RESUMO
PURPOSE: Knowledge of adolescent and adult phenotypes of women with polycystic ovary syndrome (PCOS) might drive opportune management. The aim of this study was to compare metabolic and obesity biomarkers between adolescent and adult women with PCOS. METHODS: This observational study compared biomarkers of obesity and metabolism derangements between adolescent (n = 62) and adult (n = 248) women with PCOS. Predictors of metabolic syndrome (MS) were investigated using univariate and multivariate binary logistic regression analysis. RESULTS: The postmenarcheal age of adolescents was 4.9 ± 0.03 years. Systolic blood pressure was lower in adolescents than in adults (112.3 mmHg vs 117.0 mmHg, p = 0.001) Diastolic blood pressure was also lower in adolescents (70.7 mmHg vs 75.8 mmHg, p < 0.001). Glucose intolerance (12.0% vs 19.3%) and insulin resistance (18.2% vs 17.7%) were similar in both groups (p > 0.05, for comparisons). Impaired fasting glucose was lower in adolescents (1.8% vs 11.6%, p = 0.015). Total cholesterol and low-density lipoprotein cholesterol were lower in adolescents (p < 0.001). MS in adolescents and adults were found in 10.3% and 27.8%, respectively (p = 0.005). Visceral adiposity index (VAI) was a good predictor of MS in both adolescents (OR = 12.2), and adults (OR = 9.7). CONCLUSIONS: Most biomarkers of glucose metabolism abnormalities were similar in adolescents and adults with PCOS. The prevalence of MS was lower in adolescents. VAI was a strong predictor of metabolic syndrome, both in adolescent and adult women with PCOS.
Assuntos
Glicemia/metabolismo , Doenças Metabólicas/complicações , Síndrome Metabólica/etiologia , Obesidade/complicações , Síndrome do Ovário Policístico/complicações , Adolescente , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , LDL-Colesterol/sangue , Feminino , Intolerância à Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina , Doenças Metabólicas/sangue , Doenças Metabólicas/epidemiologia , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Obesidade/sangue , Obesidade/epidemiologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/epidemiologia , Adulto JovemRESUMO
Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X-linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease-specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost-effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.
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Exoma , Doenças Raras , Criança , Estudos de Coortes , Consanguinidade , Exoma/genética , Feminino , Humanos , Gravidez , Doenças Raras/diagnóstico , Doenças Raras/genética , Sequenciamento do ExomaRESUMO
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, which affects 5-17% of reproductive age women and is often associated with obesity and metabolic impairment. Common treatment strategies are based on exercise, diet and nutrient supplementation since PCOS is often linked with obesity and metabolic impairment. Studies have recommended that nutrition is a key factor in the health maintenance of women with PCOS, however, little is known about the subject in the context of such a disease. This narrative review aims to identify dietary and nutritional aspects of PCOS and discuss the role of nutrients in management of polycystic ovary syndrome in view of clinical trials.
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Restrição Calórica , Dieta com Restrição de Carboidratos , Dieta Cetogênica , Suplementos Nutricionais , Síndrome do Ovário Policístico/dietoterapia , Dieta , Feminino , Preferências Alimentares , Humanos , Resistência à Insulina , Obesidade/dietoterapia , Obesidade/metabolismo , Síndrome do Ovário Policístico/metabolismoRESUMO
INTRODUCTION: Sexual dysfunction occurs in any phase of sexual performance or any period of the sexual response cycle, and polycystic ovary syndrome (PCOS) affects self-image with repercussions on sexuality. AIM: To evaluate sexual dysfunction in women with PCOS. METHODS: A systematic review was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The primary databases MEDLINE, EMBASE, Cochrane, and Lilacs were accessed using specific terms. There was no constraint against year of publication. The meta-analysis was conducted with RevMan program version 5.3. MAIN OUTCOME MEASURE: We evaluated the relationship between sexual dysfunction and PCOS. RESULTS: The systematic review encompassed 19 studies. The analysis indicated that 11 specific and 6 general instruments were used to measure the sexual function in PCOS women. Of these, the Female Sexual Function Index scale was used most frequently. All studies assessed different aspects of sexual performance in PCOS women, and no difference was found in between women with PCOS and control subjects. CLINICAL IMPLICATIONS: Although there were disparities regarding ethnicity, culture, religion, and economy among studies, the available evidence failed to prove a significant link between PCOS and sexual dysfunction. STRENGTH & LIMITATIONS: This systematic review addressed a multidimensional theme with many variables and with a wide diversity of measurement tools. Studies were small, and populations were not homogeneous. CONCLUSION: Despite potential risk of bias, such as inhomogeneity of study population, sexual function of both PCOS patients and women with regular menstrual cycles might, in general, be similar. Firmino Murgel AC, Santos Simões R, Maciel GAR, et al. Sexual Dysfunction in Women With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis. J Sex Med 2019;16:542-550.
