OBJECTIVE - 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.
DESIGN - A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted.
METHODS - 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).
RESULTS - 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.
CONCLUSIONS - 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.
European journal of endocrinology / European Federation of Endocrine Societies. 2016 Jan 20 [Epub]
Daniele Santi, Antonio R M Granata, Alessandro Guidi, Elisa Pignatti, Tommaso Trenti, Laura Roli, Roberto Bozic, Stefano Zaza, Chiara Pacchioni, Stefania Romano, Jerzy Roch Nofer, Vincenzo Rochira, Cesare Carani, Manuela Simoni
Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany ., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany., Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany Unit of Endocrinology & MetabolismDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, ItalyDepartment of MedicineEndocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, ItalyCenter for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, ItalyDepartment of Laboratory Medicine and Pathological AnatomyAzienda USL of Modena, Modena, ItalyPerkinElmer20126 Milan, ItalySHIMADZU ItaliaMilan, ItalyDiabetic ServiceAzienda USL of Modena, Modena, ItalyCenter for Laboratory MedicineUniversity Hospital Münster, Münster, Germany.