Search

Phosphodiesterase type-5 inhibitor (PDE5i) tadalafil administration in men with erectile dysfunction is associated with increased testosterone/estradiol ratio, leading to hypothesize a potential increased effect of androgen action on target tissues. We aimed to characterize, in a cellular model system in vitro, the potential modulation of aromatase and sex steroid hormone receptors upon exposure to tadalafil (TAD).Human osteoblast-like cells SAOS-2 were chosen as an in vitro model system since osteoblasts are target of steroid hormones. Cells were tested for viability upon TAD exposure, which increased cell proliferation. Then, cells were treated with/without TAD for several times to evaluate potential modulation in PDE5, aromatase (ARO), androgen (AR) and estrogen (ER) receptor expression.Osteoblasts express significant levels of both PDE5 mRNA and protein. Exposure of cells to increasing concentrations of TAD (10(-8)-10(-7) M) decreased PDE5 mRNA and protein expression. Also, TAD inhibited ARO mRNA and protein expression leading to an increase in testosterone levels in the supernatants. Interestingly, TAD increased total AR mRNA and protein expression and decreased ERα, with an increased ratio of AR/ER, suggesting preferential androgenic vs estrogenic pathway activation.Our results demonstrate for the first time that TAD decreases ARO expression and increases AR protein expression in human SAOS-2, strongly suggesting a new control of steroid hormones pathway by PDE5i. These findings might represent the first evidence of translational actions of PDE5i on AR, which leads to hypothesize a growing relevance of this molecule in men with prostate cancer long-term treated with TAD for sexual rehabilitation.

Men affected by multiple sclerosis often experience neurogenic overactive bladder (OAB), lower urinary tract symptoms and erectile dysfunction (ED). The aim of the study was to investigate modifications of urinary and sexual functions after administration of daily tadalafil (TAD) 5 mg. Twenty men were enrolled in a single-blind, 4-week prospective study while 10 men without treatment served as controls. Primary outcomes were changes from baseline of International Prostate Symptom (IPSS), OAB questionnaire (OAB-q-short form) and International Index of Erectile Function (IIEF-5) scores. To evaluate the influence of bladder filling on somatic reflexes, we studied variations of the H-reflex evoked by electrical stimuli applied to the tibial nerve at the popliteal fossa and recorded from the soleus muscle. Also testosterone/estradiol (T/E) ratio was measured before and after treatment. In TAD group, an improvement in IPSS (p