2.0 Methods
This review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic literature review was conducted looking at the effect of testosterone (endogenous and exogenous) on the QT interval in humans and animals. The literature search was completed using PubMed, Medline, and EMBASE. Medical Subject Headings (MeSH) terminology and specific keywords related to Testosterone and QT interval were used to develop our literature search as appropriate: Testosterone (MeSH term) OR Hypogonadism (MeSH term) OR Androgens (MeSH term) OR Gonadal steroid hormones (MeSH term) OR Hyperandrogenism (MeSH term) OR Orchiectomy (MeSH term) OR Androgen deprivation therapy OR Low testosterone OR High testosterone OR Dihydrotestosterone OR Androgen deficiency. The following keywords were used to search the literature for articles pertaining to QT interval and arrhythmias: Long QT syndrome (MeSH term) OR Arrhythmia, cardiac (MeSH term) OR Torsades de Pointes (MeSH term) OR Tachycardia (MeSH term) OR Electrocardiography (MeSH term) OR Heart conduction system (MeSH term) OR Action potential (MeSH term) OR QTc interval OR Short QT syndrome OR Action potential duration.
To be considered for this review, studies had to meet the following inclusion criteria: (i) publication from inception until January 5th, 2021, (ii) human and animal studies (iii) studies involving the administration of sex hormones, sex hormone deprivation/enhancing therapies and sex hormone abnormalities and their effect on the QT interval (iv) English and Spanish language. Papers were excluded if they didn’t include QT interval or androgen involvement, if they were review articles and if they included the use of synthetic androgens.
We employed Covidence to review the articles. Following our search, 3006 studies were imported into the program for screening. There were 1146 duplicates that were automatically removed. The remaining articles were reviewed by two investigators (GG and RW) independently, Kappa Interobserver was determined (k = 0.92) and disagreements were solved by consensus. There were 1678 studies excluded after abstract screening, and then considering the inclusion/exclusion criteria during full text review, 106 studies were selected and included in this paper (PRISMA flow diagram in Figure 2 ). Relevant articles found in the references of the included papers were also added to this review (4 papers added).
The primary outcomes of this article are: (i) to synthesize the knowledge of the effect of testosterone on the QT interval (ii) to further the clinical understanding that low testosterone states are a potential risk factor for arrhythmia development (iii) encourage clinicians to consider testosterone levels and QTc interval when prescribing potentially arrhythmogenic drugs.