J Urol. 2022 Jan;207(1):44-51. doi: 10.1097/JU.0000000000002188. Epub 2021 Aug 27.
The Effect of Route of Testosterone on Changes in Hematocrit: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Trials.
The Journal of urology
Sirpi Nackeeran, Taylor Kohn, Daniel Gonzalez, Joshua White, Jesse Ory, Ranjith Ramasamy
Affiliations
Affiliations
- University of Miami, Miller School of Medicine, Miami, Florida.
- Brady Urological Institute, Johns Hopkins Medicine, Baltimore, Maryland.
- Department of Urology, Dalhousie University, Halifax, Nova Scotia, Canada.
- Department of Urology, University of Miami, Miami, Florida.
PMID: 34445892
DOI: 10.1097/JU.0000000000002188
Abstract
PURPOSE: We sought to compare testosterone formulations and determine the degree that hematocrit increases vary by testosterone therapy formulation. As head-to-head trials are rare, network meta-analysis of the contemporary studies is the only way to compare hematocrit changes by testosterone type, including topical gels and patches, injectables (both short-acting and long-acting) and oral tablets.
MATERIALS AND METHODS: We conducted a thorough search of listed publications in Scopus®, PubMed®, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov. A total of 29 placebo-controlled randomized trials (3,393 men) met inclusion criteria for analysis of mean hematocrit change after testosterone therapy. Randomized controlled trial data for the following formulations of testosterone were pooled via network meta-analysis: gel, patch, oral testosterone undecanoate, intramuscular testosterone undecanoate, and intramuscular testosterone enanthate/cypionate.
RESULTS: All types of testosterone therapies result in statistically significant increases in mean hematocrit when compared with placebo. Meta-analysis revealed all formulations, including gel (3.0%, 95% CI 1.8-4.3), oral testosterone undecanoate (4.3%, 0.7-8.0), patch (1.4%, 0.2-2.6), intramuscular testosterone enanthate/cypionate (4.0%, 2.9-5.1), and intramuscular testosterone undecanoate (1.6%, 0.3-3.0) result in statistically significant increases in mean hematocrit when compared with placebo. When comparing all formulations against one another, intramuscular testosterone cypionate/enanthate were associated with a significantly higher increase in mean hematocrit compared to patch, but no differences in hematocrit between other formulations were detected.
CONCLUSIONS: All types of testosterone are associated with increased hematocrit; however, the clinical concern of this increase remains questionable, warranting future studies. This is the first network meta-analysis to quantify mean hematocrit change and compare formulations, given the absence of head-to-head trials.
Keywords: hematocrit; polycythemia; testosterone; testosterone congeners
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