Late-Onset Hypogonadism

Testosterone (T) levels progressively declines with aging. Symptoms of androgen deficiency are not specific and often overlap with those related to aging. Hence, it is difficult to identify and define late-onset hypogonadism (LOH). The definition of LOH and its clinical significance is a matter of debate as well as the strategies of treating this condition. During the last years, the data produced by the European Male Ageing Study (EMAS) greatly helped in advancing the knowledge on LOH. In the European general population, LOH has been defined as the presence of low T associated with three sexual symptoms. Thus defined, LOH specifically identifies a condition characterized by the classical features of androgen deficiency. However, according to the EMAS data, LOH is not a homogeneous condition. In fact, a moderate and a severe form, respectively characterized by moderate (8–11 nmol/L) or severe (<8 nmol/L) low T levels, can be identified. Severe LOH is more strongly associated with symptoms and signs of androgen deficiency, thus probably representing a more genuine form of LOH. In European general population, T levels are lower as BMI increases and, accordingly, prevalence of LOH is significantly higher in obese men. In the EMAS study, LOH has been associated also with an increased all-cause and CV mortality and, also in this case, severe LOH exhibits the strongest relationship. The evidence that, similarly to LOH, also sexual symptoms and total T < 8 nmol/L are associated, independently of each other, with an increased mortality complicates the interpretation of the clinical significance of LOH. In fact, at present, it is not clear whether LOH should be considered a pathologic condition, with consequences for well-being and quality of life as well as for general and CV health, or whether it is an epiphenomenon of poor health, representing a marker of frailty, rather than a causing condition. Pending long-term, adequately powered, and designed RCTs, it is unclear whether TRT is useful and beneficial in subjects with LOH and the treatment should be undertaken after comparing possible risks and benefits in each patient and monitoring the onset of side effects, according to the available guidelines.