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1.
Eur J Endocrinol ; 184(5): K11-K14, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33667194

RESUMO

Objective: The role of miRNA as endocrine regulators is emerging, and microRNA mir-30b has been reported to repress Mkrn3. However, the expression of miR-30b during male puberty has not been studied. Design and methods: Circulating relative miR-30b expression was assessed in sera of 26 boys with constitutional delay of growth and puberty (CDGP), treated with low-dose testosterone (T) (n =11) or aromatase inhibitor letrozole (Lz) (n =15) for 6 months and followed up to 12 months (NCT01797718). The associations between the relative expression of miR-30b and hormonal markers of puberty were evaluated. Results: During the 12 months of the study, circulating miR-30b expression increased 2.4 ± 2.5 (s.d.) fold (P = 0.008) in all boys, but this change did not correlate with corresponding changes in LH, testosterone, inhibin B, FSH, or testicular volume (P = 0.25-0.96). Lz-induced activation of the hypothalamic-pituitary-gonadal (HPG) axis was associated with more variable miR-30b responses at 3 months (P < 0.05), whereas those treated with T exhibited significant changes in relative miR-30b levels in the course the study (P < 0.01-0.05). Conclusions: Circulating miR-30b expression in boys with CDGP increases in the course of puberty, and appears to be related to the activity of the HPG axis.


Assuntos
MicroRNAs/sangue , Puberdade/sangue , Adolescente , Quimioterapia Combinada , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Gônadas/fisiologia , Transtornos do Crescimento/sangue , Transtornos do Crescimento/complicações , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Injeções Intramusculares , Letrozol/administração & dosagem , Letrozol/farmacologia , Estudos Longitudinais , Masculino , Puberdade/efeitos dos fármacos , Puberdade/genética , Puberdade Tardia/sangue , Puberdade Tardia/complicações , Puberdade Tardia/tratamento farmacológico , Testosterona/administração & dosagem , Testosterona/farmacologia , Ubiquitina-Proteína Ligases/genética
2.
Support Care Cancer ; 29(1): 387-396, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32372176

RESUMO

PURPOSE: To evaluate the efficacy of testosterone supplementation for improving aromatase inhibitor musculoskeletal symptoms (AIMSS). METHODS: Postmenopausal women experiencing moderate-to-severe arthralgias while taking adjuvant aromatase inhibitors for breast cancer were enrolled in this trial. Initially, patients were randomly allocated to receive either a subcutaneous testosterone pellet versus a placebo pellet. Due to slow accrual, the protocol was modified such that additional participants were randomized to receive either a topical testosterone gel or a placebo gel. Changes in patient-reported joint pain were compared between patients receiving testosterone and those receiving placebo using a two-sample t test. Changes in hot flashes and other vasomotor symptoms were also analyzed. Further analyses were conducted to evaluate whether 27 single nucleotide polymorphisms (SNPs) in 14 genes previously associated with AIMSS were associated with testosterone supplementation benefit. RESULTS: While 64% of patients reported an improvement in joint pain at 3 months, there were no significant differences in average pain or joint stiffness at 3 or 6 months between testosterone and placebo arms. Patients receiving testosterone did report improvements in strength, lack of energy, urinary frequency, and stress incontinence (p < 0.05). The subset of patients receiving subcutaneous testosterone also experienced improvements in hot flashes and mood swings. An inherited variant (rs7984870 CC genotype) in TNFSF11 was more likely to be associated with improvements in hot flashes in patients receiving testosterone. CONCLUSION: The doses of testosterone supplementation used in this study did not significantly improve AIMSS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01573442.


Assuntos
Inibidores da Aromatase/efeitos adversos , Artralgia/tratamento farmacológico , Fogachos/tratamento farmacológico , Dor Musculoesquelética/tratamento farmacológico , Testosterona/uso terapêutico , Administração Tópica , Artralgia/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Dor Musculoesquelética/induzido quimicamente , Polimorfismo de Nucleotídeo Único/genética , Pós-Menopausa , Qualidade de Vida/psicologia , Ligante RANK/genética , Testosterona/administração & dosagem , Resultado do Tratamento
3.
Eur J Endocrinol ; 184(1): 67-79, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33112266

