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The acute climacteric syndrome has a large scale of symptoms. Main symptoms are hot flashes and night sweats. Each symptom could be presented alone or commonly in combination with other symptoms. The acute climacteric syndrome is induced by decrease and fluctuations of estrogen and neurosteroids levels. Therapy could be focused on hormone replacement. Changes of quality of life and especially effects of the therapy could be measured by standardized questionaries.
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Fogachos , Humanos , Feminino , Inquéritos e Questionários , Menopausa/fisiologia , Qualidade de Vida , Síndrome , Sudorese/fisiologia , Climatério/fisiologiaRESUMO
PURPOSE: More women diagnosed with breast cancer (BC) are living with oncology treatment-induced hot flushes (HFs). This Australian-based survey explores why some women experience more severe or ongoing HF and whether specific population characteristics are predictive of HF occurrence, frequency, and/or severity. METHODS: A non-probabilistic anonymous survey distributed online (Register4) and two Australian hospitals collected demographic and clinical information. Eligibility was consenting Australian-based women, 18 years and over, with a primary BC diagnosis. Analysis included linear and logistic regression models. RESULTS: A total of 324 survey responses were analyzed. Chemotherapy and hormone therapy were each associated with HF occurrence (aOR = 2.92, 95% CI [1.27, 6.70], p = 0.01; and aOR = 7.50, 95% CI [3.02, 18.62], p < 0.001) and in combination (aOR = 5.98, 95% CI [2.61, 13.69], p < 0.001). Increased self-reported anxiety at BC diagnosis was significantly associated with HF frequency and severity scores (aCO = 0.71, 95% CI [0.31, 1.12], p = 0.001; and aCO = 0.44, 95% CI [0.33, 0.55], p < 0.001). Postmenopausal women had significantly lower HF severity and frequency scores than premenopausal women (aCO = -0.93, 95% CI [-1.62, -0.25], p = 0.008; and aCO = -2.62, 95% CI [-5.14, -0.11], p = 0.041). CONCLUSIONS: Women with BC receiving chemotherapy and/or hormone therapy and premenopausal or experiencing elevated anxiety and/or stress will likely experience more severe oncology treatment-related HFs. IMPLICATIONS FOR CANCER SURVIVORS: HFs continue across the BC treatment trajectory with women >5-year survivorship still reporting life impacts, with premenopausal women at the time of BC diagnosis at higher risk of experiencing severe and more frequent oncology treatment-induced HFs than postmenopausal women. Women at high risk require information on methods to moderate HF potential life impacts and maintain treatment compliance.
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OBJECTIVE: The objective of this meta-analysis is to study the effect of different strengths of resistance training programs on the severity and frequency of hot flushes in postmenopausal women with vasomotor symptoms. BACKGROUND: Menopause is defined as the state in which the menstrual cycle of a biological female spontaneously comes to a halt for a period of about 1 year. Through a detailed analysis of much of the research, it is found that the resistance training program is beneficial not only for reducing the severity as well as the frequency of hot flushes in postmenopausal women. MATERIALS AND METHODS: Online research was conducted through databases such as PubMed, Cochrane Trial Register, and Google Scholar till the 20th of March 2023. The Review Manager (version 5.4.1) was used to statistically analyze the data from the studies. Studies meeting the inclusion criteria, comparing the vasomotor symptoms in resistance training groups as compared to control were used for this meta-analysis. The primary outcome of interest was the alleviation of hot flushes in the resistance training group. Random-effect model was used to pool the studies and the result was reported in SMD with 95% Confidence Interval (CI). RESULTS: 5 studies were selected for this review. Statistical analysis shows that vasomotor symptoms were more common in the control group and decreased significantly in the resistance training group after the intervention (SMD = -1.31, 95% CI: -1.85 to -0.77, p = 0.002). CONCLUSION: Resistance Training significantly affects vasomotor symptoms and can be considered for such symptoms in postmenopausal women.
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Fogachos , Pós-Menopausa , Treinamento Resistido , Humanos , Fogachos/terapia , Feminino , Treinamento Resistido/métodos , Pós-Menopausa/fisiologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.
