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Effects of pubertal anabolic-androgenic steroid (AAS) administration on reproductive and aggressive behaviors in male rats.

Adolescence in human males is a hormonally sensitive period when many adult behaviors develop, including sexual and aggressive behaviors. Using a rat model, the authors examined the effects of three anabolic-androgenic steroids (AAS) during puberty: testosterone, nandrolone, and stanozolol. Copulation, vocalizations, scent-marking, and aggression were tested following AAS exposure. Relative to gonadally intact controls, rats injected with testosterone showed a significant increase in scent-marking and aggression in the opponent's home cage. Nandrolone had no effect. Stanozolol significantly inhibited all behaviors. Results suggest that depending on the chemical structure of the steroid, AAS exposure during puberty affects several androgen-dependent behaviors. Because adolescence in humans is a period of hormonal change, abuse of AAS, particularly stanozolol, during this time may disrupt the establishment of normal adult behavior patterns.

Age Factors↗

Prospective echocardiographic assessment of androgenic-anabolic steroids effects on cardiac structure and function in strength athletes.

Since the abuse of androgenic-anabolic steroids (AAS) has been associated with the occurrence of serious cardiovascular disease in young athletes, we performed two studies to investigate the effects of short-term AAS administration on heart structure and function in experienced male strength athletes, with special reference to dose and duration of drug abuse. In Study 1 the effects of AAS were assessed in 17 experienced male strength athletes (age 31 +/- 7 y) who self-administered AAS for 8 or 12 - 16 weeks and in 15 non-using strength athletes (age 33 +/- 5 y) in a non-blinded design. In Study 2 the effects of administration of nandrolone decanoate (200 mg/wk i. m.) for eight weeks were investigated in 16 bodybuilders in a randomised double blind, placebo controlled design. In all subjects M-mode and two-dimensional Doppler-echocardiography were performed at baseline and after 8 weeks AAS administration. In the athletes of Study 1 who used AAS for 12 - 16 weeks a third echocardiogram was also made at the end of the AAS administration period. Echocardiographic examinations included the determination of the aortic diameter (AD), left atrium diameter (LA), left ventricular end diastolic diameter (LVEDD), interventricular septum thickness (IVS), posterior wall end diastolic wall thickness (PWEDWT), left ventricular mass (LVM), left ventricular mass index (LVMI), ejection fraction (EF) and right ventricular diameter (RVD). For assessment of the diastolic function measurements of E and A peak velocities and calculation of E/A ratio were used. In addition, acceleration and deceleration times of the E-top (ATM and DT, respectively) were determined. For evaluation of factors associated with stroke volume the aorta peak flow (AV) and left ventricular ejection times (LVET) were determined. In Study 1 eight weeks AAS self-administration did not result in changes of blood pressure or cardiac size and function. Additionally, duration of AAS self-administration did not have any impact on these parameters. Study 2 revealed that eight weeks administration of nandrolone decanoate did not induce significant alterations in blood pressure and heart morphology and function. Short-term administration of AAS for periods up to 16 weeks did not lead to detectable echocardiographic alterations of heart morphology and systolic and diastolic function in experienced strength athletes. The administration regimen used nor the length of AAS abuse did influence the results. Moreover, it is concluded that echocardiographic evaluation may provide incomplete assessment of the actual cardiac condition in AAS users since it is not sensitive enough to detect alterations at the cellular level. Nevertheless, from the present study no conclusions can be drawn of the cardiotoxic effects of long term AAS abuse.

Adult↗

Analysis of non-hormonal nutritional supplements for anabolic-androgenic steroids - results of an international study.

