Late-onset hypogonadism (LOH) and androgens: validity of the measurement of free testosterone levels in the diagnostic criteria in Japan.

The basis of diagnosis of late-onset hypogonadism (LOH) is the measurement of androgen levels. Traditionally, total testosterone (total T) was also used as the primary indicator of gonadal function in Japan. In 1998, the International Society for the Study of the Aging Male was founded to conduct basic and clinical research on this issue internationally. As a result, it is said that bioavailable testosterone levels should be measured in the diagnosis of LOH. At present, however, there are a number of problems for bioavailable testosterone to become a routine diagnostic tool. Here, we will explain the various measurement indicators of androgens, measurement problems, standard values of total T, and free testosterone (free T) in Japan, and the diagnostic methods for LOH overseas. In Japan, the Japanese Urological Association and the Japanese Association of Men's Health recommend the measurement of free T levels in the diagnosis of LOH, for the following reasons: (i) It has been demonstrated that free T is more strongly correlated with calculated bioavailable testosterone, than total T, showing a statistically significant difference; (ii) The behavior of free T is highly consistent with that of bioavailable testosterone, with free T levels being markedly decreased due to aging; (iii) For the measurement of free T, a method that allows the measurement of free T only, without affecting the balance between free T and protein-bound testosterone in blood, is available; and 4) The mean total T by age range decreases only to 80% of the young adult mean even during presenile and senile periods, when LOH occurs most frequently, but the free T level shows a linear decrease with aging and drops to 50% of the young adult mean. For these reasons, we will describe the validity of the recommendation for the measurement of free T levels.