Prolonged androgenic anabolic steroid (AAS

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Apr 29, 2015 - Androgenic anabolic steroid (AAS) abuse is associated with changes in ... gested as a method of screening for AAS use in athletes despite ...

Journal Code D T A

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Article ID Dispatch: 29.05.15 8 2 6 No. of Pages: 3

CE: ME:

Drug Testing and Analysis

Short communication Received: 27 March 2015

Revised: 29 April 2015

Accepted: 20 May 2015

Published online in Wiley Online Library

(www.drugtestinganalysis.com) DOI 10.1002/dta.1826

Prolonged androgenic anabolic steroid (AAS) induced QT interval shortening: a suitable screening tool? Q1

Nicholas Sculthorpe,a* Lee Taylorb and Fergal Gracea

Q2 Androgenic anabolic steroid (AAS) abuse is associated with changes in cardiac electrophysiology. Recently QTc has been sug-

gested as a method of screening for AAS use in athletes despite conflicting reports. This study aimed to further investigate the effect of AAS on QTc in a cohort of long-term AAS users in whom the affects may be more pronounced. Using a cross-sectional cohort design with AAS using resistance trained athletes (AS n = 15) and a group of non-AAS using resistance trained, age matched controls (C n = 15). AS had a long history of AAS use (18 ± 2 yrs) and AS and C both had >19 years of resistance training. ParticiQ3 pants underwent a resting electrocardiogram (ECG), from this QT interval was calculated and corrected to QTc (Bazett formula). The main outcome measure was significant differences in mean corrected QTc between groups. A secondary outcome was to calculate a QTc that best differentiated between C and AAS. Results indicated that QTc was shorter in AS than in C (382.0 ± 21.01 ms versus 409 ± 18.77 ms for AS and C respectively p < 0.001). Chi squared analyses revealed a greater incidence of QTc < 380 ms in AS versus C p < 0.01, specificity 93% sensitivity 60%). In conclusion these results supports previous findings that AAS use causes a reduction in QTc, however, the specificity and sensitivity in our sample is lower than reported previously and precludes use as a screening tool. Copyright © 2015 John Wiley & Sons, Ltd. Keywords: doping; screening; electrophysiology

Introduction The prevalence of doping in athletics has been estimated at 14–39%[1] however, the majority of AAS use is for recreational or aesthetic purposes and is associated with numerous negative health consequences.[2] Recent evidence suggests AAS effects electrophysiology, including increased risk of cardiac electrophysiological instability.[3] However, their effect on QT interval duration remains contentious. Bigi et al. reported[4] that AAS use reduces corrected QT interval (QTc) and may be used to identify users, a concept supported in a consensus statement on ECG interpretation in athletes.[5] Schwartz et al.[6] have also reported QTc shortening following androgen administration in elderly men. Conversely, others have reported that AAS abuse has no effect on QTc[7] or their use is associated with a lengthening of QT interval.[8] Given that longer durations of abuse (>8 years) have been associated with shorter QTc intervals[4] we hypothesized that prolonged AAS use (>20 yrs) would exhibit greater QT shortening. We further hypothesized that the frequency with which QT intervals fell below the suggested screening threshold[4,5] would be greater following prolonged AAS use.

Method Following university ethical approval, subjects provided written informed consent to participate in the study. Participants were a group consisting of amateur and professional bodybuilders using high dose anabolic steroids (AS n = 15) and age-matched resistance trained controls (CON n = 15). AS trained for 3–5 days per week

Drug Test. Analysis (2015)

using heavy resistance exercise and had been engaged in combined AAS use and resistance training for >20 years (23 ± 2 years). AAS use was confirmed by urinalysis at an International Olympic Committee (IOC) accredited laboratory. CON took part in regular bodybuilding exercise (3–5 days.week 1) and had done for >15 years (19 ± 4 years). Following 10 min of supine rest, subjects underwent a resting 12 lead ECG, (CardioVit AT60, Schiller AG, Switzerland). Measurement Q4 was performed on traces recorded at a paper speed of 50 mm. s 1, subsequently digitized and QT intervals measured manually using lead II, from the beginning of Q wave to the end of the T wave (defined as its return to the TP baseline). If the end of the T wave could not be identified in lead II, lead V3 or V5 was used. QT intervals were corrected using the Bazett formula.[9]

Statistical analysis Data were analyzed using SPSS v20.0. Group differences were compared using independent t-tests. A Chi-squared test was employed to compare frequency of short QTc intervals between groups. Alpha of P < 0.05 was used to indicate statistical significance.

