title: Effects of chronic administration of the phosphodiesterase inhibitor vardenafil on serum levels of adrenal and testicular steroids in men with type 2 diabetes mellitus.
abstract: To investigate whether long-term, chronic treatment with the phosphodiesterase-5 inhibitor vardenafil affects adrenal and testicular steroidogenesis in diabetic men, using liquid chromatography-tandem mass spectrometry. A longitudinal, prospective, investigator-started, randomized, placebo-controlled, double-blind, clinical-trial was carried out, enrolling 54 male patients affected by type 2 diabetes mellitus diagnosed within the last 5 years. In total, 26 and 28 patients were followed for 1 year and assigned to the study and placebo group, respectively. Progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, corticosterone, 11-deoxycortisol and cortisol, were evaluated using liquid chromatography-tandem mass spectrometry. No differences were seen in sex testicular steroids between study and control group. As for the adrenal gland, steroids were considered according to the zona in which they are produced. No significant differences were seen in steroid produced in zona fasciculata. For the zona reticularis, dehydroepiandrosterone significantly decreased during treatment only in the study group (p = 0.007), with higher levels at visit 2 and 8 than other visits. The dehydroepiandrosterone sulfate/dehydroepiandrosterone ratio significantly increased during treatment only in the verum group. Considering the adrenal zona glomerulosa, corticosterone significantly changed among visits both in both groups (p < 0.001), with higher levels at visit 2 (p = 0.028), 8 (p = 0.003), and 10 (p = 0.044), i.e., in coincidence with the complete clinical and instrumental examination performed only at these visits according to the study protocol. Chronically administered vardenafil reduces dehydroepiandrosterone levels and increases dehydroepiandrosterone sulfate/dehydroepiandrosterone ratio as possible consequences of modulation of steroidogenic enzymes by tissue changes in cyclic adenosine monophosphate and cyclic guanosine monophosphate availability. A possibly stress-related increase in corticosterone is suggested for the first time.
authors: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. santi.daniele@gmail.com.|Department of Medicine, Endocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, Italy. santi.daniele@gmail.com.
authors: Daniele
authors: http://orcid.org/0000-0001-6607-7105
authors: D
authors: Santi
authors: Department of Medicine, Endocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, Italy.
authors: Antonio Rm
authors: AR
authors: Granata
authors: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.|Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy.
authors: Elisa
authors: E
authors: Pignatti
authors: Department of Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena, Modena, Italy.
authors: Tommaso
authors: T
authors: Trenti
authors: Department of Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena, Modena, Italy.
authors: Laura
authors: L
authors: Roli
authors: PerkinElmer, 20126, Milan, Italy.
authors: Roberto
authors: R
authors: Bozic
authors: SHIMADZU Italia, Milan, Italy.
authors: Stefano
authors: S
authors: Zaza
authors: Diabetic Service, Azienda USL of Modena, Modena, Italy.
authors: Chiara
authors: C
authors: Pacchioni
authors: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.|Department of Medicine, Endocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, Italy.
authors: Vincenzo
authors: V
authors: Rochira
authors: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Cesare
authors: C
authors: Carani
authors: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.|Department of Medicine, Endocrinology, Metabolism and Geriatrics, Azienda USL of Modena, Modena, Italy.|Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy.
authors: Manuela
authors: M
authors: Simoni
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D002853:Chromatography, Liquid; D003345:Corticosterone / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000097:blood*; D011446:Prospective Studies; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood; D000069058:Vardenafil Dihydrochloride / Q000008:administration & dosage*
chemical_list: D000728:Androgens; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D000069058:Vardenafil Dihydrochloride; D019326:17-alpha-Hydroxyprogesterone; D003345:Corticosterone; D006854:Hydrocortisone
keywords: Adrenal steroid; Mass-spectrometry; Type 2 diabetes mellitus; Vardenafil