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1.
PLoS One ; 14(12): e0226215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830090

RESUMO

Vitamin D deficiency is highly prevalent worldwide, and vitamin D-binding protein (DBP) a major regulator of serum vitamin D levels. The rs4588 and rs7041 polymorphisms of the GC gene constitute the genetic basis of the three major isoforms of circulating DBP (GC1s, GC1f, and GC2), while the rs2282679 variant is located in an important regulatory region of the GC gene. The aim of this study was to assess the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency and to ascertain whether it is associated with DBP levels and with GC gene variants. Biorepository samples of 443 women aged 20 to 72 years, with no evidence of clinical disease, were analyzed. Circulating levels of 25(OH)D were considered sufficient if ≥20 ng/mL and deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR. Mean age was 53.4±9.4 years; mean BMI was 27.8±5.8 kg/m2. The overall sample had mean 25(OH)D levels of 22.8±8.3 ng/mL; 39.7% of participants had deficient circulating 25(OH)D levels. Higher prevalence ratios (PR) of 25(OH)D deficiency were found for the CC genotype of rs2282679 (PR 1.74; 95%CI 1.30 to 2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17 to 2.38; p = 0.005), time since menopause (PR 1.02; 95%CI 1.003 to 1.03, p = 0.016), and HOMA-IR (PR 1.02; 95%CI 1.01 to 1.03, p = 0.004). DBP levels (per 30 µg/mL increase in DBP) were associated with lower PR for 25(OH)D deficiency (PR 0.89; 95%CI 0.80;0.99; p = 0.027). Except for HOMA-IR, these prevalence ratios remained significant after adjustment for age and BMI. In conclusion, the rs2282679 polymorphism and the GC2 isoform of DBP were associated with lower serum DBP levels and with susceptibility to 25(OH)D deficiency in Brazilian women with no evidence of clinical disease.

2.
BMJ Open ; 9(10): e029191, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640995

RESUMO

INTRODUCTION: Brazil is a large country, with a population of mixed ethnic background and broad variation in dietary and physical activity traits across its five main regions. Because data on Brazilian women with polycystic ovary syndrome (PCOS) are still scarce, a nation-wide collaborative study was designed to determine the prevalence of metabolic and reproductive abnormalities and the presence of anxiety and depression in Brazilian women with PCOS. In addition, the study aims at describing how these characteristics are distributed across PCOS phenotypes and at detecting associations with regional demographic and lifestyle aspects, genetic variants, and epigenetic markers. METHODS AND ANALYSIS: The Brazilian PCOS study is being conducted in the outpatient clinics of eight university hospitals within the public healthcare network (Unified Health System) across the country. Additional centres will be included following completion of the research ethics approval process. The sample includes women with PCOS according to Rotterdam criteria at inclusion in the study and a control group of healthy women matched by age, socioeconomic status and geographical region. Data will be collected in each centre and incorporated into a unified cloud database. Clinical, demographic, socioeconomic, psychological, metabolic, epigenetic and genotypic variables will be evaluated. The data resulting from this study will be useful to guide specific public strategies for primary and secondary prevention of metabolic and reproductive comorbidities in the PCOS population of Brazil. ETHICS AND DISSEMINATION: The study protocol was approved by each local Research Ethics Committee. Written informed consent will be obtained from each participant. During data collection, analysis and publication, care will be taken to ensure confidentiality of participant information. Study results will be published in peer-reviewed journals and disseminated at international conferences. This research protocol was registered with the Research Ethics Committee of HCPA, through Plataforma Brasil. TRIAL REGISTRATION NUMBER: CAAE 18082413.9.1001.5327.

