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1.
PLoS One ; 15(3): e0229576, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134933

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. METHODS AND FINDINGS: We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8-9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0-98.0) versus 80.7 (IQR: 75.1-86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85-0.93) versus 0.79 (IQR: 0.75-0.83), p < 0.01), systolic blood pressure (124 (IQR 112-135) versus 120 (IQR109-131), p < 0.04) and diastolic blood pressure (81 (IQR: 76-89) versus 78 (IQR: 71-86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1-9.4) versus 7.9 (IQR: 7.1-8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 µm (500-615) versus 684 µm (618-737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7-10.6) versus 6.0% (IQR: 3.9-9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. CONCLUSIONS: Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02616510.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Insuficiência Ovariana Primária/fisiopatologia , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus/fisiopatologia , Feminino , Glucose/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Lipídeos/sangue , Menopausa/sangue , Menopausa/metabolismo , Menopausa/fisiologia , Menopausa Precoce/sangue , Menopausa Precoce/metabolismo , Menopausa Precoce/fisiologia , Pessoa de Meia-Idade , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/metabolismo , Estudos Prospectivos , Análise de Onda de Pulso/métodos , Fatores de Risco , Rigidez Vascular/fisiologia , Circunferência da Cintura/fisiologia , Relação Cintura-Quadril/métodos
2.
Expert Opin Pharmacother ; 21(4): 409-415, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31928093

RESUMO

Introduction: Dyspareunia caused by vulvovaginal atrophy is a primary symptom of genitourinary syndrome of menopause (GSM), a chronic, progressive medical condition that results from estrogen and androgen deficiency at menopause. Dehydroepiandrosterone (DHEA, prasterone) is an endogenous precursor steroid hormone that is metabolized into both androgens and estrogens that has been recently been approved by the FDA for the treatment of moderate to severe dyspareunia caused by vulvovaginal atrophy secondary to menopause.Areas covered: This is a comprehensive drug evaluation describing the chemical composition, pharmacokinetics, metabolism, clinical efficacy and safety of dehydroepiandrosterone (prasterone) in the treatment of dyspareunia and VVA secondary to menopause. Preclinical and clinical data suggesting further potential uses, benefits, and contraindications in the genitourinary health of postmenopausal women are also considered.Expert opinion: Intravaginal dehydroepiandrosterone (prasterone) is effective for the management of dyspareunia secondary to menopause and may be effective in the treatment of other types of sexual dysfunction that are secondary to menopause. Further studies should explore additional dosing regimens and different indications.


Assuntos
Desidroepiandrosterona/uso terapêutico , Doenças Urogenitais Femininas/tratamento farmacológico , Menopausa/metabolismo , Vagina/efeitos dos fármacos , Administração Intravaginal , Androgênios/metabolismo , Atrofia , Desidroepiandrosterona/administração & dosagem , Dispareunia/tratamento farmacológico , Dispareunia/metabolismo , Estrogênios/metabolismo , Feminino , Doenças Urogenitais Femininas/metabolismo , Humanos , Resultado do Tratamento , Vagina/patologia
3.
J Ethnopharmacol ; 246: 112207, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476440

