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PubMed1980

Danazol and stanozolol in long-term prophylactic treatment of hereditary angioedema.

Treatment with 17 alpha-methyltestosterone and with some synthetic androgens prevents attacks of hereditary angioedema (HAE). However, the potential hepatotoxicity of 17 alpha-alkylated androgens raises the problem of long-term prophylactic use of these agents. Therefore we compared the efficacy in preventing HAE attacks of 17 alpha-alkylated steroids (danazol and stanozolol) with non-17 alpha-alkylated derivatives (quinbolone, nandrolone decanoate and mesterolone). As the latter group proved ineffective, it seems that a drug's efficacy in preventing HAE attacks is connected to its 17 alpha-alkylation. Moreover, our long-term observations with the minimum effective dose of danazol seem to indicate the absence of important collateral effects.

Adult↗
PubMed2006

Development of a faster determination of 10 anabolic steroids residues in animal muscle tissues by liquid chromatography tandem mass spectrometry.

A method had been developed for determination of residues of 10 anabolic steroids (ASs) in animal muscle tissues by liquid chromatography tandem mass spectrometry (LC/MS/MS). After enzymolysis, the sample was extracted with tert-butyl methyl ether, cleaned up through reverse solid-phase extraction and further determined by LC/MS/MS under multiple reaction monitoring (MRM) mode. The limits of detection (LOD) of LC/MS/MS method used for testing epitestosterone (ETS), nandrolone (17 beta-NT), 17 alpha-methyl-testosterone (MTS), testosterone 17-propionate (PTS), medroxyprogesterone (MED), progesterone (PG), estrone (ESN), 17 beta-estradiol (17 beta-ES), 17alpha-ethynylestradiol (EES) and estriol (EST) in animal muscle ranged from 0.06 to 0.22 microg/kg, and the limits of quantification (LOQ) were from 0.12 to 0.54 microg/kg. Experiments on spiked samples of pork, beef, chicken and fish showed that at addition level of 1.0 microg/kg, the average recoveries of the ASs ranged from 64% to 77%, and coefficients of variation from 7.1% to 20.3%, while at addition level of 2.0 microg/kg, the average recoveries ranged from 70% to 89%, and coefficient of variation from 7.1% to 19.1%.

Anabolic Agents↗
PubMed2005

Anabolic androgenic steroid affects social aggression and fear-related behaviors in male pair-housed rats.

This study examines the effect of chronic administration of the anabolic androgenic steroid nandrolone decanoate (ND) on dominant and subordinate male rats in a pair-housed condition. Pair-housed rats were assessed for dominance status based on their behavior and alterations in body weights. Throughout the study the rats were allowed limited social interactions on a daily basis. At all other times, a Plexiglas divider kept the rats separated, allowing olfactory and visual contact between the cage mates while preventing significant physical contact. One week into the study all subjects were subcutaneously implanted with a pellet that continuously infused either ND (15 mg/kg/day) or placebo for 21 days. Following the pellet implant, behavioral tests including reassessment for dominance status, and a conditioned fear test were conducted over a period of approximately 2 months to investigate possible long-term changes. The main finding is that during the allowed social interactions, the dominant ND-pretreated rats spent more time on highly aggressive behaviors than the dominant placebo-treated rats. In addition, the probability for highly aggressive behaviors was maintained for the ND-treated rats throughout the study, whereas it was decreased for the placebo-treated rats. The ND-treated subordinate rats showed less fear in a potential threatening situation compared to placebo-treated controls. These findings support the relatively long-term behavioral changes that have been seen in humans after abuse of ND and other anabolic androgenic steroid compounds.

Aggression↗
PubMed1998

The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area.

The level of aromatase in the preoptic area of rats is transcriptionally regulated through a specific androgen-receptor mediated mechanism and can be used as a measure of central androgenic effect. Therefore, several commonly abused anabolic-androgenic steroids (AAS) were tested for their ability to induce aromatase activity in the preoptic area of castrated rats. In addition, we determined the relative binding affinities of these compounds for the androgen receptor, as well as their ability to bind androgen receptor in vivo following subcutaneous injections. All of the AAS compounds tested significantly stimulated POA aromatase activity above castrate levels. The compounds that produced the greatest stimulation of aromatase activity were those that bound most avidly to the androgen receptor in vitro (i.e., testosterone, dihydrotestosterone and nandrolone). In contrast, the 17alpha-alkylated compounds that were tested (stanozolol, danazol, methandrostenolone) modestly stimulated aromatase and were weak competitors for the androgen receptor. The subcutaneous injection of AAS compounds increased the concentrations of occupied nuclear androgen receptors in the brain, but the magnitude of effect was not related to their potency for inducing aromatase or their relative binding affinity for the androgen receptor suggesting that androgen receptor occupancy in POA is not correlated with the action of androgen on aromatase. The present results help explain the behavioral effects of AAS compounds in rats.