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Síndrome do Ovário Policístico/fisiopatologia , Comportamento Sexual , Disfunções Sexuais Fisiológicas/fisiopatologia , Feminino , Humanos , Ciclo Menstrual/fisiologia , AutoimagemRESUMO
BACKGROUND: Polycystic ovary syndrome is a heterogeneous disorder and its presentation varies with race and ethnicity. Reproductive-age women with polycystic ovary syndrome are at increased risk of metabolic syndrome; however, it is not clear if prevalence of metabolic syndrome and clustering of its components differs based on race and ethnicity. Moreover, the majority of these women do not undergo routine screening for metabolic syndrome. OBJECTIVE: We sought to compare the prevalence of metabolic syndrome and clustering of its components in women with polycystic ovary syndrome in the United States with women in India, Brazil, Finland, and Norway. STUDY DESIGN: This is a cross-sectional study performed in 1089 women with polycystic ovary syndrome from 1999 through 2016 in 5 outpatient clinics in the United States, India, Brazil, Finland, and Norway. Polycystic ovary syndrome was defined by the Rotterdam criteria. Main outcome measures were: metabolic syndrome prevalence, blood pressure, body mass index, fasting high-density lipoprotein cholesterol, fasting triglycerides, and fasting glucose. Data from all sites were reevaluated for appropriate application of diagnostic criteria for polycystic ovary syndrome, identification of polycystic ovary syndrome phenotype, and complete metabolic workup. The US White women with polycystic ovary syndrome were used as the referent group. Logistic regression models were used to evaluate associations between race and metabolic syndrome prevalence and its components and to adjust for potential confounders, including age and body mass index. RESULTS: The median age of the entire cohort was 28 years. Women from India had the highest mean Ferriman-Gallwey score for clinical hyperandrogenism (15.6 ± 6.5, P < .001). The age-adjusted odds ratio for metabolic syndrome was highest in US Black women at 4.52 (95% confidence interval, 2.46-8.35) compared with US White women. When adjusted for age and body mass index, the prevalence was similar in the 2 groups. Significantly more Black women met body mass index and blood pressure criteria (P < .001), and fewer met fasting triglycerides criteria (P < .05). The age- and body mass index-adjusted prevalence of metabolic syndrome was highest in Indian women (odds ratio, 6.53; 95% confidence interval, 3.47-12.30) with abnormalities in glucose and fasting high-density lipoprotein cholesterol criterion and in Norwegian women (odds ratio, 2.16; 95% confidence interval, 1.17-3.98) with abnormalities in blood pressure, glucose, and fasting high-density lipoprotein cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence of metabolic syndrome and its components compared to US White women. CONCLUSION: Despite a unifying diagnosis of polycystic ovary syndrome, there are significant differences in the prevalence of metabolic syndrome and clustering of its components based on race and ethnicity, which may reflect contributions from both racial and environmental factors. Our findings indicate the prevalence of metabolic syndrome components varies in women with polycystic ovary syndrome, such that compared to White women from the United States, Black US women had the highest prevalence, whereas women from India and Norway had a higher prevalence of metabolic syndrome independent of obesity. The differences in clustering of components of metabolic syndrome based on ethnicity highlight the need to routinely perform complete metabolic screening to identify specific targets for cardiovascular risk reduction strategies in these reproductive-age women.
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Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Síndrome do Ovário Policístico/complicações , Grupos Raciais , Adulto , Brasil , Estudos Transversais , Feminino , Finlândia , Humanos , Índia , Noruega , Prevalência , Estados Unidos , Adulto JovemRESUMO
The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and prolactin receptor's (PRLR) expression in the adrenal. For this purpose, a total of 12 animals with intact ovaries were allocated to two groups: G1 (saline solution) and G2 (metoclopramide). A total of 30 oophorectomized animals was randomized to five subgroups: G3 (saline solution), G4 (metoclopramide), G5 (metoclopramide + 17ß-estradiol), G6 (metoclopramide + progesterone), and G7 (metoclopramide + 17ß-estradiol + progesterone). Immunohistochemical analyses were evaluated semi-quantitatively. For PRLR, the area fraction of labeled cells (ALC) varied from 1 (0-10%) to 3 (> 50%). Based on the mean of the immunostaining intensity, G2 and G4 showed strong expression; G6 and G7 presented a mild reaction; and G1, G3, and G5 exhibited a weak reaction. Concerning PRL, the ALC varied from 1 (0-10%) to 3 (> 50%), and groups G6 and G7 showed a strong reaction; G2, G4, and G5 showed a mild reaction; and G1 and G3 exhibited a weak reaction. These findings suggest that metoclopramide-induced hyperprolactinemia increases PRL expression in the adrenal glands of mice. Furthermore, progesterone alone or in association with estrogen also increases PRL expression, but to a lesser extent.