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang (LWDH) is a classic prescription that has been used as a traditional medicinal formula for more than 1000 years in China. In clinical, LWDF is used for treating functional decline associated with senile disease and menopausal syndrome. Studies have demonstrated that LWDH could significantly improve estrogen level and ER expression, and suspend the process of atherosclerosis. However, the under mechanism of how LWDH suppressing VSMCs phenotypic conversion and proliferation through ER is still unknown. AIM OF THE STUDY: This study was to reveal the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs. MATERIALS AND METHODS: 24 ApoE-/- mice were divided into 4 groups: sham group, model group, E2 group, and LWDH group, and 6 C57BN/L6 mice were used as control group. The primary VSMCs were divided into control group, model group, E2 group, LWDH group, LWDH + MPP group, and LWDH + PHTPP group with or without control siRNA, ERα siRNA, ERß siRNA, and myocardin siRNA. Oil red staining was used to evaluate the lipid deposition in the cardiac aorta. Serum chemistry analysis to test serum TG, TC, LDL, and HDL. Immunofluorescence staining was used to test α-SMA, osteopontin and F-actin. Immunohistochemical staining was performed to check out the myocardin in the cardiac aorta. The mRNA levels of α-SMA, osteopontin, ERα, ERß, SRC3 and myocardin were detected by Real Time-PCR, and the protein expression levels of them were detected by Western blotting. Co-immunoprecipitation was proceed to test the interaction between ERα and SRC3 and SRC3 and myocardin. Flow cytometry was used to check out the cell cycle. Wound healing assay and Transwell were managed to evaluate the migration capacity of VSMCs. RESULTS: In vivo administration of LWDH suppressed AS symptoms, decreases phenotypic marker of vascular endothelial cell, and increases phenotypic marker of VSMC in ovariectomized ApoE-/- female mice. Moreover, LWDH significantly increased the mRNA and protein expression levels of ERα, ERß, SRC3 and myocardin in the cardiac aorta of ovariectomized ApoE-/- female mice. In vitro, LWDH altered cell cycle and reduced the elevated cyclinD protein expression migration capacity and in the model VSMCs. In addition, LWDH inhibited phenotypic conversion and promoted the expression of ER, SRC3, and myocardin of the primary VSMC phenotypic conversion model. Inhibition of ERα almost completely eliminated the impacts of LWDH on α- SMA and osteopontin. Furthermore, LWDH promoted the interaction between ERα and SRC3 and up-regulated the co-activation of SRC3 and myocardin. CONCLUSIONS: LWDH could inhibit the phenotypic conversion of VSMCs in vitro and in vivo by increasing the activity of myocardin through up-regulating the expression of ERα and promoting the interaction between ERα and SRC3. Our research reveals the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs.


Assuntos
Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Aorta/metabolismo , Cápsulas , Células Cultivadas , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Menopausa/genética , Menopausa/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Proteínas Nucleares/genética , Osteopontina/genética , Osteopontina/metabolismo , Fenótipo , Ratos Sprague-Dawley , Transativadores/genética , Regulação para Cima/efeitos dos fármacos
4.
Ann N Y Acad Sci ; 1461(1): 127-143, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31868931

RESUMO

One of the leading causes for the development of adverse metabolic effects, including type 2 diabetes, dyslipidemia, and cardiovascular diseases, is the accumulation of excess body weight, often measured by body mass index (BMI). Although BMI, calculated using weight and height, is the standard measure used to determine body adiposity in clinical and public health guidelines, an inherent limitation is that BMI does not distinguish where in the body adiposity is deposited. Central obesity, characterized by greater accumulation of adiposity in the abdominal region, has been associated with a higher risk of mortality, independent of BMI. Importantly, one of the determinants of body fat distribution is sex hormones. Both estrogens and androgens appear to directly and indirectly influence body fat distribution. Our review will focus specifically on the role of estrogens and their influence in determining body fat distribution and overall health of adipose tissues, and the role of epigenetic mechanisms in regulating the production and function of estrogens.


Assuntos
Tecido Adiposo/metabolismo , Estrogênios/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/crescimento & desenvolvimento , Animais , Hormônios Esteroides Gonadais/metabolismo , Humanos , Menopausa/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
5.
PLoS Biol ; 17(12): e3000565, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805037

RESUMO

Why a postfertile stage has evolved in females of some species has puzzled evolutionary biologists for over 50 years. We propose that existing adaptive explanations have underestimated in their formulation an important parameter operating both at the specific and the individual levels: the balance between cancer risks and cancer defenses. During their life, most multicellular organisms naturally accumulate oncogenic processes in their body. In parallel, reproduction, notably the pregnancy process in mammals, exacerbates the progression of existing tumors in females. When, for various ecological or evolutionary reasons, anticancer defenses are too weak, given cancer risk, older females could not pursue their reproduction without triggering fatal metastatic cancers, nor even maintain a normal reproductive physiology if the latter also promotes the growth of existing oncogenic processes, e.g., hormone-dependent malignancies. At least until stronger anticancer defenses are selected for in these species, females could achieve higher inclusive fitness by ceasing their reproduction and/or going through menopause (assuming that these traits are easier to select than anticancer defenses), thereby limiting the risk of premature death due to metastatic cancers. Because relatively few species experience such an evolutionary mismatch between anticancer defenses and cancer risks, the evolution of prolonged life after reproduction could also be a rare, potentially transient, anticancer adaptation in the animal kingdom.