3.
Neuroendocrinology ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31461715

RESUMO

For transgender individuals, gender-affirming surgery (GAS) and cross-sex hormone therapy (CSHT) are part of the gender transition process. Scientific evidence supporting the maintenance of CSHT after GAS-related gonadectomy is accumulating. However, few data are available with respect to the impact of CSHT on brain structure following hypogonadism. Thus, we aimed to investigate links between estradiol and brain cortical thickness and cognition in 18 post-gonadectomy transgender women using a longitudinal design. For this purpose, the participants underwent a voluntary period of CSHT washout of at least 30 days, followed by estradiol re-institution for 60 days. High-resolution T1-weighted brain images, hormonal measures, working and verbal memory were collected at two time points: on the last day of the washout (t1) and on the last day of the two-month CSHT period (t2). Between these two time points, cortical thickness increased within the left precentral gyrus and right precuneus but decreased within the right lateral occipital cortex. However, those findings did not survive corrections of multiple comparisons. Nevertheless, there was a significant negative correlation between changes in estradiol levels and changes in cortical thickness. This effect was evident in the left superior frontal gyrus, the left middle temporal gyrus, the right precuneus, the right superior temporal gyrus and the right pars opercularis. Although there was improvement in verbal memory following hypogonadism correction, we did not observe a significant relationship between changes in memory scores and cortical thickness. Altogether, these findings suggest that there is a link between estradiol and cortical thickness.

4.
Arch Endocrinol Metab ; 63(3): 190-198, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31340240

RESUMO

OBJECTIVE: To summarize current evidence regarding testosterone treatment for women with low sexual desire. MATERIALS AND METHODS: The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. RESULTS: Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. CONCLUSION: Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8.


Assuntos
Androgênios/uso terapêutico , Libido/efeitos dos fármacos , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Testosterona/uso terapêutico , Adolescente , Adulto , Idoso , Androgênios/efeitos adversos , Androgênios/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Sociedades Médicas , Testosterona/efeitos adversos , Testosterona/sangue , Adulto Jovem
5.
Arch. endocrinol. metab. (Online) ; 63(3): 190-198, May-June 2019. tab
Artigo em Inglês | LILACS-Express | ID: biblio-1011166

RESUMO

ABSTRACT Objective To summarize current evidence regarding testosterone treatment for women with low sexual desire. Materials and methods The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. Results Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. Conclusion Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8

6.
J. pediatr. (Rio J.) ; 95(3): 282-290, May-June 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012607

RESUMO

Abstract Objective: To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. Methods: A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. Results: After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. Conclusions: The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients.


Resumo Objetivo: Descrever os resultados obtidos em um programa de triagem neonatal após sua implementação e avaliar os perfis clínicos e moleculares de casos confirmados e suspeitos de hiperplasia adrenal congênita. Métodos: Foi feito um estudo transversal. Recém-nascidos com suspeita da doença devido aos altos níveis de 17-alfa-hidroxiprogesterona e ajustados pelo peso ao nascer foram selecionados. A hiperplasia adrenal congênita clássica (forma perdedora de sal e forma virilizante simples) foi diagnosticada por um aumento nos níveis de 17-alfa-hidroxiprogesterona confirmado no reteste, avaliação clínica e genótipo determinado com o uso do ensaio SNaPshot e amplificação multiplex de sondas dependente de ligação. Resultados: Após 24 meses, 15 casos clássicos de hiperplasia adrenal congênita foram diagnosticados em 217.965 recém-nascidos, com uma incidência estimada de 1:14.531. De 132 pacientes, sete não clássicos e 14 heterozigotos foram submetidos à triagem para mutações no gene CYP21A2 e 96 pacientes apresentaram resultados falso-positivos com CYP21A2 do tipo selvagem. No reteste, níveis aumentados de 17-alfa-hidroxiprogesterona foram encontrados em pacientes com hiperplasia adrenal congênita clássica e mostraram correlação significativa com HAC clássica relacionada ao genótipo. As mutações mais frequentes foram IVS2-13A/C>G, seguidas de deleção gênica ou eventos de rearranjo na forma clássica. Em casos de doenças não clássicas e heterozigose, a mutação p.Val282Leu foi a mais comum. Conclusões: Os resultados ressaltam a eficácia da triagem neonatal para a hiperplasia adrenal congênita no sistema público de saúde e indicam que a estratégia adotada foi adequada. A segunda coleta de amostras, juntamente com a genotipagem dos casos suspeitos, ajudou a diagnosticar adequadamente os casos graves e mais leves e diferenciá-los de pacientes com resultado falso-positivo.

