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1.
Menopause ; 31(4): 342-354, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38471077

RESUMO

IMPORTANCE: Vasomotor symptoms (VMS) affect many postmenopausal persons and impact sleep and quality of life. OBJECTIVE: This systematic review examines the literature describing the safety and efficacy of neurokinin-3 receptor antagonists approved and in development for postmenopausal persons with VMS. EVIDENCE REVIEW: A search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted using the search terms and permutations of neurokinin-3 receptor antagonist, elinzanetant, fezolinetant, and osanetant. Inclusion criteria of reporting on efficacy or safety of fezolinetant, elinzanetant, or osanetant; studies in participants identifying as female; full record in English; and primary literature were applied. Abstract-only records were excluded. Extracted data were synthesized to allow comparison of reported study characteristics, efficacy outcomes, and safety events. Eligible records were evaluated for risk of bias via the Cochrane Risk of Bias 2 tool for randomized studies and the Grading of Recommendations Assessment, Development and Evaluation system was used. This study was neither funded nor registered. FINDINGS: The search returned 191 records; 186 were screened after deduplication. Inclusion criteria were met by six randomized controlled trials (RCT), four reported on fezolinetant, and two reported on elinzanetant. One record was a post hoc analysis of a fezolinetant RCT. An additional study was identified outside the database search. Three fezolinetant RCT demonstrated a reduction in VMS frequency/severity, improvement in Menopause-Specific Quality of Life scores, and improvement in sleep quality at weeks 4 and 12 compared with placebo without serious adverse events. The two RCT on elinzanetant also showed improvements in VMS frequency and severity. All eight records evaluated safety through treatment-emergent adverse events; the most common adverse events were COVID-19, headache, somnolence, and gastrointestinal. Each record evaluated had a low risk of bias. There is a strong certainty of evidence as per the Grading of Recommendations Assessment, Development and Evaluation system. CONCLUSIONS AND RELEVANCE: Because of the high-quality evidence supporting the efficacy of fezolinetant and elinzanetant, these agents may be an effective option with mild adverse events for women seeking nonhormone treatment of VMS.


Assuntos
Compostos Heterocíclicos com 2 Anéis , Fogachos , Menopausa , Piperidinas , Receptores da Neurocinina-3 , Sudorese , Tiadiazóis , Sistema Vasomotor , Feminino , Humanos , Compostos Heterocíclicos com 2 Anéis/farmacologia , Compostos Heterocíclicos com 2 Anéis/uso terapêutico , Menopausa/efeitos dos fármacos , Menopausa/fisiologia , Receptores da Neurocinina-3/antagonistas & inibidores , Tiadiazóis/química , Tiadiazóis/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Fogachos/tratamento farmacológico , Sudorese/efeitos dos fármacos , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/fisiopatologia
2.
Artigo em Espanhol | LILACS | ID: biblio-1431755

RESUMO

Los síntomas vasomotores (SVM) se encuentran entre los síntomas más comunes de la transición a la menopausia. Más del 70% de las mujeres de mediana edad informan SVM en algún momento durante la transición a la menopausia, y para un tercio de las mujeres los SVM son muy frecuentes o graves. Muchas mujeres recurren a terapias naturales para tratar los SVM. Esta revisión se centra en una de esas opciones naturales: el extracto purificado de polen (Serelys®). Se realizó una búsqueda e identificación de artículos publicados hasta octubre de 2022 recopilados de sistemas de búsqueda electrónicos, como Google Scholar, MEDLINE, PubMed y Scopus. Las palabras de búsqueda fueron “Vasomotor symptoms”, “menopause” AND “pollen”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre los SVM.


Vasomotor symptoms (VMS) are among the most common symptoms of the menopausal transition. More than 70% of middle-aged women report VMS at some point during the menopausal transition, and for a third of women, VMS is very common or severe. Many women turn to natural therapies to treat VMS. This review focuses on one such natural option, purified pollen extract (Serelys®). The information available until October 2022 was collected via the library and electronic search systems such as Google Scholar, MEDLINE, PubMed, and Scopus. The search words were: “Vasomotor symptoms”, “menopause” AND “pollen”. Preclinical studies point to a mechanism of action in its involvement in the serotonergic system, as well as its binding to dopamine receptors. Clinical studies demonstrate the safety and positive effect on VMS.