Assuntos
Adaptação Fisiológica/fisiologia , Menopausa/fisiologia , Neoplasias/prevenção & controle , Animais , Evolução Biológica , Feminino , Humanos , Menopausa/metabolismo , Neoplasias/fisiopatologia , Reprodução/fisiologia
6.
Int J Mol Sci ; 20(21)2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661891

RESUMO

: Worldwide, breast cancer (BC) is the most common malignancy in women, in regard to incidence and mortality. In recent years, the negative role of obesity during BC development and progression has been made abundantly clear in several studies. However, the distribution of body fat may be more important to analyze than the overall body weight. In our review of literature, we reported some key findings regarding the role of obesity in BC development, but focused more on central adiposity. Firstly, the adipose microenvironment in obese people bears many similarities with the tumor microenvironment, in respect to associated cellular composition, chronic low-grade inflammation, and high ratio of reactive oxygen species to antioxidants. Secondly, the adipose tissue functions as an endocrine organ, which in obese people produces a high level of tumor-promoting hormones, such as leptin and estrogen, and a low level of the tumor suppressor hormone, adiponectin. As follows, in BC this leads to the activation of oncogenic signaling pathways: NFκB, JAK, STAT3, AKT. Moreover, overall obesity, but especially central obesity, promotes a systemic and local low grade chronic inflammation that further stimulates the increase of tumor-promoting oxidative stress. Lastly, there is a constant exchange of information between BC cells and adipocytes, mediated especially by extracellular vesicles, and which changes the transcription profile of both cell types to an oncogenic one with the help of regulatory non-coding RNAs.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Obesidade Abdominal/complicações , Obesidade Abdominal/metabolismo , Adiponectina/efeitos adversos , Adiponectina/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Neoplasias da Mama/fisiopatologia , Transformação Celular Neoplásica/metabolismo , Estrogênios/efeitos adversos , Estrogênios/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Feminino , Humanos , Inflamação/fisiopatologia , Leptina/imunologia , Leptina/metabolismo , Menopausa/metabolismo , MicroRNAs/metabolismo , Obesidade Abdominal/fisiopatologia , Transdução de Sinais/genética , Microambiente Tumoral/imunologia
7.
PLoS One ; 14(9): e0222239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509577

RESUMO

AIM: To investigate circulating hormonal, metabolic and inflammatory biomarker profiles in obese and non-obese middle-aged women. METHODS: A total of 110 women, aged 40-60 years, were included in this cross-sectional study. Patients were allocated, according to the occurrence of menopause and body mass index (BMI), into four groups: PM0 (premenopausal non-obese), PM1 (premenopausal obese), M0 (postmenopausal non-obese), and M1 (postmenopausal obese). Serum levels of gonadotropins, sex hormones, lipid markers, leptin, hs-CRP and interleukin-6 were obtained using either colorimetric or immunoenzymatic assays. Univariate and correlation analyses were performed among all clinical and laboratorial parameters. Principal component analysis was used to characterize subsets of biomarkers, which had their discriminatory capacity tested using discriminant function analysis. RESULTS: Levels of gonadotropins and female sex hormones were similar between PM0 and PM1 and between M0 and M1 (p > 0.05), all of them varied between PM0 and M0 (p < 0.05), but only estradiol was significantly altered in the comparison between PM1 and M1 (p = 0.027). Regarding metabolic markers, leptin was lower in PM0 than in M0 (p = 0.010) and higher in M1 than in M0 (p = 0.046). In premenopausal women, BMI correlated only to leptin, while it correlated to several other markers in postmenopausal women. A combination of FSH and leptin serum levels significantly discriminated the four groups (Wilks's lambda < 0.001, in canonical functions 1 and 2). CONCLUSION: A combined analysis of hormonal biomarkers may potentially distinguish obese from non-obese women with distinct menopause status. Further research is thus required to clarify the clinical significance of such findings.


Assuntos
Menopausa/metabolismo , Obesidade/metabolismo , Biomarcadores/sangue , Índice de Massa Corporal , Brasil/epidemiologia , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/sangue , Gonadotropinas/análise , Gonadotropinas/sangue , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Leptina/análise , Leptina/sangue , Lipídeos/análise , Lipídeos/sangue , Menopausa/sangue , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Pós-Menopausa/sangue , Pré-Menopausa/sangue
8.
Front Horm Res ; 53: 135-161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31499509

