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1.
J Chromatogr A ; 1640: 461933, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588275

RESUMO

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is the gold-standard approach for androgen analysis in biological fluids, superseding immunoassays in selectivity, particularly at low concentrations. While LC-MS/MS is established for analysis of testosterone and androstenedione, 5α-dihydrotestosterone (DHT) presents greater analytical challenges. DHT circulates at low nanomolar concentrations in men and lower in women, ionizing inefficiently and suffering from isobaric interference from other androgens. Even using current LC-MS/MS technology, large plasma volumes (>0.5 mL) are required for detection, undesirable clinically and unsuitable for animals. This study investigated derivatization approaches using hydrazine-based reagents to enhance ionization efficiency and sensitivity of analysis of DHT by LC-MS/MS. Derivatization of DHT using 2-hydrazino-1-methylpyridine (HMP) and 2-hydrazino-4-(trifluoromethyl)-pyrimidine (HTP) were compared. A method was validated using an UHPLC interfaced by electrospray with a triple quadruple mass spectrometer , analyzing human plasma (male and post-menopausal women) following solid-phase extraction. HMP derivatives were selected for validation affording greater sensitivity than those formed with HTP. HMP derivatives were detected by selected reaction monitoring (DHT-HMP m/z 396→108; testosterone-HMP m/z 394→108; androstenedione-HMP m/z 392→108). Chromatographic separation of androgen derivatives was optimized, carefully separating isobaric interferents and acceptable outputs for precision and trueness achieved following injection of 0.4 pg on column (approximately 34 pmol/L). HMP derivatives of all androgens tested could be detected in low plasma volumes: male (100 µL) and post-menopausal female (200 µL), and derivatives were stable over 30 days at -20°C. In conclusion, HMP derivatization, in conjunction with LC-MS/MS, is suitable for quantitative analysis of DHT, testosterone and androstenedione in low plasma volumes, offering advantages in sensitivity over current methodologies.


Assuntos
Di-Hidrotestosterona/sangue , Hidrazinas/química , Piridinas/química , Espectrometria de Massas em Tandem/métodos , Adulto , Androgênios/sangue , Androstenodiona/sangue , Bioensaio , Calibragem , Cromatografia Líquida , Feminino , Humanos , Hidrazinas/síntese química , Masculino , Piridinas/síntese química , Padrões de Referência , Reprodutibilidade dos Testes , Testosterona/sangue
2.
Eur J Endocrinol ; 184(4): 487-501, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33524003

RESUMO

Objective: To study the impact of the quality of therapeutic control on fertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adrenal hyperplasia (CAH). Design: Combined cross-sectional and retrospective clinical study. Methods: Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis. The quality of therapeutic control was categorized as 'poor', 'moderate' or 'medium'. Evaluation of current control was based on concentrations of 17-hydroxy-progesterone and androstenedione in serum and 3 cm hair; previous control was categorized based on serum 17-hydroxy-progesterone concentrations during childhood and puberty, anthropometric and puberty data, bone age data and adrenal sizes. Results: Semen quality was similar in males with CAH and controls (P = 0.066), however patients with 'poor' past control and large TART, or with 'poor' current CAH control had low sperm counts. Follicle-stimulating hormone was decreased, if current CAH control was 'poor' (1.8 ± 0.9 U/L; 'good': 3.9 ± 2.2 U/L); P = 0.015); luteinizing hormone was decreased if it was 'poor' (1.8 ± 0.9 U/L; P = 0.041) or 'moderate' (1.9 ± 0.6 U/L; 'good': 3.0 ± 1.3 U/L; P = 0.025). None of the males with 'good' past CAH control, 50% of those with 'moderate' past control and 80% with 'poor past control had bilateral TART. The prevalence of TART in males with severe (class null or A) CYP21A2 mutations was 53% and 25% and 0% in those with milder class B and C mutations, respectively. Conclusions: TART development is favoured by inadequate long-term hormonal control in CAH. Reduced semen quality may be associated with large TART. Gonadotropin suppression by adrenal androgen excess during the latest spermatogenic cycle may contribute to impairment of spermatogenesis.