Assuntos
Humanos , Feminino , Pólen/química , Menopausa , Extratos Vegetais/administração & dosagem , Segurança , Sistema Vasomotor/fisiopatologia , Eficácia , Fogachos/tratamento farmacológico , Fitoterapia
3.
Sci Rep ; 12(1): 14652, 2022 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030298

RESUMO

We investigated the associations between serum lipid profiles and risk of early-onset vasomotor symptoms (VMSs) in premenopausal women. This cohort study comprised 2,540 premenopausal women aged 42-52 years without VMSs at baseline (median follow-up: 4.4 years). VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire (Korean version). Early-onset VMSs were defined as VMSs that occurred premenopause; moderate/severe VMSs were defined as a score of ≥ 3 points (range: 0 to 6, 6 being most bothersome). Cox proportional hazard regression models were used to estimate hazard ratios with 95% confidence intervals (CI) for the development of VMSs across the lipid levels. Higher low-density lipoprotein (LDL) cholesterol levels were positively associated with increased risk of early-onset VMSs. Compared to the < 100 mg/dL LDL group, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for incident VMSs were 1.19 (1.03-1.37) and 1.20 (1.03-1.40) in participants with LDL cholesterol levels of 100-129 mg/dL and ≥ 130 mg/dL, respectively (P for trend = 0.027). The multivariable-adjusted HR for incident moderate/severe VMSs was 1.37 (95% CI: 1.08-1.73) in participants with LDL ≥ 130 mg/dL, compared to those with LDL < 100 mg/dL. Meanwhile, triglycerides and total and high-density lipoprotein cholesterol levels were not significantly associated with early-onset VMSs risk in premenopausal women. Premenopausal women with high serum LDL cholesterol concentrations had a higher risk of incident early-onset VMSs. Further studies should confirm our findings and examine whether LDL-lowering interventions reduce the risk of early-onset VMSs among women during menopause transition.


Assuntos
LDL-Colesterol , Sistema Vasomotor , Adulto , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Triglicerídeos , Sistema Vasomotor/fisiopatologia
4.
Surgery ; 171(2): 399-404, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34706825

RESUMO

BACKGROUND: We examined the link between increased intra-abdominal pressure, intracranial pressure, and vasopressin release as a potential mechanism. Intra-abdominal pressure, produced by abdominal-cavity insufflation with carbon dioxide (CO2) during laparoscopic abdominal procedures to facilitate visualization, is associated with various complications, including arterial hypertension and oliguria. METHODS: Mean arterial pressure, optic nerve sheath diameter, measured as a proxy for intracranial pressure, plasma vasopressin, serum and urine osmolarity, and urine output were measured 4 times during laparoscopic sleeve gastrectomy in 42 patients: before insufflation with CO2 (T0); after insufflation to 15 cm water (H2O) pressure, with 5 cm H2O positive end-expiratory pressure (T1); after positive end-expiratory pressure was raised to 10 cm H2O (T2); and after a return to the baseline state (T3). Mean values at T0 to T3 and the directional consistency of changes (increase/decrease/ unchanged) were compared among the 4 data-collection points. RESULTS: Statistically significant elevations (all P ≤ .001) were noted from T0 to T1 and from T0 to T2 in mean arterial pressure, optic nerve sheath diameter, and vasopressin, followed by decreases at T3. For optic nerve sheath diameter and vasopressin, the increases at T1 and T2 occurred in 98% and 100% of patients, ultimately exceeding normal levels in 88 and 97%, respectively. Conversely, urine output fell from T0 to T1 and T2 by 60.9 and 73.4%, decreasing in 88.1% of patients (all P < .001). Patients with class II obesity exhibited statistically greater increases in optic nerve sheath diameter and vasopressin, but statistically less impact on urine output, than patients with class III obesity. CONCLUSION: Increased mean arterial pressure, intracranial pressure, and vasopressin release appear to be intermediary steps between increased intra-abdominal pressure and oliguria. Further research is necessary to determine any causative links between these physiological changes.


