Nandrolone: Use, Abuse and Side Effects



Background and Objectives:
Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly. The illicit use of AAS is diffused among adolescents and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers’ bodies.

Materials and Methods: A systematic review of the scientific literature was performed using the PubMed database and the keywords “nandrolone decanoate”. The inclusion criteria for articles or abstracts were English language and the presence of the following words: “abuse” or “adverse effects”. After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study.

Results: The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders, and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%).

Conclusions: Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings.

1. Introduction

The name “anabolic-androgenic steroids” already suggests their “anabolic” (from Greek ἀναβoλή “throw upward”) and “androgenic” (Greek ἀνδρóς “of a man” + -γενής “born”) properties. Androgens play a significant role in the development of male reproductive organs, such as the prostate, penis, seminal vesicle, ductus deferens, and epididymis. Testosterone is a steroid hormone that has an essential role in the development of the male phenotype and the regulation of reproduction of males. This hormone is effective in puberty, fertility, and sexual function in males [1,2].

Anabolic-androgenic steroids (AAS) represent a large group of synthetic derivatives of testosterone, produced to maximize anabolic effects and minimize the androgenic ones [3]. Several structural modifications have been introduced into testosterone in an attempt to maximize the anabolic effect and minimize androgenic effects. Currently, AASs are classified into 3 major classes [4] based on substitution of the base molecule. Class I is related to C-17 esterification. Class II is related to a demethylated group at C-19 and may also have C-17 esters. Class III is related to alkylation at C-17.

Nandrolone is included in the group of class II AASs, which is composed of 19-nortestosterone-derivates. In general, AASs is a broad and rapidly growing group of synthetic androgens used both clinically and illicitly.

Compared to testosterone propionate, nandrolone decanoate is considered to have strong anabolic effects but weak androgenic effects (potency ratios of 3.29–4.92 and 0.31–0.41). In particular, nandrolone esters are thought to have the highest ratio of anabolic to androgenic effects of any AAS. The low androgenicity of nandrolone decanoate is thought to be due to the fact that nandrolone is inactivated by 5α-reductase via transformation into the low-affinity androgen receptor (AR) ligand 5α-dihydronandrolone. This is thought to result in a lower incidence and magnitude of side effects.

Nandrolone has a very low affinity for human serum sex hormone-binding globulin (SHBG), about 5% of that of testosterone, and 1% of that of dihydrotestosterone (DHT). It is mainly metabolized by the enzyme 5α-reductase, into 5α-dihydronandrolone, 19-norandrosterone, and 19-noretiocholanolone, which can be detected in urine [5]. Nandrolone displays so-called flip-flop pharmacokinetics. This means that the ascending phase of the curve represents the disposition of nandrolone, and the descending part of the curve represents the rate-limiting process of release of nandrolone decanoate from the muscle into the general circulation [6]. In clinical use, nandrolone is applicable in clinical practice for burns, radiation therapy, surgery, trauma, and various forms of anemia [7]. Moreover, it has also been used for the treatment of chronic kidney disease, osteoporosis in postmenopausal women [8], inoperable breast cancer, and for patients on long-term corticosteroid therapy, as well as an adjunct to therapy for conditions characterized by a negative nitrogen balance. The drug is often used
off-label to preserve lean mass in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) associated with wasting syndrome [9].