Several recent studies have shown evidence of some nutritional supplements containing prohibited anabolic androgenic steroids, so-called prohormones, which were not declared on the label. Therefore, a broad-based investigation of the international nutritional supplement market was initiated to clarify the extent of this problem. From October 2000 until November 2001, 634 non-hormonal nutritional supplements were purchased in 13 countries from 215 different suppliers. Most supplements were bought in shops in the respective countries (578 samples = 91.2 %) and on the internet (52 samples = 8.2 %). 289 supplements were from prohormone-selling companies and 345 supplements came from companies which do not offer prohormones. After isolation from the supplement matrix 11 different anabolic androgenic steroids, mainly prohormones of testosterone and nandrolone, were analysed by gas-chromatography/mass spectrometry. Out of the 634 samples analysed 94 (14.8 %) contained anabolic androgenic steroids not declared on the label ("positive supplements"). We could not obtain reliable data for 66 samples (10.4 %) due to matrix effects. In relation to the total number of products purchased per country, most of the positive supplements were bought in the Netherlands (25.8 %), in Austria (22.7 %), in the UK (18.8 %) and the USA (18.8 %). According to the label, all positive supplements were from companies located in only five countries: the USA, the Netherlands, the UK, Italy and Germany. 21.1 % of the nutritional supplements from prohormone-selling companies contained anabolic androgenic steroids, whereas 9.6 % of the supplements from companies not selling prohormones were positive. The positive supplements showed anabolic androgenic steroid concentrations of 0.01 micro g/g up to 190 micro g/g. The administration of supplements containing nandrolone prohormones adding up to a total uptake of more than 1 micro g resulted in positive doping results for norandrosterone for several hours.

Adult↗

Doping in cyclism: results of unannounced controls in Flanders (1987-1994).

Unannounced doping control in cyclism, the most favourite sport in Flanders, resulted in 7.8% positive cases in 4374 analysed samples during the period 1987-1994. Ephedrines, amphetamine and nandrolone were frequently misused and polydrug abuse including ephedrines and amphetamine seemed to be very popular. The abuse of methamphetamine, methylphenidate and pemoline, formerly favourite drugs in cyclists is decreasing while prolintane, codeine and the anabolic steroids nandrolone and testosterone were more frequently detected. The misuse of forbidden substances by athletes competing in the official Belgian Cyclist Federation and in amateur federations was 5.8% and 8.9%, respectively. Several cyclists however attempted to circumvent doping control.

Belgium↗

The abuse of doping agents in competing body builders in Flanders (1988-1993).

Analytical findings of unannounced doping control in body builders in Flanders during 1988-1993 are reported. In some federations between 38 and 58% of the controlled athletes were found positive during this period. The results show that there was no fall in drug abuse over this period and steroids were taken even by body builders associated with an organisation against the use of anabolic steroids. In 1988 and 1989 popular anabolic steroids were nandrolone and testosterone. From 1990 on, a wide range of mostly injectable steroids including nandrolone, metenolone, drostanolone and testosterone were administered. Polydrug abuse including several anabolics in combination with stimulants and diuretics was also widespread. The beta agonist clenbuterol was detected in several urine samples taken in 1991, one year before its appearance in other sports.

Belgium↗

Over-the-counter anabolic steroids 4-androsten-3,17-dione; 4-androsten-3beta,17beta-diol; and 19-nor-4-androsten-3,17-dione: excretion studies in men.

Since the appearance of 4-androsten-3,17-dione (I) as a nutritional supplement in early 1997, we have frequently observed a characteristic deterioration of endogenous steroid profiles in athletes' urine in routine anabolic steroid testing in which concentrations of major endogenous urinary steroids and testosterone exceed normal. Human excretion studies are performed with I and newer, over-the-counter "supplements" 4-androsten-3beta,17beta-diol (II) and 19-nor-4-androsten-3,17-dione (III). Endogenous urinary steroids affected by I and II are androsterone, etiocholanolone, their hydroxylated derivatives 5alpha- and 5beta-androstan-3alpha,17beta-diols, testosterone, and epitestosterone. Their concentrations briefly increase by one to two orders of magnitude and return to normal 24 h after oral administration of I and II. The average male may test positive for testosterone because testosterone concentration rises faster than that of epitestosterone, causing the testosterone/epitestosterone (T/E) ratio to rise above the positive cutoff of 6:1. A remarkable distinction in excretion patterns was observed in eastern Asian men, for whom I and II did not affect urinary concentrations of testosterone and did not increase the T/E ratio. First-pass metabolism deactivates most of the orally administered drugs I and II, rapidly converting them into inactive androsterone and etiocholanolone. Drug II is a more effective testosterone booster because of its different metabolic pathway. After the use of III, a precursor of the potent anabolic nandrolone, high concentrations of norandrosterone and noretiocholanolone appear in urine, similar to nandrolone. These are detectable in urine for 7-10 days after a single oral dose of III (50 mg).

