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Stereological study of the effects of nandrolone decanoate on the rat prostate.

It has been shown that nandrolone decanoate which is one of the anabolic-androgenic steroid compounds changes the testis structure and sperm quality but quantitative studies of the prostate have received less attention. Control rats received the peanut oil and experimental group received nandrolone decanoate for 14 weeks. Then the rats were left untreated for 14 weeks. After 14 weeks of withdrawal, the prostate was studied using stereological methods. The mean prostate weight decreased approximately 39% (p<0.009) in nandrolone decanoate treated rats. The mean total prostate volume, glands, epithelia, fluids and collagen bundles reduced approximately 30% (p<0.03), approximately 31% (p<0.03), approximately 41% (p<0.02), approximately 31% (p<0.05) and approximately 59.5% (p<0.02) in the experimental group. The mean total luminal surface of the glands and total length of the vessels decreased approximately 40% (p<0.02) and approximately 46% (p<0.009), respectively, in the nandrolone decanoate treated rats. The height of epithelium did show no difference. It can be concluded that nandrolone decanoate causes atrophic changes in the components of rat prostate.

Animals↗

Effect of nandrolone decanoate and 1-alpha-hydroxy-calciferol on patients with vertebral osteoporotic collapse. A double-blind clinical trial.

Eighty-eight postmenopausal women with at least one vertebral collapse were randomly assigned to two groups of 44 patients each. All patients were treated for a period of 12 months with 50 mg of nandrolone decanoate every 3 weeks or 1 microgram of 1-alpha-hydroxy-calciferol daily. Both groups received an identical placebo of the inactive drug. Pain intensity was significantly decreased in the nandrolone group and mobility was improved. Patients treated with vitamin D metabolite had also a beneficial but less obvious clinical result. Bone mineral measurements showed an increase of 5% in the nandrolone decanoate group, but a 2.5% decrease in the vitamin D metabolite group. Biochemical results showed a significant hypercalciuric effect of vitamin D metabolite, while nandrolone decanoate caused a reduction in calcium/creatinine excretion. No difference in serum lipids was found during the annual treatment in both groups. It is concluded that nandrolone decanoate has a beneficial effect in clinical symptoms, bone mineral density and biochemical parameters in patients with established osteoporotic vertebral fractures.

Aged↗

Nandrolone decanoate treatment induces changes in contractile responses of rat untrained fast-twitch skeletal muscle.

This investigation was designed to examine whether short-term administration of anabolic-androgenic steroids (AAS) (nandrolone decanoate) could produce changes in contractile responses of untrained rat fast- (edl) and slow- (soleus) twitch skeletal muscle. Twenty male rats were divided into two groups, one group received weekly (for 6 weeks) an intramuscular injection of AAS, nandrolone decanoate (15 mg kg(-1)) and the second group received weekly the similar doses of vehicle (sterile peanut oil). In edl intact isolated small bundles (two to four cells), it was found that nandrolone decanoate treatment increases the K+ contracture tension (146 mM) relative to maximum tension by 56%, whereas no change was observed in the time to peak tension and in the time constant of relaxation. By contrast, in treated soleus muscle, compared with control, no significant modification was found in the K+ contracture characteristics. The change in edl contractile responses was associated with a shift to more negative potential of the voltage-dependence activation and the steady-state inactivation curves which also shifted leftward in treated soleus fibres. Furthermore, in edl skinned Triton X-100 fibres, the Ca2+ sensitivity of contractile proteins (pCa50) was increased, while electrophoresis analysis indicates no significant effect of nandrolone decanoate treatment on myosin heavy chain (MHC) isoforms. The present results show that nandrolone decanoate treatment produces more pronounced changes in untrained fast muscle function rather than soleus by acting at different levels of the excitation-contraction coupling mechanism without changes in the MHC isoforms and that contractile responses became similar to those found in soleus muscle.