8.
J Endocr Soc ; 3(5): 943-964, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31020058

RESUMO

Context: The impact of long-term cross-sex hormone therapy (CSHT) in transgender men and women is still uncertain. Objective: To perform a systematic review and meta-analysis and update the evidence regarding the effects of CSHT on bone mineral density (BMD) in transgender men and women. Data Sources: Medline, Cochrane Central Register of Controlled Trials, and Embase were searched for studies published until August 2018. Study Selection: Of 10,849 studies, 19 were selected for systematic review. All included patients were aged >16 years and received CSHT with BMD assessment by dual-energy X-ray absorptiometry (DXA). Data Extraction: Data on BMD, CSHT, and clinical factors affecting bone mass were collected. A National Institutes of Health scale was used to assess the quality of studies. Data Synthesis: Nineteen studies were meta-analyzed (487 trans men and 812 trans women). In trans men, mean BMD difference compared with natal women was not significant in any site in either cross-sectional or before-after studies. In trans women, mean BMD difference was not significant compared with natal men at the femoral neck, total femur, and lumbar spine in cross-sectional studies; before-after studies reported a slight but significant increase in lumbar spine BMD after 12 and ≥24 months of treatment. Conclusions: Long-term CSHT had a neutral effect on BMD in transgender men. In transgender women, only lumbar spine BMD seemed to be affected after CSHT. This evidence is of low to moderate quality as a result of the observational design of studies, small sample sizes, and variations in hormone therapy protocols.

9.
Gynecol Endocrinol ; : 1-5, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31006278

RESUMO

The aim of this study was to investigate the association between individual risk factors and coronary artery calcification (CAC), as a marker of subclinical cardiovascular disease, in a population-based nested cross-sectional study of midlife women. Anthropometric and metabolic data from 295 women from the South of Brazil were analyzed. Habitual physical activity was assessed by pedometer. CAC was assessed by a multi-detector computed tomography system. Average Agatston score was used to stratify participants as CAC > 0 and CAC = 0. Women with CAC > 0 (34.7%) were older (58.7 ± 5.4 vs. 56.3 ± 5.2 years, p < .001) and had higher prevalence of central adiposity (71 vs. 59%, p = .04) and hypertension (71 vs. 52%, p = .002) than women in the CAC = 0 group. Hormone therapy (HT) was more prevalent in the group with CAC = 0 (19.7 vs. 9.8%, p = .029). The prevalence ratios for CAC > 0 were 0.545 (95%CI:0.309-0.962, p = .036) for HT and 1.752 (95%CI:1.207-2.541, p = .003) for hypertension, after adjustment for age, educational level, smoking, alcohol intake, and physical activity. The present data in a population-based sample of midlife women indicate that hypertension and age were positively associated with higher risk for CAC > 0 and HT was related with CAC = 0.

10.
Fertil Steril ; 111(3): 579-587.e1, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30827526

RESUMO

OBJECTIVE: To assess the association of insulin resistance markers, body mass index (BMI), age, and androgen levels with systemic arterial hypertension (SAH) defined according to 2017 American College of Cardiology/American Heart Association (ACC/AHA) criteria in polycystic ovary syndrome (PCOS); and to determine the risk of metabolic abnormalities in the presence of SAH defined by both the 2017 ACC/AHA and Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) criteria in women with PCOS. DESIGN: Cross-sectional study. SETTING: Research center. PATIENT(S): Biobanked samples obtained from 233 women with PCOS and 70 controls without hirsute, ovulatory dysfunction. INTERVENTION(S): Metabolic, hormonal, and biochemical assessment. MAIN OUTCOME MEASURE(S): Blood pressure status according to 2017 ACC/AHA and JNC7 criteria and prevalence of metabolic abnormalities. RESULT(S): The prevalence of SAH among women with PCOS was 65% (n = 152) using 2017 ACC/AHA criteria and 26.6% (n = 62) considering JNC7 criteria. The 90 women whose SAH status was changed by 2017 ACC/AHA criteria were categorized as stage 1 SAH (systolic blood pressure 130-139 mmHg and/or diastolic blood pressure 80-89 mmHg), requiring nonpharmacologic therapy only (lifestyle changes). The prevalence of SAH in the control group was 41.4% (n = 29) according to 2017 ACC/AHA criteria and 12.8% (n = 9) according to JNC7 criteria. In all groups, SAH was associated with higher homeostasis model assessment and insulin levels compared with normal blood pressure (P<.01). In women with PCOS, the risk ratio for glucose ≥100 mg/dL (prevalence ratio 3.88, 95% confidence interval [CI] 1.30-11.55), high-density lipoprotein (HDL) <50 mg/dL (prevalence ratio 2.13, 95% CI 1.45-3.12), and triglycerides ≥150 mg/dL (prevalence ratio 3.39, 95% CI 1.56-7.35) was higher with SAH versus normal blood pressure when 2017 ACC/AHA criteria were applied, and did not increase or increased slightly when JNC7 criteria were applied (glucose ≥100 mg/dL, prevalence ratio 1.38, 95% CI 0.99-1.91), HDL <50 mg/dL (prevalence ratio 1.1, 95% CI 0.99-1.37), and triglycerides ≥150 mg/dL (prevalence ratio 1.48, 95% CI 1.13-1.94). CONCLUSION(S): The risk of cardiometabolic co-morbidities was increased in women with SAH defined by 2017 ACC/AHA criteria. Lower cutoffs for abnormal blood pressure seem appropriate for women with PCOS, providing a simple screening tool for cardiometabolic co-morbidities and an opportunity for early primary prevention.