Anabolic Agents↗

Research of stimulants and anabolic steroids in dietary supplements.

The purpose of this study was to analyze the composition of 103 dietary supplements bought on the internet. The supplements were dispatched in four different categories according to their announced contents [creatine, prohormones, "mental enhancers" and branched chain amino acids (BCAA)]. All the supplements were screened for the presence of stimulants and main anabolic steroids parent compounds. At the same time, the research was focused on the precursors and metabolites of testosterone and nandrolone. The study pointed out three products containing an anabolic steroid, metandienone, in a very high amount. The ingestion of such products induced a high quantity of metandienone metabolites in urines that would be considered as a positive antidoping test. The results have also shown that one creatine product and three "mental enhancers" contained traces of hormones or prohormones not claimed on the labels and 14 prohormone products contained substances other than those indicated by the manufacturer. The oral intake of the creatine product revealed the presence of the two main nandrolone metabolites (19-norandrosterone and 19-noretiocholanolone) in urine.

Anabolic Agents↗

Use of growth hormone and other anabolic agents in AIDS wasting.

Body wasting and loss of lean body mass (LBM) have been associated with increased mortality and disease progression, and reduced quality of life, in patients with human immunodeficiency virus (HIV) infection. The failure of nutritional therapies and, more recently, of effective viral suppression, to consistently restore LBM has prompted investigation of the pharmacologic use of a number of specific protein anabolic agents, including recombinant human growth hormone (rhGH), insulin-like growth factor I (rhIGF-I), and synthetic testosterone derivatives, such as nandrolone decanoate, oxandrolone, and oxymetholone. In a placebo-controlled trial, treatment with rhGH resulted in a significant and sustained increase in weight that was accompanied by an even greater increase in LBM and a decrease in fat, and improvement in treadmill work output. Preliminary data suggest that short-term rhGH treatment may be effective in mitigating weight loss in patients with secondary infections. Open-label studies of nandrolone decanoate suggest that this injectable agent also can increase weight and LBM. Two oral agents, oxandrolone and oxymetholone, can increase weight, but their effects on LBM in placebo-controlled trials have not been reported. Taken together, these studies demonstrate that HIV-infected individuals can regain weight and LBM under the proper therapeutic circumstances. The effects of reversal of wasting on survival and disease progression, long-term safety, and the potential value of these therapies in the treatment of fat redistribution remain to be determined.

HIV Wasting Syndrome↗

Anabolic androgenic steroids and aggression: studies using animal models.

The use of anabolic androgenic steroids (AASs) has escalated in teenagers and is associated with increased violence. Adolescent exposure to chronic high levels of AASs is of particular concern because puberty is a hormonally sensitive period during which neural circuitry for adult male patterns of behavior develop. Thus, teenage AAS use may have long-term repercussions on the potential for displaying aggression and violence. Animal models have contributed valuable information on the effects of AAS use. For example, studies in rodents confirmed that exposure to the AASs testosterone and nandrolone, but not stanozolol, does indeed increase aggression. A side effect of AAS use reported in humans is "'roid rage," characterized by indiscriminate and unprovoked aggression. Results of animal studies demonstrated that pubertal rats receiving AASs respond appropriately to social cues as they are more aggressive toward intact males than are castrates. Also, testosterone-treated males recognize appropriate environmental cues as they are most aggressive in their home cage. Thus, adolescent AAS exposure increases aggressive behaviors, but does not induce indiscriminate aggression. To assess whether AAS exposure increases aggression after provocation, rats were tested following a mild tail-pinch. In adolescent males, provocation increased aggression after withdrawal from testosterone, nandrolone, and stanozolol, an effect which persisted for many weeks. The data suggest that AASs sensitize animals to their surroundings and lower the threshold to respond to provocation with aggression. Thus, in humans, pubertal AAS exposure may not cause violent behaviors, but may increase the likelihood that aggressive acts will result in violence. This may persist into adulthood.

