ABSTRACT
OBJECTIVE: This study assessed the prevalence and impact of moderate and/or severe vasomotor symptoms and related treatment patterns in midlife women in Brazil. STUDY DESIGN: Brazilian women aged 40 to 65 years completed an online survey. The prevalence of moderate to severe vasomotor symptoms was assessed in postmenopausal women who completed a series of questionnaires to elicit responses regarding their treatment patterns and attitudes to treatments. MAIN OUTCOME MEASURES: Perimenopausal and postmenopausal women with moderate to severe vasomotor symptoms completed three standardized questionnaires (Menopause-Specific Quality of Life questionnaire, Work Productivity and Activity Impairment questionnaire, and the Patient-Reported Outcomes Measurement Information System Sleep Disturbances Short Form 8b) and answered open-ended questions. RESULTS: Of 1244 postmenopausal women who accessed the survey, 36.2 % had experienced moderate to severe vasomotor symptoms in the previous month. Moderate to severe vasomotor symptoms among 501 perimenopausal and postmenopausal women negatively affected overall quality of life (mean total score on the Menopause-Specific Quality of Life questionnaire was 3.6/8). On the Work Productivity and Activity Impairment questionnaire, women's scores for impairments in overall work and daily activities due to vasomotor symptoms were 50.3 % and 60.0 %, respectively. Overall mean (standard deviation) score on the Patient-Reported Outcomes Measurement Information System Sleep Disturbances Short Form 8b was 25.5 (5.8) on a scale of 8 to 40. Most women sought medical advice (65.5 %), but over half were not receiving treatment. Those who received treatment reported moderately favorable attitudes to hormone and nonhormone prescription medicines, but safety concerns remained. CONCLUSION: Brazilian women experienced a relatively high prevalence and burden of moderate to severe vasomotor symptoms.
Subject(s)
Hot Flashes , Menopause , Quality of Life , Humans , Female , Middle Aged , Brazil/epidemiology , Cross-Sectional Studies , Hot Flashes/epidemiology , Adult , Prevalence , Menopause/physiology , Surveys and Questionnaires , Aged , Postmenopause/physiology , Sleep Wake Disorders/epidemiology , Vasomotor System/physiopathologyABSTRACT
This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.
Subject(s)
Hot Flashes , Menopause , Humans , Female , Hot Flashes/drug therapy , Randomized Controlled Trials as Topic , Middle Aged , Treatment Outcome , Vasomotor System/drug effects , Quality of LifeABSTRACT
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.
Subject(s)
Humans , Female , Pollen/chemistry , Menopause , Plant Extracts/administration & dosage , Safety , Vasomotor System/physiopathology , Efficacy , Hot Flashes/drug therapy , PhytotherapyABSTRACT
Objective: Vasomotor symptoms affect 60-80% of women during the menopausal transition. Anxiety, depression, and anxiety sensitivity can have an important role in the distressful experience of vasomotor symptoms. Our aim was to evaluate the prevalence and association of vasomotor and negative affect symptoms. Methods: A cross-sectional study was conducted with 89 perimenopausal women aged 45-55 years. Broad psychiatric and clinical evaluations were carried out. The primary outcome was the vasomotor symptom problem rating and the main study factor was anxiety sensitivity. Linear regression analyses were conducted to examine the associations between the study factors and the primary outcome, and a multiple regression model was created to assess which variables were independently associated with vasomotor symptom problem rating. Results: The prevalence of anxiety, depression, and vasomotor symptoms were 58, 62, and 73%, respectively. Negative affect symptoms were positively associated with vasomotor symptom problem rating. The association of anxiety sensitivity and vasomotor symptom problem rating remained significant after controlling for perimenopausal stage, thyrotropin, follicle-stimulating hormone levels, and psychotropic medication use (β = 0.314, p = 0.002). Conclusion: A better understanding of the experience of vasomotor symptoms is needed, especially the role of negative affect symptoms and anxiety sensitivity. New strategies focusing on related thoughts and behaviors could improve the quality of life of perimenopausal women.