RESUMO

Background: Pharmacological doses of glucocorticoids (GC) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD). Delayed puberty and bone fragility are consequences of GC treatment. The aim of this study was to determine the acceptability of a 2-year pubertal induction regimen using 4-weekly testosterone injections and examine changes in physique, bone integrity, muscle pathology (assessed by MRI) and muscle function. Methods: Fifteen prepubertal males with DMD, aged 12-17 years and receiving GC, were treated with an incremental testosterone regimen for 2 years. Participants completed a Treatment Satisfaction Questionnaire (TSQM). Data on BMI, bone density, muscle pathology and function were collected at baseline and 2 years later. Results: Testosterone injections were well tolerated, with high TSQM scores. Baseline BMI z-score was 2.16 (0.90) and 1.64 (1.35) 2 years later. Median testosterone levels were 9.7 nmol/L (IQR: 5.7-11.1) 6-9 months after the last injection with an associated increase in testicular volume. Lumbar spine z-score was 0.22 (s.d. 2.21) at baseline and 0.35 (s.d. 2.21) after 2 years. Upper and lower limb muscle contractile cross-sectional area increased in all participants during the trial (P = 0.05 and P < 0.01, respectively). There was a reduction in T2 relaxation times in most muscle groups with stable upper limb muscle function. Conclusion: Incremental monthly testosterone injections were well tolerated, promoted endogenous testosterone production and had a positive impact on the skeleton and contractile muscle bulk with evidence suggesting a beneficial impact on the underlying disease process.


Assuntos
Androgênios/administração & dosagem , Glucocorticoides/efeitos adversos , Distrofia Muscular de Duchenne/fisiopatologia , Puberdade Tardia/tratamento farmacológico , Testosterona/administração & dosagem , Adolescente , Índice de Massa Corporal , Densidade Óssea , Criança , Humanos , Injeções Intramusculares , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/tratamento farmacológico , Satisfação do Paciente , Puberdade/efeitos dos fármacos , Puberdade Tardia/induzido quimicamente , Puberdade Tardia/fisiopatologia , Resultado do Tratamento
4.
Rev. int. med. cienc. act. fis. deporte ; 20(80): 539-551, dic. 2020.
Artigo em Espanhol | IBECS | ID: ibc-198571

RESUMO

La concepción cultural del deporte como una actividad predominantemente masculina ha dificultado la participación de algunos grupos sociales como mujeres, personas trans o intersexuales. El carácter sexuado del deporte se apoya en las diferencias fisiológicas entre mujeres y hombres, y una supuesta desventaja de las mujeres. Por ello, se establecen pruebas de sexo para las mujeres y el acceso de las personas trans e intersexuales se ve obstaculizado. En este estudio reconstruimos, a partir de las normativas y el contexto socio-histórico internacional, la evolución de la participación de personas trans e intersexuales en el deporte competitivo contemporáneo. Asimismo, se profundiza en la aplicación y gestión de dichas normas en el contexto español, apoyado en tres casos de deportistas trans e intersexuales españoles. La discriminación y humillación que han sufrido estas personas obliga a mantener una visión crítica de las políticas deportivas creadas hasta la actualidad


The cultural conception of sport as a predominantly male activity has hindered the participation of some social groups such as women, transsexual or intersex people. The sexed nature of sport is based on physiological differences between women and men, and a supposed women disadvantage. Thus, sex controls are established for women and then trans and intersex people's access to sport is hampered. In this study we reconstruct, based on the regulations and the international socio-historical context, the evolution of the participation of transsexual and intersex people in contemporary competitive sport. Likewise, the application and management of these norms in the Spanish context is deepened, supported by three cases of Spanish transsexual and intersex athletes. The discrimination and humiliation suffered by these persons enforce to maintain a critical vision of the sports policies hitherto created


Assuntos
Humanos , Masculino , Feminino , História do Século XX , Pessoas Transgênero/psicologia , Esportes/fisiologia , Esportes/legislação & jurisprudência , Sexismo/prevenção & controle , Desempenho Atlético/fisiologia , Transtornos do Desenvolvimento Sexual/complicações , Testosterona/administração & dosagem , Hormônios/uso terapêutico , Pessoas Transgênero/legislação & jurisprudência , Sexismo/ética , Equidade em Saúde/legislação & jurisprudência , Transexualidade/epidemiologia , Androgênios/uso terapêutico , Esportes/história
5.
Life Sci ; 261: 118342, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32853655

