vardenafil-dihydrochloride and Hypogonadism

Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships.. The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures.. The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included.. Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alprostadil; Carbolines; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Pyrimidines; Risk Factors; Sulfonamides; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Yohimbine

Topics: Adrenergic alpha-Antagonists; Alprostadil; Apomorphine; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Male; Penile Implantation; Physical Therapy Modalities; Piperazines; Psychotherapy; Purines; Sildenafil Citrate; Sulfones; Testosterone; Triazines; Vacuum; Vardenafil Dihydrochloride; Vascular Surgical Procedures; Vasodilator Agents; Yohimbine

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men.. A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted.. In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10  mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry).. IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects.. This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism in diabetic, hypogonadal men.

Topics: Aged; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Endothelium, Vascular; Erectile Dysfunction; Humans; Hypogonadism; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Longitudinal Studies; Male; Middle Aged; Time Factors; Vardenafil Dihydrochloride; Vascular Cell Adhesion Molecule-1

Long-acting injectable testosterone undecanoate (TU, Nebido(®)), a new parenteral testosterone preparation, has recently been introduced to avoid frequent injections of the conventional injectable esters.. To assess the efficacy and safety of long-acting injectable testosterone undecanoate (TU, Nebido(®)) in Korean patients with testosterone deficiency syndrome (TDS).. One hundred thirty-three patients who complain of erectile dysfunction with serum testosterone level less than 3.5 ng/mL were injected with 1,000 mg of TU (4 mL/ample) on day 1, followed by another injection after 6 weeks and 18 weeks. For the safety profiles, serum hemoglobin (Hb), hematocrit (Hct), glucose, lipid profile, and prostate-specific antigen (PSA) were measured.. Body mass index (BMI) was measured at the time of the first visit and after 12, 24 weeks. Primary efficacy was evaluated according to changes in the International Index of Erectile Function (IIEF) from the initial visit to the final visit (24 weeks) and from the initial visit to each visit. Secondary efficacy was assessed with changes of the Aging Males' Symptoms (AMS) Scale and the Global Efficacy Question (GEQ) for improvement of erectile function.. Mean age of patients was 54 ± 9.6 years. Compared with pretreatment, no significant improvement in BMI was observed. Serum total testosterone and free testosterone were significantly increased at 12 weeks and were maintained until 24 weeks (P < 0.001). TU significantly decreased cholesterol (P < 0.0001). TU significantly improved total IIEF, all five domain scores of IIEF (P < 0.0001) and total AMS, all three domain scores of AMS (P < 0.0001). On GEQ, TU improved erectile function in 76.9% of subjects. On safety profile, TU significantly elevated Hb, Hct, and PSA at 24 weeks but within normal range. No serious adverse reactions were observed. Drop-out rate was 15.0%.. In this prospective multicenter study, TU was effective, safe, and tolerable until 24 weeks in Korean TDS patients. Further well-controlled, long-term study should follow.

Topics: Adult; Aged; Androgens; Cross-Cultural Comparison; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Korea; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride

To study effects of different treatments on erectile and endothelial functions in patients with erectile dysfunction (ED) and age-related hypogonadism (HG).. The study included 66 males with ED who had clinical and laboratory signs of HG. All the patients were examined using questionnaires (international index of erectile function, AMS), blood hormones tests. Endothelial function was assessed with postcompression tests on the cavernous arteries and blood homocystein assay. All the patients were divided into two matched groups. Group 1 (20 males, mean age 54.6 +/- 11.5 years) received androgens only, replacement therapy consisted of testosterone undecanoate (Nebido, Shering) 1000 mg each 10-12 weeks intramuscularly, interval between the first and second injection was 6 weeks. Group 2 (46 males, mean age 53.98 +/- 10.03 years) was given combined treatment (androgens and PDE 5 inhibitors), wardenafil (Levitra, Buer Shering Pharma) was used in a dose 20 mg. The treatment lasted 6 months.. AMS points decreased in group 1 from 38.3 +/- 0.29 to 29.2 +/- 0.32, in group 2--from 39.02 +/- 0.21 to 28.6 +/- 0.95, while testosterone rose from 9.86 +/- 0.4 to 17.77 +/- 0.42 and 9.35 +/- 0.25 to 17.21 +/- 0.63 nmol, respectively. Homocystein lowering was significantly more manifest in group 2. EF index in group 2 rose from 11.4 +/- 0.77 to 25.54 +/- 0.25 points versus 11.2 +/- 1.01 to 23.95 +/- 0.71 points in group 1, improvement of EF in group 2 occurred sooner. Endothelial function by diameter of the cavernous arteries differed after treatment in group 1 and 2 (19.55 +/- 2.88 to 39.2 +/- 0.84% and 19.51 +/- 1.28 to 48.5 +/- 1.76, respectively, p<0.001).. Combined therapy improves blood homocistein, acts faster and stronger on endothelial and erectile functions and can be recommended as first line for ED and HG patients.

