Literature Study design Sample characteristics Sample size (n) Outcome measures Relevant findings
Barajas-Martinez et al. 2009 [48] Experimental study: Testosterone effect on cardiac repolarization in dog cardiomyocytes Cardiomyocytes from adult mongrel dogs weighting between 30 and 35kg N/A INa amplitude and transmural distribution Treatment with testosterone: INa (IC): reduced transmural dispersion.
Fülöp et al. 2006 [49] Experimental study: Testosterone and Estrogen effect on ECG parameters and cardiac channel expression Male and female dogs (gonadecto-mized and WT) 20 ECG parameters (HR and QTc) and protein expression analysis Treatment with testosterone: QT shortening, IK1 (IC): upregulation and Ito (IC): upregulation.
Bai et al. 2005 [50] Experimental study: Testosterone effect on cardiac repolarization via a NO-dependent mechanism White Hartrey guinea pig ventricular myocytes 36 APD and membrane current using patch clamp technique Treatment with testosterone: APD shortening, IKs (IC): upregulation, ICaL (IC): downregulation and NOS3 (E): phosphorylation.
James et al. 2004 [51] Experimental study: Ion channel expression and APD in male and female guinea pig cardiomyocytes Duncan-Hartley male and female guinea pig cardiomyocyte 33 Ion currents and APD Treatment with testosterone: APD shortening, higher IK1 (IC) and higher ICaL (IC)
Yang et al. 2010 [52] Simulation – experimental study: Testosterone effect on a guinea pig computational model Guinea pig computational model N/A Sexual hormone effects on simulated cardiac tissue Treatment with testosterone: QT shortening.
Raghu et al. 2009 [53] Experimental study: Haloperidol (Haldol®, Janssen Pharmaceuticals, Inc., Titusville, NJ) effect on cardiac electrophysiology Albino male guinea pig hearts 9 AP duration Treatment with testosterone: APD prolongation.
Argenziano et al. 2014 [54] Experimental study: DHT effect on cardiac ion channel expression Immortalized mouse cardiomyocyte (HL-1) N/A Androgenic control of gene expression Treatment with DHT: APD shortening, NCX (IC): upregulation and Kv4.3 (G): upregulation.
Brouillette et al. 2005 [55] Experimental study: Comparing testosterone levels and current density between the 2 mice strains CD-1 and C57BL/6 mice isolated ventricular myocytes 59 CD-1 and 35 C57BL/6 mice Testosterone levels and current density using whole-cell voltage clamp recoding Higher levels of testosterone: Shorter APD and higher IKur (IC) in the CD-1 strain.
Brouillette et al. 2003 [56] Experimental study: Compare the cardiac electrophysiology differences in gonadectomized and control mice CD-1 male mice 42 ECG parameters (APD and QTc) and protein expression Testosterone deficiency: QT prolongation and IKur (IC): downregulation.
Crump et al. 2016 [57] Experimental study: Effect of KCNE4 deletion in mice isolated cardiomyocytes Isolated cardiomyocytes from KCNE4 knockout C57BL/6 mice 24 Electrophysiological activity of mice cardiomyocytes KCNE4 deletion: QT prolongation.
Hu et al. 2018 [58] Experimental study: APD measurements in KCNE4 knockout male and female mice (control: wild-type mice) KCNE4 knockout mice ventricular myocytes 62 ECG parameters (QT) and testosterone measurements KCNE4 deletion: QT prolongation.
Sun et al. 2018 [59] Experimental study: Effects of Valsartan on Gonadectomized mice Male ICR mice 12 Path-clamp measurements of cardiac electrophysiology Gonadectomy: APD prolongation, Ito (IC): downregulation, IKur (IC): downregulation, INa (IC): upregulation and Connexin 43 (P): downregulation.
Tsai et al. 2015 [60] Experimental study: Study the effects of ARKO on cardiac arrhythmogenesis (control: wild-type mice) Right ventricular outflow track tissue from ARKO mice 12 Cardiac electrophysiology and arrhythmogenesis Androgen receptor knockout: APD prolongation, ICaL (IC): upregulation, NCX (IC): upregulation, RyR2 (R): upregulation, Phospholamban (R): upregulation, CAMKII (G): upregulation and GRK2 (G): upregulation.
Tsai et al. 2013 [61] Experimental study: Study the effects of ARKO in the modulation of atrial electrophysiology and arrhythmogenesis (control: wild-type mice) ARKO mice left atrium 20 Cardiac electrophysiology and protein expression Treatment with Isoproterenol: QT prolongation.