RESUMO

Menopause is the period of a woman's life that is characterized by the permanent cessation of menses associated to hormonal changes, of which the most important is the decrease of estrogen levels. Following menopause, the concentrations of circulating androgens decrease. However, increased concentrations of luteinizing hormone induce androgens secretion from the ovaries and presumably from the adrenal glands. Peripheral conversion of androgens results to the circulating hormonal androgen profile. Some pathological conditions are associated with greater concentrations of androgens after menopause than in controls, with polycystic ovary syndrome (PCOS) being the commonest. These conditions can be distinguished in non-tumorous (adrenal or ovarian) or functional and tumorous (adrenal or ovarian benign or malignant) masses. Apart from PCOS, other non-tumorous (adrenal or ovarian) causes of hyperandrogenism in post-menopausal women are obesity, non-classic congenital adrenal hyperplasia (NCCAH), endocrinopathies, such as Cushing disease or acromegaly; ovarian hyperthecosis, drug use or abuse. Tumorous (adrenal or ovarian) causes include adrenal cortical cancers, adrenal benign adenomas and even incidentalomas, or ovarian tumors such as the sex-cord stromal ovarian tumors and metastases in the ovary. The diagnosis of hyperandrogenism is made through medical history, clinical examination, and laboratory tests. Total testosterone concentration of 150 ng/dL can be used at first to distinguish a malignant from a benign cause of hyperandrogenism. Dehydroepiandrosterone sulfate concentration may support adrenal source of androgens. Imaging techniques are used to localize the source of androgens: computed tomography and magnetic resonance imaging (MRI) for the adrenals and transvaginal ultrasound or MRI for the ovaries. Finally, treatment (etiologic and symptomatic) and long-term effects of hyperandrogenism are developed in this chapter.


Assuntos
Glândulas Suprarrenais/metabolismo , Androgênios/metabolismo , Hiperandrogenismo/metabolismo , Menopausa/metabolismo , Ovário/metabolismo , Síndrome do Ovário Policístico/metabolismo , Glândulas Suprarrenais/diagnóstico por imagem , Feminino , Humanos , Hiperandrogenismo/diagnóstico por imagem , Ovário/diagnóstico por imagem , Síndrome do Ovário Policístico/diagnóstico por imagem
9.
Biomed Res Int ; 2019: 1926352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428628

RESUMO

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression.


Assuntos
Camellia sinensis/química , Córtex Cerebral , Glucose/metabolismo , Extratos Vegetais/farmacologia , Tomografia por Emissão de Pósitrons , Estresse Psicológico , Animais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Menopausa/metabolismo , Ovariectomia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo
10.
Clin Rheumatol ; 38(11): 3117-3127, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31363873

RESUMO

OBJECTIVE: Visceral adipose tissue (VAT) is becoming a recognized cardiovascular (CV) risk factor. This study aimed to evaluate body composition, especially VAT, in systemic lupus erythematosus (SLE) and to explore the association between VAT and SLE disease-related factors. METHOD: Ninety-eight inpatients with SLE and 108 age- and body mass index (BMI)-matched healthy controls were included. Demographic and clinical parameters were recorded. The VAT was measured by dual-energy x-ray absorptiometry. RESULT: The mean age and disease duration of patients were 46.4 ± 13.0 years and 8.0 ± 7.0 years, respectively. Patients with SLE had higher VAT volume (p = 0.0015) and mass (p = 0.0017) than controls, especially in premenopausal and postmenopausal groups. The subanalysis of subjects with BMI less than 25 kg/m2 indicated that patients had lower lean mass (p = 0.0005), fat-free mass (p = 0.0005), and fat-free mass index (p = 0.0001), but increased adiposity distribution than controls, including VAT volume and mass. However, overweight/obese patients had similar body composition with controls. The VAT volume correlated with BMI, age, menopausal status, hypertension, uric acid, creatinine, non-high-density lipoprotein cholesterol, and triglyceride in both groups. In the patient group, the VAT volume correlated with disease duration, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), and low serum complement, but not with SLEDAI and glucocorticoid dose. CONCLUSION: This study suggested that SLE patients had some traditional CV risk factors such as altered body composition and increased VAT. The higher VAT in patients with SLE was associated with traditional cardiometabolic risks, which may contribute to CV events in SLE populations. Key Points • Patients with SLE had increased VAT volume and mass than controls. • The VAT volume correlated with traditional cardiometabolic risk factors. • In SLE patient group, the VAT volume correlated with disease duration, SLICC/ACR-DI, and low serum complementC3/C4, but not with SLEDAI and glucocorticoid dose.


