CJK 05. Testosterone & PDE5I for ED & LUTS

It is well known that testosterone, which decreases with aging, plays many physiological roles in various organs. Late-onset hypogonadism (LOH) has received widespread attention in the last few years. Recently, the clinical practice manual for LOH was written and published by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male to recommend standard procedures for diagnosis, treatment, prevention and monitoring of adverse reactions due to testosterone replacement therapy (TRT), and post-treatment assessment. Several LOH symptoms have been reported to be improved by TRT. Testosterone is also thought to be an important determinant of prostate growth. Thus, it is thought to contribute to the development and maintenance of lower urinary tract symptom (LUTS) secondary to benign prostatic hypertrophy (BPH), which is very common among aging men. However, it was recently reported that the Impact of prostate symptom score (IPSS) showed a significant decrease after TRT for 12 months in Japanese patients. Thus, the effect of testosterone on LUTS is still controversial.

Phosphodiesterase (PDE) enzymes are involved in the regulation of the nitric oxide (NO)-cycling GMP protein kinase pathway and influence smooth muscle tone. Sildenafil, the first PDE type 5 inhibitor (PDE5I), was originally developed and studied as a cardiovascular medication. After that, because the NO system has been well characterized as the main regulator of penile corporal smooth muscle relaxation and resultant erection, PDE5Is have been used for improving the action of NO through NO cycling guanosine monophosphate (cGMP) pathway on penile smooth muscle cells. At present, on-demand PDE5Is are the first line treatment for erectile dysfunction (ED). Furthermore, PDE5Is have recently gained much interest in urological field because they can improve not only ED symptoms but also LUTS. It was shown that PDE5 is located in the transition zone of the human prostate and the human bladder neck is supplied by NO synthase (NOS)-containing nerves. NO is a major regulator of smooth muscle contractility in the prostate as well as penis. In several studies, PDE5Is had a significant effect on LUTS, with a magnitude of improvement in IPSS.

In this session, I would like to introduce several data of the treatment for patients with ED and LUTS by testosterone and PDE5I.