Assuntos
Corticosteroides/uso terapêutico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Tumor de Resto Suprarrenal/epidemiologia , Terapia de Reposição Hormonal/métodos , Análise do Sêmen , Neoplasias Testiculares/epidemiologia , Adolescente , Glândulas Suprarrenais/patologia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/fisiopatologia , Tumor de Resto Suprarrenal/patologia , Adulto , Androgênios/sangue , Humanos , Estudos Longitudinais , Masculino , Mutação , Puberdade , Espermatogênese , Neoplasias Testiculares/patologia , Ultrassonografia , Adulto Jovem
3.
Cochrane Database Syst Rev ; 1: CD013211, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482034

RESUMO

BACKGROUND: Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial. OBJECTIVES: Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work. SELECTION CRITERIA: RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 µmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels. AUTHORS' CONCLUSIONS: We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.


Assuntos
Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Idoso , Androgênios/sangue , Androstenodiona/sangue , Atorvastatina/efeitos adversos , Viés , Sulfato de Desidroepiandrosterona/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Placebos/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/efeitos dos fármacos
4.
Phytomedicine ; 80: 153395, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33137599

RESUMO

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.


Assuntos
Glicemia/análise , Curcumina/uso terapêutico , Resistência à Insulina , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Androgênios/sangue , Desidroepiandrosterona/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Hirsutismo/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Insulina/sangue , Pessoa de Meia-Idade , Placebos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Resultado do Tratamento , Adulto Jovem
5.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375030

RESUMO

Central hypogonadism is a clinical condition, characterized by sexual symptoms and low serum testosterone levels, due to an impaired function of the hypothalamus or pituitary gland. Testosterone replacement therapy (TRT) is the standard treatment for hypogonadism, but it has some disadvantages. TRT is not a good option in men wishing to preserve fertility, nor in men with (a high risk of) prostate cancer, polycythemia, thrombophilia and severe cardiovascular disease. In this review, we discuss alternative treatments for central hypogonadism. If reversible causes are present, non-pharmacological interventions can be therapeutic. Gonadotropins are a good alternative to TRT when fertility is desired in the near future though they require frequent injections. Clomiphene citrate and tamoxifen seem to be a safe alternative for the treatment of functional central hypogonadism in men, as several studies reported a significant increase in testosterone levels with these drugs. However, their use is off-label and data supporting the efficacy of clomiphene citrate and tamoxifen on hypogonadal symptoms are insufficient. For this reason, clomiphene citrate and tamoxifen should not be used in routine clinical practice to treat sexual symptoms in men with central hypogonadism.


Assuntos
Terapia de Reposição Hormonal/métodos , Hipogonadismo/tratamento farmacológico , Testosterona/uso terapêutico , Androgênios/sangue , Androgênios/uso terapêutico , Clomifeno/uso terapêutico , Fertilidade/efeitos dos fármacos , Humanos , Masculino , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Testosterona/sangue , Resultado do Tratamento
7.
J Chromatogr A ; 1628: 461445, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32822984