RESUMO

AIMS: The increased incidence of heart failure with reduced ejection fraction in men compared with women suggests that male sex hormones significantly impact myocardial contractile activation. This study aims to examine associations among molecular alterations, cellular modulations and in vivo cardiac contractile function upon deprivation of testicular hormones. MAIN METHODS: Myocardial structure and functions were compared among sham-operated control and twelve-week orchidectomized (ORX) male rats with and without testosterone supplementation. KEY FINDINGS: Echocardiography and pressure-volume relationships demonstrated a decreased left ventricular ejection fraction compared with sham-operated controls. The percentage of contractility reduction was generally similar to the decrease in tension development detected in both right ventricular trabeculae and skinned isolated left ventricular cardiomyocytes of ORX rats. Reductions in tension cost and the rate constant of tension redevelopment (ktr) in ORX samples suggested a decrease in the rate of cross-bridge formation, reflecting a reduced number of cross-bridges. Slow cross-bridge detachment in ORX rat hearts could result from a shift of myosin heavy chain isoforms towards a slower ATPase activity ß-isoform and reductions in the phosphorylation levels of cardiac troponin I and myosin binding protein-C. All the changes in the ORX rat heart, including ejection fractions and myofilament protein expression and phosphorylation, were completed attenuated by a physiological dose of testosterone. SIGNIFICANCE: Testosterone plays a critical role in regulating the mechanical and contractile dynamics of the heart. Deprivation of male sex hormones cause the loss of normal preserved cardiac contractile function leading to a high risk of severe cardiomyopathy progression.


Assuntos
Cardiomiopatias/fisiopatologia , Miócitos Cardíacos/metabolismo , Miofibrilas/metabolismo , Testosterona/metabolismo , Animais , Progressão da Doença , Coração/fisiologia , Masculino , Cadeias Pesadas de Miosina/metabolismo , Orquiectomia , Ratos , Ratos Sprague-Dawley , Volume Sistólico/fisiologia , Testosterona/administração & dosagem , Testosterona/farmacologia , Função Ventricular Esquerda/fisiologia
7.
Am J Psychiatry ; 177(10): 965-973, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32660299

RESUMO

OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Testosterona/uso terapêutico , Adulto , Idoso , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Humanos , Hidrocortisona/sangue , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Creme para a Pele , Testosterona/administração & dosagem , Testosterona/sangue , Adulto Jovem
8.
Am J Physiol Gastrointest Liver Physiol ; 318(6): G989-G999, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32363890

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.


Assuntos
Estradiol/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Testosterona/farmacologia , Aminoácidos , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Cromo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Estradiol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Insulina , Cirrose Hepática , Neoplasias Hepáticas , Masculino , Camundongos , Camundongos Knockout , Ácidos Nicotínicos , Hepatopatia Gordurosa não Alcoólica/patologia , Orquiectomia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo , Testosterona/administração & dosagem , Testosterona/deficiência , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
9.
Internist (Berl) ; 61(6): 549-557, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32377774

RESUMO

Testosterone is a natural hormone which is essential to maintaining physical and emotional wellbeing in men, regardless of age. Male hypogonadism is an endocrine condition of testosterone deficiency with the potential to cause multiple morbidities and psychosocial problems. The condition can be of primary (testicular), secondary (hypothalamic-pituitary) or so-called functional origin (as a result of inflammatory conditions, obesity or chronic illness). Testosterone deficiency can cause symptoms of a sexual nature, foster metabolic dysfunction and impair physical abilities as well as cause osteopenia/osteoporosis and anemia. Testosterone replacement therapy should not be initiated in the case of desired paternity, unclear processes of the prostate or mammary gland and high hematocrit. Diagnosis and treatment as well as monitoring of hypogonadism treatment are clearly regulated by international guidelines and replacement therapy is proven to be effective in ameliorating the above-mentioned symptoms when performed according to these guidelines. In functional hypogonadism, which is most often, but not exclusively, found in older men, treatment of the underlying condition/co-morbidity is mandatory prior to starting testosterone substitution.


