Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials

ABSTRACT

Introduction

Skeletal muscle wasting is a frequent clinical problem encountered in patients with chronic diseases. Increased levels of inflammatory markers play a role in the imbalance between muscle protein synthesis and degradation. Although testosterone has long been proposed as a treatment for patients with muscle wasting, undesirable side effects have raised concerns about prostatic hypertrophy in men as well as virilization in women. Selective androgen receptor modulators (SARMs) have demonstrated similar results like testosterone at improving lean body mass (LBM) with less side effects on androgen-dependent tissue.

Areas covered

This review outlines the ongoing clinical development in the field of SARMs and their effectiveness in improving body composition and physical function. The included articles were collected at pubmed.gov and analyzed integrally.

Expert opinion

There is an unmet clinical need for safe and effective anabolic compounds such as SARMs. Despite the effect on LBM shown by SARMs in phase II clinical trials, results on improved physical function and muscle strength are still lacking and long-term outcomes have to be assessed in these patients. Moreover, there is a need to determine the effect of resistance exercise training and protein intake associated with SARMs in the treatment of patients with muscle wasting.

KEYWORDS:

• Androgen receptor
• cachexia
• muscle wasting
• sarcopenia
• selective androgen receptor modulators
• testosterone

Article highlights

• Debatable cardiovascular risks and undesirable side effects of testosterone have encouraged the development of alternative therapies to treat declines in muscle mass and muscle function;

• Selective androgen receptor modulators (SARMs), similar to testosterone in action, has received the term ‘modulators’ due to their capability to range from full agonists in some tissues (e.g. muscle and bone) to partial agonists or full antagonists in others (e.g. reproductive organs);

• SARMs have shown to improve total lean body mass, but there is still inconclusive finding with regards to improvement in muscle strength and physical function.

• Although the side effect profile of SARMs may resemble some aspects of testosterone (reduced HDL, hepatotoxicity and hypothalamic-pituitary-gonadal axis suppression), these alterations occur to a much lesser extent degree than testosterone;

• There is still a need to determine the effect of resistance exercise training and protein intake, well-known interventions to promote changes in muscle strength and muscle mass, in the treatment of patients with muscle wasting.

• This box summarizes key points contained in the article.

Declaration of interest

S von Haehling has been a paid consultant and/or received fees for lectures from Bayer, Boehringer Ingelheim, BRAHMS/Thermo Fisher, Chugai Pharma, Grünenthal, Helsinn, Novartis, Pharmacosmos, Respicardia, Roche, Servier, and Vifor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The preparation of this manuscript was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 and by the German Center for Cardiovascular Research (DZHK).