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.