Animals↗

A controlled trial of nandrolone decanoate in the treatment of rheumatoid arthritis in postmenopausal women.

To determine whether an anabolic steroid had any benefit in the treatment of rheumatoid arthritis 47 patients entered a parallel group study. Twenty four received nandrolone decanoate 50 mg intramuscularly every third week for two years and 23 patients received no anabolic steroids. Other therapy was unaltered. Patients attended for clinical and biochemical assessments as well as the objective assessments of elementary body composition by in vivo neutron activation analysis and measurement of the mineral content of the distal femur by single photon absorptiometry on five occasions. A modest clinical deterioration (except for grip strength) was seen in both groups. No significant changes in calcium or alkaline phosphatase were seen. There was no significant change in total body calcium, total body phosphorus, body weight, or bone index/bone width measurements in either group. Significant increases occurred in total body nitrogen, total body potassium, haemoglobin, and packed cell volume (by six months) in the group treated with nandrolone decanoate. Comparison of 10 patients in the group treated with nandrolone decanoate also receiving oral steroid therapy with 14 patients in this group not receiving oral steroid therapy showed no significant differences. The main side effect of nandrolone decanoate was hoarseness. No radiological changes were seen. Nandrolone decanoate, in a dose that produces a significant anabolic effect, has no demonstrable action on bone metabolism in rheumatoid arthritis but may improve the chronic anaemia by six months.

Anabolic Agents↗

The effects of nandrolone decanoate on rarefying bone tissue.

The effects of nandrolone decanoate on rarefying bone tissue were studied with the aid of microradiography and fluorescence microscopy in tetracycline-labelled preparations of the rabbit calcaneus and the long bones of old dogs. Osteoporosis was induced in the rabbit calcaneus by resecting of the Achilles tendon. In 20 of the 24 rabbits treated with nandrolone decanoate, the osteoporosis observed was less severe than in 8 untreated controls. Furthermore, in comparison with the controls, the signs of active osteogenesis in the treated groups increased systematically. In the old dogs, nandrolone decanoate caused a new opposition, identified by tetracycline labelling, to appear at the periphery of the medullary cavity. All the observations suggest that nandrolone decanoate has a favourable effect on osteogenetic phenomena and probably an inhibitory action on bone resorption. Consequently, nandrolone decanoate is capable of preventing or, at least, of partially correcting losses of bone mass.

Animals↗

Pharmacokinetic evaluation of three different intramuscular doses of nandrolone decanoate: analysis of serum and urine samples in healthy men.

The pharmacokinetics of nandrolone in serum and urine were investigated in healthy young men after a single im injection of 50 mg (n = 20), 100 mg (n = 17), or 150 mg (n = 17) nandrolone decanoate. Blood samples were collected before treatment and for up to 32 d after dosing. In addition, in the 50- and 150-mg groups, 24-h urine samples were collected before treatment and on d 1, 7, and 33 after treatment; in the 150-mg group, additional samples were collected after 3 and 6 months. Serum concentrations and the area under the curve of nandrolone increased proportionally with the dose administered. The peak serum concentration ranged from 2.14 ng/ml in the 50-mg group to 4.26 ng/ml in the 100-mg group and 5.16 ng/ml in the 150-mg group. The peak serum concentration was reached after 30 h (50 and 100 mg) and 72 h (150 mg), whereas the terminal half-life was 7-12 d. In urine, pretreatment concentrations of 19-norandrosterone (19-NA) and/or 19-noretiocholanolone (19-NE) were detected in five of 37 subjects (14%). In the 50-mg group, 19-NA and/or 19-NE could be detected at least until 33 d after injection in 16 of 17 subjects (94%). In the 150-mg group, who were presumed to have not previously used nandrolone, nandrolone metabolites could be detected for up to 6 months in eight of 12 subjects (67%) for 19-NE and in 10 of 12 subjects (83%) for 19-NA.

Adult↗

Effects of nandrolone decanoate on VO2max, running economy, and endurance in rats.