Assuntos
Pressão Arterial , Hipertensão/diagnóstico , Síndrome do Ovário Policístico/diagnóstico , Adulto , American Heart Association , Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Brasil/epidemiologia , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia , Prevalência , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Estados Unidos , Adulto Jovem
11.
J Pediatr (Rio J) ; 95(3): 282-290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29715434

RESUMO

OBJECTIVE: To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. METHODS: A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. RESULTS: After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. CONCLUSIONS: The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Triagem Neonatal/métodos , Esteroide 21-Hidroxilase/sangue , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/genética , Biomarcadores/sangue , Brasil/epidemiologia , Estudos Transversais , Feminino , Genótipo , Humanos , Incidência , Recém-Nascido , Masculino , Mutação , Fenótipo
12.
J Pediatr (Rio J) ; 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30576629

RESUMO

OBJECTIVE: To analyze the association between age at menarche and variables of body composition in girls from the Northern region of Brazil, the Brazilian Legal Amazon. METHOD: The sample was composed of 926 school girls, aged between 8 and 18 years, divided into two groups, those who had (G1; n=727; 72.5%) and had not undergone menarche (G2; n=199; 21.5%), from public and private schools, using the stratified random proportional sampling technique. Weight, fat weight, muscle weight, and body mass index were measured using bioimpedance analysis. Body height was measured using a stadiometer. Age at menarche was obtained using the conventional method. For the evaluation of sexual maturation, self-assessment was performed according to criteria described by Tanner. RESULTS: The highest cumulative distribution of menarche was found at age 11, and presented significant differences between G1 and G2 at ages 11 and 12 years in all variables of body composition, except body mass index Z-score. Fat and muscle mass were associated with age at menarche. CONCLUSION: The present results support the notion of menarche anticipation in girls from Brazilian Amazon and its association with body composition. Further studies are needed to investigate the influence of other possible factors that may interfere with the time of growth spurt, thus determining the timing of puberty in these girls in comparison to other regions of Brazil.

13.
Endocr Connect ; 7(11): 1158-1167, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-30352422

RESUMO

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder affecting women of reproductive age. PCOS has been associated with distinct metabolic and cardiovascular diseases and with autoimmune conditions, predominantly autoimmune thyroid disease (AITD). AITD has been reported in 18-40% of PCOS women, depending on PCOS diagnostic criteria and ethnicity. The aim of this systematic review and meta-analysis was to summarize the available evidence regarding the likelihood of women with PCOS also having AITD in comparison to a reference group of non-PCOS women. We systematically searched EMBASE and MEDLINE for non-interventional case control, cross-sectional, or cohort studies published until August 2017. The Ottawa-Newcastle Scale was used to assess the methodological quality of studies. Statistical meta-analysis was performed with R. Thirteen studies were selected for the present analysis, including 1,210 women diagnosed with PCOS and 987 healthy controls. AITD was observed in 26.03% and 9.72% of PCOS and control groups respectively. A significant association was detected between PCOS and chance of AITD (OR= 3.27, 95%CI 2.32-4.63). Notably, after geographical stratification, the higher risk of AITD in PCOS women persisted for Asians (OR= 4.56, 95%CI 2.47-8.43), Europeans (OR= 3.27, 95%CI 2.07-5.15), and South Americans (OR= 1.86, 95 %CI 1.05-3.29). AIDT is a frequent condition in PCOS patients, and might affect thyroid function. Thus, screening for thyroid function and thyroid-specific autoantibodies should be considered in patients with PCOS even in the absence of overt symptoms. This systematic review and meta-analysis is registered in PROSPERO under number CRD42017079676.

