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PubMed2004

Update on nandrolone and norsteroids: how endogenous or xenobiotic are these substances?

Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In doping controls, the use of the banned xenobiotic norsteroids is detected in the competitor's urines by the measurement of norandrosterone (19-NA) and noretiocholanolone (19-NE), which are the main metabolites for nandrolone (NT) and most norsteroids with anabolic properties. In 1996, the IOC subcommission "Doping and Biochemistry of Sport" informed the Heads of the "IOC Accredited Laboratories" that the recommended cut-off limit for reporting an offence was to be 1-2 ng ml(-1) urine for either 19-NA or 19-NE. We will discuss how technical progress in gas chromatography coupled to high-resolution mass spectrometry permitted a dramatic increase in sensitivity with a detection limit of 1 pg ml(-1) urine, or less, and an assay limit of 20-50 pg ml(-1) urine, for either 19-NA or 19-NE. As a paradox, norsteroids have been known for decades as not only xenobiotics but also obligatory endogenous intermediates in the biosynthesis of estrogens from androgens in all species, man included. It is this biochemical observation which fed the active scientific and medical controversy initiated in 1998 over the possibly endogenous production of nandrolone and metabolites well over the new IOC's recommended cut-off limit of 2 ng ml(-1) urine. Notwithstanding the particular technical difficulties attached, we will provide data and discuss the minute endogenous levels detected and measured in man either at rest, after performance or training and compare them to the relatively high levels reported in male athlete's doping controls today. We will also discuss data on the pharmacological effects of some contraceptive therapies containing norsteroids in women. In view of the well-documented noxious effects repeatedly observed after anabolic steroid misuse, the confirmation and implementation of technically proven procedures for reporting norsteroid abuse in sports seems an important enough goal to protect athlete's health against such abuses and justifies up dating the review of the patent scientific and medical experience and knowledge gained over the last 50 years on nandrolone and its minor production in man and woman.

Chromatography, High Pressure Liquid↗
PubMed2004

Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fractures.

AIM: To evaluate the effects of a protein-rich liquid supplementation, alone or in combination with the anabolic steroid nandrolone decanoate, on body composition, activities of daily living (ADL) status and the health-related quality of life (HRQoL) after a femoral neck fracture. METHODS: Sixty women, aged 83 +/- 5 years (mean +/- SD), BMI < 24 kg/m2 (20.4 +/- 2 kg/m2 ) and capable of co-operating, with a femoral neck fracture treated with internal fixation, were randomised to open treatment during 6 months with a protein-rich liquid formula alone (PR, Fortimel, 200 ml/day, 20 g protein/day) or in combination with nandrolone decanoate (PR/N, Deca-Durabol 25 mg i.m./3 weeks) or to a control group (C). The patients were re-examined after 6 and 12 months regarding body weight (BW), lean body mass (LBM, DXA), ADL status according to Katz, HRQoL according to EQ 5-D and fracture healing. RESULTS: LBM decreased in the C (-1.2 +/- 2 kg) and PR groups (-1.2 +/- 1 kg) but remained the same in the PR/N group (0.3 +/- 1 kg) (P < 0.05 between groups). ADL remained at a high level in the two intervention groups but declined significantly in the C group (P < 0.005 between groups). The decline in HRQoL was least pronounced in the PR/N group at 6 months (P < 0.05 between groups). Patients with fracture healing complications lost more BW (P < 0.05) and LBM (P < 0.01) than patients with uneventful fracture healing. CONCLUSION: Protein-rich liquid supplementation in combination with nandrolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM, ADL and HRQoL.

Activities of Daily Living↗
PubMed2004

Enhanced vasoconstriction and reduced vasorelaxation induced by testosterone and nandrolone in hypercholesterolemic rabbits.