Anabolic Agents↗
PubMed2001

Measurement of androgen and estrogen receptors in breast tissue from subjects with anabolic steroid-dependent gynecomastia.

In order to assess the relationship between anabolic steroid administration and gynecomastia, we studied the effects produced by administering nandrolone decanoate and a mixture of propionate, phenilpropionate, isocaproate and testosterone decanoate to bodybuilders during a six month period. The following significant changes occurred: a 53% reduction in serum testosterone; LH and FSH levels were suppressed to 77% and 87%, respectively, in comparison to control values; and although 45% of the subjects showed an increase in serum estradiol levels, no statistically significant differences were found compared with control estradiol levels. With regard to estradiol and androgen receptors, 85% of gynecomastia tissue contained estradiol or androgen receptors, while 40% contained both. The mean values of estradiol and androgen receptors in the cytosol were 65 +/- 10 and 52 +/- 5 fmol/mg protein, respectively. Nuclear androgen and estradiol receptor levels were 33 +/- 7 and 67.5 +/- 9 fmol/mg protein, respectively. The presence of hormone receptors in gynecomastia receptive cells provides support for the hypothesis that gynecomastia is steroid-dependent.

Adult↗
PubMed2002

Effects of withdrawal from anabolic androgenic steroids on aggression in adult male rats.

In gonadally intact male rats, chronic exposure to high levels of testosterone propionate (TP) increases aggression, nandrolone (ND) has little effect and stanozolol (ST) suppresses aggression. The present experiment tested whether the effects of TP, ND and ST on aggression and reproductive tissues are reversed following anabolic androgenic steroid (AAS) withdrawal. Gonadally intact males received TP, ND, ST or vehicle for 12 weeks. Injections were then discontinued. Aggression was tested 3 weeks (short term) and 12 weeks (long term) after withdrawal of AAS treatment, with either a gonadally intact or a castrated opponent in three different environments (home, opponent's and neutral cage). After short-term withdrawal, some parameters of aggression were significantly above control levels in TP males. There were no significant differences between ND or ST males and controls, though ST males showed the lowest levels of aggression. No significant differences between any of the groups were found after long-term withdrawal. Eighteen weeks after AAS withdrawal, serum testosterone (T) and LH levels were comparable to controls in all groups. Testes weights were at control levels in ST males, but significantly higher than controls in TP and ND males. Seminal vesicle weights were significantly elevated in TP males, but similar to controls in both ND and ST males. None of the prostate weights were significantly different from controls. These results suggest that aggression gradually returns to normal following withdrawal from AAS. Some, if not all, hormone levels and tissue weights return to normal, suggesting possible long-lasting effects of chronic AAS exposure.

Aggression↗
PubMed2002

Anabolic androgenic steroid affects competitive behaviour, behavioural response to ethanol and brain serotonin levels.

The present study investigated whether anabolic androgenic steroid (AAS) treatment (daily subcutaneous injections during 2 weeks with nandrolone decanoate; 15 mg/kg) affects competitive behaviour, and locomotor activity response to a sedative dose of ethanol (0.5 g ethanol/kg). In addition, levels of brain monoamines were assessed. The results showed that AAS treated animals exhibited enhanced dominant behaviour in the competition test compared to controls. The AAS groups' locomotor activity was not affected by ethanol in contrast to the controls who showed a sedative locomotor activity. AAS animals had significant lower levels of serotonin in basal forebrain and dorsal striatum compared to controls. These findings further strengthen the fact that AAS affects behaviour, as well as biochemical parameters. Based on previous studies and results from the present study, we hypothesize that AAS abuse may constitute a risk factor for disinhibitory behaviour, partly by affecting the serotonergic system.

Anabolic Agents↗
PubMed1997

Effects of an anabolic-androgenic steroid on the regulation of the NMDA receptor NR1, NR2A and NR2B subunit mRNAs in brain regions of the male rat.

