Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications

Abstract

Introduction: Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM’s chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance enhancing agents. Here, we evaluate and summarize the current literature on SARMs. Aims: To present the background, mechanisms, current and potential clinical applications, as well as risks and benefits of SARMs. Methods: A literature review was performed in MEDLINE using the terms selective androgen receptor modulator, hypogonadism, cachexia, breast cancer, benign prostatic hyperplasia, libido and lean muscle mass. Both basic research and clinical studies were included. Results: While there are currently no FDA-approved indications for SARMs, investigators are exploring the potential uses for these compounds. Basic research has focused on the pharmacokinetics and pharmacodynamics of these agents, demonstrating good availability with a paucity of drug interactions. Early clinical studies have demonstrated potential uses for SARMs in the treatment of cancer-related cachexia, benign prostatic hyperplasia, hypogonadism, and breast cancer, with positive results. Conclusion: SARMs have numerous possible clinical applications, with promise for the safe use in the treatment of cachexia, BPH, hypogonadism, breast cancer, and prostate cancer.

Roles of Splicing Factors in Hormone-Related Cancer Progression

“…Since sex hormone signaling pathways play essential roles in cancer pathophysiology; the therapies targeting the hormones and their receptors, or endocrine therapies, are the mainstays of breast and prostate cancer treatment [22][23][24][25][26][27][28][29]. For breast cancer treatment, drugs that suppress estrogen signaling or estrogen production were used for endocrine therapies.…”

“…As androgen receptor antagonists that prevent androgen-AR interaction, flutamide and bicalutamide have been used for years, and recently more potent AR antagonists, such as enzalutamide, has been applied to CRPC and reported to decrease the risk of cancer progression and death [27]. Selective androgen receptor modulators (SARMs) that function as AR antagonists in specific cell types including prostate cancer cells, and selective androgen receptor degraders or down-regulators (SARDs) are being studied for clinical application ( Figure 1B) [28,29].…”

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

“…Due to the severe side-effects (cardiovascular events and benign prostatic hyperplasia) resulted from long-term or large dose of androgen administration, androgen supplementation is strictly limited [2], and selective androgen receptor modulators (SARMs) especially the non-steroidal tissuespecific SARMs were used currently to activate AR in specific tissue. Sufficient evidences demonstrated the enhancement of lean mass and strength obtained by SARMs in dystrophy muscle of female elderly with sarcopenia [3] and mice with myotonic dystrophy [4]. On the contrary, global AR gene knockout (ARKO) and specific skeletal muscle tissue ARKO mice showed alterations in the muscle mass (such as gastrocnemius, quadriceps and soleus) [5,6], muscle glycogen [7] and exercise performance.…”

Development and Validation of an UHPLC Method for Ostarine Determination in Dietary Supplements

“…Their uses could target pathologies characterized by a marked protein catabolism (cachexia in neoplasic diseases, sarcopenia, muscular dystrophy etc. ), osteoporosis [1], promoting male and female libido, treatment of benign prostatic hyperplasia [2].…”