RESUMO

Anabolic androgenic steroids (AAS) have been the most commonly abused substances taken by not only professional sportsmen but also recreational bodybuilders. The detection of micro-dose testosterone (T) misuse is particularly challenging as it possesses pseudo-endogenous origin and is sometimes impossible to be identified in urine samples. Dried blood (DB) obtained by finger pricking has been proven to be an alternative matrix for better correlating to physiological responses. Moreover, the introduction of the volumetric absorptive microsampling (VAMS) technology allows overcoming some major limitations of spotting blood onto a filter paper card. In this work, a fast and sensitive GC-MS/MS method was developed and validated for the quantification of AAS in DB collected by means of VAMS. T and the eight top abused synthetic AAS, namely nandrolone, boldenone, mesterolone, drostanolone, metenolone, metandienone, oxandrolone, and dehydrochloromethyl T were selected as the target analytes. The method based on VAMS exhibited good precision, accuracy as well as stability, and superior extraction recoveries over the punched DB spots reported in the literature. The chromatographic separation was achieved within 6.4 min and the detection limit is as little as 50 fg (i.e. able to detect 0.10 ng mL-1 in 20 µL of DB). Confirmed by forty real blood samples, the Deming regression and Bland-Altman analysis revealed that the VAMS DB could be employed for quantifying blood T level in agreement with using the serum specimen. The feasibility of the method was then successfully proven by the analysis of samples collected from a three-arm T administration trial. Our results highlighted that DB total T was a sensitive indicator for identifying transdermal micro-dosing of T. In the groups of receiving T gel administration, T concentrations could rise up to ten times higher than the baseline at 9 h after the application. As a future step, this approach is being expanded to a large cohort screening of bodybuilders at gym and ultimately may allow universal applications on monitoring sports drug misuse.


Assuntos
Androgênios/sangue , Teste em Amostras de Sangue Seco/métodos , Monitoramento de Medicamentos/métodos , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas em Tandem , Congêneres da Testosterona/sangue , Testosterona/análise , Humanos
8.
Lancet Diabetes Endocrinol ; 8(8): 693-702, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32707117

RESUMO

BACKGROUND: Although clinicians often measure the serum concentration of androgens in premenopausal women presenting with sexual dysfunction, with some women given testosterone or dehydroepiandrosterone as treatment if their concentrations are low, whether androgens are determinants of sexual function in women of reproductive age is uncertain. We aimed to clarify the associations between androgens and sexual function in a community-based sample of non-health-care-seeking women. METHODS: This is a substudy of the Grollo-Ruzzene cross-sectional study, which recruited women aged 18-39 years from eastern states in Australia (QLD, NSW, VIC). After providing consent, women completed an online survey that included the Profile of Female Secual Function (PFSF) questionnaire, and those who were who were not pregnant, breastfeeding, or using systemic steroids were asked to provide a blood sample. At sampling, women were asked the dates of their last menstrual bleed. Serum androgens was measured by liquid chromatography and tandem mass spectrometry and sex hormone binding globulin (SHBG) by immunoassay. Associations between androgens and domains of sexual function, assessed by the PFSF, were examined in participants with regular menstrual cycles. After univariable linear regression (model 1), age, BMI, stage of menstrual cycle, and smoking status were added to the model (model 2), and then parity, partner status, and psychotropic medication use (model 3). FINDINGS: Of 6986 women who completed the online survey (surveys completed between Nov 11, 2016, and July 21, 2017), 3698 were eligible and 761 (20·6%) provided blood samples by Sept 30, 2017. Of those who provided a blood sample, 588 (77·3%) had regular menstrual cycles and were included in the analysis. Adjusting for age, BMI, cycle stage, smoking, parity, partner status, and psychoactive medication, sexual desire was positively associated with serum dehydroepiandrosterone (ß-coefficient 3·39, 95% CI 0·65 to 6·03) and androstenedione (4·81, 0·16 to 9·12), and negatively with SHBG (-5.74, -9.54 to -1·90), each model explaining less than 4% of the variation in desire. Testosterone (6·00, 1·29 to 10·94) and androstenedione (6·05, 0·70 to 11·51) were significantly associated with orgasm, with the final models explaining less than 1% of the variation in orgasm. Significant associations were found between androstenedione (7·32, 0·93 to 13·08) and dehydroepiandrosterone (4·44, 0·86 to 7·95) and pleasure, and between testosterone and sexual self-image 5·87 (1·27 to 10·61), with inclusion of parity, partners status, and psychotropic drug use increasing the proportion of variation explained by each model to approximately 10%. There were no statistically significant associations between 11-oxygenated steroids and any PFSF domain, or between arousal or responsiveness and any hormone. No associations were seen between 11-oxygenated steroids and any sexual domain, or between arousal or responsiveness and any hormone. INTERPRETATION: Associations between androgens and sexual function in premenopausal women are small, and their measurement offers no diagnostic use in this context. Further research to determine whether 11-ketoandrostenedione or 11-ketotestosterone are of clinical significance is warranted. FUNDING: The Grollo-Ruzzene Foundation.