Androgenic-anabolic steroids (AAS) are widely abused by athletes and this abuse has been associated with many serious circulatory events including sudden cardiac death, myocardial infarction and cardiac hypertrophy. The effect of chronic treatment for 16 weeks with testosterone (25mg(-1)kg(-1)week(-1)) and nandrolone (50mg(-1)kg(-1)week(-1)) on serum lipids of male hypercholesterolemic New Zealand rabbits was investigated. The responses of isolated rabbit aortic rings to some vasoconstrictors (epinephrine, serotonin and endothelin-1) and vasodilators (adenosine and sodium nitroprusside) were also measured after treatment. Testosterone and nandrolone significantly reduced HDL-cholesterol levels, potentiated vasoconstriction responses to epinephrine, serotonin and endothelin-1, and attenuated vasorelaxant responses to sodium nitroprusside in rabbits. Nandrolone also caused a significant increase in LDL-cholesterol levels. No significant changes in adenosine relaxation were found in rabbits. The results of the present study showed that the abuse of AAS in presence of hypercholesterolemia can enhance atherogenicity and vasospasm as well as attenuation of vasorelaxation. Therefore the abuse of AAS is harmful to the vascular system and should be prohibited.

Animals↗
PubMed2000

Combined cardiac effects of cocaine and the anabolic steroid, nandrolone, in the rat.

Despite reports of an increase in the incidence of simultaneous cocaine and anabolic steroid abuse, potential adverse interactions between these two drugs on the cardiovascular system are largely unquantified. Cocaine has been reported to induce coronary vasoconstriction, cardiac arrhythmias and conduction delays. Anabolic steroids have been associated with cardiac hypertrophy and hypertension. Utilising both in vivo (radiotelemetry) and in vitro (isolated Langendorff-perfused heart) techniques, our aim was to determine whether anabolic steroids cause cardiac hypertrophy and alter cardiac function, and consequently alter the response of the heart to cocaine. It was found that 15 days of treatment of rats with nandrolone decanoate (20 mg/kg, s.c.) was not sufficient to cause hypertrophy, alter cardiac function or the spread of electrical activity through the heart. However, nandrolone pretreatment was found to significantly potentiate the heart rate response to cocaine (45 mg/kg, i.p.) in vivo. This study indicates that nandrolone significantly elevates the heart rate response to high dose cocaine without changing heart morphology. The mechanism of this interaction remains uncertain.

Anabolic Agents↗
PubMed2002

Effect of combined treatment with nandrolone and cocaine on the NMDA receptor gene expression in the rat nucleus accumbens and periaqueductal gray.

OBJECTIVE: Anabolic androgenic steroids (AAS) have been suggested to sensitize mechanisms involved in drug dependency and aggressive behaviour. Nucleus accumbens and periaqueductal gray (PAG) are believed to be critical in the functional anatomy of these two phenomena, which are partly mediated by the NMDA receptor. This study was undertaken in order to determine the relationship between the effect of AAS and cocaine (given alone or in combination) on the gene expression of the NMDA receptor subtype NR1 in the rat nucleus accumbens and PAG. METHOD: Male rats were subjected to 2 weeks of daily doses of cocaine and the anabolic-androgenic steroid nandrolone, administrated separately or in combination, and the effect on the mRNA expression for the NMDA receptor NR1 subunit was studied by Northern blot analysis. RESULTS: In the nucleus accumbens, injection of cocaine alone and the combination of cocaine and nandrolone caused a significant decrease in the NR1 mRNA level compared with that of control rats. The combined treatment significantly down-regulated the transcript in the PAG compared with the groups injected with vehicle, nandrolone or cocaine alone. CONCLUSION: It was concluded that AAS combined with cocaine may induce additive increases in glutamatergic activity in these brain areas, supporting the notion that these steroids can sensitize mechanisms involved in the reward and the expression of aggression.

Anabolic Agents↗
PubMed2005

Intracerebroventricular self-administration of commonly abused anabolic-androgenic steroids in male hamsters (Mesocricetus auratus): nandrolone, drostanolone, oxymetholone, and stanozolol.