Assuntos
Androgênios/uso terapêutico , Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Osteoporose/prevenção & controle , Testosterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Androgênios/administração & dosagem , Disfunção Erétil/etiologia , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/etiologia , Masculino , Obesidade , Osteoporose/etiologia , Testosterona/administração & dosagem , Testosterona/efeitos adversos
10.
J Urol ; 204(3): 557-563, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32294396

RESUMO

PURPOSE: To evaluate the effect of short-acting 4.5% nasal testosterone gel (Natesto) on serum testosterone, gonadotropins, total motile sperm count, health related quality of life and sexual function. MATERIALS AND METHODS: This was a single institution, open label, single arm trial conducted between November 2017 and September 2019 at the University of Miami. Men 18 to 55 years old diagnosed with symptomatic hypogonadism (total testosterone less than 300 ng/dl on 2 occasions) were included. Men with azoospermia, vasectomy or a total motile sperm count less than 5 million were excluded. Enrolled patients were treated with Natesto, a short-acting nasal testosterone (125 µl per nostril, 11.0 mg testosterone per dose, TID) for 6 months. RESULTS: In total, 60 men were enrolled in the study. Of these, 44 and 33 patients were evaluated for testosterone at 3 and 6 months, respectively. A total of 31 patients (90.9%) reached a normal testosterone level (greater than 300 ng/dl) at 6 months. Follicle stimulating hormone and luteinizing hormone levels were maintained within the normal range in 81.8% and 72.7% of patients at 6 months, respectively. Total motile sperm count was maintained with total motile sperm count greater than 5 million over the treatment period in 88.4% of men at 3 months and 93.9% at 6 months. There were statistically significant improvements on International Index of Erectile Function sexual desire and overall satisfaction domains at 6 months. CONCLUSIONS: Natesto appears to increase testosterone while maintaining semen parameters in a majority of men. Natesto has the potential to be a safe and effective treatment for men with functional hypogonadism who wish to preserve semen parameters. Long-term studies beyond 6 months are needed before we can safely prescribe nasal testosterone gel for men interested in fertility.


Assuntos
Hipogonadismo/tratamento farmacológico , Testosterona/administração & dosagem , Administração Intranasal , Adolescente , Adulto , Biomarcadores/sangue , Géis , Gonadotropinas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Contagem de Espermatozoides , Testosterona/sangue
11.
Artigo em Inglês | MEDLINE | ID: mdl-32235321

RESUMO

Testosterone could have adverse effect on fertility. In this study, we hypothesized that this hormone could reduce the number of embryo implantations via affecting the normal endometrium ultrastructure and expression of endometrial proteins involved in implantation. Therefore, the aims were to identify these adverse testosterone effects. METHODS: Intact pregnant rats were given 250 or 500 µg/kg/day testosterone for three days, beginning from day 1 of pregnancy. Rats were euthanized either at day 4 to analyze the ultra-structural changes in the endometrium and expression and distribution of MECA-79 protein, or at day 6 to determine the number of implantation sites. RESULTS: Administration of 500 µg/kg/day testosterone suppresses endometrial pinopodes development and down-regulates expression and distribution of MECA-79 protein in the uterus. In addition, the number of implantation sites were markedly decreased. CONCLUSIONS: Changes in endometrial ultrastructure and expression of implantation protein in the endometrium in early pregnancy period could be the reason for failure of embryo implantation under testosterone influence.


Assuntos
Antígenos de Superfície/metabolismo , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Testosterona/administração & dosagem , Animais , Endométrio/ultraestrutura , Feminino , Selectina L , Gravidez , Ratos
12.
Am J Surg Pathol ; 44(8): 1040-1049, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32282346

RESUMO

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation "androgen-associated prostatic metaplasia" for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.