Adolescent↗

Detection of anabolic steroids in head hair.

We developed a gas chromatography/mass spectrometry method for detection and quantitation of anabolic steroids in head hair. Following alkaline digestion and solid-phase extraction, the MO-TMS derivatives gave a specific fragmentation pattern with EI ionization. For stanozolol, the TMS-HFBA derivative showed several diagnostic ions. For androstanolone, mestanolone (methylandrostanolone), and oxymetholone two chromatographic peaks for cis and trans isomers of derivatives were seen. Recoveries were 35 to 45% for androstanolone, oxymetholone, chlorotestosterone-acetate, dehydromethyltestosterone, dehydrotestosterone, fluoxymesterone, mestanolone, methyltestosterone, and nandrolone; 52% for mesterolone, trenbolone; 65% for bolasterone; 24% for methenolone and 17% for stanozolol. Limits of detection were 0.002 to 0.05 ng/mg and of quantitation were 0.02 to 0.1 ng/mg. Seven white male steroid abusers provided head hair samples (10 to 63 mg) and urine. In the hair samples, methyltestosterone was detected in two (confirmed in urine); nandrolone in two (also confirmed in urine); dehydromethyltestosterone in four (but not found in urine); and clenbuterol in one (but not in urine). Oxymethalone was found in urine in one, but not in the hair. One abuser had high levels of testosterone: 0.15 ng/mg hair, and 1190 ng/mL urine. We conclude that head hair analysis has considerable potential for the detection and monitoring of steroid abuse.

Anabolic Agents↗

Pharmacokinetics of anabolic steroids.

After an anabolic steroid is administered orally there is a rapid increase in its concentration in the blood in the following few hours. Excretion of the compound and its metabolites takes place via the urine and faeces, usually taking several days to completely pass through the system. Parenteral anabolic preparations, such as microcrystal suspensions, implants and solutions of nandrolone esters in a vegetable oil, are absorbed slowly. The absorption of esters from the site of injection is a logarithmic process and depends on the nature of the ester concerned. The absorption rate is slower the longer the fatty acid chain in the ester. The rate of absorption is important regarding the length of the action, and is also relevant for the compound's pharmacodynamic pattern. Metabolism of anabolic steroids takes place mainly in the liver and involves reduction, hydroxylation and the formation of conjugates. The enzymes that bring about these changes and the metabolic pathways involved are similar to endogenous steroids. The presence of high concentrations of metabolites in the bile and in the intestinal tract points to enterohepatic circulation of metabolites. After the administration of slowly-absorbed nandrolone esters the excretion of the metabolites continues for weeks or even months. It is probable that the absorption rate of the esters from the injection depot is the rate-limiting process in the pharmacokinetics of these compounds.

Administration, Oral↗

Metabolic effects of anabolic steroids.