Subject(s)
Humans , Female , Quality of Life , Perimenopause , Anxiety/epidemiology , Vasomotor System , Cross-Sectional StudiesABSTRACT
Treatment with estrogens alone in women without a uterus or in combination with progestins (PG) in women with a uterus is the most effective treatment for vasomotor symptoms in the peri or postmenopausal period. However, PGs differ by their biological activities, and it is likely that not all PGs will display a class effect. The type of PG is important regarding tolerance and cardiovascular and breast cancer risk. Some studies indicate that micronized progesterone (P) is safer than synthetic PGs with an acceptable metabolic profile. For that purpose, we conducted a narrative review on the balance between benefit/risk using P versus PGs in menopause hormone therapy (MHT) to aid clinician to choose the best regimens, specifically the PG component of hormone therapy, for women with bothersome menopausal symptoms and with a uterus.
Subject(s)
Breast Neoplasms/chemically induced , Hormone Replacement Therapy/methods , Progesterone/therapeutic use , Progestins/therapeutic use , Breast/drug effects , Breast/physiology , Cardiovascular Diseases/prevention & control , Estrogen Replacement Therapy/methods , Female , Hormone Replacement Therapy/adverse effects , Humans , Menopause , Middle Aged , Perimenopause , Postmenopause , Progesterone/administration & dosage , Progesterone/adverse effects , Progestins/administration & dosage , Progestins/adverse effects , Risk Assessment , Uterus/drug effects , Vasomotor System/drug effectsABSTRACT
OBJECTIVE: Vasomotor symptoms affect 60-80% of women during the menopausal transition. Anxiety, depression, and anxiety sensitivity can have an important role in the distressful experience of vasomotor symptoms. Our aim was to evaluate the prevalence and association of vasomotor and negative affect symptoms. METHODS: A cross-sectional study was conducted with 89 perimenopausal women aged 45-55 years. Broad psychiatric and clinical evaluations were carried out. The primary outcome was the vasomotor symptom problem rating and the main study factor was anxiety sensitivity. Linear regression analyses were conducted to examine the associations between the study factors and the primary outcome, and a multiple regression model was created to assess which variables were independently associated with vasomotor symptom problem rating. RESULTS: The prevalence of anxiety, depression, and vasomotor symptoms were 58, 62, and 73%, respectively. Negative affect symptoms were positively associated with vasomotor symptom problem rating. The association of anxiety sensitivity and vasomotor symptom problem rating remained significant after controlling for perimenopausal stage, thyrotropin, follicle-stimulating hormone levels, and psychotropic medication use (ß = 0.314, p = 0.002). CONCLUSION: A better understanding of the experience of vasomotor symptoms is needed, especially the role of negative affect symptoms and anxiety sensitivity. New strategies focusing on related thoughts and behaviors could improve the quality of life of perimenopausal women.
Subject(s)
Perimenopause , Quality of Life , Anxiety/epidemiology , Cross-Sectional Studies , Female , Humans , Vasomotor SystemABSTRACT
BACKGROUND: Knowledge of the central areas involved in the control of sympathetic vasomotor activity has advanced in the last few decades. γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammal nervous system, and a microinjection of bicuculline, an antagonist of GABA type A (GABA-A) receptors, into the paraventricular nucleus of the hypothalamus (PVN) alters the pattern of sympathetic activity to the renal, splanchnic and lumbar territories. However, studies are needed to clarify the role of GABAergic inputs in other central areas involved in the sympathetic vasomotor activity. The present work studied the cardiovascular effects evoked by GABAergic antagonism in the PVN, RVLM and spinal cord. METHODS AND RESULTS: Bicuculline microinjections (400 pMol in 100 nL) into the PVN and rostral ventrolateral medulla (RVLM) as well as intrathecal administration (1.6 nmol in 2 µL) evoked an increase in blood pressure, heart rate, and renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), inducing a higher coherence between rSNA and sSNA patterns. However, some of these responses were more intense when the GABA-A antagonism was performed in the RVLM than when the GABA-A antagonism was performed in other regions. CONCLUSIONS: Administration of bicuculline into the RVLM, PVN and SC induced a similar pattern of renal and splanchnic sympathetic vasomotor burst discharge, characterized by a low-frequency (0.5 Hz) and high-amplitude pattern, despite different blood pressure responses. Thus, the differential control of sympathetic drive to different targets by each region is dependent, in part, on tonic GABAergic inputs.