Assuntos
Diferenciação Celular , Coristoma/patologia , Células Epiteliais/patologia , Próstata , Doenças do Colo do Útero/patologia , Doenças Vaginais/patologia , Adolescente , Adulto , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Criança , Coristoma/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Feminino , Disforia de Gênero/tratamento farmacológico , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Masculino , Metaplasia , Fatores de Risco , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Transexualidade/tratamento farmacológico , Doenças do Colo do Útero/induzido quimicamente , Doenças Vaginais/induzido quimicamente , Adulto Jovem
13.
NeuroRehabilitation ; 46(3): 355-368, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250330

RESUMO

BACKGROUND: Endocrinopathy, including hypogonadism, is common following traumatic brain injury (TBI). Prior evidence suggests hypogonadism is associated with poorer function. OBJECTIVE: Determine the feasibility, safety, and efficacy of testosterone (T) therapy in hypogonadal men following TBI in acute rehabilitation. DESIGN: Randomized, double blind, placebo-controlled pilot trial. SETTING: Inpatient rehabilitation brain injury unit. PARTICIPANTS: Men ages 18 -65, post moderate to severe TBI receiving inpatient rehabilitation. INTERVENTIONS: Transdermal T gel or placebo. MAIN OUTCOME MEASURES: Revised FIM™ score, strength, adverse events. RESULTS: Of 498 screened, 70 participants were enrolled, and 22 meeting all criteria were randomized into placebo (n = 10) or physiologic T therapy (n = 12). There was no significant difference between groups in rate of improvement on the FIM™ (intercepts t = -0.31, p = 0.7593, or slopes t = 0.61, p = 0.5472). The Treatment group demonstrated the greatest absolute improvement in FIM™ scores and grip strength compared to Placebo or Normal T groups. There was no difference in adverse events between groups. Percentage of time with agitation or aggression was highest in the Placebo group. CONCLUSIONS: Although there were no significant differences in rates of recovery, treatment group subjects showed greater absolute functional and strength improvement compared to the Placebo or Normal T groups.


Assuntos
Androgênios , Lesões Encefálicas Traumáticas , Eunuquismo , Testosterona , Adolescente , Adulto , Idoso , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Androgênios/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/reabilitação , Método Duplo-Cego , Eunuquismo/tratamento farmacológico , Eunuquismo/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Testosterona/uso terapêutico , Adulto Jovem
14.
Cancer Cytopathol ; 128(7): 491-498, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32125771

RESUMO

BACKGROUND: The cervical cancer screening recommendation for transgender female-to-male (FTM) patients is the same as that for cisgender females. A lack of literature on testosterone-induced changes in cervical cytology in these patients may result in interpretation errors, especially without a proper clinical history. The aim of this study was to delineate the Papanicolaou (Pap) test findings in this patient population. METHODS: A pathology laboratory information system was used to obtain a cohort of FTM transgender patients on testosterone therapy (2009-2019). A cohort of age-matched, atrophic, control cisgender female patients (postpartum or menopausal) was selected. A retrospective review of the cytomorphologic findings on cervical Pap smears, pertinent follow-up, and human papillomavirus (HPV) test results was performed. RESULTS: Fourteen transgender patients (age range, 21-64 years; mean age, 42.5 years) receiving testosterone therapy with 17 Pap smears were identified. One of the 5 available HPV tests was positive for HPV, and 4 were negative. A Pap smear review revealed the following: negative for intraepithelial lesion (NILM; 82.4%), unsatisfactory (5.9%), atypical squamous cells of undetermined significance (ASCUS; 5.9%), and low-grade squamous intraepithelial lesion (5.9%). The Pap smears of the atrophic cisgender cohort (102 patients) revealed the following: NILM (92.5%), unsatisfactory (0.9%), ASCUS (5.6%), and high-grade squamous intraepithelial lesion (0.9%). The difference between the rates of epithelial cell abnormality in the 2 cohorts was not statistically significant. Although atrophy was noted in both groups, cytomorphologic findings of transitional cell metaplasia (TCM; 88.2%) and "small cells" (82.4%) were characteristic of the testosterone-treated transgender cohort. Histologic correlates of TCM and small cells were noted in hysterectomy specimens from 6 patients. CONCLUSIONS: Small cells and TCM are common cytomorphologic findings in Pap smears of testosterone-treated transgender (FTM) patients. On the basis of histologic follow-up, small cells most likely represent atrophic parabasal cells of cervical-vaginal epithelium.


