and a non-ED (NED) group (IIEF-5 score > or = 22, n = 25). We detected the levels of blood lipid, glucose, total testosterone (TT), sex hormone-binding globulin (SHBG), sulfate dehydroepiandrosterone (DHEA-S), calculated free testosterone (cFT), and examined the complications of macroangiopathy (MA), diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and compared the above indicators between the two groups.There were no significant differences between the two groups in age, diabetes duration, body mass index, blood pressure, and blood lipid and glucose levels (P > 0.05). The incidence rate of DR was significantly higher in the ED than in the NED group (39.3% vs 4.0%, P < 0.05), but no statistically significant differences were found in the levels of TT, cFT, SHBG and DHEA-S and the incidence rates of MA and DPN between the two groups (P > 0.05).The incidence of ED is closely related to DR in young and middle-aged men with T2DM. Therefore particular attention should be paid to the erectile function of T2DM patients with DR as early as possible.

The aim of this study was to investigate possible ultrasound seminal vesicle (SV) changes in infertile patients with 'hypertrophic-congestive' (HCUF) or 'fibro-sclerotic' (FSUF) ultrasound form of male accessory gland infection (MAGI) after prolonged administration of tadalafil (TAD), a selective phosphodiesterase-5 inhibitor. Forty infertile patients with HCUF and 40 patients with FSUF and erectile dysfunction were selected and arbitrarily divided into two groups, who were prescribed TAD 5 mg daily for 3 months, the first 20 consecutive patients with HCUF (group A1) or FSUF (group A2) or placebo, the second 20 consecutive patients with HCUF (group B1) or FSUF (group B2). All patients underwent scrotal and prostate-vesicular transrectal ultrasound evaluation and semen analysis (WHO, 2010) before and after treatment. Group A1 patients showed a significant reduction in fundus/body ratio and higher pre- and post-ejaculatory body SV antero-posterior diameter difference compared with the other three groups. These patients showed also a significant increase in SV ejection fraction and a significant improvement in the total sperm count, progressive motility, seminal levels of fructose and ejaculate volume. These results suggest that infertile patients with HCUF had an improvement in SV ultrasound features suggestive of chronic inflammation after daily treatment with low doses of TAD.