Assuntos
Androgênios/sangue , Pré-Menopausa/sangue , Comportamento Sexual/fisiologia , Adolescente , Adulto , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Disfunções Sexuais Fisiológicas/sangue , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/epidemiologia , Adulto Jovem
9.
Eur J Endocrinol ; 183(1): 63-71, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32487778

RESUMO

Objectives: The clinical presentation of patients with nonclassic 21-hydroxylase deficiency (N21OHD) is similar with that for other disorders of androgen excess. The diagnosis of N21OHD typically requires cosyntropin stimulation. Additionally, the management of such patients is limited by the lack of reliable biomarkers of androgen excess. Herein, we aimed to: (1.) compare the relative contribution of traditional and 11-oxyandrogens in N21OHD patients and (2.) identify steroids that accurately diagnose N21OHD with a single baseline blood draw. Design: We prospectively enrolled patients who underwent a cosyntropin stimulation test for suspected N21OHD in two tertiary referral centers between January 2016 and August 2019. Methods: Baseline sera were used to quantify 15 steroids by liquid chromatography-tandem mass spectrometry. Logistic regression modeling was implemented to select steroids that best discriminate N21OHD from controls. Results: Of 86 participants (72 females), median age 26, 32 patients (25 females) had N21OHD. Age, sex distribution, and BMI were similar between patients with N21OHD and controls. Both testosterone and androstenedione were similar in patients with N21OHD and controls, while four 11-oxyandrogens were significantly higher in patients with N21OHD (ratios between medians: 1.7 to 2.2, P < 0.01 for all). 17α-Hydroxyprogesterone (6.5-fold), 16α-hydroxyprogesterone (4.1-fold), and 21-deoxycortisol (undetectable in 80% of the controls) were higher, while corticosterone was 3.6-fold lower in patients with N21OHD than in controls (P < 0.001). Together, baseline 17α-hydroxyprogesterone, 21-deoxycortisol, and corticosterone showed perfect discrimination between N21OHD and controls. Conclusions: Adrenal 11-oxyandrogens are disproportionately elevated compared to conventional androgens in N21OHD. Steroid panels can accurately diagnose N21OHD in unstimulated blood tests.


Assuntos
Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Androgênios/sangue , Cosintropina/uso terapêutico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Criança , Cosintropina/administração & dosagem , Feminino , Hormônios/administração & dosagem , Hormônios/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-32582576

RESUMO

COVID-19 morbidity and mortality have significant gender disparities, with higher prevalence and mortality in men. SARS-CoV-2 enters the lungs through the ACE2 enzyme, a member of the renin-angiotensin system (RAS). Although there are no data for the lung, the expressions of RAS components in other tissues are modulated by sex hormones, androgens, and estrogens. However, there are no data on sex-specific differences in ACE2 expression. If there is a sex difference in the expression of ACE2 in the lung, this could theoretically explain the gender disparity in COVID-19 disease. More importantly, although modulation of ACE2 will certainly not provide a cure for the COVID-19 disease, modulation of ACE2 by sex hormone modulators, if they affect the expression of ACE2, could potentially be developed into a supportive therapy for COVID-19 patients.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Androgênios/sangue , Betacoronavirus , Infecções por Coronavirus/patologia , Estrogênios/sangue , Feminino , Humanos , Pulmão/metabolismo , Masculino , Pandemias , Pneumonia Viral/patologia , Distribuição por Sexo , Fatores Sexuais
12.
Pediatrics ; 145(Suppl 2): S210-S218, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32358213