Subject(s)
Bicuculline/pharmacology , Brain/drug effects , GABA-A Receptor Antagonists/pharmacology , Spinal Cord/drug effects , Animals , Bicuculline/administration & dosage , Brain/metabolism , GABA-A Receptor Antagonists/administration & dosage , Male , Microinjections , Rats , Rats, Wistar , Spinal Cord/metabolism , Sympathetic Nervous System/drug effects , Vasomotor System/drug effects , gamma-Aminobutyric Acid/metabolismABSTRACT
End-expiratory occlusion test (EEOT) has been proposed as a preload responsiveness test that overcomes several limitations of pulse pressure (PPV) and stroke volume (SVV) variations. We compared the ability of EEOT versus SVV and PPV to predict fluid responsiveness during the increase of the vasomotor tone in a rabbit model of hemorrhage. Ten rabbits were anesthetized, paralyzed, and mechanically ventilated during basal load (BL), after progressive blood withdrawal (BW), and after volume replacement. Other two sets of data were obtained during vasomotor increase by phenylephrine (PHE) infusion in BL and BW. We estimated the change of stroke volume (∆SVEEOT) and aortic flow (∆AoFEEOT) during the EEOT. PPV and SVV were obtained by the variation of beat-to-beat PP and SV, respectively. Baseline PPV, SVV, ∆SVEEOT, and ∆AoFEEOT increased significantly after BW, with a decrease of aortic flow (P < 0.05). PHE induced a significant decrease of PPV and SVV, but without affecting ∆SVEEOT, and ∆AoFEEOT. We conclude that ∆SV and ∆AoF during EEOT kept the ability to predict fluid responsiveness during PHE infusion in a rabbit hemorrhage model. This result may suggest the advantage of EEOT with respect to SVV and PPV in predicting fluid responsiveness during vasomotor tone increase.
Subject(s)
Hemorrhage/physiopathology , Positive-Pressure Respiration/methods , Animals , Blood Pressure/physiology , Disease Models, Animal , Female , Fluid Therapy/methods , Hemodynamics , Monitoring, Physiologic/methods , Phenylephrine/pharmacology , Rabbits , Stroke Volume/physiology , Vasomotor SystemABSTRACT
Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.
Subject(s)
Carotid Artery, Internal/physiology , Cerebrovascular Circulation/physiology , Cerebrum/blood supply , Hyperoxia , Vasomotor System/physiology , Adult , Hemodynamics , Humans , Male , Regional Blood Flow , Vertebral Artery/physiology , Young AdultABSTRACT
Plant-derived compounds have recently attracted greater interest in the field of new therapeutic agent development. These compounds have been widely screened for their pharmacological effects. Polyphenols, such as soy-derived isoflavones, also called phytoestrogens, have been extensively studied due to their ability to inhibit carcinogenesis. These compounds are chemically similar to 17ß-estradiol, and mimic the binding of estrogens to its receptors, exerting estrogenic effects in target organs. Genistein is an isoflavone derived from soy-rich products and accounts for about 60% of total isoflavones found in soybeans. Genistein has been reported to exhibit several biological effects, such as anti-tumor activity (inhibition of cell proliferation, regulation of the cell cycle, induction of apoptosis), improvement of glucose metabolism, impairment of angiogenesis in both hormone-related and hormone-unrelated cancer cells, reduction of peri-menopausal and postmenopausal hot flashes, and modulation of antioxidant effects. Additionally, epidemiological and clinical studies have reported health benefits of genistein in many chronic diseases, such as cardiovascular disease, diabetes, and osteoporosis, and aid in the amelioration of typical menopausal symptoms, such as anxiety and depression. Although the biological effects are promising, certain limitations, such as low bioavailability, biological estrogenic activity, and effects on target organs, have limited the clinical applications of genistein to some extent. Moreover, studies report that modification of its molecular structure may eliminate the biological estrogenic activity and its effects on target organs. In this review, we summarize the potential benefits of genistein on menopause symptoms and menopause-related diseases like cardiovascular, osteoporosis, obesity, diabetes, anxiety, depression, and breast cancer.
