Phd in ENDOCRINOLOGICAL SCIENCES

Thesis title: Gli effetti degli inibitori delle 5 alfareduttasi sul metabolismo del glucosio in pazienti affetti da ipertrofia prostatica benigna e diabete mellito di tipo II

The prevalence of BPH increases with age: histologic prevalence reaches 60% at age 60 and 80% at age 80. The treatment of BPH is often multimodal and almost all guidelines reached a relatively uniform opinion considering as equal possible first treatment choices alpha 1-Blockers, muscarinic receptor antagonists or 5alpha-reductase (5AR) inhibitors (5ARis). 5ARis are widely prescribed for their antiandrogenic effects. However, 5AR are also involved in glucocorticoids metabolism and clearance: their inhibition reduces the clearance of cortisol by inhibiting its inactivation, thus leading to increased levels of active cortisol. This is particularly important considering that the circulating levels of GCs are locally regulated through a balance between synthesis in the adrenal cortex and clearance via metabolic pathways in the liver and other peripheral tissues, which accounts for the maintaining of physiological concentration of active GCs in the bloodstream and peripheral tissues. Inhibition of androgens and glucocorticoid transformation to their various metabolites may result in pathophysiological states, such as liver diseases, hyperglycemia, hyperlipidemia, IR, and type 2 diabetes mellitus (T2DM). So that, for 5ARis, it is reasonable to expect systemic effects which are not confined to the prostate gland. However, the ability of these drugs to regulate metabolic phenotype has only been examined in a very small number of studies. Most recently, analysis of data from primary care prescriptions suggested a significant association between 5alpha-RI prescriptions and the incidence of type 2 diabetes (T2D). Based on these premises, the present study will therefore aim to evaluate the effects of 5alphareductase inhibitors on glucose metabolism in patients with BPH and Type 2 diabetes mellitus over a 12-months period.