methenolone and methenolone-acetate

Topics: Blood Cell Count; Danazol; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Japan; Methenolone; Palliative Care; Prednisolone; Primary Myelofibrosis; Prognosis; Radiotherapy; Spleen; Survival Rate; Transplantation Conditioning

Between 1999 and 2005, 285 patients received new diagnoses of myelofibrosis with myeloid metaplasia (MMM) in Japan. Anemic symptoms were present in 162 patients, and hemoglobin (Hb) concentrations were <10 g/dL in 197 patients. Fifty-five MMM patients were treated with anabolic steroids, and their effect on anemia during MMM was evaluated in 39 patients. A "good" response was defined as an Hb increase of >or=1.5 g/dL, cessation of transfusion dependence, and an Hb concentration of >10 g/dL maintained for at least 8 weeks. A "minimum" response was defined as an Hb increase of >or=1.5 g/dL and transfusion independence for at least 8 weeks. Both good and minimum responses were considered "favorable." Favorable responses were achieved in 17 patients (44%, 8 good and 9 minimum responses). None of the pretreatment variables, such as the lack of transfusion dependence, a higher Hb concentration at the start of treatment, or the absence of cytogenetic abnormalities, were associated with a response to anabolic steroid therapy. Adverse events associated with anabolic steroid therapy were moderate and transient. Two patients required definitive withdrawal of treatment. Thus, anabolic steroids are well tolerated and effective for the treatment of anemia in a subset of MMM patients.

Topics: Adult; Aged; Aged, 80 and over; Anabolic Agents; Anemia; Blood Transfusion; Chromosome Aberrations; Danazol; Estrogen Antagonists; Female; Hemoglobins; Humans; Male; Methenolone; Middle Aged; Primary Myelofibrosis; Time Factors

The study of the metabolism of drugs, in particular steroids, by both in vitro and in vivo methods has been carried out in the authors' laboratory for many years. For in vitro metabolic studies, the microsomal fraction isolated from horse liver is often used. However, the process of isolating liver microsomes is cumbersome and tedious. In addition, centrifugation at high speeds (over 100 000 g) may lead to loss of enzymes involved in phase I metabolism, which may account for the difference often observed between in vivo and in vitro results. We have therefore investigated the feasibility of using homogenized horse liver instead of liver microsomes with the aim of saving preparation time and improving the correlation between in vitro and in vivo results. Indeed, the preparation of the homogenized horse liver was very simple, needing only to homogenize the required amount of liver. Even though no further purification steps were performed before the homogenized liver was used, the cleanliness of the extracts obtained, based on gas chromatography-mass spectrometry (GC-MS) analysis, was similar to that for liver microsomes. Herein, the results of the in vitro experiments carried out using homogenized horse liver for five anabolic steroids-turinabol, methenolone acetate, androst-4-ene-3,6,17-trione, testosterone, and epitestosterone-are discussed. In addition to the previously reported in vitro metabolites, some additional known in vivo metabolites in the equine could also be detected. As far as we know, this is the first report of the successful use of homogenized liver in the horse for carrying out in vitro metabolism experiments. Copyright © 2011 John Wiley & Sons, Ltd.

Topics: Androgens; Androstenes; Animals; Biotransformation; Epitestosterone; Gas Chromatography-Mass Spectrometry; Horses; In Vitro Techniques; Liver; Liver Extracts; Methenolone; Microsomes, Liver; Molecular Structure; Pharmaceutical Preparations; Testosterone

We report a case of myelodysplastic syndrome (MDS) treated effectively with testosterone enanthate. A 70-year-old man was diagnosed with low-risk MDS in 1998, and he was first given methenolone acetate orally because of gradual progression of anemia and thrombocytopenia. However, this treatment was not effective, so we changed the treatment to testosterone enanthate because of his symptoms with late-onset hypogonadism. Three months after testosterone replacement therapy (TRT), anemia and thrombocytopenia had improved, and mean platelet count and hemoglobin had significant increases from 2.36 ± 0.45 × 10(4) to 3.83 ± 0.78 × 10(4) /µL, and from 11.7 ± 0.81 to 15.2 ± 1.00 g/dL, respectively, which contributed to a decrease in platelet transfusion requirement. Since then, the patient has been on a good clinical course. The present case suggests that testosterone enanthate administration could be an alternative treatment for men with MDS, even in the case where treatment with anabolic-androgenic steroids is not successful, and suggests another interesting effect of TRT on platelets.

