Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Author:

Giagulli Vito A.1,Silvestrini Andrea2ORCID,Bruno Carmine3ORCID,Triggiani Vincenzo1,Mordente Alvaro2,Mancini Antonio3ORCID

Affiliation:

1. Internal Medicine, Geriatrics, Endocrinology and Rare Disease, Interdisciplinary Department of Medicine, University of Bari, School of Medicine, Policlinico, Bari, Italy

2. Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy

3. Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy

Abstract

Hypogonadotropic hypogonadism (HH) can be sustained by organic or functional alterations of the hypothalamic-pituitary-testicular axis. Functional HH is related to systemic alterations, such as obesity or chronic inflammatory diseases, but could contribute to a negative course of the illness. For such situation, according to results obtained in infertile women, the administration of selective estrogen receptor modulators (SERMs) has been proposed in males too, with positive results on both metabolic and sexual function. This class of medications increases gonadotropin levels via antagonism to the estrogenic receptor; similar biological effects are also exerted by aromatase inhibitors (AIs), despite different mechanism of action. After a brief review of trials regarding SERMs and AIs use in male HH, we describe the structure and function of the androgen receptor (AR) as a basis for clinical research about compounds able to bind to AR, in order to obtain specific effects (SARMs). The tissue selectivity and different metabolic fate in comparison to testosterone can potentiate anabolic versus androgenic effects; therefore, they might be a valid alternative to testosterone replacement therapy avoiding the negative effects of testosterone (i.e., on prostate, liver, and hematopoiesis). Trials are still at an early phase of investigation and, at the moment, the application seems to be more useful for chronic disease with catabolic status while the validation as replacement for hypogonadism requires further studies.

Publisher

Hindawi Limited

Subject

Endocrine and Autonomic Systems,Endocrinology,Endocrinology, Diabetes and Metabolism

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