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Glândulas Suprarrenais/química , Hiperprolactinemia/induzido quimicamente , Metoclopramida/administração & dosagem , Prolactina/análise , Receptores da Prolactina/análise , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Estradiol/administração & dosagem , Estrogênios/sangue , Feminino , Hiperprolactinemia/metabolismo , Imuno-Histoquímica , Camundongos , Ovariectomia , Progesterona/administração & dosagem , Progesterona/sangue , Prolactina/sangueRESUMO
The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17ßE (ovariectomized mice treated with metoclopramide and 17ß estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17ßE+MP (ovariectomized mice treated with metoclopramide and a solution of 17ß estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17ßE+MP presented strong PRL expression. OvMET and OvMET+17ßE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17ßE+MP showed strong reaction; GrMET, OvSS, and OvMET+17ßE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.
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Estrogênios/farmacologia , Hiperprolactinemia/metabolismo , Progesterona/farmacologia , Prolactina/metabolismo , Receptores da Prolactina/metabolismo , Útero/efeitos dos fármacos , Animais , Estradiol/sangue , Estrogênios/sangue , Feminino , Hiperprolactinemia/sangue , Hiperprolactinemia/patologia , Camundongos , Ovariectomia , Progesterona/sangue , Prolactina/sangue , Útero/metabolismoRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved. OBJECTIVE: To investigate the association between exposure to BPA and PCOS. SEARCH STRATEGY: Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases. SELECTION CRITERIA: Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS. DATA COLLECTION AND ANALYSIS: Following PRISMA guidelines, study characteristics and relevant data were extracted. MAIN RESULTS: Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present. CONCLUSIONS: Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.
Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Fenóis , Síndrome do Ovário Policístico , Humanos , Feminino , Fenóis/efeitos adversos , Fenóis/urina , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/urina , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversosRESUMO
OBJECTIVE: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. METHODS: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. RESULTS: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. CONCLUSIONS: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.
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Proteína Forkhead Box O3 , Leiomioma , Neoplasias Uterinas , Humanos , Feminino , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Neoplasias Uterinas/metabolismo , Pessoa de Meia-Idade , Leiomioma/genética , Leiomioma/patologia , Leiomioma/metabolismo , Adulto , Imuno-Histoquímica , Regulação Neoplásica da Expressão Gênica/genética , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Leiomiossarcoma/metabolismo , Tumor de Músculo Liso/genética , Tumor de Músculo Liso/patologia , Tumor de Músculo Liso/metabolismo , Regulação para Cima , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , Idoso , Miométrio/metabolismo , Miométrio/patologiaRESUMO
Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.
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Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Gravidez , Humanos , Feminino , Hiperprolactinemia/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Brasil , Prolactina , Prolactinoma/diagnósticoRESUMO
Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.
Assuntos
Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Gravidez , Humanos , Feminino , Hiperprolactinemia/tratamento farmacológico , Prolactinoma/terapia , Agonistas de Dopamina/efeitos adversos , Prolactina , Neoplasias Hipofisárias/terapia , BrasilRESUMO
To evaluate changes in joints after physiotherapy in post-menopausal women, specifically to identify clinical responses to the measurements of flexibility, functional capacity and joint pain in early and late post-menopausal women at a multi-disciplinary health education programme. A total of 69 women participated in the Integral Program for the Attention to Climacteric Women at the Department of Gynecology - Federal University of Sao Paulo and were sorted into two groups of early (n = 32) and late (n = 37) post-menopause. The average age of menopause was 47.9 ± 5.6 years. The Blatt Kupperman Menopausal Index scores for the early (baseline = 12.8 ± 6.1) and late (baseline = 14.1 ± 7.7) post-menopausal groups after the programme were 8.4 ± 7.1 and 9.4 ± 8.1, respectively. Both groups presented improvements regarding functional capacity (p < 0.01) and complaints of pain (p < 0.001) after the intervention. The group of early post-menopausal women had better flexibility for hip flexion (p < 0.001), and the late post-menopausal group showed greater improvement in shoulder flexion (p < 0.001), extension (p < 0.001) and elbow flexion (p < 0.001). After multi-disciplinary approach, both early and late post-menopausal groups experienced decrease in intensity of climacteric symptoms, reduction in pain intensity and improvement in functional capacity, but the flexibility was different between both the groups.