14.
Thromb Res ; 168: 83-95, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29936403

RESUMO

INTRODUCTION: Hormone therapy (HT) is an effective treatment for climacteric symptoms. Nevertheless, combined estrogen-progestin therapy and the oral route seem to entail higher risk of venous thromboembolism (VTE) than estrogen-only therapy and transdermal administration. The present study aimed to investigate the risk of thromboembolic events in postmenopausal women using non-oral estrogen compared to women using oral estrogen and control groups (women receiving placebo or non-users of HT), as well as to assess the thrombotic impact of estrogens alone vs. combined estrogen-progestin therapy. MATERIALS AND METHODS: Systematic review of MEDLINE, Cochrane CENTRAL, EMBASE, and ClinicalTrials.gov according to PRISMA guidelines. RESULTS: Twenty-two studies were included in the meta-analyses (9 case-control studies, 9 cohort studies, and 4 randomized controlled trials). As compared to control groups, VTE risk was not increased with non-oral HT, including users of estrogens and estrogens plus progestins (OR 0.97 [0.9-1.06]), non-oral estrogen therapy (ET)-only (OR 0.95 [0.81-1.10]), and non-oral combined estrogen-progestin therapy (OR 0.92 [0.77-1.09]). Conversely, increased risk of VTE was observed as compared with control groups in users of oral HT, including users of estrogens and estrogens plus progestins HT (OR 1.72 [1.47-2.01]), oral ET-only (OR 1.43 [1.34-1.53]), and combined oral estrogen-progestin HT (OR 2.35 [1.9-2.9]). The comparison of non-oral vs. oral HT showed increased VTE risk with oral HT (OR 1.66 [1.39-1.98]). CONCLUSIONS: VTE risk was increased in postmenopausal women with no previous thromboembolic events using oral HT. Non-oral HT did not significantly affect this risk. The quality of the evidence produced in our meta-analyses is low to moderate, and further clinical trials are needed to sort out the impact of different types of progestin and different estrogen doses and administration routes on VTE risk.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Tromboembolia Venosa/etiologia , Administração Cutânea , Administração Oral , Terapia de Reposição de Estrogênios/métodos , Feminino , Terapia de Reposição Hormonal/métodos , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Tromboembolia Venosa/patologia
15.
Neurochem Res ; 43(7): 1476-1489, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29855847

RESUMO

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification. Immediately after surgeries, the ischemic animals were treated with GUO or a saline solution. Open field and elevated plus maze tasks were conducted with ischemic and naïve animals. Cylinder task, immunohistochemistry and infarct volume analyses were conducted only with ischemic animals. Female GUO groups achieved a full recovery of the forelimb symmetry at 28-35 days after the insult, while male GUO groups only partially recovered at 42 days, in the final evaluation. The ischemic insult affected long-term memory habituation to novelty only in female groups. Anxiety-like behavior, astrocyte morphology and infarct volume were not affected. Regardless the estrous cycle, the ischemic injury affected differently female and male animals. Thus, this study points that GUO is a potential neuroprotective compound in experimental stroke and that more studies, considering the estrous cycle, with both genders are recommended in future investigation concerning brain diseases.


Assuntos
Isquemia Encefálica/prevenção & controle , Córtex Cerebral/efeitos dos fármacos , Guanosina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Caracteres Sexuais , Animais , Isquemia Encefálica/patologia , Córtex Cerebral/patologia , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia
16.
Clin Endocrinol (Oxf) ; 88(6): 856-862, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29630732