Assuntos
Gordura Intra-Abdominal , Lúpus Eritematoso Sistêmico/metabolismo , Adulto , Composição Corporal , Estudos de Casos e Controles , Feminino , Humanos , Menopausa/metabolismo , Pessoa de Meia-Idade
12.
Biomed Res Int ; 2019: 8921284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467917

RESUMO

Ideal animal models are needed to reflect the changes in the biochemical and biomechanical properties of the vagina that occur in pelvic organ prolapse (POP). In this study, we aimed to demonstrate the short and long-term effect of menopause on the biochemical and biomechanical properties of rat anterior vaginas. Here, Sprague-Dawley rats were bilaterally ovariectomized to induce menopause. Rats without ovariectomy served as the normal control group (n=12). The histology changes and the expression of collagen I, III, and a-SMA were assessed to indicate the biochemical changes in the vagina 2 weeks, 4 weeks, and 16 weeks after ovariectomy (n=6 for 2 and 4 weeks, n=12 for 16 weeks). Uniaxial biomechanical testing was conducted in the control group and ovariectomized rats 16 weeks after ovariectomy. Compared with the control group, the ovariectomy group showed a significant increase in the expression of collagen I 2 weeks after ovariectomy, while collagen III showed a declining trend. Two weeks after ovariectomy, the smooth muscle bundles began to become disorganized, and the fraction of smooth muscle in the nonvascular muscularis of the proximal vagina was significantly decreased (P<0.001). However, there was no difference in the expression of a-SMA in the distal vagina. Compared with the control group, the ovariectomy group had stiffer vaginas with a declining trend in the ultimate load 16 weeks after ovariectomy. In conclusion, surgically induced menopause had a significant short- and long-term impact on tissue composition and biomechanical properties of the rat vagina, which may lead to increased susceptibility to POP development.


Assuntos
Colágeno/metabolismo , Ovariectomia , Vagina/metabolismo , Animais , Colágeno/genética , Feminino , Humanos , Menopausa/genética , Menopausa/metabolismo , Músculo Liso/metabolismo , Prolapso de Órgão Pélvico/metabolismo , Ratos , Ratos Sprague-Dawley , Vagina/fisiologia
13.
Cancer Control ; 26(1): 1073274819865279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31343899

RESUMO

Little is known about breast cancer in Vietnamese women. Previous studies have reported the frequencies of prognostic factors of breast cancer in this population. The aim of this study was to examine the prognostic factors associated with the survival rates of patients with breast cancer treated at the National Cancer Hospital, Hanoi, Vietnam. We recruited 248 women with operable breast cancer treated with surgery and adjuvant therapy. Tumor tissue samples were stained by many immunohistochemical approaches and analyzed for estrogen receptor, progesterone receptor, and HER2 gene amplification status. A Cox model was used to determine the relationship between survival and the prognostic factors. The disease-free survival rate, overall survival rate, and cancer-specific survival rate were 75.8%, 80.6%, and 86.4%, respectively, at 5 years and 62.3%, 68.1%, and 78.9%, respectively, at 10 years. The lung was the most common metastatic site. Women with factors associated with a poor prognosis (eg, advanced clinical stage, high tumor grade, progesterone receptor [PR] negativity, HER2 amplification) had significantly lower survival rates. Patients with PR-negative breast cancer had significantly worse survival rates compared to those who were PR positive, according to multivariate analysis (hazard ratio = 1.77, 95% confidence interval: 1.01-3.11, P = .045); however, there was only a statistically significant difference in postmenopausal patients. The PR was a prognostic factor in postmenopausal women with breast cancer, but not in premenopausal women.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Mama/patologia , Adulto , Idoso , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Menopausa/metabolismo , Pessoa de Meia-Idade , Pré-Menopausa/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Vietnã/epidemiologia
14.
Discov Med ; 27(149): 177-188, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31361980

RESUMO

Genistein is an isoflavone derived from soy-rich products, which is known to exhibit several beneficial biological effects, such as anti-tumor activity, improvement of glucose metabolism, and reduction of the frequency of peri-menopausal hot flashes, and thus has potential for clinical application. Certain limitations and side effects, such as low bioavailability, biological estrogenic activity, and detrimental effects on thyroid function, have restricted its clinical applications to some extent. Recently, it has been reported that fermentation, use of micromicelles, and modification of its chemical structure can enhance the bioavailability of genistein. Moreover, the modification of its molecular structure may also eliminate its biological estrogenic activity and adverse effects on thyroid function. In this review, we summarize the clinical application prospects and limitations of genistein, as well as the plausible solutions to overcome its low bioavailability, phytoestrogenic activity, and adverse effects on thyroid function.