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasia Intraepitelial Cervical/patologia , Citodiagnóstico/métodos , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/complicações , Testosterona/administração & dosagem , Neoplasias do Colo do Útero/patologia , Adulto , Androgênios/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/virologia , Neoplasia Intraepitelial Cervical/tratamento farmacológico , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Pessoas Transgênero , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
15.
J Sex Med ; 17(4): 570-584, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32111534

RESUMO

BACKGROUND: There is a general lack of recommendations for and basic information tailored at sexologists and other health-care professionals for when they encounter trans people in their practice. AIM: We present to clinicians an up-to-date overview of clinical consensus statements on trans health care with attention for sexual function and satisfaction. METHODS: The task force consisted of 7 clinicians experienced in trans health care, selected among European Society for Sexual Medicine (ESSM) scientific committee. The consensus was guided by clinical experience and a review of the available literature and by interactive discussions on trans health, with attention for sexual function and satisfaction where available. OUTCOMES: The foci of the study are assessment and hormonal aspects of trans health care. RESULTS: As the available literature for direct recommendations was limited, most of the literature was used as background or indirect evidence. Clinical consensus statements were developed based on clinical experiences and the available literature. With the multiple barriers to care that many trans people experience, basic care principles still need to be stressed. We recommend that health-care professionals (HCPs) working with trans people recognize the diversity of genders, including male, female, and nonbinary individuals. In addition, HCPs assessing gender diverse children and adolescents should take a developmental approach that acknowledges the difference between prepubescent gender diverse children and pubescent gender diverse adolescents and trans adults. Furthermore, trans people seeking gender-affirming medical interventions should be assessed by HCPs with expertise in trans health care and gender-affirming psychological practice. If masculinization is desired, testosterone therapy with monitoring of serum sex steroid levels and signs of virilization is recommended. Similarly, if feminization is desired, we recommend estrogens and/or antiandrogen therapy with monitoring of serum sex steroid levels and signs of feminization. HCPs should be aware of the influence of hormonal therapy on sexual functioning and satisfaction. We recommend HCPs be aware of potential sexual problems during all surgical phases of treatment. CLINICAL IMPLICATIONS: This is an up-to-date ESSM position statement. STRENGTHS & LIMITATIONS: These statements are based on the data that are currently available; however, it is vital to recognize that this is a rapidly changing field and that the literature, particularly in the field of sexual functioning and satisfaction, is limited. CONCLUSION: This ESSM position statement provides relevant information and references to existing clinical guidelines with the aim of informing relevant HCPs on best practices when working with transgender people. T'Sjoen G, Arcelus J, De Vries ALC, et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med 2020;17:570-584.


Assuntos
Hormônios Esteroides Gonadais/administração & dosagem , Satisfação Pessoal , Pessoas Transgênero/psicologia , Transexualidade , Adolescente , Adulto , Criança , Consenso , Estrogênios/administração & dosagem , Feminino , Terapia de Reposição Hormonal , Humanos , Masculino , Sociedades Médicas , Testosterona/administração & dosagem
16.
Top Companion Anim Med ; 38: 100405, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115076

RESUMO

The monitoring of serum prostatic biomarkers during the treatment will help clinicians to know the statement of the response to finasteride in dogs affected by benign prostatic hyperplasia (BPH). The present study was aimed to assess changes in the serum canine prostate-specific esterase (CPSE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, dihydrotestosterone (DHT) and prostate volume evaluation using ultrasonographic examination during the treatment with finasteride in BPH-induced dogs. Twenty dogs were divided into 4 groups (n = 5): BPH + finasteride group, dogs which were induced for BPH and received oral finasteride once daily for 1 month; BPH group, dogs which were induced for BPH and received placebo; finasteride group, normal dogs which received finasteride; and normal group, normal intact dogs which did not receive treatment. Blood sampling and ultrasonography examination were performed on days 0, 14, and 28. The administration of finasteride led to a significant decrease in the concentration of the prostate-specific biomarkers (PSA, CPSE), DHT, testosterone, and the volume of the prostate in BPH + finasteride group compared with the BPH group during 1 month. Interestingly, the PAP concentration did not change in the BPH-induced dogs and in dogs treated with finasteride. It seems that the monitoring of serum PSA and CPSE levels and ultrasonographic examination of the prostate are useful methods for following up the response to finasteride treatment in dogs affected by BPH.


