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Fertility and Sterility Jan 2011This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and efficacy of low-dose esterified estrogens and methyltestosterone, alone or combined, for the treatment of hot flashes in menopausal women: a randomized, double-blind, placebo-controlled study.
This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.30-mg methyltestosterone combination was the lowest effective dose, and our results are consistent with the known safety profile of estrogen and androgen combination products.
Topics: Anabolic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Estrogen Replacement Therapy; Estrogens; Estrogens, Esterified (USP); Female; Hot Flashes; Humans; Menopause; Methyltestosterone; Placebos; Severity of Illness Index; Treatment Outcome
PubMed: 20850731
DOI: 10.1016/j.fertnstert.2010.08.005 -
Fertility and Sterility Jun 2003In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire.
OBJECTIVE
In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire.
DESIGN
Double-blind randomized trial.
SETTING
Healthy volunteers in a multicenter research environment.
PATIENT(S)
Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire.
INTERVENTION(S)
4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107).
MAIN OUTCOME MEASURES
Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire.
RESULT(S)
Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated.
CONCLUSION(S)
Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.
Topics: Administration, Oral; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Estrogens; Female; Humans; Methyltestosterone; Middle Aged; Sexual Behavior; Testosterone
PubMed: 12798881
DOI: 10.1016/s0015-0282(03)00358-3 -
Nephron 1991
Topics: Cyclosporine; Drug Interactions; Humans; Kidney; Kidney Transplantation; Liver; Male; Methyltestosterone; Middle Aged
PubMed: 1944742
DOI: 10.1159/000186548 -
Frontiers in Cellular Neuroscience 2013Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle...
Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.
PubMed: 23675320
DOI: 10.3389/fncel.2013.00069 -
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 -
Fertility and Sterility Aug 1985The enigmatic disease of endometriosis continues to baffle both the scientist and the clinician. An encompassing theory of pathogenesis has failed to emerge from... (Comparative Study)
Comparative Study Review
The enigmatic disease of endometriosis continues to baffle both the scientist and the clinician. An encompassing theory of pathogenesis has failed to emerge from contemporary understanding of the immunologic manifestations, the hormonal aberrations, or the evasive infertility associated with endometriosis. Similarly unsettling is the failure of medical or conservative surgical maneuvers to eradicate endometriosis in a manner commensurate with castration. It is hoped that further insight into these areas of research will resolve both of these dilemmas.
Topics: Autoimmune Diseases; Danazol; Endometriosis; Female; Humans; Infertility, Female; Luteal Phase; Menstruation Disturbances; Methyltestosterone; Pregnancy; Progestins; Prolactin; Prostaglandins; Salpingitis
PubMed: 3894056
DOI: 10.1016/s0015-0282(16)48729-7 -
Ecotoxicology and Environmental Safety Jan 2023Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the...
Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory testing to evaluate endocrine disruption is time-consuming, costly, and animal-intensive. Here, we combined sublethal zebrafish embryo assays with transcriptomics and proteomics for well-characterized endocrine disrupting reference compounds to identify predictive biomarkers for sexual endocrine disruption in this model. Using RNA and protein gene expression fingerprints from two different sublethal exposure concentrations, we identified specific signatures and impaired biological processes induced by ethinylestradiol, tamoxifen, methyltestosterone and flutamide 96 h post fertilization (hpf). Our study promotes vtg1 as well as cyp19a1b, fam20cl, lhb, lpin1, nr1d1, fbp1b, and agxtb as promising biomarker candidates for identifying and differentiating estrogen and androgen receptor agonism and antagonism. Evaluation of these biomarkers for pre-regulatory zebrafish embryo-based bioassays will help identify endocrine disrupting hazards of compounds at the molecular level. Such approaches additionally provide weight-of-evidence for the identification of putative EDs and may contribute significantly to a reduction in animal testing in higher tier studies.
Topics: Animals; Biomarkers; Embryo, Nonmammalian; Endocrine Disruptors; Endocrine System; Estrogens; Gene Expression; Phosphatidate Phosphatase; Water Pollutants, Chemical; Zebrafish
PubMed: 36608563
DOI: 10.1016/j.ecoenv.2023.114514 -
International Journal of Molecular... Feb 202317α-Methyltestosterone (17MT), a synthetic organic compound commonly found in sewage waters, can affect reproduction in aquatic animals, such as tilapia and yellow...