RESUMO

OBJECTIVE: Cross-sex hormone therapy (CSHT) has been associated with changes in bone and lean/fat mass. This study assessed bone mineral density (BMD), appendicular lean mass (ALM), and total fat mass in transwomen undergoing CSHT. PATIENTS AND DESIGN: We evaluated 142 transwomen (mean age: 33.7 ± 10.3 years; BMI: 25.4 ± 4.6; 86.6% with previous CSHT) during the first 3 months of regular oestrogen treatment (with or without anti-androgens). A reference group including 22 men and 17 cis women was also studied. MEASUREMENTS: Clinical and hormonal evaluation and dual-energy X-ray absorptiometry (DXA). RESULTS: Bone mineral density was similar in trans and reference women, and lower at all sites in transwomen vs men. Low bone mass for age was observed in 18% of transwomen at baseline vs none of the reference women or men. Appendicular lean mass and total fat mass were positively correlated with L1-L4 BMD, explaining 14.9% of the observed variation in lumbar spine BMD and 20.6% of the variation in total femur BMD. Appendicular lean mass was similar in trans and reference women, and lower in transwomen vs men. Total fat mass was lower in trans vs reference women. Densitometry was repeated after a mean of 31.3 ± 6.5 months in 46 transwomen. There was a significant increase in total fat mass and a significant decrease in ALM. Bone mineral density remained stable over time. CONCLUSIONS: The fairly high prevalence of low bone mass in this sample of transwomen from southern Brazil seems to be related to lower ALM. Non-pharmacological lifestyle-related strategies for preventing bone loss could be beneficial for transgender women receiving long-term CSHT.


Assuntos
Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Transexualismo/tratamento farmacológico , Absorciometria de Fóton , Adolescente , Adulto , Composição Corporal/fisiologia , Índice de Massa Corporal , Densidade Óssea/fisiologia , Brasil , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Humanos , Modelos Lineares , Masculino , Adulto Jovem
17.
Reprod Biol Endocrinol ; 16(1): 38, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29669566

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder determined by polygenic traits as well as environmental factors. Lower vitamin D levels have been detected in PCOS women and related to hormone and metabolic disturbances. Vitamin D acts in tissues through the vitamin D receptor (VDR). VDR gene variants have been associated with worse metabolic profile in the general population. We investigated the genotype and haplotype distribution of the Bsm-I (rs1544410), Apa-I (rs7975232), and Taq-I (rs731236) VDR gene polymorphisms in PCOS and non-hirsute women from southern Brazil. We further investigated the associations of these gene variants and their haplotypes with PCOS, vitamin D levels, and metabolic abnormalities, including the metabolic syndrome (MetS). METHODS: A group of 191 women with PCOS (Rotterdam criteria) and 100 non-hirsute controls with regular ovulatory cycles were genotyped for all polymorphisms by real-time PCR, with allelic discrimination assays. MetS and the cutoffs for its isolated components were defined in accordance with the Joint Scientific Statement. RESULTS: Women with PCOS were younger and had significantly higher BMI and total testosterone levels than controls (p < 0.05). The frequency of MetS in PCOS and controls was 26.5% and 4.8% respectively. The CC genotype of Apa-I entailed higher risk of MetS in PCOS (OR: 2.133; 95% CI 1.020-4.464, p = 0.042), and was associated with higher systolic blood pressure (p = 0.009), total cholesterol (p = 0.040), and LDL-cholesterol (p = 0.038) in both PCOS and control groups (two-way ANOVA). The frequencies of VDR haplotypes were similar in PCOS and control women. CONCLUSIONS: The present results suggest that the Apa-I variant in VDR gene may be associated with MetS in southern Brazilian women with PCOS, and with blood pressure, total cholesterol, and LDL-c in women with and without PCOS.


Assuntos
Síndrome Metabólica/genética , Síndrome do Ovário Policístico/complicações , Polimorfismo Genético , Receptores de Calcitriol/genética , Fatores Etários , Índice de Massa Corporal , Estudos Transversais , Feminino , Haplótipos , Humanos , Síndrome Metabólica/complicações , Síndrome do Ovário Policístico/genética , Testosterona/sangue , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética
18.
Medicine (Baltimore) ; 97(8): e9881, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29465575

RESUMO

Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003-1.034]), total cholesterol (P = .038 [CI: 1.004-1.164]), fibrosis grade (P < .001 [CI: 0.000-0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus-host interaction.