Assuntos
Hipertensão Intra-Abdominal/fisiopatologia , Hipertensão Intracraniana/fisiopatologia , Oligúria/fisiopatologia , Pneumoperitônio Artificial/efeitos adversos , Vasopressinas/metabolismo , Adulto , Idoso , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Hipertensão Intra-Abdominal/epidemiologia , Hipertensão Intra-Abdominal/etiologia , Hipertensão Intracraniana/epidemiologia , Hipertensão Intracraniana/etiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Oligúria/epidemiologia , Oligúria/etiologia , Estudos Prospectivos , Sistema Vasomotor/fisiopatologia , Adulto Jovem
5.
Gynecol Oncol ; 163(3): 598-604, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34649724

RESUMO

OBJECTIVE: We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). METHODS: 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). RESULTS: Mean age at the survey was 62 [21-83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). CONCLUSIONS: VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.


Assuntos
Sobreviventes de Câncer , Carcinoma Epitelial do Ovário/fisiopatologia , Menopausa/fisiologia , Neoplasias Ovarianas/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Qualidade de Vida , Fatores Sociodemográficos , Sistema Vasomotor/fisiopatologia , Adulto Jovem
6.
Lancet HIV ; 8(9): e591-e598, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34384545

RESUMO

People living with HIV are ageing, and a growing number of women living with HIV are entering menopause. Women living with HIV commonly have bothersome vasomotor symptoms and onset of menopause at earlier ages; both factors go on to affect quality of life and systemic health. Vasomotor symptoms and early menopause are both indications for menopausal hormone therapy; however, current evidence suggests that this therapy is seldom offered to women living with HIV. Additionally, women living with HIV have several risks to bone health and are likely to benefit from the bone-strengthening effects of menopausal hormone therapy. We present an assessment of the benefits and risks of menopausal hormone therapy in the context of HIV care and propose a practical approach to its prescription. If considered in the appropriate clinical context with discussion of risks and benefits, menopausal hormone therapy might provide substantial benefits to symptomatic menopausal women living with HIV and improve health-related quality of life.


Assuntos
Infecções por HIV/tratamento farmacológico , Sobreviventes de Longo Prazo ao HIV , Terapia de Reposição Hormonal , Antirretrovirais/uso terapêutico , Interações Medicamentosas , Feminino , Infecções por HIV/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Menopausa Precoce , Qualidade de Vida , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/fisiopatologia
7.
Int J Mol Sci ; 22(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205652

RESUMO

(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced in anaesthetized rats by weight drop model, and then MCAs were isolated and transferred into a pressure-flow chamber. The internal diameter was measured by a video-microscopy. (3) Results: In MCAs from intact rats, increases in flow and pressure + flow elicited constrictions (-26 ± 1.9 µm and -52 ± 2.8 µm, p < 0.05), which were significantly reduced after TBI or in the presence of thromboxane-prostanoid (TP receptor) antagonist SQ 29,548. Flow-induced constrictions were significantly reduced by HET0016, inhibitor of cytochrome P450 4A (CYP450 4A). Arachidonic acid, (AA, 10-7 M), and CYP-450 4A metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) elicited constrictions of intact MCA (-26 ± 2.3% and -31 ± 3.6%), which were significantly reduced after TBI (to 11 ± 1.3% and -16 ±2.5%). The TP receptor agonist U46619 (10-7 M) elicited substantial constrictions of MCA from intact rats (-21 ± 3.3%), which were also significantly reduced, after TBI (to -16 ± 2.4%). (4) Conclusions: Flow-induced constrictor response of MCA is impaired by traumatic brain injury, likely due to the reduced ability of cytochrome P450 4A to convert arachidonic acid to constrictor prostaglandins and the mitigated sensitivity of thromboxane-prostanoid receptors.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Artéria Cerebral Média/fisiopatologia , Sistema Vasomotor/fisiopatologia , Animais , Lesões Encefálicas Traumáticas/metabolismo , Citocromo P-450 CYP4A/metabolismo , Técnicas In Vitro , Masculino , Ratos Endogâmicos WKY , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo
8.
J Korean Med Sci ; 36(17): e122, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942581

RESUMO

BACKGROUND: To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. METHODS: Data on 3,298 women, aged 40-80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. RESULTS: In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. CONCLUSION: Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.