RESUMO

Polycystic ovary syndrome (PCOS) is a common female reproductive disorder that often manifests during adolescence and is associated with disruptions in health-related quality of life. Prompt evaluation and clinical support after diagnosis may prevent associated complications and optimize overall health management. This article incorporates the most recent evidence and consensus guidelines to provide an updated review of the pathogenesis, clinical presentation, diagnostic evaluation, and management strategies for adolescents with this complex condition. We will review the recent international guidelines on PCOS; because the diagnosis of PCOS remains controversial, management of this condition is inconsistent. In 2019, PCOS remains a common, yet neglected, condition, in part, because of the lack of agreement around both diagnosis and management.


Assuntos
Síndrome do Ovário Policístico/diagnóstico , Qualidade de Vida/psicologia , Adolescente , Androgênios/sangue , Feminino , Seguimentos , Fidelidade a Diretrizes , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/psicologia , Síndrome do Ovário Policístico/terapia , Fatores de Risco
13.
Am Heart J ; 224: 65-76, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32335402

RESUMO

BACKGROUND: Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES: Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS: In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS: Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS: In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT: In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.


Assuntos
Androgênios/deficiência , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Síndrome Metabólica/complicações , Medição de Risco/métodos , Testosterona/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Androgênios/sangue , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Método Duplo-Cego , Seguimentos , Humanos , Incidência , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
15.
Toxicol Appl Pharmacol ; 393: 114952, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32165126

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) is a phthalate commonly used for its plasticizing capabilities. Because of the wide production and use of DEHP, humans are exposed to DEHP on a daily basis. Diisononyl phthalate (DiNP) is often used as a DEHP replacement chemical, and because of the increased use of DiNP, humans are increasingly exposed to DiNP over time. Of concern is that DEHP and DiNP both exhibit endocrine disrupting capabilities, and little is known about how short-term exposure to either of these phthalates affects aspects of female reproduction. Thus, this study tested the hypothesis that short-term exposure to DEHP or DiNP during adulthood has long-lasting consequences on ovarian follicles and hormones in female mice. Female CD-1 mice aged 39-40 days were orally dosed with either vehicle control (corn oil), DEHP (20 µg/kg/day-200 mg/kg/day), or DiNP (20 µg/kg/day-200 mg/kg/day) for 10 days. Ovarian follicle populations, estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), and inhibin B were analyzed at time points immediately post-dosing and 3, 6, and 9 months post-dosing. The results indicate that 10 days of exposure to DEHP and DiNP changed the distribution of ovarian follicle populations and sex steroid hormones at multiple time points, including the last time point, 9 months post-dosing. Further, FSH was increased at multiple doses up to 6 months post-dosing. Inhibin B was not affected by treatment. These data show that short-term exposure to either DEHP or DiNP has long-term consequences that persist long after cessation of exposure.


Assuntos
Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Folículo Ovariano/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade , Reprodução/efeitos dos fármacos , Androgênios/sangue , Animais , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Hormônios/sangue , Camundongos
16.
Rev Assoc Med Bras (1992) ; 66(1): 36-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32130379

RESUMO

OBJECTIVE: Acne vulgaris in female adolescents, when severe or accompanied by other signs of androgenization, may represent a sign of hyperandrogenemia often underdiagnosed, which will have harmful consequences for adult life. The objective of this cross-sectional and retrospective study was to demonstrate the incidence of hormonal changes in the cases of female adolescents with severe or extensive acne, with or without other signs of hyperandrogenism, and propose a hormonal research pattern which should be indicated in order to detect early hyperandrogenemia. METHODS: The medical records of 38 female patients aged between 9 and 15 years old with grade II and/or III acne were analyzed. The dehydroepiandrosterone sulfate, dehydroepiandrostenedione, and androstenedione, total testosterone, and dihydrotestosterone sulfate hormones were required prior to initiation of treatment. The hormonal dosages were performed in the serum after at least 3 hours of fasting by means of radioimmunoassay tests. RESULTS: Of the 38 patients included, 44.7% presented changes in androgen levels (hyperandrogenemia), and the two most frequently altered hormones were DHEA and androstenedione, with the same incidence (23.6%). CONCLUSIONS: The correct and early diagnosis provides an effective and agile approach, including antiandrogen therapy, with the purpose of avoiding the reproductive and metabolic repercussions, besides controlling the inflammatory picture and avoid aesthetic complications.