The compound is famous not only among adults but also adolescents because of its anabolic, muscle-building properties [10–13]. Skeletal muscle can be considered as the primary target tissue for the anabolic effects of AAS, which are mediated by androgenic receptors which, after exposure to AAS, are up-regulated, and their number increases with bodybuilding [14].
Therefore, AAS determines an increase in muscle size as a consequence of dose-dependent hypertrophy resulting in an increase of the cross-sectional areas of both type I and type II muscle fibers and myonuclear domains [15]. It is administered via intramuscular injection and is metabolized in a similar manner to testosterone, with conversion into 3-norandrosterone by5α-reductase [16]. The recommended therapeutic dose of ND for humans is 0.4 mg/kg/day [17]. Its consumption can trigger a series of adverse side effects in the body, both acute and chronic [18]. However, acute adverse effects have also been described, primarily consisting of headaches, fluid retention, gastrointestinal irritation, diarrhea, abdominal pain, jaundice, menstrual abnormalities, and hypertension. The chronic effects of AAS abuse, aside from neuropsychiatric and behavioral effects, include a wide range of somatic consequences. Many organs and systems are targets of AAS action. Consequently, AASs may exert negative effects on reproductive, hepatic, musculoskeletal, endocrine, renal, immunologic, cardiovascular, cerebrovascular, and hematological systems [19–22].

4.1. Endocrine and Genital Disorders

4.2. Cardiovascular Disorders

4.3. Skin Disorders

4.4. Psychiatric and Neurological Disorders

4.5. Musculoskeletal Disorders

4.6. Excretory and Liver Disorders

4.7. Immune Disorders

5. Conclusions

The anabolic-androgenic steroids are a family of hormones abused by athletes because of their well-known properties on increasing muscle mass and strength, and among them, ND is the most used one. Historically, it was used for the treatment of anemia of chronic kidney disease, or osteoporosis in postmenopausal women.

This review evidences that improper usage and abuse of AASs cause several adverse effects in all body tissues and organs, highlighting the mechanics behind side effects. To sum up, inflammatory cytokines, oxidative stress, protein synthesis alteration, and apoptosis are common mechanisms involved in AAS-related damage.

Several studies showed cardiovascular and endocrine system, reproductive system, musculoskeletal system, as well as kidney and liver are affected by side effects in most cases. To date, most experimental studies have been conducted on animal models because it would be unethical to administer high doses of AASs over prolonged periods of time. Much remains to be investigated about the basic mechanisms in humans. Moreover, the habit of polydrug abuse makes it hardly possible to distinguish the toxic effects of AASs from those caused by other drugs [138]. In addition, a general limitation of human studies is the fact that data about the modality and doses of AAS use/abuse are often self-reported. Furthermore, there is a tendency to abuse multiple substances at the same time. Lastly, the susceptibility of individuals is influenced by genetic factors that are well known as key factors in developing adverse events [139]

In a systematic review of the literature on online resources, we found a total of 766 articles, but only 33 studies reported data about subjects abusing ND. Most reported adverse effects were endocrine (18 studies, 42%), cardiovascular (six studies, 14%), skin (five studies, 12%), and psychiatric (four studies, 9%) disorders.

Side effects secondary to the use of ND may arise in some cases since the first administration. Some side effects regress quickly after suspension (for example, side effects on the skin or blood changes). However, there are some side effects that persist for some time and may not regress completely on suspension (for example, side effects on the reproductive, hormonal, nervous, and immune systems, organ damage to the kidney and liver, and cardiovascular or behavioral changes).

The result of this review highlights the need to investigate the consequences of the use of these substances because, currently, there are discordant results in many studies.


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Table 1. Classification of anabolic androgenic steroids (AAS).
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Figure 2. This graph summarizes the adverse effects reported. Endocrine, cardiovascular, skin, and psychiatric disorders are the most reported.
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Figure 3. Graph representing side effects for treatment or abuse related administration. (a) Treatment-related. (b) Abuse related
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Figure 5. Where is the balance between known positive effects and underestimated or unknown side effects? This image tries to summarize this concept because nandrolone decanoate is a molecule that affects several systems at the same time and sometimes in an irreversible way.
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*Side effects secondary to the use of ND may arise in some cases since the first administration. Some side effects regress quickly after suspension (for example, side effects on the skin or blood changes). However, there are some side effects that persist for some time and may not regress completely on suspension (for example, side effects on the reproductive, hormonal, nervous, and immune systems, organ damage to the kidney and liver, and cardiovascular or behavioral changes).

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