Subject(s)
Genistein/pharmacology , Menopause/drug effects , Antidepressive Agents/pharmacology , Cardiotonic Agents/pharmacology , Female , Genistein/chemistry , Humans , Vasomotor System/drug effectsABSTRACT
Resumen Introducción: Los síntomas vasomotores y la disfunción endotelial probablemente resulten del déficit estrogénico postmenopausia; no obstante, la relación de ambos con la progresión de la aterosclerosis es un tema controversial. Objetivo: Identificar en mujeres de edad mediana con disfunción endotelial, la presencia de aterosclerosis subclinica y de cambios cardiometabólicos durante la transición a la menopausia. Método: Estudio observacional de corte transversal, en el que incluyeron 43 mujeres con edad entre 40-59 años, con disfunción endotelial previa y 14 mujeres con función endotelial normal. En cada mujer se identificaron: manifestaciones de rigidez arterial y del grosor de la grasa epicárdica y su relación con variables antropométricas, intensidad de los síntomas vasomotores, etapas del climaterio y niveles de estradiol. Análisis estadístico: Regresión lineal múltiple y regresión logística para identificar asociación entre intensidad de los síntomas vasomotores, parámetros de rigidez arterial y cardiometabólicos (p< 0,05) para significación estadística. Resultados: Los parámetros de rigidez arterial (VLPP, CA, AI), de aterosclerosis (GIMc) y el grosor de la grasa epicárdica no mostraron cambios compatibles con daño arterial. A mayor intensidad de los síntomas vasomotores se encontró mayor probabilidad de incremento de la VLPP. Evolutivamente un subgrupo de mujeres desarrolló cambios metabólicos y disfunción endotelial sin asociación con el hipoestrogenismo, la edad ni la etapa del climaterio. Conclusiones: Una mayor intensidad de los síntomas vasomotores podría constituir un marcador que identifique de manera temprana el riesgo de desarrollar aterosclerosis clínica.
Abstract Introduction: Vasomotor symptoms and endothelial dysfunction probably result in a post-menopausal oestrogen deficiency. However, the relationship of both with the progression of atherosclerosis is a controversial subject. Objective: To identify the presence of sub-clinical atherosclerosis in middle-aged women with endothelial dysfunction, as well as cardiometabolic changes during the transition to the menopause. Method: A cross-sectional, observation study was conducted on 43 women between 40 and 59 years of age, with previous endothelial dysfunction, and 14 women with normal endothelial function. The variables recorded in each woman were, signs of arterial stiffening epicardial fat thickness and their relationship with anthropometric variables, intensity of the vasomotor symptoms, stages of menopause, and oestradiol levels. Statistical analysis: Multiple linear regression and logistic regression was performed in order to identify an association between the intensity of the vasomotor symptoms, arterial stiffness, and cardiometabolic parameters. A P< .05 was significantly significant. Results: The arterial stiffness parameters (pulse wave propagation (PWP), Arterial distensibility, augmentation index), and that of atherosclerosis (carotid intima-media thickness, GIMc), and the thickness of the epicardial fat showed no changes compatible with arterial damage. At a higher intensity of vasomotor symptoms, a higher probability of an increase in PWP was found. Evolutionarily, a sub-group of women developed metabolic changes and endothelial dysfunction with no relationship with low oestrogens, age, or the stage of the menopause. Conclusions: A greater intensity of vasomotor symptoms could be a marker for the early identification of the risk for clinical atherosclerosis.
Subject(s)
Humans , Female , Middle Aged , Climacteric , Endothelial Cells , Vasomotor System , AtherosclerosisABSTRACT
INTRODUCTION: The acute blood pressure (BP) decrease is greater after evening than morning exercise, suggesting that evening training (ET) may have a greater hypotensive effect. OBJECTIVE: This study aimed to compare the hypotensive effect of aerobic training performed in the morning versus evening in treated hypertensives. METHODS: Fifty treated hypertensive men were randomly allocated to three groups: morning training (MT), ET, and control (C). Training groups cycled for 45 min at moderate intensity (progressing from the heart rate of the anaerobic threshold to 10% below the heart rate of the respiratory compensation point), while C stretched for 30 min. Interventions were conducted 3 times per week for 10 wk. Clinic and ambulatory BP and hemodynamic and autonomic mechanisms were evaluated before and after the interventions. Clinic assessments were performed in the morning (7:00-9:00 AM) and evening (6:00-8:00 PM). Between-within ANOVA was used (P ≤ 0.05). RESULTS: Only ET decreased clinic systolic BP differently from C and MT (morning assessment -5 ± 6 mm Hg and evening assessment -8 ± 7 mm Hg, P < 0.05). Only ET reduced 24 h and asleep diastolic BP differently from C and MT (-3 ± 5 and -3 ± 4 mm Hg, respectively, P < 0.05). Systemic vascular resistance decreased from C only in ET (P = 0.03). Vasomotor sympathetic modulation decreased (P = 0.001) and baroreflex sensitivity (P < 0.02) increased from C in both training groups with greater changes in ET than MT. CONCLUSIONS: In treated hypertensive men, aerobic training performed in the evening decreased clinic and ambulatory BP due to reductions in systemic vascular resistance and vasomotor sympathetic modulation. Aerobic training conducted at both times of day increases baroreflex sensitivity, but with greater after ET.