Previous studies by the authors have shown voluntary intracerebroventricular (icv) testosterone self-administration in hamsters (Mesocricetus auratus). Here, the authors compared icv self-administration of 4 anabolic steroids (drostanolone, nandrolone, oxymetholone, and stanozolol) at 0.1, 1.0, and 2.0 microg/microl, each for 8 days. Males (n=8/group) showed the highest levels of operant behavior for injectable steroids (drostanolone, nandrolone) compared with orally active androgens (oxymetholone, stanozolol). For nandrolone, responses on the active and inactive nose-pokes averaged 22.3 +/- 4.6/4 hr and 10.7 +/- 2.0/4 hr, respectively. Responding for drostanolone was similar. Males self-administering oxymetholone or stanozolol did not prefer the active nose-poke. These data demonstrate that injectable androgens are more reinforcing than oral steroids.

Analysis of Variance↗
PubMed1994

Stability of zeranol, nandrolone and trenbolone in bovine urine.

The stability of some growth promoting agents in cattle urine, under various temperature storing conditions, was investigated. Bovine urine samples obtained from previous excretion studies which contained zeranol, nandrolone and trenbolone respectively, were stored frozen, at room temperature and in direct sunlight. On days 0, 2, 4, 7 and 10, zeranol and nandrolone were quantified by selective ion monitoring analysis on a gas chromatography-mass selective detector and trenbolone by using an enzyme linked immunosorbent assay. Zeranol and its metabolite taleranol are stable under all of these storage conditions. There is a remarkable decrease in the concentration of 17 alpha-19-nortestosterone, the main metabolite of nandrolone in cattle, when stored at room temperature and in direct sunlight. There is also a decrease in concentration of trenbolone when stored in direct sunlight. From the results it can be concluded that urine specimens obtained from cattle for residue analysis should be frozen as soon as possible after collection.

Animals↗
PubMed2002

Molecular imprinted polymer coated QCM for the detection of nandrolone.

An acoustic wave sensor coated with an artificial biomimetic recognition element has been developed to selectively screen for nandrolone in the liquid phase. A highly specific covalently imprinted polymer (MIP) was spin coated onto one electrode of a quartz crystal microbalance (QCM) as a thin permeable film. Selective rebinding of the nandrolone was observed as a frequency shift in the QCM for concentrations up to 0.2 ppm with the sensor binding shown to favour nandrolone over analogous compounds.

Anabolic Agents↗
PubMed2001

Effects of nandrolone treatment on recovery in horses after strenuous physical exercise.

To test the effect of nandrolone on their recovery, six adult half-bred riding horses performed a competition exercise test (CET) and a standardized exercise test (SET) on consecutive days before and after a 2-week treatment with the anabolic steroid nandrolone laurate. Blood samples were collected during and between these tests for the determination of red cell volume and concentrations of blood lactate, plasma glucose, non-esterified fatty acids, glycerol, triglycrides, erythropoietin, cortisol, insulin, and glucagon. Muscle biopsy specimens were taken immediately after the CET and before the SET for analysis of glycogen content, citrate synthase, and 3-hydroxyacyl CoA dehvdrogenase activity. Nandrolone administration increased the rate of muscle glycogen repletion after exercise, an increase that may be explained by increased glucose output by the liver, higher plasma insulin concentration, and increased insulin-independent glucose transport, but not by better availability of lipid fuels during recovery.

Anabolic Agents↗
PubMed2001

Body composition and anthropometry in bodybuilders: regional changes due to nandrolone decanoate administration.

