Tadalafil and Steroid Hormones Interactions in Adipose, Bone and Prostate Tissues: Focus on Translational Perspectives

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH)-associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout the human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity and cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells, where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review, we summarize basic research and translational results applicable to the use of tadalafil in the treatment of obesity, bone loss and prostate cancer.