The Journal of Steroid Biochemistry and Molecular Biology
Long term perturbation of endocrine parameters and cholesterol metabolism after discontinued abuse of anabolic androgenic steroids
Highlights
► 1 year follow-up study in androgenic anabolic steroids abusers. ► Compromised hypothalamic–pituitary–adrenal axis in all volunteers. ► Main urinary nandrolone metabolite is detected up to 12 months after abuse cessation. ► HDL increased and LDL decreased observed until 6 month after abuse cessation. ► Long term consequences might be expected.
Introduction
Anabolic androgenic steroids (AAS) including testosterone, other endogenous androgenic hormones and synthetic compounds structurally related to these compounds are the most frequently detected doping agents in sports. They accounted for about 59% of adverse analytical findings in 2008 in accredited doping laboratories around the world (WADA 2008 Adverse Analytical Findings and Atypical Findings reported by accredited laboratories, Montreal, 2009 (http://www.wada-ama.org)). However, the abuse of these agents for cosmetic purposes among non-competitive recreational body-builders and non-athletes is a major societal concern. In fact, AAS abuse has become a growing public health problem [5], [11], [24].
The current test to detect abuse of testosterone is based on determination of the urinary testosterone glucuronide/epitestosterone glucuronide ratio (T/E). When the T/E is above 4.0, doping in sports is suspected (WADA Technical document TD2004EAAS, reporting and evaluation guidance for testosterone, epitestosterone, T/E ratio and other endogenous steroids, Montreal, 2004 (http://www.wada-ama.org)) and such samples must be subject to further analyses for determination of the origin of testosterone. The major enzyme responsible for testosterone glucuronidation is UGT2B17 [9]. We have shown that the T/E ratio after a single dose of testosterone is highly dependent on the UGT2B17 deletion polymorphism [23] and that there are large inter ethnic differences in the distribution of this trait [9].
In order to detect nandrolone intake, the urinary nandrolone metabolites 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are used as markers. These metabolites can be endogenously produced at low levels in some cases [15]. When the urine concentration exceeds the threshold of 2 ng/ml, additional investigations are required to avoid a competitive athlete being wrongly subjected to disciplinary proceedings (WADA Technical document TD2010NA, Harmonization of analysis and reporting of 19-norsteroids related to nandrolone, Montreal, 2010 (http://www.wada-ama.org)).
The side effects related to the abuse of these steroids and other AAS are based on empirical observations, so the potential of serious and persisting health risks associated with the abuse of these steroids is still largely unexplored. Reported endocrine adverse reactions to AAS-abuse include acne, gynecomastia, testicular atrophy and decreased secretion of the pituitary hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) [3], [17], [18], [20]. Moreover, cardiovascular side effects such as disturbances in the cholesterol profile, i.e. increased low density lipoproteins (LDL) and decreased high density lipoprotein (HDL) have been reported (reviewed by [1], [28]). However, the time course and possible reversibility of these alterations following abuse of AAS is not known. In the present study we addressed these issues in a 12 months follow-up study in AAS abusers that were recruited to the study at cessation of their abuse. We also studied the impact of the UGT2B17 deletion polymorphism on the T/E ratio and the urinary excretion of 19-NA in AAS abusers.
Section snippets
Subjects
Fifty-six men between 18 and 57 years old were recruited to the project between 1998 and 2002. A few were referred from colleagues working in emergency medicine, but most were asked to participate when contacting the Anti-Doping Hot-Line, a free telephone counseling service for individuals affected by or people concerned with abuse of anabolic androgenic steroids [5]. A genuine desire to give up using AAS was a prerequisite to be included. Participation was commenced after informed consent, and
Characteristics of the AAS-abusers
Three individuals were positive for narcotics and were subsequently excluded from the study. Of the 53 individuals that showed up for the first visit, 35 tested positive for nandrolone, testosterone and/or stanozolol (see Fig. 1). Among the volunteers tested positive to 19-NA, two individuals did not claim to have abused nandrolone. This might be due to nandrolone contamination of steroid preparations or memory default in a multiple steroid abuse pattern. Thus, one of these individual was
Discussion
Interestingly, the urinary nandrolone metabolite 19-NA remained detectable for a long period of time. For some of the individuals, the 19-NA was detected up to one year after their last injection of nandrolone decanoate. This finding is in agreement with a previous study showing that exogenous 19-NA could be detected for 6 months in some individuals after a single dose of 150 mg nandrolone decanoate [4]. In a case report, 19-NA and 19-NE levels in urine were detectable for 8 months [12]. It is
Acknowledgements
Supported by grants from Stockholm County Council and the World Anti-Doping Agency and Swedish National Centre for Research in Sports. This work was also supported in part by a grant from the Swiss National Science Foundation (project no.: 129016). C. Möller, J. Börjesson, A.C. Eklöf, A.M. Thurelius are gratefully acknowledged for valuable contributions to the clinical handling of the participants.
References (29)
- et al.
Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm
Am. J. Cardiol.
(2010) - et al.
Dual use of anabolic-androgenic steroids and narcotics in Sweden
Drug Alcohol Depend.
(2010) - et al.
Doping control for nandrolone using hair analysis
J. Pharm. Biomed. Anal.
(2001) - et al.
Evidence for the presence of endogenous 19-norandrosterone in human urine
J. Chromatogr. B: Biomed. Sci. Appl.
(1999) - et al.
Use of anabolic androgenic steroids in substance abusers arrested for crime
Drug Alcohol Depend.
(2010) - et al.
Effect of testosterone enanthate on testis size
J. Urol.
(1981) - et al.
Serum and urinary markers of exogenous testosterone administration
J. Steroid Biochem. Mol. Biol.
(1995) - et al.
Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests
Steroids
(2009) - et al.
Use of doping agents, particularly anabolic steroids, in sports and society
Lancet
(2008) - et al.
Profiling of 19-norandrosterone sulfate and glucuronide in human urine: implications in athlete's drug testing
Steroids
(2009)
Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15
Genomics
Serum lipids in power athletes self-administering testosterone and anabolic steroids
Int. J. Sports Med.
Response of serum hormones to androgen administration in power athletes
Med. Sci. Sports Exerc.
Pharmacokinetic evaluation of three different intramuscular doses of nandrolone decanoate: analysis of serum and urine samples in healthy men
J. Clin. Endocrinol. Metab.
Cited by (49)
Androgenic steroid excess in women
2023, Annales d'EndocrinologieAndrogenic Steroids Use and Abuse: Past, Present, and Future
2022, Urologic Clinics of North AmericaCitation Excerpt :Ideally, 2 seminal fluid samples obtained after 2 to 7 days of ejaculatory abstinence should be analyzed. The time to recovery of the hypothalamic-pituitary-gonadal axis varies based on duration and route of AAS use, and it can be months27 or years.28,29 For those who have been using AAS for considerably longer than 1 to 2 years, the recovery is slower and requires longer term monitoring.
Use, Misuse and Abuse of Testosterone and Other Androgens
2022, Sexual Medicine ReviewsAdverse health effects of androgen use
2018, Molecular and Cellular EndocrinologyAtypical excretion profile and GC/C/IRMS findings may last for nine months after a single dose of nandrolone decanoate
2016, SteroidsCitation Excerpt :However, it was concluded that 19-NA sulfates were detectable over a longer period of time compared to the other metabolites after ingestion of 100 mg 19-nor-4-androstenedione [26] In agreement with other studies a large inter-subject variation in 19-NT, 19-NA and 19-NE excretion rate after the injection were noted [12,11,13]. As expected, the concentration of 19-NT was correlated to body weight.