Effects of chronic administration of the phosphodiesterase inhibitor Vardenafil on serum levels of adrenal and testicular steroids in men with type 2 diabetes mellitus

Background . Steroidogenesis is a complex enzymatic process in which cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) play an important role. Phosphodiesterase-5 inhibitors(PDE5i) increase cGMP, improving NO availability. Objective . to investigate whether long-term, chronic treatment with the PDE5i Vardenafil affects adrenal and testicular steroidogenesis in diabetic men, using liquid chromatography-mass spectrometry (LC-MS/MS). Design . A longitudinal, prospective, investigator-started, randomized, placebo-controlled, double-blind, clinical-trial was carried out. Setting and Participants . 54 male patients affected by T2DM diagnosed within the last 5 years were enrolled. 26 and 28 patients were assigned to the verum and placebo-group, respectively. Interventions . The study consisted of an enrolment phase, a treatment phase (24weeks) (Vardenafil/placebo 10mg twice-daily), and a follow-up phase (24weeks). Outcome measurements : progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), corticosterone, 11-deoxycortisol and cortisol (C), were evaluated using LC-MS/MS. Results . No differences were seen in sex testicular steroids between study and control group. For the adrenal gland, steroids were considered according to the zona in which they are produced. Considering steroids produced in the zona fasciculata, no significant differences were seen in 11-deoxycortisol and C among visits, both in the study and in the control group. For the zona reticularis, DHEA significantly decreased during treatment only in the study group (p=0.007). At post-hoc test DHEA showed higher levels at visit 2 and 8 than in other visits. The DHEAS/DHEAS ratio significantly increased during treatment only in the verum group. Considering the adrenal zona glomerulosa, corticosterone significantly changed among visits both in the study and in the control group (p