Assuntos
Peso Corporal/fisiologia , Fogachos/etnologia , Aprendizado de Máquina , Menopausa/fisiologia , Sistema Vasomotor/fisiopatologia , Saúde da Mulher , Sistemas de Apoio a Decisões Clínicas , Feminino , Fogachos/etiologia , Humanos , Pessoa de Meia-Idade , Monócitos , República da Coreia , Sudorese , Tireotropina
10.
Psychophysiology ; 58(5): e13800, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33645659

RESUMO

This study investigated the cardiac, vasomotor, and myocardial branches of the baroreflex in fibromyalgia using the spontaneous sequence method. Systolic blood pressure (SBP), interbeat interval (IBI), stroke volume (SV), pre-ejection period (PEP), and total peripheral resistance (TPR) were continuously recorded in 40 fibromyalgia patients and 30 healthy individuals during a cold pressor test and a mental arithmetic task. Sequences of covariation between SBP and IBI (cardiac branch), SV and PEP (myocardial branch), and TPR (vasomotor branch) were identified. Baroreflex sensitivity (BRS) was represented by the slope of the regression line between values in the sequences; baroreflex effectiveness (BEI) was indexed by the proportion of progressive SBP changes that elicited reflex responses. Patients exhibited lower BRS in the three branches, lower BEI in the cardiac and vasomotor branches, and reduced reactivity in cardiac BRS and BEI, SBP, IBI, SV, and PEP. Moreover, BRS and BEI were inversely related to clinical pain, cold pressor pain, depression, trait anxiety, sleep problems, and fatigue. Reduced function of the three baroreflex branches implies diminished resources for autonomic inotropic, chronotropic, and vascular regulation in fibromyalgia. Blunted stress reactivity indicates a limited capacity for autonomic cardiovascular adjustment to situational requirements. The associations of BRS and BEI with pain perception may reflect the antinociceptive effects arising from baroreceptor afferents, where reduced baroreflex function may contribute to the hyperalgesia characterizing fibromyalgia. The associations with affective impairments, sleep problems, and fatigue suggest that baroreflex dysfunctions are also involved in the secondary symptoms of the disorder.


Assuntos
Barorreflexo/fisiologia , Depressão/fisiopatologia , Fadiga/fisiopatologia , Fibromialgia/fisiopatologia , Contração Miocárdica/fisiologia , Dor/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Estresse Psicológico/fisiopatologia , Adulto , Ansiedade/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Temperatura Baixa , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Feminino , Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Hiperalgesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Resistência Vascular/fisiologia , Sistema Vasomotor/fisiopatologia
11.
Physiol Rep ; 9(3): e14753, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33587331

RESUMO

Chlorisondamine (CSD) has been used to assess the neurogenic contribution to blood pressure (BP) and vasomotor sympathetic tone in animal models. It is assumed that the reduction in BP following CSD administration is associated to decreases in cardiac output (CO) and peripheral resistance, reflecting cardiac and vasomotor sympathetic tone, respectively. Surprisingly, this has not been characterized experimentally in mice, despite the extensive use of this animal model in cardiovascular research. We hypothesize that a specific dose of CSD can selectively block the sympathetic vasomotor tone. To test this hypothesis, we evaluated the effects of different doses of CSD (intraperitoneal) on BP and heart rate (HR) using telemetry, and on CO using echocardiography. BP and HR in normotensive C57Bl/6J mice reduced to a similar extent by all CSD doses tested (1-6 mg/kg). CSD at 6 mg/kg also reduced CO without affecting left ventricular stroke volume or fractional shortening. On the other hand, lower doses of CSD (1 and 2 mg/kg) produced significantly larger BP and HR reductions in DOCA-salt-induced hypertensive mice, indicating a greater neurogenic BP response. In addition, all doses of CSD reduced CO in hypertensive mice. Our data suggest that the BP response to CSD in mice likely reflects reduced CO and vasomotor sympathetic tone. We conclude that CSD can be used to assess the neurogenic contribution to BP in mice but may not be appropriate for specifically estimating vasomotor sympathetic tone.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/inervação , Clorisondamina/farmacologia , Hipertensão/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Simpatolíticos/farmacologia , Animais , Débito Cardíaco/efeitos dos fármacos , Acetato de Desoxicorticosterona , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/etiologia , Masculino , Camundongos Endogâmicos C57BL , Cloreto de Sódio na Dieta , Sistema Nervoso Simpático/fisiopatologia , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/fisiopatologia
12.
PLoS One ; 16(2): e0246254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529222

RESUMO

Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5ß-dihydrotestosterone (5α- and 5ß-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5ß-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5ß-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5ß-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5ß-DHT previously described in conscious SHR and WKY rats, pointing to 5ß- DHT as a potential drug for the treatment of hypertension.