Topics: Aged; Androgens; Humans; Male; Methenolone; Myelodysplastic Syndromes; Testosterone; Treatment Failure

The use of anabolic steroids has been banned in the European Union since 1981. In this study, the metabolism of the anabolic steroid methenolone acetate, was investigated in a male veal calf. After daily oral administration of methenolone acetate, three main metabolites were detected in both urine and faeces samples. Among these metabolites, alpha-methenolone was apparently the main one, but 1-methyl-5alpha-androstan-3,17-diol and 3alpha-hydroxy-1-methyl-5alpha-androstan-17-one were also observed. The parent compound was still detectable in faeces. As a consequence, abuse of methenolone acetate as growth promoter can be monitored by analysing urine and faeces samples. A few days after the last treatment, however, no metabolites were observed. Alpha-methenolone was detectable in urine until 5 days after the last treatment, but in faeces no metabolites were detectable after 3 days.

Topics: Anabolic Agents; Animals; Cattle; Feces; Gas Chromatography-Mass Spectrometry; Male; Methenolone

Many athletes use drugs, especially anabolic androgenic steroids (AAS), but there are few reports on the endocrinological and pathological changes in AAS abusers. In this study we reported the results of endocrinological examinations in rats administered AAS and also physical changes. We separated 37 male Wistar rats (7 weeks old) into 3 groups: Group A was medicated with nandrolone decanoate, metenolone acetate, and dromostanolone; Group B with nandrolone decanoate and saline; and Group C was given only saline. They were given subcutaneous injections of the medications or the control vehicle once a week for 6 weeks. Medications were stopped for 4 weeks, and then resumed for another 6 weeks. After that, rats were sacrificed. Serum testosterone level in Group A was significantly higher than that in Group C. Serum dihydrotestosterone in Group A was significantly higher than that in both Groups B and C. Serum estradiol-17beta levels in Groups A and B were significantly higher than that in Group C. In pathological evaluation, heart, testis, and adrenal gland were severely damaged. These findings indicate that there is a high degree of risk related to the use of AAS.

Topics: Adrenal Glands; Anabolic Agents; Androgens; Androstanols; Animals; Behavior, Animal; Dihydrotestosterone; Estradiol; Male; Methenolone; Myocardium; Nandrolone; Nandrolone Decanoate; Rats; Rats, Wistar; Testis; Testosterone

A 54-year-old female, who had been treated for aplastic anemia by metenolone acetate since 1981, developed a sudden unconsciousness in September 1995. On admission, she was drowny, CT showed a subarachnoid hemorrhage (SAH) in the right Sylvian fissure. Angiography demonstrated a complete occlusion of the superior sagittal sinus. The SAH was assumed to be originated from rupture of the right Sylvian vein, which was irregularly dilated on angiography. The dural sinus thrombosis was thought to be caused by a long term use of metenolone acetate, and it was discontinued. But her platelet count dropped due to the aggravation of aplastic anemia, and she developed repeated hemorrhagic infarction. An active anticoagulant therapy for the dural sinus thrombosis was thought to be inappropriate because she had the aplastic anemia and the hemorrhagic infarction recurred. We have successfully treated this case by mild anticoagulant therapy with nafamostat mesilate (Futhan).

Topics: Anemia, Aplastic; Anticoagulants; Benzamidines; Female; Guanidines; Humans; Magnetic Resonance Imaging; Methenolone; Middle Aged; Sinus Thrombosis, Intracranial; Subarachnoid Hemorrhage; Tomography, X-Ray Computed

