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Annals of Internal Medicine Dec 1978Androgens are effective therapeutic agents in postmenopausal women with metastatic breast cancer. Early studies with testosterone propionate showed objective regression... (Review)
Review
Androgens are effective therapeutic agents in postmenopausal women with metastatic breast cancer. Early studies with testosterone propionate showed objective regression rates of slightly more than 20%. Subsequent work with synthetic androgens has failed to show a significant reduction in toxicity or an increase in therapeutic efficacy over testosterone propionate. Calusterone (7 beta,17 alpha-dimethyltestosterone), in early clinical trials, showed both of these qualities and was believed by some to be the "ideal androgen." As with many new drugs, subsequent work failed to confirm these early findings, and most of the later data gathered on calusterone are inconsistent. We conclude from our knowledge at present that calusterone offers no real advantages or disadvantages over other androgens in the treatment of breast cancer.
Topics: Breast Neoplasms; Chemical Phenomena; Chemistry; Female; Humans; Methyltestosterone; Neoplasm Metastasis
PubMed: 152592
DOI: 10.7326/0003-4819-89-6-945 -
Canadian Journal of Ophthalmology.... Dec 1985A 59-year-old man presented with a 3-month history of night blindness and a 9-month history of steatorrhea. Both symptoms had appeared after he had begun taking...
A 59-year-old man presented with a 3-month history of night blindness and a 9-month history of steatorrhea. Both symptoms had appeared after he had begun taking methyltestosterone. Investigations revealed low serum levels of carotene (0.1 mmol/L) and vitamin A (0.4 to 0.7 mmol/L), anomalous colour perception, elevation of the rod threshold by 3.5 log units in dark adaptometry, and decreased b-wave amplitudes in photopic and scotopic electroretinograms. No biochemical evidence of cholestasis was elicited. The symptoms and the biochemical and electrophysiologic abnormalities resolved within 9 months of the discontinuation of methyltestosterone.
Topics: Color Perception; Electroretinography; Erectile Dysfunction; Humans; Male; Methyltestosterone; Middle Aged; Night Blindness; Vitamin A Deficiency
PubMed: 3879195
DOI: No ID Found -
Methyltestosterone pharmacokinetics and oral bioavailability in rainbow trout (Oncorhynchus mykiss).Aquatic Toxicology (Amsterdam,... May 200114C-methyltestosterone pharmacokinetics after intraarterial (2 and 20 mg/kg) and oral (30 mg/kg) administration were investigated in rainbow trout at 15 degrees C....
14C-methyltestosterone pharmacokinetics after intraarterial (2 and 20 mg/kg) and oral (30 mg/kg) administration were investigated in rainbow trout at 15 degrees C. Plasma concentrations of methyltestosterone were determined by reverse phase high performance liquid chromatography (HPLC) in combination with reverse isotope dilution for up to 6 and 12 days after oral and intraarterial administration, respectively. Methyltestosterone pharmacokinetic parameter values after intraarterial administration were determined using a two compartment model (WinNonlin). For the 2 and 20 mg/kg doses, respectively, the parameter values were, area under the plasma concentration-time curve (11.2 and 82.3 micromol h/l), total body clearance (0.640 and 0.903 l/h per kg), distribution half-life (4.13 and 8.23 h), elimination half-life (54.9 and 58.6 h), volume of the central compartment (3.83 and 13.9 l/kg), volume of distribution at steady state (6.06 and 26.8 l/kg), and the mean residence time (9.57 and 22.7 h). After oral administration, the following parameter values were assessed using a model-independent method, peak concentration (3.03 micromol/l), time of concentration peak (8.80 h), mean absorption time (13.8 h), and area under curve (AUC)(0-->infinity) (90.2 micromol h/l). A two compartment model analysis of the average plasma concentration-time profile after oral administration showed that absorption followed first-order kinetics with a half-life of 4.7 h. The oral bioavailability of methyltestosterone from food was about 70%.
