Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats.

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats.

The toxic effects of anabolic steroids "nandrolone decanoate" on cardiac and skeletal muscles with the potential ameliorative effects of silymarin and fenugreek seeds extract in adult male albino rats.

BACKGROUND: Anabolic steroids (AS) are commonly abused by body builders and athletes aiming to increase their strength and muscle mass but unfortunately, the long-term use of AS may lead to serious side effects. Nandrolone Decanoate is one of the Class II anabolic androgenic steroids which quickly spread globally and used clinically and illicitly. Our research was directed to assess the toxic effects of anabolic steroids on cardiac and skeletal muscles in male albino rats and to evaluate the potential ameliorative effects of fenugreek seeds extract and silymarin. METHODS: Our research was done on 120 male albino rats that were allocated into 6 groups; group I: Served as a control group, group II: Received the anabolic steroid Nandrolone Decanoate, group III: Received silymarin orally, group IV: Received fenugreek seeds extract orally, group (V): Received the anabolic steroid Nandrolone Decanoate and silymarin and group (VI): Received the anabolic steroid Nandrolone Decanoate and fenugreek seeds extract. By the end of the study, rats were sacrificed, and blood samples were collected for biochemical analysis and autopsy samples for histopathological examination. RESULTS: The anabolic steroids toxic effects on rats showed a significant decrease in serum High Density Lipoprotein (HDL) level and increase in cholesterol, triglycerides, and Low-Density Lipoprotein (LDL) levels. There was a significant elevation in cardiac troponin I level. As regards to histopathological examination of the cardiac and skeletal muscles, the study showed marked degenerative changes and necrosis. Both silymarin and fenugreek seeds extract provided a protective effect on the biochemical and histopathological changes. The antioxidant effects of silymarin and fenugreek seeds extract were evaluated on the heart, skeletal muscles and showed that, the tissue levels of Superoxide dismutase (SOD), Catalase and reduced glutathione (GSH) decreased in AS treated rats compared to the control group. On the other hand, the tissue Malondialdehyde (MDA) levels were elevated. CONCLUSIONS: Anabolic steroids have a toxic effect on the cardiac and skeletal muscles of albino rats with improvement by treatment with fenugreek seeds extract and silymarin.

Adenosine receptors participate in anabolic-androgenic steroid-induced changes on risk assessment/anxiety-like behaviors in male and female rats.

Anabolic-androgenic steroids (AAS) and caffeine can induce several behavioral alterations in humans and rodents. Administration of nandrolone decanoate is known to affect defensive responses to aversive stimuli, generally decreasing inhibitory control and increasing aggressivity but whether caffeine intake influences behavioral changes induced by AAS is unknown. The present study aimed to investigate behavioral effects of caffeine (a non-selective antagonist of adenosine receptors) alone or combined with nandrolone decanoate (one of the most commonly AAS abused) in female and male Lister Hooded rats. Our results indicated that chronic administration of nandrolone decanoate (10 mg/kg, i.m., once a week for 8 weeks) decreased risk assessment/anxiety-like behaviors (in the elevated plus maze test), regardless of sex. These effects were prevented by combined caffeine intake (0.1 g/L, p.o., ad libitum). Overall, the present study heralds a key role for caffeine intake in the modulation of nandrolone decanoate-induced behavioral changes in rats, suggesting adenosine receptors as candidate targets to manage impact of AAS on brain function and behavior.

Effects of nandrolone decanoate on telomere length and clinical outcome in patients with telomeropathies: a prospective trial.

Androgens have been reported to elongate telomeres in retrospective and prospective trials with patients with telomeropathies, mainly with bone marrow failure. In our single-arm prospective clinical trial (clinicaltrials gov. Identifier: NCT02055456), 17 patients with short telomeres and/or germline pathogenic variants in telomere biology genes associated with at least one cytopenia and/or radiologic diagnosis of interstitial lung disease were treated with 5 mg/kg of intramuscular nandrolone decanoate every 15 days for 2 years. Ten of 13 evaluable patients (77%) showed telomere elongation at 12 months by flow-fluorescence in situ hybridization (average increase, 0.87 kb; 95% confidence interval: 0.20-1.55 kb; P=0.01). At 24 months, all ten evaluable patients showed telomere elongation (average increase, 0.49 kb; 95% confidence interval: 0.24-1.23 kb; P=0.18). Hematologic response was achieved in eight of 16 patients (50%) with marrow failure at 12 months, and in ten of 16 patients (63%) at 24 months. Seven patients had interstitial lung disease at baseline, and two and three had pulmonary response at 12 and 24 months, respectively. Two patients died due to pulmonary failure during treatment. In the remaining evaluable patients, the pulmonary function remained stable or improved, but showed consistent decline after cessation of treatment. Somatic mutations in myeloid neoplasm-related genes were present in a minority of patients and were mostly stable during drug treatment. The most common adverse events were elevations in liver function test levels in 88%, acne in 59%, and virilization in 59%. No adverse events grade ≥4 was observed. Our findings indicate that nandrolone decanoate elongates telomeres in patients with telomeropathies, which correlated with clinical improvement in some cases and tolerable adverse events.

Sensitive and selective simultaneous biosensing of nandrolone and testosterone as two anabolic steroids by a novel biosensor assisted by second-order calibration.

Recently, our research group have focused on an interesting project in which a novel dual template molecularly imprinted (DTMIP) biosensor was fabricated and assisted by second-order differential pulse voltammetric (DPV) data for simultaneous determination of nandrolone decanoate (ND) and testosterone decanoate (TS). An indium tin oxide (ITO) was modified with multiwalled carbon nanotubes-graphene-ionic liquid (MWCNT-Gr-IL) and then, the fullerene C60 was casted onto the surface of MWCNT-Gr-IL/ITO and electrochemically reduced. Finally, DTMIPs were electrosynthesized by electropolymerization of 4-aminobenzoic acid (ABA) as monomer with ND and TS as template molecules to obtain the final structure of the biosensor (DTMIP/C60/MWCNT-Gr-IL/ITO). Structure of the biosensor was electrochemically and microscopically characterized. The ND and TS generated two severely overlapped DPVs at the surface of the biosensor which forced us to assist the biosensor with three-way calibration by second-order DPV data to simultaneous determine them. Two second-order algorithms including multivariate curve resolution alternating least squares (MCR-ALS) and parallel factor analysis2 (PARAFAC2) were used to build second-order calibration models and evaluation of their performance in the analysis of synthetic samples showed more superiority of the MCR-ALS than PARAFC2 which motivated us to select PARAFC2 for the analysis of urine samples as real cases. Application of the biosensor assisted by PARAFC2 for the analysis of urine samples towards simultaneous determination of ND and TS was successful.

The effect of supraphysiological dose of nandrolone decanoate administration on the inflammatory, neurotrophin and behavioral response in adult and old male mice.

This study examined the effect of 6 weeks of supraphysiological nandrolone decanoate (ND) administration in adult mice (7 months) on cognitive function and neuroinflammation during aging. Male C57BL/6 mice were randomized into ND (10 mg·kg-1·wk-1) or control (CTL) groups. Half of the mice were tested at a young (Y) age (ND-Y and CTL-Y), 1 week following final ND administration, while the remaining mice were tested at 16 months (O) (ND-O and CTL-O). Learning and memory were better in young mice compared to older mice, regardless of treatment. ND-O displayed decreased anxiety as compared to all other groups. TNFα and IL1ß expression were higher in older mice, regardless of treatment. ND administration in young mice appeared to attenuate the neuroinflammatory response in aging mice as evidenced by decreased COX2, IL-4 and increased IL-10 expression in ND-O compared to CTL-O. BDNF AR and ER expression increased in ND-O compared to CTL-O. Results of the study indicated that supraphysiological ND administration had no negative effect on learning and memory but may attenuate anxiety in older mice. In addition, ND administration in young adult mice may attenuate the inflammatory response during aging, which may be related to elevations in both AR and ER expression.

Association between neuronal degeneration and supraphysiological doses of two types of anabolic steroids in rat brain.

The anabolic androgenic steroids (AAS) are natural compounds that are precursors or derivatives of testosterone and, as a consequence of indiscriminate use, cause irreversible neuronal effects. For this study, 70 brain samples were used from male Wistar rats, separated into 14 groups, divided into: control, sedentary, and exercise groups; in the concentrations: 5 mg, 10 mg, and 15 mg. Two different AAS were used: Testosterone Cypionate (TC) and Nandrolone Decanoate (ND). The encephali followed all the conventional histological procedures, for further analysis of the estimates of neuron bodies of the Locus coeruleus; also being carried out the techniques of the Tunnel Assay and Von Kossa staining. The results obtained show significant values different from the control group: Testosterone Cypionate (TCS): 5 mg (25,00 ± 4,47); 10 mg (23,67 ± 4,45) and 15 mg (21,93 ± 5,65), as well as for Nandrolone Decanoate (ND) in the doses: 5 mg (23,40 ± 3,81); 10 mg (22,80 ± 3,80) and 15 mg (22,80 ± 4,54) being the values of the control group (CGS) 34,27 ± 6,06. For the groups that exercised, the values were: TCT 5 mg 20,87 ± 3,23; TCT 10 mg 21,93 ± 4,91 and TCT 15 mg 21,47 ± 4,36 while, the Nandrolone Decanoate (ND) groups, in the different doses were: NDT 5 mg 21,53 ± 4,34; NDT 10 mg 23,53 ± 1,68 and NDT 15 mg 23,40 ± 2,20, also expressing significant values different from the control group. When comparing the sedentary control group with the animals that exercised, a statistically significant difference was observed being: CGS 34,27 ± 6,06; TCT 5 mg; 20,87 ± 3,23; NDT 5 mg 21,53 ± 4,34; TCT 10 mg 21,93 ± 4,91; NDT 10 mg 23,53 ± 1,68; TCT 15 mg 21,47 ± 4,36 and NDT 15 mg 23,40 ± 2,20. The results of this study, point out that both steroids drastically reduce neuronal density in the Locus coeruleus area inferring that, the possible cause of neuronal death is necrosis, caused by intracellular calcium imbalance.

Experimental studies on androgen administration in animal models: current and future perspectives.

PURPOSE OF REVIEW: This review aims to report the most recent (2020-2022) experimental scientific studies conducted on animal models, in order to highlight the relevant findings on the adverse effects related to androgen administration. RECENT FINDINGS: Forty-one studies published between January 2020 and July 2022 were selected. The majority of studies investigated the effects of one androgen, whereas only four studies analyzed the effects of two drugs. Nandrolone decanoate was the most investigated drug (20 articles), boldenone was tested in 8 articles, testosterone and stanozolol were used in 7 articles each, 17b-trenbolone, metandienone, and oxandrolone were tested in 1 article each. The articles clarify the adverse effects of androgen administration on the heart, brain, kidney, liver, reproductive and musculoskeletal systems. SUMMARY: The main findings of this review highlight that androgen administration increases inflammatory mediators, altering different biochemical parameters. The results concerning the reversibility of the adverse effects are controversial: on the one hand, several studies suggested that by stopping the androgen administration, the organs return to their initial state; on the other hand, the alteration of different biochemical parameters could generate irreversible organ damage. Moreover, this review highlights the importance of animal studies that should be better organized in order to clarify several important aspects related to androgen abuse to fill the gap in our knowledge in this research field.

Nandrolone decanoate and testosterone undecanoate differently affect stress hormones, neurotransmitter systems, and general activity in the male rat.

Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also experience psychiatric and behavioral changes after long-term use. The AAS-induced effects on the brain seem to depend on the type of steroid used, but the rationale behind the observed effect is still not clear. The present study investigated and compared the impact of nandrolone decanoate and testosterone undecanoate on body weight gain, levels of stress hormones, brain gene expression, and behavioral profiles in the male rat. The behavioral profile was determined using the multivariate concentric squared field test (MCSF-test). Blood plasma and brains were collected for further analysis using ELISA and qPCR. Nandrolone decanoate caused a reduction in body weight gain in comparison with both testosterone undecanoate and control. Rats receiving nandrolone decanoate also demonstrated decreased general activity in the MCSF. In addition, nandrolone decanoate reduced the plasma levels of ACTH in comparison with the control and increased the levels of corticosterone in comparison with testosterone undecanoate. The qPCR analysis revealed brain region-dependent changes in mRNA expression, where the hypothalamus was identified as the region most affected by the AAS. Alterations in neurotransmitter systems and stress hormones may contribute to the changes in behavior detected in the MCSF. In conclusion, both AAS affect the male rat, although, nandrolone decanoate has more pronounced impact on the physiological and the behavioral parameters measured.

Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice.

Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

Nandrolone decanoate safely combats catabolism in burned patients: A new potential indication after recall.

INTRODUCTION: The hyper-catabolic state is a devastating pathophysiological response to severe injury, infection or burns. Nandrolone decanoate (ND) is a potent anabolic steroid have many clinical indications, but not investigated in burn injuries yet. PATIENTS AND METHODS: A prospective randomized control study included 40 burned patients who were treated in Burn unit from burn injuries ranged from 20 to 40%. Both groups are objectively assessed, clinically and laboratory during treatment period till full recovery from burns' injury. Recall assessment of the drug safety after many years is achieved. RESULTS: ND showed highly significant results supporting its use in combating catabolic insults in burns patient. Both clinical findings and laboratory findings are correlated and highly support the use of ND in burns as new effective and safe long-lasting indication. CONCLUSION: This study results showed preservation of lean body mass and protein partition, as well as the near normal nitrogen balance in burn patients. Study proposes that nandrolone decanoate could be used in safe and effective way to combat hypercatabolic impact in burn injury.

Nandrolone decanoate and resistance exercise affect body composition and energy metabolism.

Our aim was to evaluate the independent and associated effects of nandrolone decanoate (DECA) and resistance exercise (REx) on central and peripheral hormones and neuropeptides related to energy balance in male rats. The experimental protocol was performed for eight weeks and comprised four groups: control (C) - exposed to vehicle 3x/wk; trained (T) - REx 5x/wk and vehicle 3x/wk; decanoate (D) - exposed to DECA (5 mg/kg) 3x/wk, and REx with DECA (TD) - submitted to REx 5x/wk and DECA (5 mg/kg) 3x/wk. Cross-sectional area analysis of the gastrocnemius muscle was higher in the T and TD groups compared to the C group. Biometrical analyses showed a decrease in body weight only in the TD compared to the C group, however, a reduction in total fat mass was observed in both the T and TD when compared to the C group. In respect of hypothalamic mRNA expression, there was an increase in prepro-orexin in the T compared to the C group. In mesenteric fat there was a decrease in leptin expression in the T and TD compared to the C group. Plasma evaluations showed reduced leptin concentrations in D, T and TD compared to C, and an increase in orexin-A in the D group compared to the C and T groups. Our data showed that REx was related to central and peripheral changes in energy metabolism, while DECA changed only peripheral components. REx associated with DECA promoted peripheral changes in energy metabolism and decreased body and fat weights.

[Administration of Anabolic Steroids in Combination with Vitamin D in the Early Stage of Treatment of Polytrauma Patients - a Dead End?] / Aplikace anabolických steroidu s vitaminem D v casné fázi lécby polytraumatizovaných pacientu ­ slepá ulicka?

PURPOSE OF THE STUDY Persistent catabolism is one of the main causes of delayed healing in polytrauma patients. The purpose of this study is to verify the effect of early administration of an anabolic steroid in combination with vitamin D on the process of bone healing in polytrauma patients. MATERIAL AND METHODS In this prospective study, the patients with a serious trauma were divided into two groups (a control group and a treatment group), with the treatment group being treated with nandrolone decanoate, an anabolic steroid in combination with vitamin D. In all the patients, bone metabolism markers and sex hormone levels (men only) were monitored through lab testing for the period of 70 days and the results of both the groups were subsequently compared. RESULTS The study included a total of 64 patients, 32 in the control group and 32 in the treatment group. The differences between the groups in gender (p = 0.387) as well as in the age of patients (p = 0.436) were statistically non-significant. There was a significant difference in the Injury Severity Score (48 in the treatment group as against 41 in the control group, p = 0.022). Even though this difference was statistically significant, it cannot be considered clinically significant since all the patients met the major trauma criteria. No positive effect of this treatment on bone metabolism parameters was established; on the very contrary, the only statistically significant changes were observed in the control group. To be specific, in levels of one of the bone formation markers, bone alkaline phosphatase on Day 7 after the injury (an increased level in the control group; p = 0.002) and in one of the bone resorption markers (bone acid phosphatase) on Day 70 after the injury (an increased level in the treatment group; p = 0.042). In the treatment group, 70 days after the injury a higher 25(OH)vitamin D level (p < 0.001) was reported and starting from Day 7 in men in the treatment group a significantly lower testosterone level and free testosterone level were observed. The level of androgenic hormones dramatically dropped in both the groups during the first days after the trauma, the dynamics of its normalization was faster in patients in the control group than in the treatment group. DISCUSSION The administration of nandrolone decanoate, an anabolic steroid, in combination with vitamin D did not produce the expected effect, i.e. an improvement in bone healing markers in polytrauma patients. One would expect that in polytrauma patients with a bone fracture or fractures during bone healing higher levels of all the markers of bone resorption as well as bone formation will persist. Similar increases in bone metabolism levels, however, were observed also in patients with injuries in other somatic regions. This indicates the importance of bone tissue involvement in the overall response of the organism to polytrauma. A faster normalization of the levels of testosterone, dihydrotestosterone and free testosterone in the control group compared to the treatment group corresponds with the supplemental effect of anabolic steroids and reduced production of these hormones as a feedback to hypothalamic-pituitary-adrenal axis. CONCLUSIONS In the follow-up period, the positive effect of anabolic steroid and vitamin D administration on bone metabolism in polytrauma patients was not confirmed. Key words: polytrauma, anabolic steroids, vitamin D, bone metabolism.

Effects of nandrolone decanoate on femur morphology. Experimental study.

PURPOSE: To evaluate the immediate and late effects of nandrolone on femur morphology of rats. METHODS: Twenty-eight animals with 20 weeks of age were divided into four groups: C28, control animals that were euthanized eight weeks after the experiment started; C40, control animals euthanized 20 weeks after the experiment started; T28, treated animals receiving nandrolone during eight weeks and euthanized immediately after the treatment period; and T40, animals treated during eight weeks and euthanized 12 weeks after the end of the treatment. Treated animals received nandrolone decanoate during eight weeks and control groups received peanut oil by intramuscular injection. After euthanasia, femurs were removed, dissected, weighted and measured by digital pachymeter. RESULTS: The T40 group presented an increase on distal epiphysis diameter when compared to C40 group. There was no difference between treated and control groups in relation to body and femur absolute weight, relative weight and length of femur. There was also no difference in relation to diameter of proximal epiphysis and diameter of diaphysis among the groups. CONCLUSIONS: Nandrolone decanoate does not produce significant effect on femur, exception on its distal extremity at late period. The effects of such drug may depend on the time after administration.

Swim training reverses some effects of nandrolone decanoate in wistar rats / El entrenamiento en natación revierte algunos efectos del decanoato de nandrolona en los ratones wistar / Treinamento de natação reverte alguns efeitos do decanoato de nandrolona em ratos wistar

ABSTRACT Introduction: The indiscriminate use of androgenic steroids may have deleterious effects on human tissue. Objectives: Evaluate the effects of chronic administration of the steroid nandrolone decanoate (DECA) on autonomic cardiovascular modulation, kidney morphometry and the association between these variables in Wistar rats subjected to physical training with swimming. Methods: Thirty-two male Wistar rats aged 20 weeks were distributed among four experimental groups according to the training received: sedentary control (SC), sedentary treated with DECA (SD), trained control (TC) and trained treated with DECA (TD). The hemodynamic parameters, including blood pressure and variations in systolic blood pressure (SBPV) and diastolic blood pressure (DBPV), and kidney morphometry were evaluated. The level of significance adopted was 5%. Results: The SD group had higher baseline SBP and DBP values when compared to the SC, TC and TD groups, which were similar to each other. The rats in the SD group had higher systolic blood pressure (SBPV) and diastolic blood pressure (DBPV) variation values and higher absolute and normalized values in the LF band of the DBPV when compared to the animals in the SC, TC and TD groups. The animals in the SD group had a significantly higher rate of kidney fibrosis compared to the SC, TC and TD groups. There were no significant differences between the sympathetic modulation of SBPV through the LF component and kidney fibrosis. Conclusions: Physical training with swimming was effective in preventing the increase in blood pressure levels and lowering the occurrence of kidney fibrosis in animals treated with anabolic steroids. Level of Evidence IV; Series of cases .

RESUMEN Introducción: El uso indiscriminado de esteroides androgénicos puede tener consecuencias nocivas para el organismo. Objetivo: Evaluar los efectos de la administración crónica del esteroide decanoato de nandrolona (DECA) en ratones Wistar sometidos a entrenamiento físico con natación, sobre la modulación autonómica cardiovascular, morfometría renal y asociación entre esas variables. Métodos: Fueron utilizados 32 ratones Wistar machos con edad de 20 semanas, distribuidos en 4 grupos experimentales de acuerdo con el tratamiento recibido: sedentarios controles (SC), sedentarios que recibieron el DECA (SD), entrenados controles (EC) y entrenados que recibieron el DECA (ED). Se evaluaron parámetros hemodinámicos, como presión arterial y variación de la presión arterial sistólica (VPAS) y diastólica (VPAD) y morfometría renal. El nivel de significancia adoptado fue de 5%. Resultados: El grupo SD presentó valores basales mayores de PAS y PAD cuando comparados a los grupos SC, EC y ED, los cuales fueron semejantes entre sí. Los animales del grupo SD tuvieron valores mayores de la variancia de VPAS y VPAD y valores absolutos mayores y normalizados de la banda LF de la VPAD, en comparación con los animales de los grupos SC, EC y ED. El grupo SD tuvo tasa significativamente mayor de fibrosis renal en comparación con los animales de los grupos SC, EC y ED. No se evidenciaron diferencias considerables entre la modulación simpática de la VPAS a través del componente LF y fibrosis renal. Conclusiones: El entrenamiento físico con natación fue efectivo en prevenir el aumento de niveles presóricos y disminuir la ocurrencia de fibrosis renal en animales tratados con esteroide anabolizante. Nivel de Evidencia IV; Serie de casos .

RESUMO Introdução: O uso indiscriminado de esteroides androgênicos pode ter consequências deletérias no organismo. Objetivo: Avaliar os efeitos da administração crônica do esteroide decanoato de nandrolona (DECA) em ratos Wistar submetidos a treinamento físico com natação sobre a modulação autônoma cardiovascular, morfometria renal e associação entre essas variáveis. Métodos: Foram utilizados 32 ratos Wistar machos com idade de 20 semanas, distribuídos em 4 grupos experimentais de acordo com o tratamento recebido: sedentários controles (SC), sedentários que receberam o DECA (SD), treinados controles (TC) e treinados que receberam o DECA (TD). Avaliaram-se parâmetros hemodinâmicos, como pressão arterial e variação da pressão arterial sistólica (VPAS) e diastólica (VPAD) e morfometria renal. O nível de significância adotado foi de 5%. Resultados: O grupo SD apresentou valores basais maiores de PAS e PAD quando comparado aos grupos SC, TC e TD, os quais foram semelhantes entre si. Os animais do grupo SD tiveram valores maiores da variância da VPAS e VPAD e valores absolutos maiores e normalizados da banda LF da VPAD, em comparação com os animais dos grupos SC, TC e TD. O grupo SD teve taxa significativamente maior de fibrose renal em comparação com os animais dos grupos SC, TC e TD. Não se evidenciaram diferenças consideráveis entre a modulação simpática da VPAS através do componente LF e fibrose renal. Conclusões: O treinamento físico com natação foi efetivo em prevenir o aumento de níveis pressóricos e diminuir a ocorrência de fibrose renal em animais tratados com esteroide anabolizante. Nível de Evidência IV; Série de casos .

Nandrolone decanoate causes uterine injury by changing hormone levels and sex steroid receptors in a dose- and time-dependent manner.