Subject(s)
Blood Pressure/physiology , Exercise/physiology , Hypertension/physiopathology , Physical Conditioning, Human , Adult , Antihypertensive Agents/therapeutic use , Baroreflex/physiology , Humans , Hypertension/drug therapy , Male , Middle Aged , Time Factors , Vascular Resistance/physiology , Vasomotor System/physiologyABSTRACT
PURPOSE: Calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed in the central and peripheral nervous systems, which is known as a potent vasodilator. Postmenopausal women who experience hot flushes have high levels of plasma CGRP, suggesting its involvement in menopausal vasomotor symptoms. METHODS: In this review, we describe the biochemical aspects of CGRP and its effects associated with deficiencies of sexual hormones on skin temperature, vasodilatation, and sweating as well as the possible peripheral and central mechanisms involved in these events. RESULTS: Several studies have shown that the effects of CGRP on increasing skin temperature and inducing vasodilatation are potentiated by a deficiency of sex hormones, a common condition of postmenopausal women. Additionally, the medial preoptic area of the hypothalamus, involved in thermoregulation, contains over 25-fold more CGRP-immunoreactive cells in female rodents compared with male rodents, reinforcing the role of female sex hormones on the action of CGRP. Some studies suggest that ovarian hormone deficiency decreases circulating endogenous CGRP, inducing an upregulation of CGRP receptors. Consequently, the high CGRP receptor density, especially in blood vessels, amplifies the stimulatory effects of this neuropeptide to raise skin temperature in postmenopausal women during hot flushes. CONCLUSIONS: The duration of the perception of each hot flush in a woman is brief, while local reddening after intradermal administration of α-CGRP persists for 1 to 6 h. This contrast remains unclear.
Subject(s)
Calcitonin Gene-Related Peptide/physiology , Hot Flashes/etiology , Menopause/physiology , Vasomotor System/physiopathology , Animals , Calcitonin Gene-Related Peptide/blood , Female , Hot Flashes/blood , Hot Flashes/physiopathology , Humans , Male , Menopause/blood , Rodentia , Vasodilation/physiologyABSTRACT
BACKGROUND: Gln27Glu (rs1042714) polymorphism of the ß2-adrenergic receptor (ADRB2) has been association with cardiovascular functionality in healthy subjects. However, it is unknown whether the presence of the ADRB2 Gln27Glu polymorphism influences neurovascular responses during exercise in patients with acute coronary syndromes (ACS). We tested the hypothesis that patients with ACS homozygous for the Gln allele would have increased muscle sympathetic nerve activity (MSNA) responses and decreased forearm vascular conductance (FVC) responses during exercise compared with patients carrying the Glu allele (Gln27Glu and Glu27Glu). In addition, exercise training would restore these responses in Gln27Gln patients. METHODS AND RESULTS: Thirty-days after an ischemic event, 61 patients with ACS without ventricular dysfunction were divided into 2 groups: (1) Gln27Gln (n = 35, 53±1years) and (2) Gln27Glu+Glu27Glu (n = 26, 52±2years). MSNA was directly measured using the microneurography technique, blood pressure (BP) was measured with an automatic oscillometric device, and blood flow was measured using venous occlusion plethysmography. MSNA, mean BP, and FVC were evaluated at rest and during a 3-min handgrip exercise. The MSNA (P = 0.02) and mean BP (P = 0.04) responses during exercise were higher in the Gln27Gln patients compared with that in the Gln27Glu+Glu27Glu patients. No differences were found in FVC. Two months of exercise training significantly decreased the MSNA levels at baseline (P = 0.001) and in their response during exercise (P = 0.02) in Gln27Gln patients, but caused no changes in Gln27Glu+Glu27Glu patients. Exercise training increased FVC responses in Gln27Glu+Glu27Glu patients (P = 0.03), but not in Gln27Gln patients. CONCLUSION: The exaggerated MSNA and mean BP responses during exercise suggest an increased cardiovascular risk in patients with ACS and Gln27Gln polymorphism. Exercise training emerges as an important strategy for restoring this reflex control. Gln27Glu polymorphism of ADRB2 influences exercise-induced vascular adaptation in patients with ACS.