The purpose of the present study was to investigate regional changes in body composition and anthropometric variables induced by nandrolone decanoate in bodybuilders. In a randomized, double blind, placebo controlled design 16 subjects received weekly intramuscular injections containing 200 mg nandrolone decanoate (ND) or placebo. Composition of total body and body parts were assessed using dual energy X-ray absorptiometry (DEXA), skinfolds and circumferences. Measurements were performed at baseline, after 8 weeks ND administration period and 6 weeks after drug withdrawal. DEXA revealed that total body mass (from 76.16 +/- 2.70 to 78.73 +/- 4.07 kg, p<0.5) and bone-free lean mass (from 59.54 +/- 2.36 to 63.06 +/- 2.99 kg, p < 0.025) increased significantly during ND administration whereas bone mineral mass remained unchanged. Six weeks after drug cessation bone-free lean mass was still increased compared to baseline levels. During ND administration significant increments of bone-free lean mass of the trunk (+ 2.03 kg) and legs (+ 1.08 kg) could be observed. Percentage fat of the legs decreased during the drug intervention period (-1.9%) and remained lowered six weeks after drug withdrawal. No alteration in any variable of the arms was observed. Skinfolds did not change during the entire study period in both groups. After 8 weeks ND administration circumference of the neck was increased (+0.9 cm) significantly although all circumferences underwent non-significant gains. In conclusion, the intramuscular administration of nandrolone decanoate (200 mg per week) during eight weeks induced an increase of body weight and bone-free lean body mass in bodybuilders that was mainly situated in the trunk and legs as determined by DEXA. The changes in the trunk were reflected in the circumferences but not the alterations in the legs. Skinfolds were not able to detect changes of fat mass of body parts. DEXA revealed that total fat mass and total percentage fat remained unaffected by drug administration while percentage fat of the legs decreased and remained lowered after drug cessation. These data indicate that changes of the composition of body parts induced by ND are elucidated less accurately by circumferences or skinfolds rather than by DEXA.

Absorptiometry, Photon↗
PubMed1997

Androgen receptors and skeletal muscle composition in trotters treated with nandrolone laureate.

To study the effects of nandrolone laureate (19-nortestosterone) on muscle hypertrophy and concentration of androgen receptors (AR), biopsy specimens were taken from the middle gluteal muscle of 6 Finnhorse trotters (geldings and mares) undergoing training before, immediately after, and 13 weeks after a 14-week treatment with nandrolone. Another 6 similarly trained horses served as controls. An additional 10 mares and 10 geldings were used to study annual variation in muscle concentration of AR. AR was immunohistochemically localized in the nuclei. AR concentration remained constant during the first 14 weeks of the study, but increased significantly during the 13-week follow-up period in both groups. This finding can be explained by the annual variation in AR. In the anabolic steroid (AS)-treated horses, but not in the controls (C), the cross-sectional area of the type I fibres increased significantly during the treatment period, and the percentage of type IIA fibres correlated positively with AR concentration at the end of nandrolone treatment. In the AS group, the concentration of DNA decreased during the 13-week follow-up period, and the percentage of H-chains in the isoenzymes of LDH increased. Protein concentration increased in both groups during the follow-up period. Glycogen content and the activity of citrate synthase in muscle during the study remained unchanged. It can thus be concluded that AS produce differing effects on type I and type II fibres, and the AR concentration in equine muscle may contribute to the change observed in the middle gluteal muscle.

Anabolic Agents↗
PubMed1982

Effects of nandrolone phenylpropionate in the horse: (2) general effects in animals undergoing training.

The effect of 11 weekly injections of nandrolone phenylpropionate (400 mg) was investigated by a crossover trial (2 training periods) in 6 Thoroughbred geldings undergoing training. A decrease in body weight and flank measurement occurred only during the first training period and was not modified by the anabolic steroid. Urinary nitrogen excretion was lower in the anabolic treated animals only in the first training period. Neither training nor training plus nandrolone phenylpropionate administration caused any marked alteration in blood biochemistry or haematology. A significant decrease in plasma chloride and increase in haematocrit occurred independent of treatment in the latter, more extensive anaerobic training of both parts of the crossover. No change in urinary pH or specific gravity was found throughout the study. No evidence of improved racing performance due to nandrolone phenylpropionate administration was observed. Behavioural changes attributed to the drug could be detected for at least 6 weeks after the cessation of treatment.

Anabolic Agents↗
PubMed2004

Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they are on regular follow-up. Two women after 10 and 14 months in PR developed acute leukemia and died. In conclusion, combination therapy with EPO, nandrolone decanoate and low-dose methylprednisolone may be effective as an alternative treatment for RBC transfusion-dependent patients with RA unresponsive to EPO administration alone.

Aged↗
PubMed1977

Randomized study of nandrolone therapy for anemias due to bone marrow failure.