After 1935 the best method of discovering and measuring the protein-building action of androgenic steroids in humans proved to be metabolic balance studies. In 1955, when anabolic steroids with less androgens were developed, the nitrogen-balance method was used again to evaluate and compare the nitrogen-sparing effect of the various preparations. The findings of the numerous balance studies that were performed are as follows: The injectable 17 beta-esters, such as nandrolone phenylpropionate, nandrolone decanoate and methenolone oenanthate exert a strong anabolic action for several weeks, amounting to 2-2.50 g nitrogen/day, which corresponds to a daily gain of 12-15 g protein or 60-75 g lean body mass. The orally active 17-alkyl derivatives induce a dose-dependent nitrogen-saving effect of the same order. While the drug is being administered, nitrogen-, calcium- and phosphorus-balance studies in osteoporotic patients show calcium and phosphorus retention in most cases. Anabolic steroids can abolish a negative nitrogen balance brought about by the administration of corticosteroids and anti-androgens. They thus possess anti-catabolic properties. Nitrogen loss after surgical procedures and following accidental traumata can be significantly reduced by pre-operative or post-operative treatment with anabolic agents. Comparison of the metabolic balance method with isotope studies showed a satisfactorily positive correlation. Later calcium metabolism studies in osteoporotic patients were mostly performed with various methods such as in vivo neutron activation analysis and osteodensitometry. They confirm the calcium anabolic effect of certain anabolic steroids.

Administration, Oral↗

Severe anemia as a manifestation of metastatic jugular paraganglioma.

A young woman who had a right glomus jugulare paraganglioma had diffuse pulmonary metastases three years after surgical excision of the paraganglioma. Associated with these developments were profound anemia and an extraordinarily rapid ESR. These findings have been previously noted in patients with metastatic paraganglioma and have not as yet, to our knowledge, had a satisfactory explanation. Noteworthy in our patient was a diminished serum erythropoietin level, which may indicate that metastatic paragangliomas inhibit production of or interfere with maintenance of serum erythropoietin. Symptomatic palliation of the severe anemia was attained in this patient by injections of nandrolone decanoate. Follow-up examinations of patients with paragangliomas should include surveillance of the CBCs and ESR, both of which may reflect tumor activity.

Adult↗

Myotrophic effects of an anabolic steroid in rabbit limb muscles.

There has been no reliable evidence that the actions of anabolic steroids extend to limb muscles. In this study, female rabbits were treated with anabolic steroid (nandrolone decanoate) or arachis oil placebo for 4 weeks or 12 weeks. After 12 weeks, tibialis anterior muscles of treated animals showed highly significant increases in wet weight (38%), twitch tension (66%), maximum isometric tetanic tension (48%), maximum cross-sectional area (27%), and specific tension (17%). Fiber type composition showed a significant trend toward a less oxidative metabolic character. The experiments provided clear physiological and morphological evidence of a steroid-induced hypertrophy that was not attributable to fluid retention or changes in body weight. Of the muscles examined, the myotrophic effect was confined to the tibialis anterior muscle; extensor digitorum longus, plantaris, and soleus muscles showed no significant response. The work establishes an experimental model for the responses of limb muscles to anabolic compounds.

Anabolic Agents↗

Decrease in androgen binding and effect of androgen treatment in a case of X-linked bulbospinal neuronopathy.

X-linked recessive bulbospinal neuronopathy is a motoneuron disorder to be distinguished from amyotrophic lateral sclerosis, Effective treatment is not known. Patients with X-linked recessive bulbospinal neuronopathy may show gynecomastia and testicular atrophy, and a mutation in the androgen receptor gene has been found associated with the disease. Intermediate steps leading from the androgen receptor abnormality to the clinical syndrome have not yet been elucidated. Therefore, binding of androgen ([3H]dihydrotestosterone) to its specific receptor by genital skin fibroblasts cultured from a patient with X-linked recessive bulbospinal neuronopathy and confirmed androgen receptor mutation was studied. Markedly decreased binding capacity was found. We treated the patient for 6 months with nandrolone-decanoate. No effect on his neuromuscular status was observed during 2 years of follow-up.

Anabolic Agents↗

Reversibility of the haemodynamic effects of anabolic steroids in rats.

