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World J Clin Cases. Apr 16, 2015; 3(4): 338-344
Published online Apr 16, 2015. doi: 10.12998/wjcc.v3.i4.338
Review of health risks of low testosterone and testosterone administration
Huanguang Jia, Charles T Sullivan, Sean C McCoy, Joshua F Yarrow, Matthew Morrow, Stephen E Borst
Huanguang Jia, Charles T Sullivan, Sean C McCoy, Joshua F Yarrow, Center of Innovation on Disability and Rehabilitation Research, North Florida/South Georgia Veterans Health System (151b), Gainesville, FL 32608, United States
Matthew Morrow, Pharmacy Services, Malcom Randall VA Medical Center, Gainesville, FL 32605-1197, United States
Stephen E Borst, Geriatric Research, Education and Clinical Center, Malcom Randall VA Medical Center, Gainesville, FL 32605-1197, United States
Author contributions: All authors shared equally in the creation of the following: outline, concept, content, interpretation of published literature, and editing; Jia H and Sullivan CT jointly created the initial draft; final approval was jointly agreed upon by Jia H and Borst SE; the accuracy of all work was jointly evaluated by all authors.
Conflict-of-interest: In accordance with the ICMJE guidelines regarding disclosure of potential conflicts of interests, all authors declare they have nothing to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Charles T Sullivan, MS, Center of Innovation on Disability and Rehabilitation Research, North Florida/South Georgia Veterans Health System (151b), 1601 SW Archer Road, Gainesville, FL 32608, United States. charles.sullivan1@va.gov
Telephone: +1-352-3761611 Fax: +1-352-2714540
Received: October 3, 2014
Peer-review started: October 3, 2014
First decision: December 12, 2014
Revised: January 15, 2015
Accepted: January 30, 2015
Article in press: February 2, 2015
Published online: April 16, 2015
Abstract

Hypogonadism is prevalent in older men and testosterone replacement therapy (TRT) for older hypogonadal men is a promising therapy. However, a number of important clinical concerns over TRT safety remain unsolved due to a lack of large-scale randomized clinical trials directly comparing the health risks of untreated hypogonadism vs long-term use of TRT. Meta-analyses of clinical trials of TRT as of 2010 have identified three major adverse events resulting from TRT: polycythemia, an increase in prostate-related events, and a slight reduction in serum high-density lipoprotein cholesterol. There are other purported health risks but their incidence can be neither confirmed nor denied based on the small number of subjects that have been studied to date. Furthermore, subsequent literature is equivocal with regard to the safety and utility of TRT and this topic has been subject to contentious debate. Since January 2014, the United States Food and Drug Administration has released two official announcements regarding the safety of TRT and clinical monitoring the risks in TRT users. Additionally, the health risks related to the clinical presentation of low or declining testosterone levels not been resolved in the current literature. Because TRT is prescribed in the context of putative risks resulting from reduced testosterone levels, we reviewed the epidemiology and reported risks of low testosterone levels. We also highlight the current information about TRT utilization, the risks most often claimed to be associated with TRT, and current or emerging alternatives to TRT.

Keywords: Hypogonadism, Epidemiology, Aging, Low testosterone, Testosterone replacement therapy

Core tip: The topic of testosterone replacement therapy which has seen two official announcements for the United States Food and Drug Administration in 2014, is the subject of several large studies both prospective and retrospective, and there is unsettled debate about the safety and efficacy of this treatment. Readers should become familiar with this topic and be aware that further publications and announcements are likely in the near future.