Topics: Administration, Oral; Animals; Biological Availability; Infusions, Intra-Arterial; Methyltestosterone; Oncorhynchus mykiss; Random Allocation
PubMed: 11239680
DOI: 10.1016/s0166-445x(00)00146-6 -
American Journal of Obstetrics and... Mar 1998
Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; Drug Combinations; Estrogen Replacement Therapy; Female; Humans; Methyltestosterone; Middle Aged; Tablets
PubMed: 9539547
DOI: 10.1016/s0002-9378(98)70463-6 -
Chemical Senses Jan 2010In the tinfoil barb (Barbonymus schwanenfeldii; family Cyprinidae), we previously found that increased olfactory sensitivity to a female prostaglandin pheromone could...
In the tinfoil barb (Barbonymus schwanenfeldii; family Cyprinidae), we previously found that increased olfactory sensitivity to a female prostaglandin pheromone could induce sexual behavior display in juvenile fish treated with androgens. Here, we determined if this phenomenon is widespread among cyprinid fishes by adding 17alpha-methyltestosterone (MT) to aquaria containing juveniles of 4 cyprinid species (tinfoil barbs; redtail sharkminnows, Epalzeorhynchos bicolor; goldfish, Carassius auratus; zebrafish, Danio rerio) and then using electro-olfactogram (EOG) recordings and behavioral assays to determine if androgen treatment enhances pheromone detection and male sex behaviors. In all 4 cyprinids, MT treatment increased the magnitudes and sensitivities of EOG response to prostaglandins and, consistent with our initial study on tinfoil barbs, did not affect EOG responses to the free and conjugated steroid to which each species is most sensitive. In zebrafish, EOG responses to prostaglandins were similar in MT-treated juveniles and adult males, whereas responses of control (ethanol exposed) fish were similar to those of adult females. Finally, as previously observed in tinfoil barbs, MT treatment of juvenile redtail sharkminnows increased courtship behaviors (nuzzling and quivering) with a stimulus fish. We conclude that androgen-induced increase in olfactory responsiveness to pheromonal prostaglandins is common among the family Cyprinidae. This phenomenon will help us unravel the development of sexually dimorphic olfactory-mediated behavior.
Topics: Animals; Cyprinidae; Electrophysiological Phenomena; Female; Goldfish; Male; Methyltestosterone; Prostaglandins; Sexual Behavior, Animal; Smell; Zebrafish
PubMed: 19965901
DOI: 10.1093/chemse/bjp085 -
Rapid Communications in Mass... Oct 2020Although the metabolism of methyltestosterone (MT) has been extensively studied since the 1950s using different techniques, the aim of this study was to investigate the...
RATIONALE
Although the metabolism of methyltestosterone (MT) has been extensively studied since the 1950s using different techniques, the aim of this study was to investigate the hydroxylation in positions C2, C4 and C6 after in vitro experiments and in vivo excretion studies using gas chromatography time-of-flight (GC/TOF) and gas chromatography/tandem mass spectrometry (GC/MS/MS). The results could be influenced by the mass spectrometric analyser used.
METHODS
Incubations were carried out with human liver microsomes and six enzymes belonging to the cytochrome P450 family using MT as a substrate. The trimethylsilyl derivatives of the samples were analysed using GC/TOF and GC/MS/MS once the correct MS/MS transitions had been selected, mainly for 6-hydroxymethyltestosterone (6-OH-MT) to avoid artefact interferences. A urinary excretion study was then performed after the administration of a 10 mg single oral dose of MT to a volunteer.
RESULTS
The formation of hydroxylated metabolites of MT in the C6, C4 and C2 positions after both in vitro and in vivo experiments was observed. Sample evaluation using GC/TOF showed an interference for 6-OH-MT that could only be resolved in GC/MS/MS by monitoring specific transitions. The transitory detection of these hydroxylated metabolites in urine agrees with previous investigations that had described this metabolic route as being of little significance.
