Pharmacological management of late-onset hypogonadism

Introduction: The frequency of late-onset hypogonadism (LOH) ranges between 2 and 15%. Up to 85% of LOH is due to a functional impairment of the hypothalamus–pituitary–testicular axis, mostly secondary to metabolic conditions.

Areas covered: This paper provides a comprehensive review of all the available medications for treating LOH, including antiestrogens, gonadotropins and testosterone therapy (TTh). In addition, the evidence on clinical outcomes of these treatments is provided by meta-analyzing the results from the available randomized clinical trials.

Expert commentary: The present data indicate that antiestrogens are able to increase testosterone levels without changing gonadotropins or even increasing them. Therefore, they may maintain, and even to stimulate spermatogenesis. However, their efficacy in treating LOH-associated symptoms has been scarcely tested and their use in LOH is off-label. In contrast, gonadotropins are indicated for hypogonadism, in particular when fertility is required. Information on the effects of gonadotropins on LOH is scanty and the impractical administration limits their use. TTh can be administered with different modalities, making it a suitable option for LOH, when fertility is not desired. The available meta-analyses show that TTh is able to improve sexual function and body composition, with more evident results obtained with transdermal and injectable preparations.