Subject(s)
Acute Coronary Syndrome/genetics , Forearm/blood supply , Receptors, Adrenergic, beta-2/genetics , Vasomotor System , Acute Coronary Syndrome/physiopathology , Acute Coronary Syndrome/therapy , Exercise Therapy , Female , Gene Frequency , Genetic Association Studies , Hand Strength , Humans , Male , Middle Aged , Muscle Contraction , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
OBJECTIVE: The aim of the study was to assess the efficacy and safety of RAD1901, an oral estrogen receptor ligand, for the treatment of moderate-to-severe vasomotor symptoms of menopause. METHODS: This was a randomized, placebo-controlled, double-blind, dose-ranging, proof-of-concept trial. Postmenopausal women with a minimum of 7 moderate-to-severe, diary-reported hot flashes per day, or 50 per week, were randomized to one of five blinded dose groups (0 [placebo], 10, 25, 50, or 100âmg RAD1901 daily for 28 d). Efficacy endpoints included frequency and severity of hot flashes over 4 weeks of treatment. RESULTS: One hundred participants were randomized across the five treatment regimens. The frequency of moderate-to-severe hot flashes decreased in all groups over the treatment period (mean percent change from baseline at 4 wk, -54.1%, -77.2%, -51.8%, -53.8%, and -67.0% for placebo, 10, 25, 50, and 100âmg groups). The response in the 10âmg group was significantly different from placebo at 4 weeks (Pâ=â0.024). No other dose group was significantly different from placebo. There were no statistically significant differences in severity of hot flashes between placebo and any dose group. Treatment was well tolerated; most treatment-emergent adverse events were mild to moderate in severity. CONCLUSIONS: Daily treatment with 10âmg RAD1901 over 4 weeks resulted in a statistically significant reduction in the frequency of moderate-to-severe hot flashes compared with placebo, with an acceptable safety profile. Further clinical trials are warranted to investigate RAD1901's utility as a potential treatment for vasomotor symptoms.
Subject(s)
Hot Flashes/drug therapy , Postmenopause/physiology , Selective Estrogen Receptor Modulators/administration & dosage , Tetrahydronaphthalenes/therapeutic use , Vasomotor System/drug effects , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Ligands , Middle Aged , Selective Estrogen Receptor Modulators/blood , Severity of Illness Index , Treatment OutcomeABSTRACT
Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.
Subject(s)
Breath Holding , Carotid Stenosis/diagnostic imaging , Cerebrovascular Circulation/physiology , Oxygen/blood , Vasomotor System/diagnostic imaging , Aged , Aged, 80 and over , Blood Flow Velocity , Carotid Stenosis/physiopathology , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Ultrasonography, Doppler, Transcranial , Vasomotor System/physiopathologyABSTRACT
BACKGROUND: Low temperatures and slow blood flow may result from peripheral neuropathy caused by leprosy, and the simple detection of cold fingers could already be a preliminary classification for these patients. OBJECTIVE: To investigate whether infrared thermography would be able to measure this change in temperature in the hands of people with leprosy. METHOD: The study assessed 17 leprosy patients who were under treatment at the National Reference Center for Sanitary Dermatology and Leprosy, Uberlândia/MG, and 15 people without leprosy for the control group. The infrared camera FLIR A325 and Therma CAM Researcher Professional 2.9 software were used to measure the temperature. The room was air-conditioned, maintaining the temperature at 25°C; the distance between the camera and the limb was 70 cm. The vasomotor reflex of patients was tested by a cold stress on the palm. RESULTS: The study showed a significant interaction between the clinical form of leprosy and temperature, where the control group and the borderline-borderline form revealed a higher initial temperature, while borderline-lepromatous and lepromatous leprosy showed a lower temperature. Regarding vasomotor reflex, lepromatous leprosy patients were unable to recover the initial temperature after cold stress, while those with the borderline-tuberculoid form not only recovered but exceeded the initial temperature. CONCLUSION: Thermography proved a potential tool to assist in the early detection of neuropathies, helping in the prevention of major nerve damage and the installation of deformities and disabilities that are characteristic of leprosy.