Assuntos
Antineoplásicos Fitogênicos , Estrogênios , Genisteína , Fogachos/tratamento farmacológico , Menopausa/metabolismo , Glândula Tireoide/metabolismo , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Estrogênios/farmacocinética , Estrogênios/uso terapêutico , Feminino , Genisteína/farmacocinética , Genisteína/uso terapêutico , Fogachos/metabolismo , Fogachos/patologia , Humanos , Micelas
15.
Carcinogenesis ; 40(8): 1031-1041, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31168625

RESUMO

It is generally accepted that androgen receptors increase the risk of hepatocellular carcinoma (HCC), and that estrogen reduces risk of HCC. Many studies regarding this have involved males. We, therefore, have focused our attention on females, especially postmenopausal females, who typically have limited supplies of estrogen. By using sex hormone-binding globulin (SHBG) transgenic mice, we produced a humanoid environment, and facilitated deposition and modulation of sex hormones. After exposure to diethylnitrosamine to induce HCC and upon reaching the age of 40 weeks, mice were fed the fat-rich diet for 5 months. Fat-rich diet fed or ovariectomized (OVX) wild-type mice aged 62 weeks showed HCC progression, whereas fat-rich diet fed SHBG mice or OVX SHBG mice displayed fewer tumors. In the liver of fat-rich diet fed SHBG mice, estrogenic conditions including high levels of 17ß-estradiol and estrogen receptor alpha led to the induction of the lipogenesis inhibitor, phosphorylated acetyl-CoA carboxylase, and consequently suppressed fatty liver. The presence of plasma SHBG in HCC bearing mice suppressed the levels of steatosis and inflammation in a process mediated by estrogens and estrogen receptor alpha. Conversely, in the liver of OVX SHBG mice, lipogenic inhibition was also observed under conditions where the supply of estrogens is limited. Through in vitro experiment, it was confirmed SHBG suppresses lipogenesis via inhibition of acetyl-CoA carboxylase level. In conclusion, our results show that plasma SHBG might have a clinical impact on lipid-mediated hepatic diseases.


Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Globulina de Ligação a Hormônio Sexual/genética , Acetil-CoA Carboxilase/genética , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Dieta Hiperlipídica , Dietilnitrosamina/toxicidade , Modelos Animais de Doenças , Estradiol/metabolismo , Receptor alfa de Estrogênio/genética , Estrogênios/metabolismo , Feminino , Humanos , Lipogênese/genética , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Menopausa/genética , Menopausa/metabolismo , Camundongos , Camundongos Transgênicos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Androgênicos/genética
16.
Ren Fail ; 41(1): 507-520, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31216906

RESUMO

Menopause is an important physiological event associated with structural and functional changes in the kidneys. An animal model of bilateral ovariectomy was used to study the effects of estrogen depletion, replacement and antiestrogen on renal structure and endocrine function. Sixty female rats were divided into six groups; group I was the control group, the remaining five groups underwent ovariectomy: group II received no treatment. The other groups received estradiol in group III, tamoxifen in group IV, estradiol followed by tamoxifen in group V and tamoxifen followed by estradiol in group VI. Serum creatinine, blood urea nitrogen, and endocrine functions of kidney were measured. Tissue samples were examined both microscopically for beta estrogen receptors and ultrastructurally for cell changes. Groups II, IV & VI showed a significant increase in creatinine, blood urea nitrogen, renal malondialdehyde, renal erythropoietin, plasma renin and plasma prostaglandin E2 and a significant decrease in renal antioxidants and serum vitamin D3. Groups III &V had a significant decrease in creatinine, blood urea nitrogen, renal malondialdehyde and renal erythropoietin with an increase in renal antioxidants, plasma prostaglandin E2 and serum vitamin D3. Histopathological and ultrastructural examinations revealed atrophic tubular changes in group II. The changes were less marked in groups III &V and more extensive in groups IV & VI. Estrogen receptor beta staining showed progressively increased expression in the absence of estrogen. Structural and most endocrine functions of the kidney were significantly affected by estradiol deficiency. Estradiol replacement exhibited a protective effect on renal tissue and endocrine functions.