Assuntos
Hepatite C Crônica/sangue , Hepatite C Crônica/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Proteína de Ligação a Vitamina D/genética , Vitamina D/análogos & derivados , Estudos Transversais , Feminino , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/sangue , Vitamina D/genética
19.
J Steroid Biochem Mol Biol ; 177: 209-215, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28734987

RESUMO

Polycystic ovary syndrome (PCOS) is a common condition characterised by both reproductive and metabolic features (obesity, insulin resistance, diabetes risk). Some evidence suggests that women with PCOS have lower vitamin D levels compared to healthy controls. Vitamin D binding protein (DBP) is the main carrier of vitamin D in circulation and plays an important role in regulating vitamin D concentration and bioavailability for target tissues. To our knowledge, no previous studies have examined DBP, bioavailable and free 25-hydroxyvitamin D (25(OH)D) in women with PCOS. The primary aim of this study was to compare DBP, bioavailable and free 25(OH)D concentrations in women with PCOS and controls. The secondary aim was to investigate relationships between DBP, bioavailable and free 25(OH)D and metabolic features (anthropometric measures, insulin resistance, and lipid profile). In a cross sectional study using bio-banked samples, we measured 25(OH)D, DBP and albumin. Bioavailable and free 25(OH)D were calculated using previously validated formula. BMI, body composition (dual X-ray absorptiometry, DXA), insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR)) and glucose infusion rate (GIR) from hyperinsulinaemic euglycaemic clamp and serum lipids (ELISA) were also measured in a physically and biochemically well-characterised cohort of women with and without PCOS. We studied 90 women with PCOS and 59 controls aged 18-48 years. DBP concentrations were lower in PCOS compared to controls (median [IQR]: 443.40 [314.4] vs 482.4 [156.8] µg/ml, p=0.02). No significant differences were found in bioavailable or free 25(OH)D concentrations between groups. DBP was not associated with BMI, percent body fat or markers of insulin resistance (all p>0.2). High-density lipoprotein (HDL) was the main determinant of DBP in the overall cohort (ß=-0.12, p=0.02), after adjusting for covariates including PCOS/control status, age, BMI, total 25(OH)D and HOMA-IR. In PCOS, total and free 25(OH)D were related to markers of insulin resistance and lipids. Only the associations between free 25(OH)D and triglycerides (p=0.02), and HDL (p=0.03) remained significant after adjusting for age and BMI. In conclusion, women with PCOS had lower DBP, but similar bioavailable or free 25(OH)D concentrations compared to controls, independent of BMI and age. DBP was not associated with insulin resistance or BMI in PCOS. Further studies are needed to investigate the pathophysiology and clinical implications of reduced DBP in PCOS.


Assuntos
Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Proteína de Ligação a Vitamina D/sangue , Vitamina D/análogos & derivados , Adolescente , Adulto , Glicemia/análise , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Pessoa de Meia-Idade , Vitamina D/sangue , Adulto Jovem
20.
Ann Nutr Metab ; 71(3-4): 224-233, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29136632

RESUMO

BACKGROUND/AIMS: There is a heightened risk for cardiovascular diseases in women with polycystic ovary syndrome (PCOS). Alterations in heart rate variability (HRV) may reflect subclinical cardiovascular disease, with a putative association between HRV and dietary fat. This study evaluated HRV in PCOS and control women based on the dietary intake of saturated fatty acid (SFA). METHODS: Biochemical/hormonal profile, resting metabolic rate, physical activity, HRV in response to the Stroop test, and dietary intake were assessed in 84 PCOS and 54 control women stratified by median SFA intake in the PCOS group (8.5% of daily energy intake). RESULTS: Body mass index (p = 0.041), blood pressure (p < 0.01), and HOMA-IR (p = 0.003) were higher in PCOS vs. CONTROLS: PCOS women had higher testosterone (p = 0.001), dehydroepiandrosterone sulfate (p = 0.012), and free androgen index (p = 0.001), and lower sex hormone-binding globulin levels than controls (p = 0.001). In both groups, the clinical profile and calorie intake were similar between SFA categories. In PCOS, testosterone was lower when SFA intake <8.5%. PCOS women with SFA <8.5% consumed more beans, fruits, and vegetables and had better frequency and time domain HRV indices. No differences in HRV were detected between SFA categories in controls. In PCOS, age and SFA intake were independent predictors of HRV. CONCLUSIONS: Lower SFA intake is related to improved cardiovascular autonomic function in PCOS.


Assuntos
Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Frequência Cardíaca , Síndrome do Ovário Policístico/terapia , Adolescente , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , Dieta , Feminino , Humanos , Síndrome do Ovário Policístico/fisiopatologia , Testosterona/sangue , Adulto Jovem
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