# Exogenous Versus Endogenous Nandrolone in Doping Investigations: A Systematic Literature Review
## 2 Materials and Methods  
This systematic review adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines [10], with the study protocol registered on PROSPERO (CRD42024512477).  
A comprehensive literature search of PubMed, Scopus, and Web of Science was conducted to identify studies published in English through May 2024.  
This review aimed to analyze existing research on nandrolone metabolism and factors that may affect its production, potentially leading to positive doping results. Additionally, it examined analytical methods that help differentiate between endogenous and exogenous sources of nandrolone.  
The generic free-text search terms were as follows: (\"Nadrolone\" [All Fields] OR \"19-norandrosterone\" [All Fields] OR \"19-noretiocholanone\" [All Fields]) AND (\"endogenous\" [All Fields]) AND (\"human\" [All Fields]) AND (\"urine\" [All Fields]) AND (\"doping\") [All Fields]) AND (\"athletes\") [All Fields]).  
Two researchers independently conducted searches in PubMed, Scopus, and Web of Science, while three other researchers evaluated whether the chosen articles met the inclusion criteria. The following information was recorded from the selected studies: authors, publication year, title, analytical techniques, production and metabolism mechanisms, factors influencing endogenous production, and cut-off values. The search results were further refined based on language (English), as well as relevance in titles, abstracts, methods, and keywords. Only studies meeting the following specified inclusion criteria were ultimately selected for analysis:  
* Analysis performed on human urine;
* Clarifications on the metabolism of nandrolone;
* Detection of nandrolone and its metabolites;
* Factors influencing the production of nandrolone;* Analytical techniques used to identify and quantify randomone and its metabolites. Non-inclusion and exclusion criteria were the following:
* Analysis performed on human tissues and fluids;
* Analysis performed on animals.  
This study followed PRISMA guidelines, as illustrated in Figure 1, and descriptive statistics were applied to analyze the data. The selected articles were examined to explore factors influencing endogenous nandrolone production and to assess analytical techniques that differentiate between endogenous and exogenous nandrolone.  
Before beginning the data extraction process, the items were subjected to an assessment of their quality. Specifically, the Johanna Briggs Institute's (JBI) evaluation criteria were used. Each question on the checklist was assigned a score of 0 when the answer was \"no\", 1 when it was \"yes\", and \"NA\" when the criterion was not applicable to the work. Eighteen articles were not submitted for quality assessment because they were method validation papers. The summary table of the quality study is given in the Supplementary Materials in Table S1. We decided to include articles that reached a score of at least 4.  
Data collection involved both study selection and data extraction. As noted, three researchers independently screened titles and abstracts for inclusion criteria. In cases of discrepancy in the evaluation of papers, the researchers involved conducted a joint examination of the disputed papers. These were reviewed together until a unanimous consensus was reached. Two researchers initially extracted the data, which was then reviewed by two others and subsequently validated by an additional pair of investigators.