Assuntos
Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Rim/metabolismo , Menopausa/efeitos dos fármacos , Animais , Antagonistas de Estrogênios/administração & dosagem , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Menopausa/metabolismo , Modelos Animais , Ovariectomia/efeitos adversos , Ratos , Tamoxifeno/administração & dosagem
17.
Am J Physiol Heart Circ Physiol ; 317(2): H395-H404, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31173499

RESUMO

Despite significant decreases in cardiovascular disease (CVD) mortality in the past three decades, it still remains the leading cause of death in women. Following menopause and the accompanying loss of estrogen, women experience a unique, accelerated rise in CVD risk factors. Dysfunction of the endothelium represents an important antecedent to CVD development, with rapid declines in endothelial vasodilator function reportedly taking place across the menopause transition. Importantly, the decline in endothelial function is independent of chronological age and is associated with estrogen deficiency. Estrogen-mediated effects, including increasing nitric oxide bioavailability and attenuating oxidative stress and inflammation, contribute to preserving endothelial health. This review will discuss studies that have probed the role of estrogen on endothelial vasodilator function in women at discrete stages of the menopause transition and the effects of estradiol supplementation in postmenopausal women. Estrogen receptor signaling is also an important aspect of endothelial function in women, and studies suggest that expression is reduced with both acute and prolonged estrogen deficiency. Changes in regulatory mechanisms of estrogen receptor-α expression as well as sensitivity to estrogen may underlie the differential effects of estrogen therapy in early (≤5 yr past final menstrual period) and late postmenopausal women (>5 yr past final menstrual period). Lastly, this review presents potential therapeutic targets that include increasing l-arginine bioavailability and estrogen receptor activation to prevent endothelial dysfunction in postmenopausal women as a strategy for decreasing CVD mortality in this high-risk population.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Endotélio Vascular/metabolismo , Estrogênios/metabolismo , Vasodilatação , Adulto , Fatores Etários , Idoso , Animais , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/metabolismo , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Menopausa/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Transdução de Sinais , Vasodilatação/efeitos dos fármacos
18.
Gene ; 711: 143937, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31228541

RESUMO

BACKGROUND & OBJECTIVES: Vaginal atrophy is characterized by thinning of vaginal epithelial layers and decreased local blood flow. We aimed to evaluate the regenerative effects of Adipose derived mesenchymal stem cells (ADMSC) and Bone marrow derived mesenchymal stem cells (BMDSC) on vaginal atrophy in rat menopause model. MATERIALS AND METHODS: Rats were randomly divided into 4 (four) groups: sham, control, ADMSC, BMDSC. Vaginal epithelial thickness, structure of the lamina propria, blood vessels in the lamina propria, collagen deposition, and muscle structure were evaluated. Anti ER α, VEGF, VEGFR 1, Bax and bcl-2 antibodies were analyzed. Beta actin gene was used as endogenous control. Genetical differences among the groups were compared by using Kruskal Wallis and Mann Whitney U test. p < 0.05 was regarded as statistically significant. RESULTS: Epithelial thickness of ADMSC group was higher than control group, but less than sham group Epithelial thickness of BMDSC group was less than sham group. Lamina propria and muscle tissue of ADMSC and BMDSC groups were found to be similar to sham group. VEGFR-1, VEGF, Bax and ER-α staining levels were higher in ADMSC and BMDSC groups than control group. ADMSC group stained stronger with VEGFR-1 and VEGF than BMDSC group. Bcl-2 staining level was increased in ADMSC applied group. No statistically significant difference was detected in Bax and Bcl-2 genes and Bax-/Bcl-2 ratio. CONCLUSIONS: Although genetic expression might have ended and could not be significantly demonstrated, histological and immunohistochemical results favor ADMSC application in vaginal atrophy rather than BMDSC.