PURPOSE: The aim of the present study was to determine the effects of treatment with an anabolic androgenic steroid (AAS), nandrolone decanoate, on the submaximal running endurance (SRE), maximum oxygen consumption (VO2max), running economy (VO2submax), and blood oxygen carrying capacity of endurance trained rats. METHODS: Forty male Wistar rats were randomly allocated into two groups: a sedentary group and an exercising group training on treadmill for 8 wk. Half of the trained and half of the sedentary rats received weekly either nandrolone decanoate (10 mg x kg(-1)) or placebo (Pl) for the last 6 wk of experiment. SRE and VO2max tests were performed several times for all four groups (N = 10 each).Red blood cells parameters were measured at the end of the experiment. RESULTS: The trained rats had increased their SRE compared with sedentary rats throughout the experiment. At the end of the trial, the trained rats receiving nandrolone decanoate ran 46% longer than trained rats receiving Pl during the SRE test (P < 0.05). At the end of the experiment, trained rats had greater maximal time to exhaustion and higher VO2max than those of the sedentary rats but there were no differences in VO2max, VO2submax, and red blood cells parameters between the trained rats receiving nandrolone decanoate and those receiving Pl. CONCLUSIONS: Nandrolone decanoate has no effect on the SRE, VO2max and VO2submax of untrained rats. AAS treatment combined with submaximal training enhances SRE more than training alone but exerts no additive effects on VO2max, running economy, and oxygen carrying capacity of blood. The results suggest that this improvement in SRE of trained rats is due to the impact of AAS on other factors involved in exercise adaptation.

Animals↗

Implications of basic pharmacology in the therapy with esters of nandrolone.

Experiments in rats have shown that esters of nandrolone injected intramuscularly, are absorbed from the depot according to the kinetics of a first-order reaction. The nature of the fatty acid chain in the ester determines the half-life of the compound in the depot. Once released from the depot, the ester is rapidly hydrolyzed by the esterases in the plasma. As a result, free nandrolone is the pharmacologically active agent whereas its availability to the target organs depends on the half-life time of the ester in the depot. It has been demonstrated that various androgenic target organs respond in a different manner to the changes in the concentration of nandrolone occurring during the period of resorption of the ester. This might explain the dissociation of anabolic from androgenic effects observed with esters of nandrolone. Knowing that the half-life for nandrolone decanoate in man is similar to that in rats, theoretical considerations are given with a number of dosing schemes.

Animals↗

Testing for nandrolone metabolites in urine samples of professional athletes and sedentary subjects by GC/MS/MS analysis.

The concentrations of nandrolone metabolites, 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) were analysed in urine samples of professional athletes doing intense physical activity and sedentary subjects to verify if there was endogenous production of nandrolone and if there was any link between physical effort and the urinary metabolites of the steroid. We collected 18 urine samples from professional footballers age range 20-30 years, all from the same team, and 18 urine samples from males not doing any physical activity, age range 20-30 years. Neither group used nandrolone. Qualitative and quantitative analyses of urinary nandrolone metabolites were carried out by GC/MS followed by GC/MS/MS to confirm positive samples. This technique has been demonstrated to be an excellent analytical approach for the determination of anabolic steroids at very low detection limits in complex matrices such as urine. In five urine samples from professional footballers traces of 19-NA were detected. No trace of 19-NA was found in the group of sedentary subjects and no trace of 19-NE was found in any urine sample. The absence of nandrolone metabolites in sedentary subjects supports the hypothesis that the presence of 19-NA and 19-NE could be linked to physical effort even though the origin is not yet clear.

Adult↗

The determination of nandrolone and its metabolites in urine by gas chromatography-mass spectrometry.