Subject(s)
Hand/physiopathology , Leprosy/physiopathology , Skin Temperature/physiology , Thermography/methods , Vasomotor System/physiopathology , Adult , Aged , Cross-Sectional Studies , Female , Hand/innervation , Humans , Male , Middle Aged , Muscle Strength/physiology , Sensitivity and Specificity , Thermogenesis , Time Factors , Ulnar Nerve/physiopathology , Young AdultABSTRACT
Abstract: Background: Low temperatures and slow blood flow may result from peripheral neuropathy caused by leprosy, and the simple detection of cold fingers could already be a preliminary classification for these patients. Objective: To investigate whether infrared thermography would be able to measure this change in temperature in the hands of people with leprosy. Method: The study assessed 17 leprosy patients who were under treatment at the National Reference Center for Sanitary Dermatology and Leprosy, Uberlândia/MG, and 15 people without leprosy for the control group. The infrared camera FLIR A325 and Therma CAM Researcher Professional 2.9 software were used to measure the temperature. The room was air-conditioned, maintaining the temperature at 25°C; the distance between the camera and the limb was 70 cm. The vasomotor reflex of patients was tested by a cold stress on the palm. Results: The study showed a significant interaction between the clinical form of leprosy and temperature, where the control group and the borderline-borderline form revealed a higher initial temperature, while borderline-lepromatous and lepromatous leprosy showed a lower temperature. Regarding vasomotor reflex, lepromatous leprosy patients were unable to recover the initial temperature after cold stress, while those with the borderline-tuberculoid form not only recovered but exceeded the initial temperature. Conclusion: Thermography proved a potential tool to assist in the early detection of neuropathies, helping in the prevention of major nerve damage and the installation of deformities and disabilities that are characteristic of leprosy.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Skin Temperature/physiology , Vasomotor System/physiopathology , Thermography/methods , Hand/physiopathology , Leprosy/physiopathology , Time Factors , Ulnar Nerve/physiopathology , Cross-Sectional Studies , Sensitivity and Specificity , Thermogenesis , Muscle Strength/physiology , Hand/innervationABSTRACT
We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase.
Subject(s)
Baroreflex , Blood Pressure , Heart Rate , Liver Cirrhosis/physiopathology , Splanchnic Nerves/physiopathology , Vasomotor System/physiopathology , Animals , Cardiovascular Diseases/physiopathology , Disease Models, Animal , Male , Rats , Rats, WistarABSTRACT
OBJECTIVE: The aim of this study was to identify the facial areas defined by thermal gradient, in individuals compatible with the pattern of normality, and to quantify and describe them anatomically. METHODS: The sample consisted of 161 volunteers, of both genders, aged between 26 and 84 years (63 ± 15 years). RESULTS: The results demonstrated that the thermal gradient areas suggested for the study were present in at least 95% of the thermograms evaluated and that there is significant difference in temperature between the genders, racial group and variables "odontalgia", "dental prothesis" and "history of migraine" (p < 0.05). Moreover, there was no statistically significant difference in the absolute temperatures between ages, and right and left sides of the face, in individuals compatible with the pattern of normality (ΔT = 0.11°C). CONCLUSIONS: The authors concluded that according to the suggested areas of thermal gradients, these were present in at least 95% of all the thermograms evaluated, and the areas of high intensity found in the face were medial palpebral commissure, labial commissure, temporal, supratrochlear and external acoustic meatus, whereas the points of low intensity were inferior labial, lateral palpebral commissure and nasolabial.