While T is undoubtedly the most important androgen, it is worth remembering that the AR also binds its metabolite, 5α-dihydrotestosterone (DHT). Polymorphisms of the AR gene CAG repeats have also been associated with symptoms of aging in men, namely those of psychological nature but also worse sexual function.

Īndrogen action is mediated through the androgen receptor (AR) changes in its structure lead to different clinical phenotypes, ranging from complete androgen insensitivity syndrome (CAIS) to apparently normal males. Testosterone treatment should be considered following diagnosis confirmation, to improve sexual and non-sexual symptoms of hypogonadism.

However, signs and symptoms of hypogonadism are mandatory for diagnosis, together with biochemical confirmation of T deficiency, and should not be overlooked. Signs and symptoms associated with hypogonadism are largely variable: the most common ones, such as fatigue, impaired erectile function and reduced sexual drive, might be the result of several other conditions and are often disregarded as “common features of aging” by patients and clinicians alike. Accordingly, guidelines for the treatment of men with functional hypogonadism have recently been published. The T-Trials were performed in elderly men with functional hypogonadism and demonstrated benefits in several dimensions of symptoms. Apparently, this addresses men with so-called functional hypogonadism, a condition associated with comorbidities such as obesity/type 2 diabetes mellitus. This has led to an FDA warning allowing the use of T only in cases of confirmed low T levels and only in “men with disorders of the testicles, pituitary gland or brain that cause hypogonadism”, as to avoid “attempts to relieve symptoms in men who have low T for no apparent reason other than aging”. Most of the reported side effects of T administration had occurred in subjects with high baseline serum T-i.e., subjects who should not have received any kind of androgen replacement therapy-in the hope of improving sexual health and/or physical function. Several studies have rekindled scientific interests on the side effects and benefits of testosterone (T) administration and have had their coronation in the Testosterone Trials, a series of seven placebo-controlled, double-blind trials in elderly hypogonadal subjects. Treatment of male hypogonadism has been one of the most controversial topics in endocrinology during the last few years.

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