Topics: Drug Therapy, Combination; Endothelium, Vascular; Erectile Dysfunction; Homocysteine; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Risk Factors; Sulfones; Testosterone; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Diabetes Mellitus, Type 2; Endothelium, Vascular; Erectile Dysfunction; Humans; Hypogonadism; Inflammation; Male; Vardenafil Dihydrochloride

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Inflammation; Male; Prospective Studies; Treatment Outcome; Vardenafil Dihydrochloride

The role of testosterone in erectile dysfunction (ED) is increasingly recognized. It is suggested that assessment of testosterone deficiency in men with ED and symptoms of hypogonadism, prior to first-line treatment, may be a useful tool for improving therapy.. In this prospective, observational, and longitudinal study, we investigated the effects of vardenafil treatment as adjunctive therapy to testosterone undecanoate in hypogonadal ED patients who failed to respond to testosterone treatment alone.. One hundred twenty-nine testosterone deficient (serum total testosterone ≤ 3.4 ng/mL) patients aged 56 ± 3.9 years received intramuscular injections of long-acting parenteral testosterone undecanoate at 3-month intervals for 8 months mean follow-up.. Scores on the International Index of Erectile Function Questionnaire-five items (IIEF-5) and partner survey scores were compared at baseline and posttreatment with testosterone therapy alone or in combination with vardenafil. Patient baseline demographics and concomitant disease were correlated with patients' IIEF-5 scores.. Seventy one (58.2%) responded well to monotherapy within 3 months. Nonresponders had lower testosterone levels and higher rates of concomitant diseases and smoking. Thirty-four of the 51 nonresponders accepted the addition of 20 mg vardenafil on demand. Efficacy assessments were measured by the IIEF-erectile function domain (IIEF-EF, questions 1-5 plus 15, 30 points) and partner self-designed survey at baseline after 4-6 weeks and at study end point. Thirty out of 34 patients responded well to this combination. IIEF-EF Sexual Health Inventory for Men score improved from 12 to 24 (P < 0.0001), and partner survey showed significantly higher satisfaction (P < 0.001). These patients reported spontaneous or nocturnal and morning erections or tumescence. No changes in adverse effects were recorded.. These data suggest that combination therapy of testosterone and vardenafil is safe and effective in treating hypogonadal ED patients who failed to respond to testosterone monotherapy.

Topics: Aged; Aged, 80 and over; Drug Therapy, Combination; Erectile Dysfunction; Female; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Penile Erection; Personal Satisfaction; Piperazines; Prospective Studies; Sexual Partners; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride

Endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. Circulating EPC concentration is low in conditions characterized by endothelial dysfunction but their number can be increased by treatment with phosphodiesterase-5 (PDE5) inhibitors. EPCs are also reduced in hypogonadal men and testosterone (T) treatment restores their concentration.. To evaluate the relationship between the effect of PDE5 inhibitors and T on EPCs, we analysed the acute effect of vardenafil on the number of EPCs in hypogonadotrophic hypogonadal (HH) patients, before and after T treatment.. A case-control study at a university andrology centre.. Fifteen HH subjects and 25 aged-matched controls.. The number of circulating EPCs and progenitor cells (PCs) in HH patients was evaluated after acute vardenafil administration at baseline and after 6 months of T supplementation.. At baseline, HH men had significantly lower numbers of PCs and EPCs with respect to controls and vardenafil administration had no effect on the number of these cells. After 6 months of T treatment, all HH patients were eugonadal. With respect to baseline, PCs and EPCs were significantly higher and reached the levels observed in controls. Vardenafil administration in HH men at the end of T treatment induced a significant increase in PCs and EPCs in a manner similar to that in controls.. This study showed that normal T levels are necessary to restore the responsiveness of EPCs to PDE5 inhibitors, suggesting that T positively modulates PDE5 in bone marrow.

Topics: Adult; Case-Control Studies; Cell Count; Cells, Cultured; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelial Cells; Humans; Hypogonadism; Imidazoles; Male; Piperazines; Stem Cells; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride; Young Adult

This study examined 72 patients with obstructive sleep apnoea syndrome (OSAS), confirmed by polysomnography. Thirty-two patients were suffering from erectile dysfunction (ED) assessed by IIEF-5 questionnaires and confirmed by nocturnal penile tumescence examination. Their testosterone levels were measured. Eight patients had normal testosterone levels and were treated with a PDE-5 inhibitor (vardenafil) only; after 6 months of treatment, 6 of these patients (75%) showed significant improvement in erectile function. The remaining 24 patients with OSAS, ED and hypogonadism (total testosterone <12 nmol l(-1)), were divided into two groups based on the indication for continuous positive airway pressure (CPAP) therapy: five patients received CPAP therapy (group 1) and 19 patients did not (group 2). The patients of group 2 received only a PDE-5 inhibitor (vardenafil 20 mg) for ED; and eight patients (42%) showed an improvement after 3 months of treatment. The five patients receiving CPAP therapy were treated with a combination of parenteral testosterone undecanoate and a PDE-5 inhibitor (vardenafil) and all had normal erectile function after 3 months of therapy. The results suggest positive effects of addition of testosterone to treatment with PDE-5 inhibitors in hypogonadal men with OSAS, which should be confirmed in larger controlled studies.

Topics: Adult; Continuous Positive Airway Pressure; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Sleep Apnea, Obstructive; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride