High Doses Of Anabolic Androgenic Steroids Research Articles

Use, Misuse and Abuse of Testosterone and Other Androgens.

For several decades, testosterone and its synthetic derivatives have been used for anabolic and androgenic purposes. Initially restricted to professional bodybuilders, these substances gradually became more popular with recreational weightlifters. Considering its increasing prevalence, the consumption of anabolic androgenic steroids (AAS) has become a matter of great concern. Although most side effects are mild and reversible, some of them can cause permanent damage or can be potentially life threatening. To review and summarize medical literature regarding misuse and abuse of testosterone and other androgens, in order to provide evidence-based information on the main topics related to this subject, such as how to identify and how to deal with these patients, and to elucidate the multiple possible adverse effects secondary to this practice. Key studies were retrieved from PubMed (1989-2021) with reference searches from relevant articles. Search terms included "hypogonadism", "anabolic androgenic steroids", "androgens", "misuse AND testosterone", "abuse AND testosterone", and "side effects AND testosterone". There is a significant lack of information in the peer-reviewed literature describing demographic data, implications for different organ systems and the management of current or former AAS users; however, androgen abuse has been already linked to a wide variety of cardiovascular diseases, metabolic, endocrine, neurological, psychiatric and liver disorders. Despite all this, most physicians still feel uncomfortable and hesitate to discuss the issue with patients. The chronic use of high doses of AAS is associated with adverse effects in several organ systems; however, there are still many gaps in our knowledge about the long-term consequences of this practice and how to deal with these patients. Healthcare professionals have a crucial role in combating this public health problem, recognizing and preventing the spread of androgen abuse.

Anabolic-androgenic steroid use among Iranian male gym-goers

ABSTRACT Background Anabolic-androgenic steroids (AAS) have positive anabolic effects on muscle mass. Some bodybuilders use high doses of AAS to build more muscle mass and strength. This study was conducted to measure the extent of AAS use among Iranian male bodybuilders and associated risk factors. Methods A cross-sectional study was carried out among 588 male bodybuilders from July to August 2020 in Isfahan. Isfahan city was divided into 15 clusters according to Isfahan municipal districts. In each cluster, three clubs were randomly selected. A self-administered questionnaire including demographic information and AAS usage data was completed by a consecutive sample of bodybuilders. Results One hundred and seventy-one (29.1%) participants were current users and 32 (7.7%) planned to use AAS in the future. AAS users had higher incomes, longer gym memberships, and more weekly sessions. They significantly used more supplements and other substances including growth hormone, caffeine, insulin, and glucocorticoid. The most prevalent AAS was testosterone enanthate. Income, length, and frequency of workouts could predict AAS use. Conclusion Increasing AAS consumption seems to become a public health concern that suggests the need to develop some new policies and programs which would educate and inform bodybuilders and coaches about the adverse effects of AAS use.

Abuse of Anabolic-Androgenic Steroids and Adverse Effects on Human Organ Health: A Review

Anabolic-androgenic steroids (AAS) are large groups of molecules structurally and functionally similar to the male hormone testosterone. The use of AAS is well known and widespread worldwide due to its androgenic and anabolic properties that can increase muscle mass and strength to support athlete performance. The prevalence of AAS worldwide reaches an incidence of 5% and is generally used by men aged 18-35. AAS has many side effects on the body's organs and is a serious problem for public health and athletics. This review aims to highlight the abuse of AAS and its detrimental effects on the health of human organs. Oxidative stress and apoptosis are common mechanisms that cause organ damage due to AAS use. Chronic administration of high doses of AAS results in cardiac dysfunction and increases the risks of life-threatening arrhythmias and sudden death. In addition, several organs that have the potential to be damaged by the use of AAS include the liver, kidneys, brain, musculoskeletal system, and reproductive organs. In this regard, education intervention and knowledge sharing are the important factors that should be used to raise awareness about preventing AAS abuse.

Impacts of dose and length of exposure to boldenone and stanazolol on enzymatic antioxidant systems, myeloperoxidase and NAGase activities, and glycogen and lactate levels in rat liver

We investigated the adverse effects of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) on the enzymatic antioxidant systems of the rat liver. Male Wistar rats were divided in three protocols (P): PI, 5 mg/kg BOL or ST once a week for 4 weeks; PII, 2.5 mg/kg BOL or ST once a week for 8 weeks; PIII, 1.25 mg/kg BOL or ST once a week for 12 weeks. AAS were administered intramuscularly (0.2 ml, olive oil vehicle) once a week in all protocols. Activities of the enzymes glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), were investigated. We assessed the content of hydrogen peroxide (H2O2), glycogen and lactate; and enzyme markers of neutrophils (myeloperoxidase, MPO) and macrophages (NAGase). PI and PII altered the SOD and CAT activities and increased the H2O2 content. PI led to increases in the MPO and NAGase activities. In contrast, changes in GPx, GST and, GR were observed under PII and, to a greater extend, under PIII. Following PIII, GPx, GR, and GST exhibited reduced activities. All protocols altered the glycogen and lactate content. The use of high doses of AAS for a short duration first alters SOD/CAT activity. In contrast, at lower doses of AAS for long periods is associated with changes in the glutathione system. Protocols with high doses of AAS for a short duration exert the most deleterious effects on redox status, markers of cellular infiltration, and the metabolic functioning of hepatic tissues.

Adverse effects of doping with anabolic androgenic steroids in competitive athletics, recreational sports and bodybuilding.

Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of athletes admits to their unabated application. In competitive athletics, bodybuilding and in recreational sports anabolic androgenic steroids (AAS) continue to be the substances most abused. This review summarizes the side effects of AAS abuse on organs and system functions in both sexes. High doses of AAS cause a significant increase of erythrocytes and hemoglobin concentration, which may lead to thromboembolism, intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence of arrhythmias, atherosclerosis, concentric left-ventricular myocardial hypertrophy with impaired diastolic function and also sudden cardiac death. Changes of liver function and structure, up to hepatocellular carcinoma, have been described, mainly in cases of chronic misuse of 17α-alkylated AAS. Sleeplessness, increased irritability, depressive mood status are often observed in AAS abuse. In former AAS abusers depression, anxiety and melancholy may persist for many years. Due to negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of spermatogenesis up to azoospermia. In women the changes most often caused by AAS abuse are hirsutism, irreversible deepening of voice, dysmenorrhea, secondary amenorrhea with anovulation and infertility. AAS abuse notwithstanding, under clinical conditions testosterone remains the most important hormone for substitution therapy of male hypogonadism.

Influence of chronic administration of anabolic androgenic steroids and taurine on haemostasis profile in rats

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with thrombogenic potential in high doses and long-term administration. Taurine, a widely distributed amino-sulfonic acid, is known for its beneficial effects in hypercoagulable states. In order to assess the impact of chronic administration of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar rats were divided into four equal groups: control group (group C) - no treatment; androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate (DECA); taurine (group T) - received oral supplementation of 2% taurine in drinking water; androgen and taurine group (group AT) - concomitant administration of DECA and taurine. After 12 weeks, blood samples were collected and haemostasis parameters were assessed with the thrombelastographic (TEG) analysis system: reaction time, clot kinetics (K, α), final clot strength, coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased reaction time in group A compared with control (P<0.001), whereas taurine significantly increase reaction time (P=0.01), and this effect was maintained in group AT compared with group A (P=0.009). Similar differences between groups have been recorded for the clot kinetics parameters K, α. The final clot strength and coagulation index were significantly increased in group A versus group C (P=0.04, respectively P<0.001), but not in group AT versus group C (P>0.05). There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an accelerated clot development and an increased clot firmness in Wistar rats. Taurine association ensures a protective effect against this hypercoagulable state, partially restoring the altered parameters of the coagulation profile.

Combination of running exercise and high dose of anabolic androgenic steroid, nandrolone decanoate, increases protamine deficiency and DNA damage in rat spermatozoa

High doses of anabolic-androgenic steroids (AAS) are used by some athletes to increase muscle mass, that is often associated with male infertility. The aim of this study was to investigate the possible cause/s of male infertility using a rat model by analysing sperm quality, including its protamine content and DNA integrity, as well as pregnancy rate. Five groups of male Wistar rats were treated for 10 weeks as follows: nandrolone decanoate (10 mg kg(-1) per week) (ND); running exercise (50 min per day, 5 days a week) (EX); Combination of ND and exercise (ND-EX); nandrolone decanoate solvent (Sham); and control without any injection or exercise (CO). Deterioration in sperm quantity was observed in all test groups (P ≤ 0.01). The frequency of fertile rats was decreased in the ND-EX and ND groups (P ≤ 0.05). Chromomycin-A3 staining showed a protamine deficiency in the epididymal spermatozoa in the ND-EX rats (P ≤ 0.05). Chromatin analysis indicated an abnormal maturation of the sperm nuclei in all test groups compared with the controls (P ≤ 0.05). TUNEL analyses showed a highly significant increase in apoptosis in the EX, ND, and ND-EX groups (P ≤ 0.01). Our data show that a combination of exercise and high doses of nandrolone decanoate negatively influences the DNA integrity and protamine content resulting in lower sperm quality and reduced pregnancy rate.

Nandrolone and stanozolol upregulate aromatase expression and further increase IGF-I-dependent effects on MCF-7 breast cancer cell proliferation

Several doping agents, such as anabolic androgenic steroids (AAS) and peptide hormones like insulin-like growth factor-I (IGF-I), are employed without considering the potential deleterious effects that they can cause. In addition, androgens are used in postmenopausal women as replacement therapy. However, there are no clear guidelines regarding the optimal therapeutic doses of androgens or long-term safety data. In this study we aimed to determine if two commonly used AAS, nandrolone and stanozolol, alone or in combination with IGF-I, could activate signaling involved in breast cancer cell proliferation. Using a human breast cancer cell line, MCF-7, as an experimental model we found that both nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and, consequently, estradiol production. Moreover, when nandrolone and stanozolol were combined with IGF-I, higher induction in aromatase expression was observed. This increase involved phosphatidylinositol 3-kinase (PI3K)/AKT and phospholipase C (PLC)/protein kinase C (PKC), which are part of IGF-I transductional pathways. Specifically, both AAS were able to activate membrane rapid signaling involving IGF-I receptor, extracellular regulated protein kinases 1/2 (ERK1/2) and AKT, after binding to estrogen receptor (ER), as confirmed by the ability of the ER antagonist ICI182, 780 to block such activation. The estrogenic activity of nandrolone and stanozolol was further confirmed by their capacity to induce the expression of the ER-regulated gene, CCND1 encoding for the cell cycle regulator cyclin D1, which represents a key protein for the control of breast cancer cell proliferation. In fact, when nandrolone and stanozolol were combined with IGF-I, they increased cell proliferation to levels higher than those elicited by the single factors. Taken together these data clearly indicate that the use of high doses of AAS, as occurs in doping practice, may increase the risk of breast cancer. This potential risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS with this type of cancer.

Nandrolone and stanozolol induce leydig cell tumor proliferation through an estrogen‐dependent mechanism involving IGF‐I system

Several substances such as anabolic androgenic steroids (AAS), peptide hormones like insulin-like growth factor-I (IGF-I), aromatase inhibitors and estrogen antagonists are offered via the Internet, and are assumed without considering the potential deleterious effects that can be caused by their administration. In this study we aimed to determine if nandrolone and stanozolol, two commonly used AAS, could have an effect on Leydig cell tumor proliferation and if their effects could be potentiated by the concomitant use of IGF-I. Using a rat Leydig tumor cell line, R2C cells, as experimental model we found that nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and estradiol (E2) production. When used in combination with IGF-I they were more effective than single molecules in inducing aromatase expression. AAS exhibited estrogenic activity and induced rapid estrogen receptor (ER)-dependent pathways involving IGF1R, AKT, and ERK1/2 phosphorylation. Inhibitors for these kinases decreased AAS-dependent aromatase expression. Up-regulated aromatase levels and related E2 production increased cell proliferation as a consequence of increased cyclin E expression. The observation that ER antagonist ICI182,780 was also able to significantly reduce ASS- and AAS + IGF-induced cell proliferation, confirmed a role for estrogens in AAS-dependent proliferative effects. Taken together these data clearly indicate that the use of high doses of AAS, as it occurs in doping practice, enhances Leydig cell proliferation, increasing the risk of tumor development. This risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS and testicular cancer.

Acute cardiovascular response in anabolic androgenic steroid users performing maximal treadmill exercise testing

The purpose of this study was to investigate the cardiovascular effects of anabolic androgenic steroid (AAS) use, specifically the hemodynamic response, during maximal treadmill exercise testing by comparing the exercise response between users of AAS (U-AAS) and non-AAS users (N-AAS). Twenty-four men (n=12; 29+/-3.4 years and n=12; 29.5+/-8.2 years for the U-AAS and N-AAS groups, respectively) with regular participation in both resistance (mean=6 d.wk) and aerobic exercise (mean=2 d.wk) volunteered for the study. Both groups of subjects completed a ramp-protocol maximal treadmill exercise test to volitional fatigue. Several hemodynamic and metabolic measures were obtained before, during, and after testing. The results demonstrate for the first time that chronic administration of high doses of AAS (355.4+/-59.47 mg.wk) lead to hemodynamic and metabolic response impairment. In conclusion, the chronotropic significant incompetence in the current study was reflected by an exaggerated hemodynamic response to exercise. Furthermore, the findings suggest that nonusers of AAS showed increases in VO2max when compared to the AAS group. Therefore, this study provides a contraindication to AAS use, especially in those at increased risk of cardiovascular events.

Exercise and Supraphysiological Dose of Nandrolone Deconoate Increase Apoptosis in Spermatogenic Cells

Anabolic-androgenic steroids are used at high doses by athletes for improving athletic ability, physical appearance and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of anabolic-androgenic steroids may influence the hypothalamic-pituitary-gonadal axis, which can in turn affect testicular apoptosis. However, the effect of the combination of exercise and high dose of anabolic-androgenic steroids on testicular apoptosis is not known. We investigated the combined effects of exercise and high doses of nandrolone decanoate on apoptosis in the spermatogenic cell lineage. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (Sham); nandrolone decanoate (10 mg/kg/weekly) (nandrolone decanoate); exercise (1 hr/day, 5 days a week) (exercise); nandrolone decanoate (10 mg/kg/weekly) and exercise (1 hr/day, 5 days a week) (nandrolone decanoate exercise); and sedentary control without any injection or exercise (Control). Apoptosis in the male germ line was characterized by TUNEL, caspase-3 assay and transmission electron microscopy. The weights of the testis and accessory sex organs, as well as sperm parameters significantly decreased in the experimental groups relative to the sham and control groups (p < or = 0.05). Germ cell apoptosis and a significant decrease in the number of germ cell layers in nandrolone decanoate exercise-treated testes were observed (p < or = 0.05). Exercise training seems to increase the extent of apoptotic changes caused by supraphysiological dose of nandrolone decanoate in rats, which in turn affects fertility.

The postoperative catabolic state: when do you intervene?

The postoperative catabolic state: when do you intervene?

The effect of supraphysiological doses of anabolic androgenic steroids on collagen metabolism.

We examined the effect of supraphysiological doses of anabolic androgenic steroids (AAS) on collagen metabolism and whether the changes reflect the alterations in muscle, bone, and tendon collagen metabolism, possibly in a tissue-specific manner. Serum carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), aminoterminal propeptide of type III procollagen (PIIINP), urine hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP) as well as urine creatinine were determined from 17 men abusing AAS. Measurements were made twice during the intake of AAS and twice during the subsequent withdrawal period. When the volunteers were on steroids, their serum PIIINP concentrations and urine HP/LP ratio were significantly higher and their serum ICTP concentrations were significantly lower than during the withdrawal period (p < 0.05). Serum PIIINP correlated with total cumulative doses of injectable intramuscular steroids, and serum ICTP correlated with the duration of the steroid intake period (p<0.05). The results suggest that high doses of AAS decrease the degradation and seem to increase the synthesis of type I collagen. Furthermore, high doses of AAS are suggested to enhance soft tissue collagen metabolism on the basis of increased type III collagen synthesis and elevated HP/LP ratio during the steroid administration period. Although the tissue-specific turnover of collagen of soft connective tissues remains unknown, the turnover of bone collagen seems not to change following the use of high doses of AAS, at least within the time interval of the present study.

Chronic anabolic-androgenic steroid treatment during adolescence increases anterior hypothalamic vasopressin and aggression in intact hamsters

The present study examines the hypothesis that exposure to anabolic-androgenic steroids (AAS) during adolescent development predisposes hamsters to heightened levels of aggressive behavior by influencing the anterior hypothalamic-arginine vasopressin (AH-AVP) neural system. To test this, adolescent male hamsters (Mesocricetus auratus) were treated with high doses of AAS, tested for offensive aggression in the absence or presence of AH-AVP receptor antagonists, and then examined for changes in AH-AVP expression and neural organization. AAS exposure during adolescence significantly increased aggression intensity (number of attacks and bites) and initiation (latency to the first bite). Yet, only increases in aggression intensity were inhibited by AH-AVP receptor antagonism. Adolescent AAS-treated hamsters showed significant increases in AH-AVP fiber density and peptide content. However, no alterations in AH-AVP neuronal organization or mRNA expression were found. Together, these data suggest that adolescent AAS exposure increase aggression intensity by altering AH-AVP expression and activity, providing direct evidence for a causal role of AH-AVP expression and function in early onset AAS-stimulated aggression.

