Correcting imbalance of sex hormones by a phosphodiesterase 5 inhibitor improves copulatory dysfunction in male rats with type 2 diabetes

INTRODUCTION: Sexual dysfunction is a common complication in men with type 2 diabetes and is often refractory to treatment. This study investigated the long-term influence of the phosphodiesterase 5 inhibitor (PDE5I) tadalafil on the level of sex hormones and sexual function in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model of spontaneous type 2 diabetes. RESEARCH DESIGN AND METHODS: We treated 36-week-old male OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats with oral tadalafil (100 µg/kg/day) for 12 weeks; sham groups received vehicle for 12 weeks. Before and after tadalafil treatment, serum levels of total and free testosterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone and proinflammatory cytokines were compared among four treatment groups. Copulatory function was examined by matching each rat to an estrous female. After completion of the experiment, total fat mass in the abdomen was measured. RESULTS: Testosterone levels were significantly lower in OLETF versus LETO rats at 36 weeks. After 12 weeks of tadalafil treatment, levels of testosterone were significantly increased both in OLETF-tadalafil and LETO-tadalafil groups versus vehicle groups. Tadalafil decreased estradiol levels both in OLETF and LETO rats. Furthermore, tadalafil increased serum LH levels with a reduction of proinflammatory cytokines. Total fat mass was significantly lower in the OLETF-tadalafil group versus the OLETF-vehicle group. A significant suppression of copulatory behavior, that is, elongation of intromission latency was found in OLETF rats. However, tadalafil treatment for 12 weeks shortened the intromission latency. CONCLUSION: Our results indicate that tadalafil treatment might improve copulatory disorder in the type 2 diabetic model via improvement of an imbalance in sex hormones and an increase in LH levels.