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Artralgia/terapia , Modalidades de Fisioterapia , Pós-Menopausa/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Fatores Etários , Artralgia/epidemiologia , Artralgia/fisiopatologia , Peso Corporal/fisiologia , Brasil/epidemiologia , Feminino , Humanos , Comunicação Interdisciplinar , Pessoa de Meia-Idade , Educação de Pacientes como AssuntoRESUMO
INTRODUCTION: Women with premature ovarian insufficiency (POI) are exposed to a long period of estrogenic deficiency, which potentially brings higher health risks, especially regarding bone health. We performed a systematic review of the literature to evaluate the effect of hormone therapy (HT) on bone mineral density (BMD) in women with POI. MATERIALS AND METHODS: A systematic search was performed of the MEDLINE and EMBASE databases up to September 2021. We included studies that analyzed women with idiopathic (spontaneous) POI treated with HT, and those who had BMD evaluated. Analysis of risk of bias of studies selected was performed. RESULTS: We found 335 articles and selected 16 studies according to the inclusion criteria. Most of the studies revealed lower bone density in both the femoral neck and lumbar spine of women with POI compared with healthy women. Bone mass had the tendency to remain stable in women treated with estrogen + progestin therapy. However, in women already with bone mass loss, the therapy - in the doses most frequently used - was not able to revert the loss. Higher doses of estrogen seem to have a positive impact on BMD, as did combined oral contraceptives used continuously. Also, the interruption of HT for longer than one year was linked to significant bone loss. CONCLUSION: Although HT brings clear benefits, further studies are needed to establish its long-term effects, as well as doses and formulations with better protective effects on the bone mass of these women.
Assuntos
Menopausa Precoce , Insuficiência Ovariana Primária , Feminino , Humanos , Densidade Óssea , Insuficiência Ovariana Primária/tratamento farmacológico , Estrogênios/uso terapêutico , Terapia de Reposição HormonalRESUMO
PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erß, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.
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Anovulação , Hiperandrogenismo , Síndrome do Ovário Policístico , Gravidez , Recém-Nascido , Feminino , Humanos , Síndrome do Ovário Policístico/induzido quimicamente , Hiperandrogenismo/complicações , Anovulação/complicações , Fenóis/toxicidadeRESUMO
CONTEXT: Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database. OBJECTIVE: We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline. DESIGN: Observational, retrospective, and cross-sectional study. SETTING: This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center. PATIENTS AND METHODS: Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed. RESULTS: We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P < 0.001). CONCLUSIONS: The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Masculino , Humanos , Animais , Camundongos , Prolactinoma/tratamento farmacológico , Prolactinoma/genética , Agonistas de Dopamina/uso terapêutico , Cabergolina/uso terapêutico , Receptores da Prolactina , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/genética , Prolactina/genética , Ergolinas/farmacologia , Ergolinas/uso terapêutico , Estudos Retrospectivos , Estudos Transversais , Camundongos KnockoutRESUMO
BACKGROUND: We followed polycystic ovary syndrome (PCOS) women with metabolic syndrome (MS) over a six-year treatment period and evaluated the influence of PCOS phenotypes on MS and on the risk for type 2 diabetes mellitus (T2DM). METHODS: This was an observational study of 457 PCOS women, whose demographic, clinical, hormonal, and metabolic data underwent analysis. The PCOS women were divided into four groups per NIH recommendations. RESULTS: After a follow-up of a mean of six years (1-20 years), 310 patients were selected to assess the development of T2DM and MS. The clinical and biochemical parameters, along with the Rotterdam phenotypes, were evaluated. Data were analyzed using Student's t- and the Pearson chi-square tests for data variation and group proportions, respectively. Additionally, multivariate analysis was applied to evaluate the effect of PCOS phenotypes on the risk for MS and T2DM. Patients of the four PCOS phenotypes did not differ in age, body mass index, total testosterone, insulin resistance, and dyslipidemia, but phenotype A patients showed the highest risk for T2DM. A decrease in androgen levels was not followed by an improved metabolic profile; instead, there was a significant increase in the number of T2DM cases. CONCLUSION: Phenotype A women are at the highest risk for type 2 diabetes mellitus.