The expression of the N-methyl-D-aspartate (NMDA) receptor subunits NR1, NR2A and NR2B mRNAs was examined in discrete areas of the male rat brain (including hippocampus, hypothalamus, nucleus accumbens and cortex) following 14 days daily intramuscular injections of high doses (5 and 15 mg/kg) of an anabolic-androgenic steroid (AAS) (nandrolone decanoate). The results indicated that the drug produced a significant decrease in the mRNA expression of the NR2A receptor subunit both in the hypothalamus and hippocampus. A decrease in the level of NR2B receptor mRNA was observed in hypothalamus at the lower dose of the AAS but in other areas examined, this receptor subunit mRNA was not affected. Except for a decreased expression in the nucleus accumbens at the higher dose of AAS the NR1 receptor subunit mRNA was not affected by the drug. The three subunit mRNAs in cortex were not significantly altered. The effects of the steroid on the mRNA expression for the NMDA receptor subunits in hippocampus and hypothalamus are suggested to be involved in the mechanism behind aggressive behaviour, a feature previously associated with AAS misuse. The downregulation of the mRNA for the NR1 receptor subunit in nucleus accumbens may relate to a mechanism involved in the recently suggested AAS-induced stimulation of the brain reward system.

Animals↗
PubMed1996

Anabolic steroids and lymphocyte function in sedentary and exercise-trained rats.

The effects of the administration of suprapharmacological doses of anabolic steroids (AASs) on the immune system were examined in sedentary and exercise-trained rats by testing mobility and proliferative response in cultures of thymus and spleen-derived lymphocytes. Male Wistar rats were exercise-trained following two programmes of treadmill running of 3 months duration, differing in intensity, in the absence of treatment or with simultaneous i.m. administration of a suprapharmacological dose (10 mg/kg/week) of nandrolone decanoate (ND) or stanozolol (ST) during the past two months. At this dose ND reduced body weight gain, promoted a redistribution of immune cells from thymus to spleen, impaired lymphocyte mobility and inhibited the mitogen-induced proliferative response (about 90% inhibition for thymus-derived cells). Stanozolol (ST) treatment was without effect on body weight gain, but it also induced a redistribution of lymphocytes and modified the in vitro lymphocyte activity, although less severely than ND. Application of the high-intensity training programme reduced lymphocyte mobility and proliferation in vitro and a simultaneous treatment with anabolic steroids further impaired some of the immune cell responses. Application of the endurance-directed training programme, however, did not reduce mobility or mitogen-induced proliferation of lymphocytes, and normalized the activity of these cells in anabolic steroid-treated rats. So, endurance exercise, contrary to high-intensity training, could counteract the apparent negative effects of high doses of androgens on lymphocyte function.

Adrenal Glands↗
PubMed1972

Anabolic steroids and bone marrow toxicity during therapy with methotrexate.

The effect of the anabolic steroids nandrolone decanoate and oxymetholone on the peripheral blood haemoglobin, total leucocyte and platelet counts was studied in a controlled trial in which patients received standardized chemotherapy for one form of malignant disease. The results indicate that these agents have no protective effect on bone marrow suppression during cytotoxic chemotherapy. It was observed that the time interval between the initial nadir total leucocyte count and the return to pre-treatment values in those patients receiving the anabolic steroids was significantly shorter than in the control group.

Adolescent↗
PubMed1977

A controlled trial of nondrolone decanoate in the treatment of uremic anemia.

Thirty-seven male dialysis patients, from three university hospital centers known to have adequate iron B12, and folate stores, were entered into a controlled trial to study the effects of nandrolone decanoate (200 mg i.m. weekly) on their anemia. An initial six-month stabilization period was followed by a randomized 12-month study, with crossover between treatment and control groups occurring at six months. Patients received parenteral iron therapy plus oral folate throughout the trial. All serious illnesses or major blood losses excluded the patients from analysis. The 24 patients with remnant kidneys showed an increase in hemoglobin and hematocrit of 24% by the end of six months of treatment (P less than 0.005), with a corresponding decrement during the six months of control, but the five anephric patients showed no statistically significant change compared to those patients whose kidneys were in place during the study. Complications of treatment were minimal, with injection site hematoma the only significant local effect and a rise in triglyceride the only significant systemic disturbance. Despite the improvement in anemia, the disadvantages, including the high cost of treatment, the apparent plateauing of benefits by five months, the minimal subjective improvement in life style, the risk of i.m. injection, plus the long term effects of increased lipids, should limit this therapy to patients with remnant kidneys who have severe symptomatic anemia or frequent transfusion requirements.

Adult↗
PubMed1998

Utility of isolated hepatocytes and radio-HPLC-MSn for the analysis of the metabolic fate of 19-nortestosterone laurate in cattle.

