title: Six months of daily treatment with vardenafil improves parameters of endothelial inflammation and of hypogonadism in male patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, prospective trial.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: 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 santi.daniele@gmail.com.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santi
authors.affiliation: 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.
authors.forename: Antonio R M
authors.initials: AR
authors.lastname: Granata
authors.affiliation: 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.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Guidi
authors.affiliation: 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.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pignatti
authors.affiliation: 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.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Trenti
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Roli
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bozic
authors.affiliation: 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.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zaza
authors.affiliation: 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.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pacchioni
authors.affiliation: 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.
authors.forename: Stefania
authors.initials: S
authors.lastname: Romano
authors.affiliation: 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.
authors.forename: Jerzy Roch
authors.initials: JR
authors.lastname: Nofer
authors.affiliation: 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.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rochira
authors.affiliation: 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.
authors.forename: Cesare
authors.initials: C
authors.lastname: Carani
authors.affiliation: 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.
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D007172:Erectile Dysfunction / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D000069058:Vardenafil Dihydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000069058:Vardenafil Dihydrochloride; D002097:C-Reactive Protein