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.