Different doses of nandrolone decanoate (ND) were used to investigate the expression of uterine sex steroid receptors (AR, ER-α, and ER-ß) and the levels of serum sex hormones after treatment and recovery periods in adult rats. ND doses of 1.87, 3.75, 7.5, or 15 mg/kg b.w. or mineral oil (control group) were injected subcutaneously for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment followed by 30-day-recovery and (c) ND treatment followed by 60-day-recovery. Estrous cycle was monitored daily. At the end of each experimental period, rats were euthanized for the collection of serum samples and uterine tissues. All animals showed persistent diestrus and only the highest ND dose was capable of inducing persistent diestrus until 60-day-recovery. Immunoexpression of uterine sex steroid receptors varied in a time-dependent manner. While AR expression was increase after treatment period, ER-α and ER-ß expressions decreased after 60- and 30-day-recovery, respectively. ND also increased the serum levels of testosterone, 17ß-estradiol, and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg until 30 days of recovery. The levels of progesterone were significantly reduced in all ND-treated animals. No significant difference was observed in the levels of follicle-stimulating hormone, whereas the levels of luteinizing hormone varied according to specific dose and period. We conclude that uterine sex steroid receptors and sex hormones are affected by ND administration and these alterations can be only restored following lower doses and long recovery periods.

Effects of nandrolone decanoate on femur morphology. Experimental study

ABSTRACT Purpose To evaluate the immediate and late effects of nandrolone on femur morphology of rats. Methods Twenty-eight animals with 20 weeks of age were divided into four groups: C28, control animals that were euthanized eight weeks after the experiment started; C40, control animals euthanized 20 weeks after the experiment started; T28, treated animals receiving nandrolone during eight weeks and euthanized immediately after the treatment period; and T40, animals treated during eight weeks and euthanized 12 weeks after the end of the treatment. Treated animals received nandrolone decanoate during eight weeks and control groups received peanut oil by intramuscular injection. After euthanasia, femurs were removed, dissected, weighted and measured by digital pachymeter. Results The T40 group presented an increase on distal epiphysis diameter when compared to C40 group. There was no difference between treated and control groups in relation to body and femur absolute weight, relative weight and length of femur. There was also no difference in relation to diameter of proximal epiphysis and diameter of diaphysis among the groups. Conclusions Nandrolone decanoate does not produce significant effect on femur, exception on its distal extremity at late period. The effects of such drug may depend on the time after administration.

Nandrolone Decanoate: 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 adolescent 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.

Involvement of kynurenine pathway in depressive-like behaviour induced by nandrolone decanoate in mice.

Nandrolone decanoate (ND) belongs to the class II of anabolic-androgenic steroids (AAS), which is composed of 19-nor-testosterone-derivatives. AAS represent a group of synthetic testosterone that is used in clinical treatment. However, these drugs are widely abused among individuals as a means of promoting muscle growth or enhancing athletic performance. AAS in general and ND in particular have been associated with several behavioral disturbances, such as anxiety, aggressiveness and depression. A factor that contributes to the development of depression is the brain activation of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of kynurenine pathway (KP). In the present study, we examined the involvement of KP in depressive phenotype induced by a ND treatment (10 mg/kg/day/s.c., for 28 days) that mimics human abuse system (e.g. supraphysiological doses) in C57B/6J mice. Our results showed that ND caused depressive like-behavior in the tail suspension test and anhedonic-like state measured in the sucrose preference test. ND administration decreased the levels of brain-derived neurotrophic factor and neurotrophin-3 and reduced Na+,K+-ATPase activity in the hippocampus, striatum and prefrontal cortex. We also found that ND elicited KP activation, as reflected by the increase of IDO activity and kynurenine levels in these brain regions. Moreover, ND decreased serotonin levels and increased 5-hydroxyindoleacetic acid levels in the brain. Treatment with IDO inhibitor 1-methyl-dl-trypthophan (1 mg/kg/i.p.) reversed the behavioral and neurochemical alterations induced by ND. These results indicate for the first time that KP plays a key role in depressive-like behavior and neurotoxicity induced by supraphysiologicaldoses of ND in mice.