Assuntos
Biomarcadores/sangue , Doenças do Cão/tratamento farmacológico , Finasterida/farmacologia , Hiperplasia Prostática/veterinária , Inibidores de 5-alfa Redutase , Fosfatase Ácida/sangue , Animais , Di-Hidrotestosterona/sangue , Doenças do Cão/sangue , Doenças do Cão/enzimologia , Cães , Esterases/sangue , Estradiol/administração & dosagem , Masculino , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Testosterona/administração & dosagem , Testosterona/sangue , Ultrassonografia/veterinária
17.
Am J Physiol Renal Physiol ; 318(4): F922-F935, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32116019

RESUMO

There are substantial sex differences in renal structure and ammonia metabolism that correlate with differences in expression of proteins involved in ammonia generation and transport. This study determined the role of testis-derived testosterone in these differences. We studied 4-mo-old male C57BL/6 mice 4 and 8 wk after either bilateral orchiectomy (ORCH) or sham-operated control surgery and determined the effect of testosterone replacement to reverse the effects of ORCH. Finally, we determined the cellular expression of androgen receptor (AR), testosterone's canonical target receptor. ORCH decreased kidney and proximal tubule size, and testosterone replacement reversed this effect. ORCH increased ammonia excretion in a testosterone-dependent fashion; this occurred despite similar food intake, which is the primary component of endogenous acid production. ORCH increased expression of both phosphoenolpyruvate, a major ammonia-generating protein, and Na+-K+-2Cl- cotransporter, which mediates thick ascending limb ammonia reabsorption; these changes were reversed with testosterone replacement. Orchiectomy also decreased expression of Na+/H+ exchanger isoform 3, which mediates proximal tubule ammonia secretion, in a testosterone-dependent pattern. Finally, ARs are expressed throughout the proximal tubule in both the male and female kidney. Testosterone, possibly acting through ARs, has dramatic effects on kidney and proximal tubule size and decreases ammonia excretion through its effects on several key proteins involved in ammonia metabolism.


Assuntos
Amônia/metabolismo , Terapia de Reposição Hormonal , Rim/efeitos dos fármacos , Eliminação Renal/efeitos dos fármacos , Testosterona/administração & dosagem , Animais , Feminino , Rim/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Orquiectomia , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Fatores Sexuais , Simportadores de Sódio-Bicarbonato/genética , Simportadores de Sódio-Bicarbonato/metabolismo , Trocador 3 de Sódio-Hidrogênio/genética , Trocador 3 de Sódio-Hidrogênio/metabolismo , Membro 1 da Família 12 de Carreador de Soluto/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Testosterona/deficiência
19.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
20.
Int J Pharm ; 578: 119132, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32057892

RESUMO

This study investigated the effects of drug recrystallization on the in vitro performance of testosterone drug-in-adhesive transdermal delivery system (TDS). Six formulations were prepared with a range of dry drug loading in the adhesive matrix from 1% to 10% w/w with the aim of generating TDS with various levels of drug crystals. We visually quantified the amount of crystals in TDS by polarized light microscopy. The effect of drug recrystallization on adhesion, tackiness, cohesive strength, viscoelasticity, drug release, and drug permeation through human cadaver skin were evaluated for these TDS samples. The Optical images showed no crystals in 1% and 2% testosterone TDSs; however, the amount of crystals increased by increasing testosterone loading from 4 to 10%. A proportional and significant decrease (p < 0.05) in tack, peel, and shear strength of the adhesive matrix with increasing amount of crystals in TDS was observed. The drug crystals resulted in a proportional deterioration of the viscoelastic properties of the adhesive matrix. The 2% testosterone TDS showed faster drug release rate when compared to 1% testosterone TDS. The increase in drug loading from 2% to 4% w/w slightly increased the cumulative amount of testosterone released. Further increase in drug loading in TDS to 6, 8, and 10% was nonsignificant (p > 0.05) to affect the drug release and permeation. In conclusion, this study demonstrated that the extent of drug recrystallization can be quantitatively correlated with the deterioration of performance characteristics of TDS products.


Assuntos
Adesivos/química , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Pele/efeitos dos fármacos , Testosterona/administração & dosagem , Testosterona/química , Administração Cutânea , Idoso , Cristalização/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Permeabilidade/efeitos dos fármacos , Reologia/métodos , Absorção Cutânea/efeitos dos fármacos , Adesivo Transdérmico
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