The Effect of Anabolic-Androgenic Steroids on Sexual Behavior and Reproductive Tissues in Male Rats

Feinberg, M. J., A. R. Lumia and M. Y. McGinnis. The effect of anabolic-androgenic steroids on sexual behavior and reproductive tissues in male rats. Physiol Behav 62(1) 23–30, 1997.—This study assessed the effects of high doses of anabolic-androgenic steroids (AAS) and their withdrawal on male reproductive behavior and reproductive tissues during development. Prepubertal, peripubertal, and adult male Long Evans rats were divided into 4 groups: 1) Testosterone propionate for 16 weeks (TP), 2) TP for 3 weeks and withdrawn for 13 weeks (TPWL), 3) TP for 16 weeks and withdrawn for 3 weeks (TPWS), 4) propylene glycol (control vehicle) for 16 weeks (PG). As determined by sexual performance and sexual preference tests, administration of high doses of AAS to the peripubertal animals enhanced sexual performance and sexual motivation. There was no significant effect on sexual behavior of the prepubertal animals. High doses of anabolic-androgenic steroids depleted Leydig cell number in the prepubertal and adult rats, but had no effect on the Leydig cell number of the peripubertal animals. After long-term withdrawal from AAS no significant effects on sexual behavior were found. The depletion of Leydig cells that occurred in the prepubertal animals after withdrawal was reversible, while the depletion of the Leydig cells of the adult animals did not return to the control level suggesting a long lasting alteration.

Anabolic-Androgenic Steroid Exposure During Adolescence and Aggressive Behavior in Golden Hamsters

Melloni, R.H., Jr., D. F. Connor, P. T. Xuan Hang, R. J. Harrison and C. F. Ferris. Anabolic-androgenic steroid exposure during adolescence and aggressive behavior in golden hamsters. Physiol Behav 61(3) 359–364, 1997.—Anabolic androgenic steroid (AAS) abuse by adolescents represents a significant health care risk due to the potential for long-term negative physical and psychological sequelae, including increased aggressive behavior. The current experiments examined the effects of AAS use in young male adolescent hamsters ( Mesocricetus auratus) and their consequences on aggressive behavior. It was hypothesized that AAS administration during adolescence predisposes hamsters to heightened levels of aggressive behavior (i.e., offensive aggression). To test this hypothesis, adolescent male hamsters were administered high doses of synthetic AAS to mimic a ‘heavy use’ self-administration regimen used by athletes. Immediately following the exposure to AAS, hamsters were tested for aggressive behavior using a resident-intruder model. Animals treated with high doses of AAS during their adolescent development showed heightened measures of offensive aggression (i.e., decreased latency to bite and increased total number of attacks and bites) during the test period, while measures of total activity (total contact time) between the animals remained unchanged. AAS-treated males did not differ in body weight from controls, suggesting that the increased aggression was not due to increased body mass. The results of this study show that exposure to AAS during adolescence facilitates aggressive response patterns, but does not alter body weight.

Anabolic-androgenic steroid and adrenal steroid effects on hippocampal plasticity

Anabolic-androgenic steroids (AAS) are synthetic androgen-like compounds which are taken in high doses by athletes with the intention of enhancing muscular appearance, strength and/or athletic performance. Recent research indicates that high doses of AAS may influence the functions of the hippocampus. This evidence led us to explore the extent to which chronic AAS treatments influence spatial memory and the integrity of the hippocampus in the rat. Gonadally intact adult male Long-Evans rats were treated with either the AAS methandrostenolone, a steroid ‘cocktail’ (TNB; testosterone cypionate, boldenone undecylenate and nandrolone decanoate), or the oil vehicle daily for 12 weeks. A group of male rats treated with corticosterone (CORT; 10 mg/day) was also examined. Spatial memory was assessed in the Morris water maze after 10 weeks of hormone treatment. At 12 weeks, the animals were sacrificed, blood collected and the brain sectioned to assess hippocampal cell number. There were no impairments in the acquisition or retention of the Morris water maze in any hormone treatment group. Although serum testosterone levels were elevated in rats treated with TNB relative to the oil controls, neither the TNB or methandrostenolone treatments produced changes in hippocampal cell number. Serum CORT levels were significantly elevated in the rats treated with CORT and cell loss (15%) was detectable in the CA3b subfield in this group of animals. These results indicate that the AAS administered in the present study were not detrimental to hippocampal spatial memory or cell survival and that, while chronic CORT may produce mild hippocampal cell loss, this loss is not accompanied by deficits on a spatial memory task.

Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver.

The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein-cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function.