A 63-year-old woman was found to have thrombocythemia and was referred to our hospital for further evaluation in September 1990. Peripheral blood showed platelet 170.0 x 10(4)/microliter, WBC 14,900/microliter and Hb 9.8 g/dl. Bone marrow was hypercellular with increased megakaryocytes and normal karyotype. She was diagnosed as essential thrombocythemia (ET), and treated with 2 mg of busulfan daily for 3 months until her platelet count decreased to 33.1 x 10(4)/microliter. Busulfan was given again for 40 days (a total of 80 mg) in another hospital when the platelet count increased to 71.1 x 10(4)/microliter in September 1991. In December 1991, she was admitted to our hospital because of pancytopenia. Examination of blood revealed platelet 0.4 x 10(4)/microliter, WBC 1,800/microliter and Hb 7.0 g/dl with hypocellular marrow. A diagnosis of busulfan-induced severe bone marrow aplasia was made. We administered metenolone acetate 15 mg and G-CSF 300 micrograms daily. Blood transfusions were given frequently. However, no effect was observed during her hospitalization. After discharge, G-CSF 600 micrograms and erythropoietin 24,000 units were continued twice a week in combination with metanolone acetate. Pancytopenia gradually began to improve as of June 1992, and then trilineage recovery was achieved in March 1994 with platelet 13.3 x 10(4)/microliter, WBC 5,500/microliter and Hb 12.1 g/dl. The platelet count has been within the normal range for more than 2 years after recovery.

Topics: Anemia, Aplastic; Busulfan; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Methenolone; Middle Aged; Remission Induction; Thrombocythemia, Essential

Topics: Aged; Anabolic Agents; Anemia, Aplastic; Fatal Outcome; Female; Humans; Liver; Methenolone; Peliosis Hepatis

Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.

Topics: Animals; Cardiomyoplasty; Female; Immunohistochemistry; Methenolone; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Myosin Heavy Chains; Sheep; Stimulation, Chemical

Initial treatment with androgen (metenolone acetate) alone for 19 weeks had no effect in a 45-year-old Japanese female with refractory anemia (RA). The patient achieved trilineage hematologic recovery after addition of recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (Epo) to the androgen therapy. Anemia progressed after the cessation of metanolone acetate, but was effectively treated by the readministration of metenolone acetate. Thus, the androgen therapy in combination with hematopoietic growth factors such as G-CSF and/or Epo may be effective in patients with RA.

Topics: Anemia, Refractory; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Methenolone; Middle Aged; Recombinant Proteins

Topics: Anemia, Aplastic; Cholestasis; Humans; Male; Methenolone; Middle Aged; Remission Induction

Anabolic-androgenic steroids are widely misused in human sports and are also used as growth promoters in livestock. Athletes who consume meat containing such hormone residues may risk failing a sports drug test. Prompted by an athlete's defense case, we questioned whether the consumption of small livestock given doses of anabolic steroid, orally or intramuscularly, could generate positive results in samples tested by our analytical procedures. We analyzed urine from eight men who consumed chickens that had been either fed with methenolone acetate (1 mg/day) from day 0 to 21 or injected with methenolone heptanoate depot (1 mg/intramuscular injection) on days 0, 7, and 14 and slaughtered on day 22. No methenolone or characteristic major metabolite was detected in samples from subjects who ate meat from the orally dosed chickens. However, 50% of the samples collected 24 h after consumption of the intramuscularly dosed chickens were confirmed positive. Hence, eating meat containing small amounts of injected hormone may constitute a serious liability to the athlete.

Topics: Administration, Oral; Adult; Anabolic Agents; Animals; Chickens; Delayed-Action Preparations; Doping in Sports; False Positive Reactions; Humans; Injections, Intramuscular; Male; Meat; Methenolone; Middle Aged

A 75-year-old man suffering from severe aplastic anemia was treated first with cyclosporin A, then with steroid pulse therapy, and subsequently with metenolone acetate. Marked elevation of transaminases was detected following initiation of treatment with metenolone acetate. This was followed by hepatic failure and death. Histopathological findings in autopsy specimens were compatible with the diagnosis of drug-induced liver impairment, for which metenolone acetate was considered the most likely causative agent. Liver impairment as a side effect of the use of this drug has been thought to be mild, reversible and rather infrequent. However, as demonstrated in the case described here, it is apparent that extreme caution should be exercised when using this drug in debilitated patients.