Assuntos
Acne Vulgar/sangue , Androgênios/sangue , Hiperandrogenismo/diagnóstico , Adolescente , Criança , Feminino , Humanos , Hiperandrogenismo/sangue , Índice de Gravidade de Doença
17.
Arch Endocrinol Metab ; 64(1): 4-10, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32187268

RESUMO

Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10.


Assuntos
Tecido Adiposo/anatomia & histologia , Biomarcadores/sangue , Doenças Metabólicas/sangue , Síndrome do Ovário Policístico/sangue , 17-alfa-Hidroxiprogesterona/sangue , Adiponectina/sangue , Adolescente , Adulto , Androgênios/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante/sangue , Glucose/análise , Humanos , Insulina/sangue , Resistência à Insulina , Interleucina-6/sangue , Leptina/sangue , Hormônio Luteinizante/sangue , Fatores de Risco , Comportamento Sedentário , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
18.
Fertil Steril ; 113(3): 636-641, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32192596

RESUMO

OBJECTIVE: To determine whether biochemical or clinical markers of androgenic activity predict live birth rate with ovarian stimulation in the unexplained infertility population. DESIGN: Secondary analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): Nine hundred couples with unexplained infertility were included. Women were 18-40 years old with regular menses, a normal uterine cavity, at least one patent fallopian tube, and a male partner with ≥5 million motile sperm. Women were randomized to receive gonadotropin, clomiphene, or letrozole with IUI for four or fewer four treatment cycles. Women were evaluated for biochemical (total testosterone, DHEAS, and free androgen index) and clinical markers of androgenic activity (sebum, acne, and hirsutism). Multivariable logistic regression models adjusting for treatment group, maternal age, and body mass index were performed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Secondary outcomes included conception, clinical pregnancy, and pregnancy loss. RESULT(S): When comparing 900 women in the AMIGOS trial based on quartiles of serum TT, women were of younger age, higher body mass index, and higher waist circumference with increasing TT. Increasing quartiles of TT also showed increasing DHEAS and free androgen index values. Serum androgens were not associated with outcomes of live birth, conception, clinical pregnancy, or pregnancy loss. Clinical androgen markers were not associated with pregnancy outcomes. CONCLUSION(S): In a randomized cohort of women with unexplained infertility, biochemical and clinical measures of androgens did not predict live birth rate after ovarian stimulation treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.


Assuntos
Androgênios/sangue , Infertilidade Feminina/sangue , Infertilidade Feminina/terapia , Técnicas de Reprodução Assistida , Adulto , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Recém-Nascido , Infertilidade Feminina/epidemiologia , Nascimento Vivo/epidemiologia , Masculino , Indução da Ovulação/métodos , Indução da Ovulação/estatística & dados numéricos , Gravidez , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Resultado do Tratamento
19.
Eur J Endocrinol ; 182(4): 413-421, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32045360