Assuntos
Tecido Adiposo/citologia , Biomarcadores/metabolismo , Células da Medula Óssea/citologia , Menopausa/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Vagina/patologia , Tecido Adiposo/metabolismo , Animais , Atrofia , Células da Medula Óssea/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Menopausa/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos , Vagina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteína X Associada a bcl-2/metabolismo
19.
Am J Physiol Heart Circ Physiol ; 317(2): H415-H423, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31099612

RESUMO

Although it is known that the prevalence and severity of hypertension increases in women after menopause, the contribution of T cells to this process has not been explored. Although the immune system is both necessary and required for the development of angiotensin II (ANG II) hypertension in men, we have demonstrated that premenopausal women are protected from T cell-mediated hypertension. The goal of the current study was to test the hypotheses that 1) female protection against T cell-mediated ANG II hypertension is eliminated following progression into menopause and 2) T regulatory cells (Tregs) provide premenopausal protection against ANG II-induced hypertension. Menopause was induced in Rag-1-/- mice (via 4-vinylcyclohexene diepoxide), and all mice received a 14-day ANG II infusion. Donor CD3+ T cells were adoptively transferred 3 wk before ANG II infusion. In the absence of T cells, systolic blood pressure responses to ANG II were similar to those seen in premenopausal mice (Δ12 mmHg). After adoptive transfer of T cells, ANG II significantly increased systolic blood pressure in postmenopausal females (Δ28 mmHg). A significant increase in F4/80 positive renal macrophages, an increase in renal inflammatory gene expression, along with a reduction in renal expression of mannose receptor C-type 1, a marker for M2 macrophages, accompanied the increase in systolic blood pressure (SBP). Flow cytometric analysis identified that Tregs were significantly decreased in the spleen and kidneys of Rag-1-/- menopausal mice versus premenopausal females, following ANG II infusion. In a validation study, an anti-CD25 antibody was used to deplete Tregs in premenopausal mice, which induced a significant increase in SBP. These results demonstrate that premenopausal protection against T cell-mediated ANG II hypertension is eliminated once females enter menopause, suggesting that a change in hormonal status upregulates macrophage-induced proinflammatory and T cell-dependent responses. Furthermore, we are the first to report that the presence of Tregs are required to suppress ANG II hypertension in premenopausal females.NEW & NOTEWORTHY Whether progression into menopause eliminated female protection against T cell-mediated hypertension was examined. Menopausal mice without T cells remained protected against angiotensin II (ANG II) hypertension; however, in the presence of T cells, blood pressure responses to ANG II increased significantly in menopause. Underlying mechanisms examined were anti-inflammatory protection provided by T regulatory cells in premenopausal females and renal inflammatory processes involving macrophage infiltration and cytokine activation.


Assuntos
Pressão Sanguínea , Fatores de Transcrição Forkhead/imunologia , Hipertensão/imunologia , Depleção Linfocítica , Menopausa/imunologia , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Angiotensina II , Animais , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/metabolismo , Frequência Cardíaca , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Rim/imunologia , Rim/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Menopausa/metabolismo , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fatores Sexuais , Baço/imunologia , Baço/metabolismo , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/transplante
20.
J Physiol Sci ; 69(4): 673-681, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31062233

RESUMO

Japanese menopausal women who feel cold, even in a warm room, are said to be experiencing "hie-sho." We assessed the magnitude of coldness by a "hie-sho" interview score. The association between the magnitude of coldness and female hormones, fat intake, and menopausal symptoms is unknown. The aim of the present study was to elucidate the relationship between the hie-sho interview scores and female hormones, fat intake, Kupperman index in pre- (pre group) and post- (post group) menopausal women. The hie-sho interview scores, Kupperman index questionnaire results, dietary survey to analyze fat intake, and body weight were analyzed, and plasma estradiol, progesterone, and lipid levels were measured in the subjects in the pre (n = 9) and post (n = 11) groups. Plasma female hormones and fat intake were different, but the total Kupperman index was not different between pre and post groups. Plasma progesterone was positively correlated with the hie-sho score only in the post group. Plasma triglyceride was positively correlated with the hie-sho score only in the pre group. Intake of cholesterol, arachidonic acid, and docosapentaenoic acid was negatively correlated with the hie-sho score only in the pre group. The positive correlation between total Kupperman index and hie-sho score was observed only in the pre group. These results indicated that progesterone level was related to coldness in post-menopausal women. Fat intake, plasma triglyceride, and menopausal symptoms may be related to coldness in pre-menopausal women.


Assuntos
Ingestão de Alimentos/fisiologia , Gorduras/metabolismo , Menopausa/sangue , Menopausa/metabolismo , Pós-Menopausa/sangue , Pós-Menopausa/metabolismo , Progesterona/sangue , Índice de Massa Corporal , Peso Corporal/fisiologia , Colesterol/sangue , Dieta , Estradiol/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Projetos Piloto , Triglicerídeos/sangue
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