# Exogenous Versus Endogenous Nandrolone in Doping Investigations: A Systematic Literature Review
## 4 Discussion  
In this systematic review, all 57 scientific articles examined used urine as the primary biological matrix for detecting nandrolone and its metabolites. The majority of these studies concentrated solely on analytical methods designed to identify and measure molecules of interest. Eight of the studies also considered dietary variations as a potential factor that could influence urinary concentrations of nandrolone, investigating how different diets might affect these levels [13; 14; 29; 39; 55; 59; 65]. Additionally, six articles specifically addressed the endogenous production of nandrolone in women, examining physiological factors like pregnancy and the menstrual cycle that might alter metabolite concentrations [5; 15; 16; 30; 41; 46; 54]. Some other studies focused on measuring nandrolone and its metabolites in urine following the administration of drugs containing 19-nortestosterone or other pharmaceutical masking agents, aiming to understand how these substances impact metabolite levels. Finally, a significant portion of the selected publications reviewed and expanded upon previous research regarding nandrolone's metabolic pathway, with an emphasis on the precise quantification of its metabolites throughout the metabolic process. The metabolic pathway of nandrolone is well documented, culminating in its elimination through urine. While a small portion of nandrolone may be excreted unchanged, it is more commonly converted into its primary metabolites, 19-norandrostoreno (19-NA) and 19-nortiochanolone (19-NE), in forms conjugated either to glucuronic acid or sulfate. However, the detected concentrations of these metabolites alone are insufficient to definitively distinguish between nandrolone naturally produced by the body and nandrolone that may result from the intake of synthetic steroids. To make this determination with high accuracy, advanced analysis using GC-C-IRMS is required [32; 40]. An important finding in this area of research is the increased excretion of conjugated 19-NA sulfate in urine over time, suggesting that time-related factors may influence urinary levels of this metabolite. This observation could be particularly relevant for improving retrospective analyses in doping control by considering time-based variations in metabolite excretion [38]. Additionally, research conducted on professional athletes has explored changes in the urinary  
Figure 3: Factors influencing endogenous production. ratio of 19-NA glucuronide to 19-NA sulfate. The findings showed that when athletes were administered exogenousendocrine, 100% of the detected 19-NA was present in the glucuronidated form. By contrast, under normal physiological conditions, at least 30% of 19-NA was excreted as a sulfate conjugate [23]. This differentiation could offer a useful indicator in anti-doping efforts to help distinguish between endogenous production and the intake of synthetic nandrolone. In exploring the mechanisms behind nandrolone production and metabolism, it is worth noting that several biological and lifestyle factors can significantly impact the body's natural production of nandrolone and its metabolites. This review considered various parameters, including biological sex, pregnancy status, and levels of physical activity. For instance, it appears that pregnancy can elevate the production of 19-nortestosterone metabolites to such an extent that it suggests the need for a higher cut-off threshold for female athletes [54]. Furthermore, studies also analyzed endogenous nandrolone production following intense physical exertion or engagement in professional sports [23]. However, results from these studies displayed considerable variability between individuals, preventing researchers from establishing a clear correlation between physical activity and the increase or decrease in urinary concentrations of 19-NA and 19-NE.