Topics: Aged; Anemia, Aplastic; Hepatic Encephalopathy; Humans; Male; Methenolone

The influence of metenolone acetate (1 mg/kg b.m. orally) on intact and chronically thioacetamide-injured rat liver (experimental liver cirrhosis) was investigated over 14 d. Histological examination revealed nodular transformation of liver structure according to cirrhosis like lesions with hepatocellular and cholangiocellular proliferations. These structural alterations were more serious in the group treated with metenolone compared with the group without metenolone. Metanolone administration to animals with thioacetamide-induced experimental liver cirrhosis led to an increase in liver injury. This treatment seems to promote hepatic preneoplastic lesions induced by thioacetamide reflected by histology and induction of gamma-glutamyltranspeptidase and 7-ethoxycoumarin O-deethylase in injured livers. Metenolone did not interfere directly with the processes of connective tissue synthesis and degradation after thioacetamide pretreatment. Only little changes of the investigated biochemical parameters were seen after metenolone administration to animals with intact liver function: increases in serum cholinesterase and tissue N-acetyl-beta-D-glucosaminidase activity; decreases in N-acetyl-beta-D-glucosaminidase in serum, liver hydroxyproline content and hepatic gamma-glutamyltranspeptidase activity. The observed changes reflect hepatic adaption processes under the influence of metenolone. The results of this study indicate that the risk of anabolic steroids in adjuvant therapy of liver cirrhosis cannot be calculated at present.

Topics: 7-Alkoxycoumarin O-Dealkylase; Animals; Biotransformation; Connective Tissue; Female; gamma-Glutamyltransferase; Glutathione; Liver; Liver Cirrhosis, Experimental; Methenolone; Rats; Thioacetamide

We retrospectively evaluated the efficacy of androgen in the treatment of refractory anemia (RA) and compared patient characteristics and the probability of survival in androgen-responder and nonresponder groups. Forty patients with RA were treated in our hospital between 1975-1989, and 27 were treated with various derivatives of androgen. Eleven of the latter responded effectively to androgen therapy, representing an efficacy rate of 40.7%, higher than that of any other treatments thus far reported. The probability of 10-year survival estimated by the Kaplan-Meier method was 75.0% for the responder group and 41.3% for nonresponders, with a median follow-up of 1202 and 1272 days, respectively. In addition, the percent probability of transformation-free survival was higher among androgen-responders than among nonresponders, though the difference was not significant. Transformation from RA to RAEB or overt leukemia was seen in only one case among the former group, but in six among the latter. With respect to patient characteristics, only the percentage of marrow myeloblasts differed significantly between the groups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Androstanols; Anemia, Refractory; Danazol; Drug Evaluation; Fluoxymesterone; Follow-Up Studies; Humans; Life Tables; Methenolone; Middle Aged; Retrospective Studies

The metabolism of methenolone acetate (17 beta-acetoxy-1-methyl-5 alpha-androst-1-en-3-one), a synthetic anabolic steroid, has been investigated in man. After oral administration of a 50 mg dose of the steroid to two male volunteers, twelve metabolites were detected in urine either in the glucuronide, sulfate or free steroid fractions. Methenolone, the parent steroid was detected in urine until 90 h after administration. Its cumulative urinary excretion accounted for 1.63% of the ingested dose. With the exception of 3 alpha-hydroxy-1-methylen-5 alpha-androstan-17-one, the major biotransformation product of methonolone acetate, metabolites were excreted in urine at lower levels, through minor metabolic routes. Most of methenolone acetate metabolites were isolated from the glucuronic acid fraction, namely methenolone, 3 alpha-hydroxy-1-methylen-5 alpha-androstan-17-one, 3 alpha-hydroxy-1 alpha-methyl-5 alpha-androstan-17-one, 17-epimethenolone, 3 alpha,6 beta-dihydroxy-1-methylen-5 alpha-androstan-17-one, 2 xi-hydroxy-1-methylen-5 alpha-androstan-3,17-dione, 6 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3,17-dione, 16 alpha-hydroxy-1-methyl-5 alpha-androst-1-en-3,17-dione and 3 alpha,16 alpha-dihydroxy-1-methyl-5 alpha-androst-1-en-17-one. Interestingly, the metabolites detected in the sulfate fraction were isomeric steroids bearing a 16 alpha- or a 16 beta-hydroxyl group, whereas 1-methyl-5 alpha-androst-1-en-3,17-dione was the sole metabolite isolated from the free steroid fraction. Steroids identity was assigned on the basis of the mass spectral features of their TMS ether, TMS enol-TMS ether, MO-TMS, and d9-TMS ether derivatives and by comparison with reference and structurally related steroids. The data indicated that methenolone acetate was metabolized into several compounds resulting from oxidation of the 17-hydroxyl group and reduction of A-ring substituents, with or without concomitant hydroxylation at the C6 and C16 positions.