CONCLUSIONS
In doping analysis, the formation of 4-hydroxymethyltestosterone (oxymesterone) from MT cannot be underestimated. Although it is only detected as a minor and short-term excretion metabolite, it cannot be overlooked as it was found in both in vitro and in vivo experiments. The use of a combination of different mass spectrometric instruments allowed reliable conclusions to be reached, and it was shown that special attention must be given to artefact formation.
Topics: Cytochrome P-450 Enzyme System; Gas Chromatography-Mass Spectrometry; Humans; Hydroxylation; Male; Methyltestosterone; Microsomes, Liver; Middle Aged
PubMed: 32570291
DOI: 10.1002/rcm.8870 -
Molecules (Basel, Switzerland) Mar 2021Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected...
Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. Following the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone ("oral turinabol"), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including the synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights into the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations to the D-ring.
Topics: Anabolic Agents; Gas Chromatography-Mass Spectrometry; Healthy Volunteers; Humans; Methandrostenolone; Methyltestosterone; Middle Aged; Reference Standards; Tandem Mass Spectrometry
PubMed: 33802606
DOI: 10.3390/molecules26051354 -
Journal of Environmental Science and... 2020The 17 alpha methyltestosterone (MT) hormone is fed to larvae in fish farms with the purpose of inducing sex reversal. The aim of this study was to evaluate the...
The 17 alpha methyltestosterone (MT) hormone is fed to larvae in fish farms with the purpose of inducing sex reversal. The aim of this study was to evaluate the toxicity and sub-lethality of MT (99.9% purity) and cMT (a commercial MT with 90% purity) in zebrafish () adults, where the animals were exposed to concentrations of 0, 4, 23, 139, 833 and 5000 µg/L for 96 hours. Genotoxicity was evaluated by micronucleus test (MN), nuclear abnormalities (NA) and comet assay. A low genotoxic potential of MT was showed, inducing micronucleus, nuclear abnormalities and DNA damage in , depending on the use of MT or cMT, gender and tested concentrations. In the sub-lethality trials, there was a basal difference in the activity of the enzymatic biochemical markers for males and females, while the Glutatione S transferase (GST) activity decreased in all analyzed tissues, and for males the enzymatic activity decreased only in the intestine. Results suggest that MT has a toxic potential to fish because it alters enzymatic metabolic pathways and may pose a risk to the ecosystems.
Topics: Androgens; Animals; Cichlids; Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Ecosystem; Female; Fisheries; Larva; Male; Methyltestosterone; Micronuclei, Chromosome-Defective; Water Pollutants, Chemical; Zebrafish
PubMed: 32654587
DOI: 10.1080/10934529.2020.1790954 -
Sensors (Basel, Switzerland) Apr 2015An indirect competitive enzyme-linked immunosorbent assay (icELISA) and an immunochromatographic strip assay using a highly specific monoclonal antibody, were developed...
An indirect competitive enzyme-linked immunosorbent assay (icELISA) and an immunochromatographic strip assay using a highly specific monoclonal antibody, were developed to detect methyltestosterone (MT) residues in animal feed. The optimized icELISA had a half-inhibition concentration value of 0.26 ng/mL and a limit of detection value of 0.045 ng/mL. There was no cross-reactivity with eight analogues, revealing high specificity for MT. Based on icELISA results, the recovery rate of MT in animal feed was 82.4%-100.6%. The results were in accordance with those obtained by gas chromatography-mass spectrometry. The developed immunochromatographic strip assay, as the first report for MT detection, had a visual cut-off value of 1 ng/mL in PBS, 2.5 ng/g in fish feed, and 2.5 ng/g in pig feed. Therefore, these immunoassays are useful and fast tools for MT residue detection in animal feed.
Topics: Animal Feed; Enzyme-Linked Immunosorbent Assay; Gas Chromatography-Mass Spectrometry; Immunoassay; Methyltestosterone; Reproducibility of Results
PubMed: 25938198
DOI: 10.3390/s150510059 -
JAMA Jan 1972
Topics: Breast Neoplasms; Humans; Methyltestosterone
PubMed: 5066647
DOI: No ID Found