The metabolic fate of 19-nortestosterone laurate in cattle was investigated to evaluate target analyte(s) appropriate to surveillance for illicit use as a growth promoting agent. Bovine hepatocytes were incubated with either [3H]19-nortestosterone laurate (19-NTL; 4-estren-17 beta-laurate-3-one) or [3H]19-nortestosterone (19-NT; 4-estren-17 beta-ol-3-one; nandrolone). Hepatocyte medium was extracted with solid phase C18 media and analysed by narrow bore radio-HPLC-MSn (LCQ, Finnigan) to evaluate the structure of metabolites of 19-NTL and 19-NT. Radio-HPLC of hepatocyte medium extracts following incubation with [3H]19-NTL confirmed that the first step of biotransformation in liver was hydrolysis of the fatty acid ester to release [3H]19-NT, which, in turn, was converted into a range of metabolites of diverse polarity. Hydrolysis of hepatocyte medium extracts with beta-glucuronidase (Helix pomatia) indicated that some of these metabolites were glucuronide or sulfate conjugates. Structural analysis of unconjugated metabolities by positive-ion atmospheric pressure chemical ionisation MS2 and comparison with available reference preparations indicated biotransformation of 19-NT to 4-estren-17 alpha-ol-3-one, 4-estren-3, 17-dione (major metabolite after 1 h), n-hydroxy-4-estren-3, 17-dione, n-hydroxy-4-estren-17-ol-3-one, 5 beta-estran-3 alpha-ol-17-one (noretiocholanolone) and 5 beta-estran-3 alpha, 17 beta-ol (major metabolite after 4 h). Conjugated metabolites were analysed by electrospray ionization, which revealed the presence of glucuronide conjugates of alpha-(trace) and beta-epimers of 19-NT, n-hydroxy-4-estren-3, 17-dione, n-hydroxy-4-estren-17-ol-3-one and 5 beta-estran-3 alpha, 17 beta-diol. These studies provide a clear indication of the route of hepatic metabolism in the bovine, which may now be readily substantiated by reference to samples, such as urine or bile, derived from animals treated with unlabelled 19-NTL.

Anabolic Agents↗
PubMed1998

Residues and metabolism of 19-nortestosterone laurate in steers.

The illegal use of 19-nortestosterone (19NT; 4-estren-17 beta-ol-3-one; nandrolone) and its esters in livestock, for growth promotion purposes, has been widely reported in the European Union. The target residues for surveillance of abuse in bovine urine and bile samples are 17 alpha- and 17 beta-19NT, although this choice of target residues is not based on in vivo radiotracer biotransformation data. In this study, four steers were administered [3H2]- and [2H3] 17 beta-19NT laurate (2 mg kg-1 body mass) by intramuscular injection and blood, urine, faeces and bile samples were taken for 30 d until slaughter, after which tissues were sampled for total residue analysis. Total plasma radiolabelled residues reached a maximum of 56.3 +/- 15.9 pmol ml-1 at 36 h and were still appreciable (13.3 +/- 1.6 pmol ml-1) 30 d after treatment. Throughout the study period, total residue concentrations in bile (about 2-16 nmol ml-1), urine and faeces (0.5-3 nmol ml-1 or g-1) were higher than in other tissues sampled at slaughter. At slaughter there was evidence of residue accumulation in pigmented eye tissue (33.1 +/- 6.1 pmol g-1) and in white (13.4 +/- 3.4 pmol g-1) and black hair (28.9 +/- 8.9 pmol g-1). Evaluation of radio-HPLC profiles of urine and bile extracts generally indicated that 19NT and 19NT laurate residues were present in relatively small amounts among a complex mixture of metabolites. GC-MS analysis of glucuronidase-hydrolysed bile extracts indicated that the major metabolites were 5 beta-estrane-3 alpha, 17 alpha-diol, 5 alpha-estrane-3 beta, 17 alpha-diol. 5 alpha-estran-3 alpha-ol-17-one (norandrosterone) and estra-1,3,5(10)-triene-3,17 alpha-diol (17 alpha-estradiol).

Anabolic Agents↗
PubMed1994

Survey of the hormones used in cattle fattening based on the analysis of Belgian injection sites.

Although the illegal use of orally administered compounds in cattle fattening has gained popularity, injection sites are still frequently found during control experiments on the carcasses in the slaughterhouses. The high concentrations of hormones in injection sites enable screening for the presence of 39 different hormones by a simple extraction followed by a fast and simple high-performance thin-layer chromatography analysis. Analysis of injection-site tissue is particularly successful for determining the hormones that are illegally injected. This data can not be obtained by analysis of other biological matrices like faeces, kidney fat or urine, owing to metabolization and selective excretion and/or deposition of these compounds. Since 1989, over 2000 injection sites have been analysed in our laboratory, which yielded a good survey of the hormones that were illegally injected. Over this period, the natural hormones estradiol and testosterone (mostly present as their esters) have obviously been used extensively. It is clear that since 1990 clostebol acetate has remained the most abused exogenous hormone. Additionally, some distinct trends were noticed, e.g., a tendency towards a highly decreased use of nandrolone, an increased use of progesterone and an increased occurrence of certain androgens like stanozolol and fluoxymesterone.