Assuntos
Androgênios/farmacologia , Artérias Mesentéricas/fisiopatologia , Sistema Vasomotor/fisiopatologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Testosterona/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Sistema Vasomotor/efeitos dos fármacos
13.
PLoS One ; 16(1): e0245444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503073

RESUMO

Many women going through the menopausal transition experience vasomotor symptoms (VMS), and research has shown that there is a large amount of variation in their frequency and severity. Many lifestyle factors have been found to co-vary with VMS, including the level of social support received by the woman, and how stressed she is. Stress is well documented to worsen menopause symptoms, and there is some evidence that support eases them; however, there is little research into whether support is an effective buffer against the negative effects of stress on VMS. Using nine years of data from the Study of Women's Health Across the Nation (n = 2718), we use multilevel Poisson regression with random effects to test: 1) if more social support is associated with decreased VMS frequency, 2) if increased life stress worsens VMS, and 3) if support acts as a buffer against stress. After adjusting for age, marital status, smoking, self-perceived overall health, ethnicity, and menopausal status, we find that stress increases the frequency of VMS. Contrary to our hypothesis, we did not find strong evidence that emotional support led to lower VMS frequency, or that support buffers against the effects of stress. Experience of a stressful event, but not amount of social support, was included in the best fitting model; with the degree to which the woman was upset by the life stressor having the largest effect on menopause symptoms. Here, women who said they were currently upset by a stressful event experienced 21% more VMS than women who had experienced no life stressor. This research highlights that social factors may impact the menopausal transition.


Assuntos
Fogachos/etiologia , Menopausa , Estresse Psicológico/complicações , Adulto , Feminino , Fogachos/fisiopatologia , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Fatores de Risco , Apoio Social , Estresse Psicológico/fisiopatologia , Sistema Vasomotor/fisiopatologia , Saúde da Mulher
14.
J Am Heart Assoc ; 10(3): e017416, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33470142

RESUMO

Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women's Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in-person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1-5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow-up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow-up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05-2.17], P=0.03; 1-5 days: HR [95% CI], 1.02 [0.75-1.39], P=0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33-2.35], P<0.0001, multivariable). Conclusions Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female-specific CVD risk factor.


Assuntos
Doenças Cardiovasculares/epidemiologia , Previsões , Menopausa/fisiologia , Medição de Risco/métodos , Sistema Vasomotor/fisiopatologia , Saúde da Mulher , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
15.
Am J Physiol Heart Circ Physiol ; 320(3): H1080-H1088, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416458