* Correspondence to: Nicholas Sculthorpe, Institute of Clinical Exercise and Health Science, School of Science and Sport, University of the West of Scotland, Hamilton, Scotland ML3 0BJ, UK. E-mail: [email protected] a Institute of Clinical Exercise and Health Science, School of Science and Sport, University of the West of Scotland, Hamilton, Scotland ML3 0BJ, UK b Institute of Sport and Physical Activity Research, University of Bedfordshire, Bedford MK41 9EA, UK

Copyright © 2015 John Wiley & Sons, Ltd.

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Drug Testing and Analysis

N. Sculthorpe, L. Taylor and F. Grace

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1 sensitivity was weaker than originally reported (83%[4]), but similar Results 2 to those described by Djordjvic et al.,[7] with only 53% of long-term 3 AS were significantly heavier than C (P < 0.01), with higher resting AAS users being correctly identified. Furthermore, although sensi4 T1 heart rate (HR) and systolic blood pressure (P < 0.05, Table 1). QTc tivity exceeded 80%, the proportion of non-users is likely to be 5 was lower in AS (378 ± 20 ms) versus C (397 ± 18 ms; P < 0.05). large, thus a 20% false-positive rate is unfeasibly high for QTc to 6 Chi-squared analyses using the previously published criteria of be an effective screening tool in sport or otherwise. 7 QTc < 380 ms[4] indicated significantly higher incidence of low AAS users often engage in polypharmacy with doping or recrea8 QTc amongst AS (8/15) compared to C (3/15; P < 0.05) with resultional drugs[2] that may also affect QTc. Furthermore AAS them9 Q5 T2 tant 53% sensitivity and 80% specificity (Table 2). selves are associated with pathologies that also increase QTc such 10 as ischemia, fibrosis. and altered glucose metabolism.[2] Such 11 changes could mask any AAS-induced shortening of QTc further 12 Discussion limiting its usefulness in doping identification. In addition there 13 are other possibilities that could explain shortened QTc in both The main finding of the present study is that prolonged use of AAS 14 AAS users and non-users; hypercalcaemia,[11] elevated vitamin reduces QTc duration, but falls short of being a robust method to 15 D,[12] thiazide diuretics,[13] and hyperparathyroidism[14] are all assoscreen for illicit AAS use. The shortened QTc evident amongst AS 16 ciated ion changes resulting in reduced QTc. Although the present supports previous demonstration of alterations in myocardial 17 study established the absence of such agents by questionnaire [4] [8] repolarization and is contrary to reports of increased or 18 rather than blood measures, it is clear that there is significant po[7] unchanged QTc amongst AAS users. Our findings add to the small 19 tential for such medicines to adversely affect the false positive rate body of work suggesting that supraphysiological doses of AAS have 20 of any QTc test. [2,3,6] Furthermore, significant effects on cardiac electrophysiology. 21 There are a number of potential reasons for the differences the interval seen in our control group is in line with those values 22 between our data and those previously reported. Earlier investipreviously reported in healthy sedentary controls[8,10] suggesting 23 gations have used either sedentary[4,7] or endurance trained[7,8] that long-term resistance exercise without concomitant AAS use 24 controls whereas the present study used age and resistance has no effect on QT interval. In addition QTc duration amongst AS 25 trained non-AAS using controls. Moreover, QTc duration inwere similar to those reported in cohorts with relatively shorter du26 creases with age[15] and participants in the present study were [4,7] rations of AAS use, suggesting that the majority of QTc shorten27 older than in others.[4,7,8] Similarly, AAS are associated with ing happens in the earlier stages (

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