The determination of nandrolone and its major metabolites in urine of a healthy volunteer is typically performed by fused-silica capillary column gas chromatography with electron impact quadropole mass spectrometry. Two well-known urinary metabolites of nandrolone, 19-norandrosterone and 19-norethiocholanolone, were isolated by XAD-2 adsorption from urine, eluted with methanol and separated into unconjugated and conjugated fractions. The conjugated fraction was hydrolyzed with beta-glucuronidase from Escherichia coli and the samples derivatized with MSTFA/ammonium iodide/dithioerythritol. Ion fragmentograms of the bis-trimethylsilyl derivatives of nandrolone and its metabolites displayed molecular ions of M+ = 420 and M(+) -15 = 405. Extraction yield and the minimum detection limit of nandrolone in urine were identified. Finally, excretion rates of nandrolone and its metabolites in urine were determined.

Adult↗

Effects of nandrolone on acute morphine responses, tolerance and dependence in mice.

Anabolic-androgenic steroid exposure has been proposed to present a risk factor for the misuse of other drugs of abuse. We now examined whether the exposure to the anabolic-androgenic steroid, nandrolone, would affect the acute morphine responses, tolerance and dependence in rodents. For this purpose, mice received nandrolone using pre-exposure (for 14 days before morphine experiments) or co-administration (1 h before each morphine injection) procedures. Nandrolone treatments increased the acute hypothermic effects of morphine without modifying its acute antinociceptive and locomotor effects. Nandrolone also attenuated the development of tolerance to morphine antinociception in the hot plate test, but did not affect tolerance to its hypothermic effects, nor the sensitisation to morphine locomotor responses. After nandrolone pre-exposure, we observed an attenuation of morphine-induced place preference and an increase in the somatic manifestations of naloxone-precipitated morphine withdrawal. These results indicate that anabolic-androgenic steroid consumption may induce adaptations in neurobiological systems implicated in the development of morphine dependence.

Anabolic Agents↗

Doping control for nandrolone using hair analysis.

A sensitive, specific and reproducible method for the quantitative determination of nandrolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml NaOH IN, 15 min at 95 degrees C, in presence of 10 ng nandrolone-d(3) used as an internal standard. The homogenate was neutralized and extracted using consecutively a solid phase (Isolute C18) and a liquid--liquid (pentane) extraction. The residue was derivatized by adding 50 microl MSTFA/NH4I/2-mercaptoethanol (1000:2:5; v/v/v), then incubated for 20 min at 60 degrees C. A 4-microl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl--95% methylsiloxane, 30 m x 0.25 mm i.d. x 0.25 mm film thickness) of a Hewlett Packard (Palo Alto, CA) gas chromatograph (6890 Series) via a Hewlett Packard (7673) autosampler. The assay was capable of detecting 0.5 pg of nandrolone per mg of hair when approximately 100 mg of hair were processed. Linearity was observed for nandrolone concentrations ranging from 1 to 50 pg/mg with a correlation coefficient of 0.997. Intra-day and between-day precisions at 10 pg/mg were 11.2 and 15.1%, respectively, with an extraction recovery of 81.7%. The analysis of three strands of hair, obtained from three bodybuilders, revealed the presence of nandrolone at the concentration of 1, 3.5 and 7.5 pg/mg.

Doping in Sports↗

The enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation.

The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly, as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.

Animals↗

Nandrolone decanoate treatment affects sarcoplasmic reticulum Ca(2+) ATPase function in skinned rat slow- and fast-twitch fibres.

The effects of anabolic-androgenic steroid administration on the function of the sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats. Twenty male rats were divided into two groups, one group received an intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8 weeks, the second received similar weekly doses of vehicle (sterile peanut oil). Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+) loading in EDL and soleus fibres by 49% and 29%, respectively. In control and treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+) loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was not significantly modified by nandrolone decanoate treatment. Nandrolone decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type dependent manner.

Anabolic Agents↗

Treatment of postmenopausal osteoporosis: is the anabolic steroid nandrolone decanoate a candidate?