A prospective, randomized, double-blind study was designed to determine the effectiveness and toxicity of nandrolone phenpropionate in the treatment of anemias due to bone marrow failure. Twenty-four patients were initially entered; 21 now may be evaluated: seven with aplastic anemia, six with myelofibrosis, and eight with refractory anemia. Six patients improved, but only three were taking nandrolone, the other three placebo. Response did not correlate with type of anemia. No serious drug toxicity was noted. One patient with myelofibrosis improved dramatically with placebo therapy alone, no longer requiring frequent transfusions because of a hemoglobin level increase from 5.4 to 15.8 gm/100 ml. We conclude that no substantial improvement of anemia due to marrow failure can be ascribed to nandrolone as given, and that clinical trials in these conditions should be controlled to exclude spontaneous remissions as a cause of apparent improvement.

Adult↗
PubMed1981

The effects of nandrolone, testosterone and their decanoate esters on murine lupus.

Treatment of NZB/NZW F1 (B/W) female and castrated male mice with testosterone or 19-nortestosterone (nandrolone), either by implantation in silastic tubing or by subcutaneous injections of their decanoate esters, reduced in a dose-dependent manner symptoms associated with murine lupus (proteinuria, IgG antibodies to DNA) and prolonged survival. These phenomena were observed under both prophylactic (start at 3-4 weeks) and therapeutic treatments (start 27-29 weeks). Nandrolone and its decanoate ester were at least as potent as testosterone and testosterone decanoate. As the unwanted androgenic properties of nandrolone and its ester are significantly less pronounced than those of testosterone and its ester, also in these NZB/NZW mice, the beneficial effect on murine lupus does not seem to be associated with these properties.

Animals↗
PubMed2001

Interaction between nandrolone decanoate and calcitonin in bone formation markers (osteocalcin and bone specific alkaline phosphatase) and IGF-I in rats.

Bone tissue has been shown to contain numerous cell-to-cell signaling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling, due to their potent effects on bone cell metabolism. Our investigation was intended to assess the effect of nandrolone decanoate and calcitonin treatment on biochemical markers of bone formation (bone alkaline phosphatase - osteocalcin) and insulin-like growth factor-I in rats. We studied 48 adult male rats. The animals were divided into four groups. Group (A) served as control. Animals in Group (B) were injected with 4 mg/kg/day nandrolone decanoate. Animals in Group (C) were injected with 400mU/rat/day calcitonin and Group (D) received combined therapy for seven days. Nandrolone decanoate and calcitonin have a mild but significant effect on insulin-like growth factor-I without affecting osteocalcin levels, while calcitonin alone decreases the BALP levels. The coadministration of two agents caused notable elevation on insulin-like growth factor-I, followed by a significant increase of osteocalcin and bone alkaline phosphatase.

Journal Article↗
PubMed1991

Calcium-deficient diet in ovariectomized dogs limits the effects of 17 beta-estradiol and nandrolone decanoate on bone.

Postmortem measurements by dual-photon absorptiometry of the femur and the second lumbar vertebra in adult dogs indicated bone loss after ovariectomy, which was more pronounced when calcium-deficient diet was given in ovariectomized dogs. This bone loss was nonhomogeneous throughout the femur. Ovariectomy resulted in trabecular and cortical bone loss, and additional calcium-deficient diet resulted in a further highly significant trabecular bone loss at the proximal epiphysis of the femur and in the vertebra. This bone loss was presumably the result of increased bone turnover, as reflected by the highly significant increase in serum alkaline phosphatase. Estrogens could only partially prevent the bone loss induced by calcium deficiency after ovariectomy, and nandrolone decanoate was not effective. We conclude that (1) ovariectomy results in bone loss in adult dogs, (2) this bone loss is more pronounced after calcium-deficient diet, (3) calcium deficiency could be a limiting factor for the preventive effect of estrogens and nandrolone decanoate, and (4) dual-photon absorptiometry allows the evaluation of nonhomogeneous bone loss throughout excised bones.

Absorptiometry, Photon↗