Anabolic Agents↗
PubMed1993

Anabolic steroids and craniofacial growth in the rat.

Anabolic steroids are misused by adolescents as well as adults to increase muscle and improve appearance and athletic performance. Since these substances strongly enhance protein synthesis, it was speculated that craniofacial changes in bone size and, perhaps, skeletodental relationships might also occur. Eighty rat pups were divided into three groups: (1) sham-treated controls, (2) a low-dose group (1 mg/kg/wk nandrolone phenpropionate), and (3) a high-dose group (10 mg/kg/wk). The high-dose regimen more closely mimics dosages used by abusers. Steroid therapy significantly increased all measures of the craniofacial complex (k = 20)--on the order of 3.5%-except some precocious calvarial dimensions. Importantly, significant alterations also occurred in facial morphology. The low-dose group exhibited proportionate increases in most craniofacial dimensions, but the high-dose produced overt shape changes, notably a maxillomandibular, anteroposterior jaw discrepancy due to maxillary excess. In sum, this anabolic steroid significantly altered facial growth in this animal model; by extension, steroid abuse by adolescent humans may produce discernible changes in their craniofacial complexes.

Anabolic Agents↗
PubMed1999

Effects of anabolic/androgenic steroids on regenerating skeletal muscles in the rat.

We have examined the effect of male sexual hormones on the regeneration of skeletal muscles. Degeneration/regeneration of the left soleus and extensor digitorum longus muscles (EDL) of Wistar male rats was induced by an injection of snake venom (2 microg, Notechis scutatus scutatus). During the muscle regeneration (25 days), rats were treated with either oil (CON), nandrolone (NAN), NAN combined with exercise (NAN + EXE) or were castrated (CAS). Muscle growth and myosin heavy chain (MyHC) isoform content of regenerating muscles were studied. Castration altered the concentrations of MyHC in venom-treated EDL (P < 0.01) and soleus (P < 0.05). NAN increased the mass (P < 0.01) of regenerating soleus and decreased the relative amount of fast MyHC protein (% of total, P < 0.05). The effect of NAN + EXE on the fast MyHC proteins of venom-treated soleus was opposite (P < 0.05). NAN and NAN + EXE were without effect on the regenerating EDL (P > 0.05). In conclusion, it is possible that male sexual hormones play a role in the growth (synthesis of contractile proteins) of regenerating muscles in rat. In addition, contrary to NAN + EXE, NAN could be beneficial to soleus regeneration.

Anabolic Agents↗
PubMed1999

Poststeroid balance disorder--a case report in a body builder.

The authors describe a case of poststeroid balance disorder in a 20-year-old athlete. Previous information of such a doping pathology among sportsmen taking anabolics was not found. That anabolic steroids had a harm to central activities and could be suspected especially on the basis of reported psychiatric sequels and cerebrovascular disorders. The case described is of a patient who had been given metandienone, oxymetholone, and nandrolone phenyloproprionate in two courses. Vertigo appeared twice just after introducing doping and persisted in spite of a 1.5 year break in taking anabolics. In the electronystagmography a positional nystagmus was detected, the eye-tracking test was distempered, and abnormal responses in the caloric tests were obtained. In the computed dynamic posturography the number and length of body sway were increased and, consequently, the field of the outspread area was enlarged. The moment of appearance and long-lasting vertigo as well as the results of laboratory examinations indicate a poststeroid permanent disorder of the central part of the equilibrium organ. Such a diagnosis seems to be most probable here.

Adult↗
PubMed1995

Pubertal benzpyrene exposition decreases durably the sexual activity of the adult male and female rats.

Single benzpyrene treatment of 5 week old male and female rats significantly decreased their sexual activity at 3 months of age. Among the hormone preparations used nandrolone was comparatively practically ineffective, while estradiol decreased the lordosis quotient of females. In males benzpyrene produced a total failure of ejaculation. These results draw attention to the wide time-scale of receptorine and behavioral effects of the aromatic hydrocarbon, benzpyrene. These effects are detectable following fetal, neonatal or pubertal treatments, especially in females. In males, the negative effect was manifested after neonatal and pubertal treatments only. The experiments suggest that in some cases hormonal imprinting does not develop solely in the perinatal period but it might develop later.

Anabolic Agents↗