RESUMO

Insufficient sleep is associated with endothelial vasomotor dysfunction and increased cardiovascular risk. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn, reducing cardiovascular risk. We tested the hypotheses that regular aerobic exercise would 1) improve endothelial vasodilation and 2) decrease endothelin (ET)-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep <7 h/night. Thirty-six healthy, middle-aged adults were studied: 16 with normal sleep duration (age: 57 ± 2 yr; sleep duration: 7.4 ± 0.1 h/night) and 20 with short sleep duration (age: 56 ± 1 yr; sleep duration: 6.2 ± 0.1 h/night). The 20 short sleepers completed a 3-mo aerobic exercise training intervention. Forearm blood flow was determined (via plethysmography) in response to intra-arterial acetylcholine (ACh), BQ-123 (ETA receptor antagonist), ACh + BQ-123, and sodium nitroprusside. Forearm blood flow responses to ACh were lower (∼20%; P < 0.05) in the short (from 4.2 ± 0.2 to 10.5 ± 0.6 mL/100 mL tissue/min) versus normal (4.2 ± 0.2 to 12.7 ± 0.6 mL/100 mL tissue/min) sleepers. In response to BQ-123, the short-sleep group had a significantly greater increase in resting forearm blood flow than the normal-sleep group (∼25% vs. ∼8%). ACh + BQ-123 resulted in a significant (∼25%) increase in the ACh-mediated vasodilation in the short-sleep group only. After exercise training, although nightly sleep duration was unchanged (6.4 ± 0.1 h/night), ACh-mediated vasodilation was significantly higher (∼20%), ET-1-mediated vasoconstriction was significantly lower (∼80%), and the vasodilator response to ACh was not increased with ETA receptor blockade. Regular aerobic exercise, independent of changes in nightly sleep duration, can counteract insufficient sleep-related endothelial vasomotor dysfunction.NEW & NOTEWORTHY Habitual insufficient nightly sleep (<7 h/night) is associated with increased risk of cardiovascular disease and events. Endothelial dysfunction, specifically reduced endothelium-dependent vasodilation and increased endothelin (ET)-1-mediated vasoconstriction, is considered to be a major contributing mechanism underlying increased vascular risk with insufficient sleep. In contrast to insufficient sleep, regular aerobic exercise enhances endothelial vasomotor function, reducing the risk of cardiovascular disease and associated events. In the present study, we determined the effects of aerobic exercise training on endothelium-dependent vasodilation and ET-1 vasoconstriction in adults who habitually sleep <7 h/night. After exercise training, although nightly sleep duration was unchanged, endothelium-dependent vasodilation was significantly enhanced and ET-1-mediated vasoconstrictor tone was significantly reduced in adults who sleep <7 h/night. Regular aerobic exercise training can mitigate insufficient sleep-related endothelial vasomotor dysfunction and, in turn, potentially reduce the cardiovascular risk associated with habitual insufficient nightly sleep.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/fisiopatologia , Exercício Físico , Hemodinâmica , Privação do Sono/terapia , Sono , Sistema Vasomotor/fisiopatologia , Acetilcolina/farmacologia , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Endotelinas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Estilo de Vida Saudável , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento de Redução do Risco , Privação do Sono/diagnóstico , Privação do Sono/fisiopatologia , Fatores de Tempo , Vasoconstrição , Vasoconstritores/farmacologia , Vasodilatação , Vasodilatadores/farmacologia , Sistema Vasomotor/efeitos dos fármacos
16.
Muscle Nerve ; 63(2): 170-177, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32989823

RESUMO

Idiopathic small fiber neuropathy (iSFN) lacks broadly accepted diagnostic criteria, which hinders its timely diagnosis and treatment. A systematic literature review was performed to assess the published screening and diagnostic criteria for iSFN, excluding studies where SFN was of well-established etiology. Eighty-four clinical studies and seven guideline/review publications were included in this systematic review. Substantial heterogeneity existed in iSFN diagnostic criteria. The most common set of criteria to diagnose iSFN [presence of any symptoms of iSFN, absence of large fiber involvement, and reduced intraepidermal nerve fiber density (IENFD)] was used in only 14% of studies. Mandatory individual criteria to confirm iSFN included any sensory symptoms (60% of studies), pain (19% of studies), small fiber signs (20% of studies), absence of large fiber signs (62% of studies), reduced IENFD (38% of studies), and autonomic symptoms (1% of studies). This review highlights a clear need for standardized, evidence-based guidelines for diagnosing iSFN.


Assuntos
Epiderme/patologia , Hiperalgesia/fisiopatologia , Hipestesia/fisiopatologia , Fibras Nervosas/patologia , Neuralgia/fisiopatologia , Parestesia/fisiopatologia , Neuropatia de Pequenas Fibras/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Eletrodiagnóstico , Resposta Galvânica da Pele , Humanos , Condução Nervosa , Prurido/fisiopatologia , Neuropatia de Pequenas Fibras/patologia , Neuropatia de Pequenas Fibras/fisiopatologia , Sistema Vasomotor/fisiopatologia
17.
BJOG ; 128(3): 603-613, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33135854

RESUMO

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.


Assuntos
Fatores Etários , Fogachos/etiologia , Menarca/fisiologia , Menopausa/fisiologia , Sistema Vasomotor/fisiopatologia , Austrália/epidemiologia , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Fogachos/epidemiologia , Humanos , Hiperidrose/epidemiologia , Hiperidrose/etiologia , Modelos Logísticos , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Razão de Chances , Fatores de Risco , Sudorese , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
18.
J Clin Endocrinol Metab ; 106(1): 1-15, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095879

RESUMO

CONTEXT: Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. EVIDENCE ACQUISITION: A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. EVIDENCE SYNTHESIS: The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. CONCLUSIONS: The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.