Topics: Anabolic Agents; Chromatography, Gas; Humans; Hydroxylation; Male; Mass Spectrometry; Methenolone; Trimethylsilyl Compounds

A highly accurate method has been developed for detection and quantitation of 3 alpha-hydroxy-1-methylen-5 alpha-androstan-17-one, the major urinary metabolite of methenolone acetate (Primobolan) in man. Unlabelled as well as 2H-labelled 3 alpha-hydroxy-1-methylen-5 alpha-androstan-17-one were synthesized from 1-methylen-5 alpha-androstane-3,17-dione. A fixed amount of the internal standard was added to a fixed amount of urine and the mixture was treated with Helix pomatia for 24 h. After extraction and purification by t.l.c., the mixture was converted into methoxime--trimethylsilyl derivative and analyzed by combined GC--MS. Unlabelled 3 alpha-hydroxy-1-methylen-5 alpha-androstan-17-one could be quantitated from the ratio between the tracings of the ions at m/z 372 and m/z 375 (corresponding to the M-31 ions). In alternative procedures, the ions at m/z 403 and m/z 406 (molecular ions) as well as m/z 282 and m/z 285 (M-90-31 ions) could be used. Under the conditions employed, the metabolite could be identified and quantitated in concentrations exceeding 10 ng/ml. Significant amounts of the metabolite could be detected in urine during 5 days after a single oral ingestion of 10 mg of Primobolan. The method has been successfully used for analyses of urine samples obtained from athletes involved in competition.

Topics: Deuterium; Gas Chromatography-Mass Spectrometry; Humans; Kinetics; Methenolone; Radioisotope Dilution Technique

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Female; Follow-Up Studies; Humans; Male; Methenolone; Middle Aged; Preleukemia; Retrospective Studies; Syndrome

The medical records of 66 women treated with metenolone for metastasized breast carcinomas were analysed. In 26 patients a remission developed with a mean duration of 8.2 (3-29) months. Patients whose treatment started in the first year after the menopause as well as patients with a beneficial effect of a therapeutic ovariectomy in the past were more often improved by metenolone than average. Metenolone had a better effect against osseous metastases than against visceral metastases. In most cases the treatment was well tolerated. In four patients, however, the treatment had to be interrupted because of cholestasis, pulmonary embolism and hypercalcaemia.

Topics: Adult; Aged; Anabolic Agents; Breast Neoplasms; Castration; Female; Humans; Mastectomy; Menopause; Methenolone; Middle Aged

Topics: Adolescent; Anabolic Agents; Biomedical Research; Body Weight; Child; Drug Therapy; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Methenolone; Steroids; Testosterone Congeners; Thinness

Topics: Anabolic Agents; Blood Chemical Analysis; Blood Sedimentation; Humans; Kidney Diseases; Methenolone; Nephritis; Nephrosis; Steroids

Topics: Anabolic Agents; Calcium; Methenolone; Osteoporosis; Pharmacology; Rats; Research; Spine; Steroids; Testosterone

Topics: Anatomy; Hepatitis; Hepatitis A; Humans; Liver Cirrhosis; Liver Diseases; Methenolone; Steroids

Topics: Acetates; Adenosine Triphosphate; Anabolic Agents; Animals; Body Weight; Glycogen; Kidney; Metabolism; Methenolone; Mice; Muscles; Proteins; Research; Steroids; Testosterone Congeners

Topics: Androgens; Biomedical Research; Methenolone

Topics: Acetates; Androgens; Animals; Body Weight; Enzymes; Growth; Heptanoates; Methenolone; Testosterone