17α-Methyltestosterone (17MT), a synthetic organic compound commonly found in sewage waters, can affect reproduction in aquatic animals, such as tilapia and yellow catfish. In the present study, male were exposed to 25, 50, and 100 ng/L of 17α-methyltestosterone (17MT) for 7 days. We first analyzed miRNA- and RNA-seq results to determine miRNA-target gene pairs and then developed miRNA-mRNA interactive networks after 17MT administration. Total weights, total lengths, and body lengths were not significantly different between the test groups and control groups. The paraffin slice method was applied to testes of in the MT exposure and control groups. We found that there were more mature sperm (S) and fewer secondary spermatocytes (SSs) and spermatogonia (SGs) in the testes of control groups. As 17MT concentration increased, fewer and fewer mature sperm (S) were observed in the testes of male . The results showed that FSH, 11-KT, and E2 were significantly higher in individuals exposed to 25 ng/L 17MT compared with the control groups. VTG, FSH, LH, 11-KT, and E2 were significantly lower in the 50 ng/L 17MT exposure groups compared to the control groups. VTG, FSH, LH, 11-KT, E2, and T were significantly lower in the groups exposed to 100 ng/L 17MT. High-throughput sequencing revealed 73,449 unigenes, 1205 known mature miRNAs, and 939 novel miRNAs in the gonads of . With miRNA-seq, 49 (MT25-M vs. Con-M), 66 (MT50-M vs. Con-M), and 49 (MT100-M vs. Con-M) DEMs were identified in the treatment groups. Five mature miRNAs (miR-122-x, miR-574-x, miR-430-y, lin-4-x, and miR-7-y), as well as seven differentially expressed genes (, , , , , , and ), which may be associated with testicular development, metabolism, apoptosis, and disease response, were assayed using qRT-PCR. Furthermore, miR-122-x (related to lipid metabolism), miR-430-y (embryonic development), lin-4-x (apoptosis), and miR-7-y (disease) were differentially expressed in the testes of 17MT-exposed This study highlights the role of miRNA-mRNA pairs in the regulation of testicular development and immune response to disease and will facilitate future studies on the miRNA-RNA-associated regulation of teleost reproduction.
Topics: Animals; Male; Testis; Methyltestosterone; MicroRNAs; RNA, Messenger; Cyprinidae; Semen; Cypriniformes; Follicle Stimulating Hormone
PubMed: 36835651
DOI: 10.3390/ijms24044239 -
General and Comparative Endocrinology May 2023The division of the brain manifests in lateralized physical behaviors, where specific tasks originate from one side of the body. Previous studies have shown that birds...
The division of the brain manifests in lateralized physical behaviors, where specific tasks originate from one side of the body. Previous studies have shown that birds and reptiles mediate aggression in their right hemisphere and focus on opponents with their left eye. Degree of lateralization varies between sexes, likely due to androgen inhibition of lateralization in mammals, birds, and fish, but remains untested in herpetofauna. In this experiment, we investigated the effect of androgen exposure on cerebral lateralization in the American Alligator, Alligator mississippiensis. Alligator eggs were collected and incubated at female producing temperature with a subset dosed with methyltestosterone in ovo. Dosed hatchlings were randomly paired with control individuals and their interactions were recorded. The number of bites initiated by focus from each eye and the number of times an animal was bitten on each side of the body was recorded for each individual to elucidate cerebral lateralization in aggression. Control alligators had a significant bias towards left-eye bite initiation whereas androgen exposed alligators used both eyes indiscriminately. No significance was found in injury patterns. This study suggests that androgen exposure inhibits cerebral lateralization in alligator brains and corroborates right-hemisphere mediation of aggression, something previously unstudied in crocodilians.
Topics: Animals; Female; Alligators and Crocodiles; Androgens; Eggs; Mammals; Methyltestosterone; Temperature
PubMed: 36848983
DOI: 10.1016/j.ygcen.2023.114248 -
Biology of Reproduction May 2020Genital tubercle has bisexual potential before sex differentiation. Females exposed to androgen during sex differentiation show masculinized external genitalia, but the...
Genital tubercle has bisexual potential before sex differentiation. Females exposed to androgen during sex differentiation show masculinized external genitalia, but the effects of different androgens on tubular urethral and penile formation in females are mostly unknown. In this study, we compared the masculinization effects of commonly used androgens methyltestosterone, dihydrotestosterone, and testosterone on the induction of penile formation in females. Our results suggested that prenatal treatment with low doses of methyltestosterone, but not same doses of dihydrotestosterone or testosterone, could induce penile formation in female mice. The minimum dose of dihydrotestosterone and testosterone for inducing tubular urethral formation in female mice was, respectively, 50 and 20 times higher than that of methyltestosterone. In vivo methyltestosterone treatment induced more nuclear translocation of androgen receptors in genital tubercles of female mice, affected Wnt signaling gene expressions, and then led to similar patterns of cell proliferation and death in developing genital tubercles to those of control males. We further revealed that low-dose methyltestosterone, but not same dose of dihydrotestosterone or testosterone, treatment induced penile formation in female guinea pigs. Exposure of female mouse genital tubercle organ culture to methyltestosterone, dihydrotestosterone, or testosterone could induce nuclear translocation of androgen receptors, suggesting that the differential effect of the three androgens in vivo might be due to the hormonal profile in mother or fetus, rather than the local genital tissue. To understand the differential role of these androgens in masculinization process involved is fundamental to androgen replacement therapy for diseases related to external genital masculinization.
Topics: Active Transport, Cell Nucleus; Androgen Antagonists; Animals; Animals, Newborn; Cell Death; Cell Proliferation; Dihydrotestosterone; Drug Therapy, Combination; Female; Flutamide; Genitalia, Female; Guinea Pigs; Male; Methyltestosterone; Mice; Penis; Pregnancy; Receptors, Androgen; Sex Determination Analysis; Testosterone
PubMed: 32219310
DOI: 10.1093/biolre/ioaa035