Assuntos
Terapia de Reposição de Estrogênios , Menopausa/fisiologia , Avaliação de Sintomas , Terapia de Reposição de Estrogênios/métodos , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Feminino , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/fisiologia , Hormônios Esteroides Gonadais/uso terapêutico , Fogachos/diagnóstico , Fogachos/epidemiologia , Fogachos/etiologia , Fogachos/terapia , Humanos , Perimenopausa/fisiologia , Qualidade de Vida , Avaliação de Sintomas/métodos , Sistema Vasomotor/fisiopatologia
19.
Climacteric ; 24(2): 151-156, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33103941

RESUMO

PURPOSE: This study aimed to find the associations between vasomotor symptoms (VMS) and metabolic syndrome (MetS) in Chinese middle-aged women in a cross-sectional study. METHODS: A total of 675 participants were recruited from an urban Chinese community. MetS was defined by the 2009 criteria of the Joint Interim Statement. VMS including hot flashes and sweats, blood pressure, weight, height, waist circumference (WC), serum glucose, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), estradiol, and follicle-stimulating hormone (FSH) were collected. RESULTS: The presence of hot flashes was independently associated with the risk of MetS after adjusting for age, menopausal status, FSHlog, estradiollog, and physical activity (odds ratio: 1.98, 95% confidence interval: 1.21-3.24, p = 0.006). Both hot flashes and sweats were also independently associated with WC (for hot flashes, p = 0.016; and for sweats, p = 0.007) and triglycerides (for hot flashes, p = 0.041; and for sweats, p = 0.014) significantly. However, VMS were not significantly associated with blood pressure, glucose, HDL, and LDL. CONCLUSION: Women with hot flashes had a higher risk of MetS. Both hot flashes and sweats were related to a higher amount of central fat indicated by WC and higher triglycerides, but were not related to blood pressure, glucose, and HDL in Chinese women.


Assuntos
Fogachos/fisiopatologia , Menopausa/metabolismo , Síndrome Metabólica/fisiopatologia , Sudorese/fisiologia , Sistema Vasomotor/fisiopatologia , Adulto , Idoso , Glicemia/análise , Pressão Sanguínea , Fatores de Risco Cardiometabólico , China , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Estradiol/sangue , Exercício Físico , Feminino , Hormônio Foliculoestimulante/sangue , Fogachos/sangue , Fogachos/complicações , Humanos , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Triglicerídeos/sangue , População Urbana , Circunferência da Cintura
20.
Am J Hypertens ; 34(1): 100-109, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33057586

RESUMO

BACKGROUND: Emerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown. METHODS: Pancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined. Wavelet transform analysis was performed to convert pancreatic microhemodynamic signals into time-frequency domains and construct 3-dimensional spectral scalograms. The amplitudes of characteristic oscillators including endothelial, neurogenic, myogenic, respiratory, and cardiac oscillators were compared among groups. Plasma nitrite/nitrate levels were measured using a Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase, and interleukin-6 levels were determined by enzyme-linked immunosorbent assay. RESULTS: SHRs exhibited a reduced blood distribution pattern with progressively decreased average blood perfusion, amplitude, and frequency of microvascular vasomotion. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators from 8- to 18-week-old SHRs. Additionally, the blood microcirculatory chemistry complements explained the microhemodynamic profiles partially, as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, and interleukin-6 levels and a decreased superoxide dismutase level in SHRs. CONCLUSIONS: Pancreatic microcirculation profiles are abnormal in the progression of hypertension in SHRs, including a disarranged blood distribution pattern, impaired microvascular vasomotion, and reduced amplitudes of endothelial oscillators.


Assuntos
Hipertensão , Microcirculação/fisiologia , Pâncreas/irrigação sanguínea , Sistema Vasomotor , Animais , Pressão Sanguínea/fisiologia , Progressão da Doença , Endotelina-1/sangue , Hemodinâmica/fisiologia , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Malondialdeído/sangue , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Superóxido Dismutase/sangue , Sistema Vasomotor/metabolismo , Sistema Vasomotor/fisiopatologia , Análise de Ondaletas
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