The haemodynamic effects of 6 weeks nandrolone decanoate treatment (total dose 30 mg.kg-1) (SG I, n = 12) and their reversibility were studied in anaesthetised, open-chest male rats exposed to 5 min isoproterenol (2.5 micrograms.kg-1) and CaCl2 (25.0 mg.kg-1) loads. In SG I, the heart weight and its ratio to body weight were greater than in the untreated rats (CG I, n = 13) (p less than 0.05 and p less than 0.01 respectively). The initial heart rate and the inotropic and chronotropic responses to isoproterenol were lower in SG I than in CG I (p less than 0.05 in all cases). Peripheral resistance decreased during both infusions in SG I but remained unaltered in CG I (p less than 0.05). 6 weeks after finishing anabolic steroid treatment (SG II, n = 11), in the CaCl2-test the ejection fraction (p less than 0.05) and stroke index were smaller than in control rats of the same age (CG II, n = 12). Mean aortic pressure was lower in SG II than in CG II. In the CaCl2-test peripheral resistance was initially higher, but decreased during the infusion in SG II while it increased in CG II (p less than 0.05 in both cases). In conclusion, anabolic steroid treatment reversibly reduces the left ventricular response to isoproterenol. It decreases peripheral vascular tone during inotropic loads. Six weeks after the cessation of treatment, the pumping efficiency of the heart is reduced.

Anabolic Agents↗

Misuse of androgenic-anabolic steroids and human deltoid muscle fibers: differences between polydrug regimens and single drug administration.

The objective of this investigation was to study the effects of androgenic-anabolic steroid (AAS) misuse on deltoid muscle fiber characteristics in experienced, male strength-trained athletes. In a double-blind study, 15 volunteers were administered nandrolone decanoate (ND) for 8 weeks (200 mg/week, intramuscularly). In an additional study, 12 subjects self-administered various AASs at supratherapeutic dosages (AAS group), while 7 non-users served as controls. In all subjects, a percutaneous needle biopsy sample of the deltoid muscle was obtained at baseline and after 8 weeks. Muscle sections were pre-incubated at pH 4.4, stained with adenosine triphosphatase and analyzed morphometrically. In each biopsy sample, at least 150 fibers were classified for "gray level" and "lesser fiber diameter" to determine the mean fiber size, the sizes of type I and type II fibers, and the fiber type distribution. ND administration did not seem to affect any of those parameters. In the AAS group, mean muscle fiber size (+ 12.6%), and the size of type I (+ 10.8%) and type II (+ 14.6%) muscle fibers increased. The fiber type distribution remained unaltered. We conclude that polydrug regimens of AAS misuse at supratherapeutic dosages increased the size of deltoid muscle fibers (especially type II fibers) in experienced strength-trained athletes, while ND at a therapeutic intramuscular dose of 200 mg did not exert any effect.

Adult↗

Cardiac autonomic dysfunction in rats chronically treated with anabolic steroid.

To date no published data exist regarding the effects of chronic high-dose anabolic-androgenic steroid administration on tonic cardiac autonomic control. The aim of this study was to evaluate, by power spectral analysis of heart rate variability (HRV), the effects of chronic treatment with supraphysiological doses of nandrolone decanoate (DECA) on tonic cardiac autonomic regulation in sedentary rats. Male Wistar rats were treated weekly with 10 mg kg(-1) of DECA (n=7) or vehicle (CONTROL, n=7) for 10 weeks. At the 8th week of treatment, electrocardiogram was recorded in the conscious state, for time- and frequency-domain HRV analysis. Parasympathetic indexes were reduced in DECA group: high-frequency power (CONTROL=11.1+/-3.0 ms2 vs. DECA=3.8+/-0.6 ms2, P<0.05), RMSSD (CONTROL=5.9+/-0.9 ms vs. DECA 3.5+/-0.3 ms; P<0.05) and pNN5 (CONTROL=31.5+/-7.5 ms vs. DECA=13.2+/-2.6 ms; P<0.05). The sympathetic index LF/HF tended to be higher in DECA group (CONTROL=0.65+/-0.15 vs. DECA=1.17+/-0.26, P=0.0546). In conclusion, chronic treatment with DECA, in rats, impairs tonic cardiac autonomic regulation, which may provide a key mechanism for anabolic steroid-induced arrhythmia and sudden cardiac death.

Anabolic Agents↗