RESUMO

Context: The human adrenal is the dominant source of androgens in castration-resistant prostate cancer (CRPC) and classic 21-hydroxylase deficiency (21OHD). Abiraterone, derived from the prodrug abiraterone acetate (AA), inhibits the activity of cytochrome P450 17-hydroxylase/17,20-lyase (CYP17A1), the enzyme required for all androgen biosynthesis. AA treatment effectively lowers testosterone and androstenedione in 21OHD and CRPC patients. The 11-oxygenated androgens are major adrenal-derived androgens, yet little is known regarding the effects of AA administration on 11-oxygenated androgens. Objective: To test the hypothesis that AA therapy decreases 11-oxygenated androgens. Design: Samples were obtained from 21OHD or CRPC participants in AA or AA plus prednisone (AAP)-treatment studies, respectively. Methods: We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure the 11-oxygenated androgens, 11ß-hydroxyandrostenedione, 11-ketoandrostenedione, 11ß-hydroxytestosterone, and 11-ketotestosterone, in plasma or serum samples from six 21OHD and six CRPC patients before and after treatment with AA or AAP, respectively. Results: In CRPC patients, administration of AAP (1000 mg/day AA with prednisone and medical castration) lowered all four 11-oxygenated androgens to below the lower limits of quantitation (<0.1-0.3 nmol/L), equivalent to 64-94% reductions from baseline. In 21OHD patients, administration of AA (100-250 mg/day for 6 days) reduced all 11-oxygenated androgens by on average 56-77% from baseline. Conclusions: We conclude that AA and AAP therapies markedly reduce the production of the adrenal-derived 11-oxygenated androgens, both in patients with high (21OHD) or normal (CRPC) 11-oxygenated androgens at baseline, respectively. Reduction of 11-oxygenated androgens is an important aspect of AA and AAP pharmacology.


Assuntos
Acetato de Abiraterona/farmacologia , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Androgênios/sangue , Androstenos/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/sangue , Adulto , Cromatografia Líquida , Quimioterapia Combinada , Humanos , Masculino , Prednisona/administração & dosagem , Neoplasias da Próstata/sangue , Espectrometria de Massas em Tandem , Testosterona/sangue
20.
J Steroid Biochem Mol Biol ; 198: 105615, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32014605

RESUMO

Adrenal steroids are generated in the adrenal cortex and metabolized by various enzymes such as hydroxylases, dehydrogenases, and reductases. Determining the comprehensive metabolic signatures of adrenal steroids can provide insight into their metabolic functions and roles in the pathophysiology of adrenal diseases, including Cushing's syndrome (CS) and congenital adrenal hyperplasia (CAH). To this end, we developed an advanced quantitative profiling method of serum adrenal steroids with liquid chromatography-mass spectrometry (LC-MS) under molecular-specific scan modes. Twenty-seven steroids were separated on a 1.9-µm particle C18 column (50 × 2.1 mm) at a flow rate of 250 µL/min and quantified via triple-quadrupole MS with electrospray ionization. During validation, linearities ( r2) were higher than 0.940 with a limit of quantification of 0.1-5.0 ng/mL, and precision (coefficient of variation) and accuracy (%bias) of 3.7-14.3 % and 96.3-113.1 %, respectively. In contrast with the significantly increased serum levels of mineralocorticoids (P <  0.001), the present LC-MS assay revealed remarkably decreased levels of all glucocorticoids and androgens in a patient diagnosed with 17α-hydroxylase deficiency CAH (P <  0.001) compared to those of age- and sex-matched healthy and CS subjects. In the CAH patient, the metabolic ratios for 17α-hydroxylase were significantly decreased, whereas there was no reduction in the metabolic ratio of 17-hydroxyprogesterone to androstenedione, indicating 17,20-lyase activity. In particular, both pregnenolone and dehydroepiandrosterone sulfates, and their metabolic ratio, were identified as potential biomarkers for 17α-hydroxylase deficiency (all P <  0.001), which were also distinct from those of CS patients. The devised LC-MS assay clearly revealed the metabolic signatures of 17α-hydroxylase deficiency, as a rare phenotype of CAH, compared to both healthy and CS subjects, indicating its utility for screening adrenal diseases.


Assuntos
Hiperplasia Suprarrenal Congênita/sangue , Esteroides/sangue , Adulto , Androgênios/sangue , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Glucocorticoides/sangue , Humanos , Mineralocorticoides/sangue , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos
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