Thirty-nine postmenopausal women (aged 55-75 years) with at least one osteoporotic fracture were allocated to one year of treatment with the anabolic steroid nandrolone decanoate (50 mg i.m. every 3 weeks) or placebo injection. Both groups also received a daily intake of 500 mg calcium. Thirty-six women (92%) completed the study. In the nandrolone decanoate-treated group the fat corrected bone mineral content in the proximal part of the distal forearm (measured by single photon absorptiometry) showed a significant increase of 3% compared with placebo (P less than 0.01), and the same tendency was seen in the bone mineral content of the distal part of the distal forearm and density of the lumbar spine (measured by dual photon absorptiometry). However, this did not reach significance. In the placebo group all bone mineral measurements remained unchanged. The biochemical estimates of bone formation (plasma bone Gla protein (BGP), serum alkaline phosphatase) and whole body retention (WBR) of 99mTc-diphosphonates were not statistically significantly changed by the nandrolone decanoate therapy. We conclude that treatment with nandrolone decanoate does increase the bone mineral content; however, this may not be due to a direct increase in bone formation. The mechanism may theoretically be a combination of decreased bone resorption and increased muscle mass, which both play a beneficial role in conserving bone.

Aged↗

Bone mineral content, cortical thickness and fracture rate in osteoporotic women after withdrawal of treatment with nandrolone decanoate, 1-alpha hydroxyvitamin D3, or intermittent calcium infusions.

Twenty-six post-menopausal osteoporosis patients were studied prospectively over a 2-yr period after the cessation of 2 yr of treatment with either nandrolone decanoate (anabolic steroid), 1 alpha hydroxyvitamin D3 or intermittent calcium infusions, the total observation period being 4 yr. Serial evaluations of bone mineral content in the radius, cortical thickness of the metacarpals and spinal roentgenograms were obtained. Nine patients who had been treated with 50 mg nandrolone decanoate every three weeks did not lose bone from the radius or the metacarpals during the 2 yrs following withdrawal of therapy. Eight patients who had received 1 microgram/day of oral 1 alpha hydroxyvitamin D3 retained a positive bone mineral content in the radius but lost cortical thickness from the metacarpals after withdrawal of therapy. Nine patients who had been treated with intermittent calcium infusions over 12 consecutive days annually did not lose further bone mineral content from the radius, but did lose cortical thickness at the expected rate during the 2-yr post-treatment period. The fracture rate at the end of the 4-yr observation period was 40% lower in the nandrolone decanoate group than in the 1-alpha-hydroxyvitamin D3 and calcium infusion groups. The results of this study indicate that, in contrast to oestrogen and calcium therapy, nandrolone decanoate and 1-alpha-hydroxyvitamin D3 have lasting beneficial effects, and that data obtained by photon absorptiometry do not always coincide with those obtained by radiogrammetry. These findings are highly relevant to the design of future therapeutic trials.

Aged↗

Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment.

This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats.

Anabolic Agents↗

Increased dopamine transporter density in the male rat brain following chronic nandrolone decanoate administration.

Adolescent males currently employ anabolic-androgenic steroids (AAS) to become intoxicated, besides the traditional desires of an improved physical appearance and enhanced sports performance. Several studies indicate that AAS affect the brain reward system. Recently chronic administration with nandrolone decanoate to male rats has been shown to increase the dopamine transporter (DAT) density in the striatum visualised in vivo by positron emission tomography. The present study aimed to investigate if the increased DAT density could be confirmed using in vitro autoradiography following a comparable regimen of nandrolone treatment. Specific binding of 50 pM [125I] RTI-55 in the presence of 1 microM citalopram was used to label DAT. Two weeks of nandrolone decanoate administration at the supra-therapeutic doses 1, 5 and 15 mg/kg per day increased DAT density in the caudate putamen at all three doses. In conclusion, this study confirms that chronic nandrolone administration increases dopamine transporter density in the CPU and therefore supports the theory that AAS affects the dopamine system in the male rat brain.

Anabolic Agents↗