RESUMO
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy, which etiology encompasses complex genetic traits associated with epigenetic factors, including differences in microRNA (miRNA) expression in a variety of tissues. The circulating form of these molecules is raising attention in the syndrome not only as potential biomarkers of PCOS but also as possible therapeutic targets. The aim of this study was to explore the circulating miRNA profiles present in a cohort of Brazilian women with and without PCOS and to evaluate the potential role of miRNAs in the pathophysiology of the syndrome. METHODS: Cross-sectional study of 36 well-characterized PCOS women and 16 healthy controls. Clinical, hormone and metabolic data were recorded and evaluated. The expression profile of the 201 circulating miRNA selected were analyzed by taqman quantitative real time polymerase chain reactions (RT-PCR) using a customized Open Array platform. Statistical and bioinformatic analyzed were performed. RESULTS: Circulating miR-21-5p, miR-23a-3p and miR-26a-5p were upregulated, and miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p were downregulated in women with PCOS compared to healthy normo-ovulatory controls. miR-21-5p, miR-103a-3p and miR-376a-3p levels correlated positively with androgen levels. These miRNAs, in combination, were related to pathways involved in insulin signaling, steroids biosynthesis and endothelial regulation as well as in folliculogenesis. CONCLUSION: In this study, we identified a specific circulating miRNA signature in Brazilian women with PCOS. According to our data, circulating miR-21-5p, miR-23a-3p, miR-26a-5p, miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p may represent potential candidates for differential diagnosis of PCOS in the future.
Assuntos
MicroRNA Circulante , Insulinas , MicroRNAs , Síndrome do Ovário Policístico , Androgênios , Biomarcadores , Brasil/epidemiologia , MicroRNA Circulante/genética , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , EsteroidesRESUMO
Background: The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. Methods: This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. Results: The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance ≥ 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values ≥ 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. Conclusions: In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.
RESUMO
Thyroid diseases are relatively common in women in the reproductive period. It is currently understood that clinically-evident thyroid disorders may impair ovulation and, consequently, fertility. However, to date it has not been proven that high serum levels of thyroid-stimulating hormone and/or positivity for antithyroid antibodies are associated to a reduction in fertility, mainly in the absence of altered thyroxine levels. The present comprehensive review aims to present current data on the association between subclinical hypothyroidism and/or thyroid autoimmunity and reproductive outcomes.
As doenças da tireoide são relativamente comuns em mulheres no período reprodutivo. Atualmente, entende-se que distúrbios da tireoide clinicamente evidentes podem prejudicar a ovulação e, consequentemente, a fertilidade. No entanto, não se provou até o presente que níveis séricos altos do hormônio estimulador da tireoide e/ou positividade para anticorpos antitireoidianos estão associados a uma redução na fertilidade, sobretudo na ausência de níveis alterados de tiroxina. Esta revisão narrativa tem como objetivo apresentar dados atuais sobre a associação entre hipotireoidismo subclínico e/ou autoimunidade tireoidiana e resultados reprodutivos.
Assuntos
Hipotireoidismo/sangue , Complicações na Gravidez/sangue , Aborto Espontâneo , Doenças Assintomáticas , Feminino , Humanos , Gravidez , Resultado da Gravidez , Cuidado Pré-NatalRESUMO
Polycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in part from hypothalamic alterations in the pulsatile secretion of gonadotropin-releasing hormone (GnRH). The neuropeptide kisspeptin participates in the mechanism through stimulation of the hormone's production. The purpose of this study was to review the articles which compared kisspeptin levels in women with PCOS with those of controls. A systematic review of observational studies was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. The selected studies encompassed a population of patients with PCOS and controls, whose serum kisspeptin levels were evaluated. The studies were retrieved from the Medline, Cochrane, and Embase databases, and four of them were chosen for the review. In most studies, the serum kisspeptin levels were higher in women with PCOS than in controls notwithstanding the BMI. One of the articles showed that circulating plasma levels of kisspeptin were significantly higher in women with PCOS whose BMI was lower than 25 than in obese and overweight women. Our data suggest a higher concentration of serum kisspeptin in women with PCOS irrespective of their BMI. Further experimental and clinical studies are needed to ascertain the role of kisspeptin in PCOS.