Zhang et al. 2017 [62]
Experimental study: Gonadectomy and susceptibility to atrial fibrillation
Male ICR mice
18
Susceptibility to atrial fibrillation
Gonadectomy: QT prolongation and INa (IC): upregulation. Gonadectomy increased the incidence of atrial fibrillation. Parameters returned to normal after DHT administration.
Drici et al. 1996 [63]
Experimental study: Effect of sexual hormones on cardiac repolarization (control: no DHT or E2 treatment)
Female albino New Zealand white rabbit hearts
24
ECG parameters (QT), mRNA expression and cardiac electrophysiology
Quinidine (Quinidex®, Wyeth Pharms Inc., Philadelphia, PA) treatment: QT prolongation and IKr (IC): downregulation. Treatment with DHT or E2 in OVX rabbits: QT prolongation, IKs (IC): downregulation and IKur (IC): downregulation.
Lang et al. 2016 [64]
Experimental study: Specific differences in cardiac electrophysiology in a rabbit model (control: no DHT or E2 treatment)
Male and female rabbits
43
ECG measurements (QT)
Ovariectomy in female rabbits: SERCA (IC): downregulation. Testosterone treatment: IKr (IC): upregulation, IK1 (IC): upregulation and IKs (IC): upregulation.
Liu et al. 2003 [45] Experimental study: DHT treatment in ORX rabbits (control: no DHT treatment) Hearts isolated from ORX New Zealand male white rabbits 35 ECG and patch-clamp recordings Treatment with DHT in ORX rabbits: QT shortening, IK1 (IC): upregulation and IKr (IC): upregulation.
Pham et al. 2002 [65] Experimental study: DHT or E2 treatments on gonadectomized rabbits (control: no DHT or E2 treatment) Epicardial and endocardial myocytes isolated from New Zealand White rabbits gonadectomized at age 50–60 days 36 ICaL density and function using patch clamp technique Treatment with DHT or E2 in OVX rabbits: QT prolongation and ICaL (IC): Increased transmural dispersion.
Pham et al. 2001 [66] Experimental study: Dofetilide exposure in gonadectomized rabbits (control: no gonadectomy) Isolated right ventricular endocardium from control and gonadectomized rabbits 16 APD measurements using microelectrodes Exposure to Dofetilide (Tikosyn®, Pfizer, NY, NY) in gonadectomized rabbits: APD prolongation and IKr (IC): blocking.
Pham et al. 2002 [67] Experimental study: DHT treatment in female rabbits (control: no DHT treatment) Ventricular myocardium from female rabbits 61 ECG parameters using micro-electrodes (APD) Treatment with DHT: APD shortening and IKr (IC): upregulation.
Valverde et al. 2003 [44] Experimental study: Gender differences in cardiac repolarization in rabbits New Zealand white rabbits 44 ECG parameters and microelectrode recordings (APD) Testosterone in male rabbits: APD shortening.
Argenziano et al. 2017 [68] Experimental study: Androgenic inhibition in male rats (control: placebo instead of androgenic inhibition) Right ventricular free wall from male Wistar rats 20 ECG (APD) and electrophysiology measures Androgenic inhibition with Finasteride (5a-reductase inhibitor) or Flutamide: QT prolongation, Ito (IC): downregulation and NCX (IC): downregulation.
Ayaz et al. 2015 [69] Experimental study: ORCX rats treated with E2 (control: no gonadectomy and no E2 treatment) Left ventricular tissue from Male Wistar rats 27 APD and contraction measurements and expression of Ca2+ and K+ channels Orchiectomy: APD prolongation, K+ channel: downregulation and ICaL (IC): upregulation.
Eleawa et al. 2013 [70] Experimental study: Gonadectomy and testosterone treatment in male rats (control: no testosterone treatment) Male rats 104 ECG parameters (QT) and protein expression Orchiectomy: QT prolongation, IK1 (IC): downregulation and INa (IC): downregulation.
Masuda et al. 2018 [8] Experimental study: Testosterone treatment in gonadectomized rats Male and female rats 6 ECG parameters (QTc) and IKs expression and density Treatment with testosterone: QT shortening and IKs (IC): upregulation.
Shuba et al. 2001 [71] Experimental study: Testosterone and neuroleptic – Haloperidol Pimozide and Fluspirilene treatment in Xenopous oocytes hERG expressing Xenopous oocytes 32 hERG expression Treatment with neuroleptics: QT prolongation and hERG (G): downregulation.