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Densidade Óssea , Colo do Fêmur , Vértebras Lombares , Estudos Observacionais como Assunto , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Pós-Menopausa , Humanos , Densidade Óssea/fisiologia , Feminino , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/epidemiologia , Osteoporose Pós-Menopausa/fisiopatologia , Osteoporose Pós-Menopausa/complicações , Colo do Fêmur/fisiopatologia , Vértebras Lombares/fisiopatologia , Pós-Menopausa/fisiologia , Fogachos/fisiopatologia , Fogachos/complicações , Sistema Vasomotor/fisiopatologia , Medição de Risco/métodos , Fatores de RiscoRESUMO
BACKGROUND & OBJECTIVE: Vasomotor symptoms (VMS) are the most common symptoms during menopause including hot flushes and night sweats. They are highly disruptive to the quality of life. Fezolinetant is an FDA-approved non-hormonal selective neurokinin3 receptor antagonist for the treatment of VMS. In this study, we aim to assess the efficacy and safety of fezolinetant for VMS associated with menopause. METHODS: Databases were searched until September 2023 for relevant studies comparing fezolinetant against placebo. Data was extracted into an online form and analyzed using RevMan (Version 5.4.1). The GRADE approach was conducted to evaluate the quality of evidence regarding efficacy outcomes. We included randomized controlled trials (RCTs) comparing fezolinetant to placebo in postmenopausal women experiencing VMS. Exclusion criteria comprised studies involving participants with contraindications to fezolinetant or those evaluating its efficacy for indications other than VMS associated with menopause. RESULTS: Six studies were included in this study involving 3301 patients. Compared to placebo, fezolinetant reduced the frequency of VMS episodes from baseline (SMD = -0.64, 95 % CI [-0.77, -0.5]) and (SMD = -0.63, 95 % CI [-0.72, -0.53] at weeks 4 and 12 respectively. Additionally, fezolinetant reduced VMS severity score (SMD = -0.59, 95 %CI [-0.77, -0.42]) and (SMD = -0.4, 95 % CI [-0.54, -0.27]) at weeks 4 at 12 respectively. These reductions were positively reflected on Menopause specific quality of life score (SMD = -0.46, 95 %CI [-57, -0.34]), (SMD = -0.37, 95 %CI [-0.48, -0.25]) at weeks 4 and 12 respectively. Regarding safety analysis, fezolinetant showed increased risk for drug-related TEAEs (RR = 1.47, 95 %CI [1.06,2.04]), serious TEAEs (RR = 1.67, 95 %CI [1.09,2.55]), fatigue (RR = 4.05, 95 %CI [1.27,12.88]), arthralgia (RR = 2.83, 95 %CI [1.02,7.8]) and ALT or AST > 3 times (RR = 2, 95 %CI [1.12,3.57]), with no other statistically significant difference regarding other safety terms. CONCLUSION: Fezolinetant has demonstrated efficacy in reducing the frequency and severity of VMS in postmenopausal women, leading to an improvement in their quality of life. These findings suggest that Fezolinetant may serve as a viable alternative to hormonal therapy for managing VMS.
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Fogachos , Menopausa , Humanos , Fogachos/tratamento farmacológico , Feminino , Menopausa/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Qualidade de Vida , Resultado do Tratamento , Sistema Vasomotor/efeitos dos fármacos , Compostos Heterocíclicos com 2 Anéis , TiadiazóisRESUMO
INTRODUCTION: Menopausal vasomotor symptoms (VMS) are experienced by most women and are often debilitating and can last for years. While hormone replacement therapy is effective, it carries risks that have impacted its wider use, and it can be contraindicated. There is a large unmet need for a safe, effective non-hormonal therapy. AREAS COVERED: The importance of the neurokinin (NK) system in the hypothalamic regulation of the vasomotor center has become clear. NK antagonists, previously developed for other indications, have therefore been investigated for the treatment of VMS. Elinzanetant is a potent antagonist at both NK1 (endogenous ligand Substance P) and NK3 (neurokinin B) receptors, whereas other related drugs in development are selective NK3 antagonists. Elinzanetant has been investigated in 2 Phase II trials for menopausal VMS, demonstrating rapid onset and dose-dependant efficacy for the relief of VMS and improvement in quality of life for up to 12 weeks. Phase III trials are underway in women both with physiological menopause and after treatment for breast cancer. EXPERT OPINION: Elinzanetant is a very promising non-hormonal approach to a highly prevalent symptom constellation, with rapid onset and high efficacy. Wider indications are being explored in current Phase III trials.
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Neoplasias da Mama , Fogachos , Humanos , Feminino , Fogachos/tratamento farmacológico , Pós-Menopausa/fisiologia , Qualidade de Vida , Menopausa/fisiologiaRESUMO
Insomnia is one of the major complaints of menopausal women with advancing age and may be complexly related to a variety of causes. However, there is still a lack of standards on the general approach and treatment for insomnia in menopausal women. The aim of this review is to summarize recent pathogenic theories of sleep disturbance in the menopausal period and discuss the approach and management of insomnia in postmenopausal women. Sleep disturbances in menopausal women may be associated with physical and psychiatric factors and other comorbid diseases. Careful history taking and multidisciplinary physical and psychosocial evaluation are necessary and, in particular, comorbidities related to sleep disorders, such as obstructive sleep apnea, must be taken into consideration. A unique aspect of insomnia in postmenopausal women is that menopausal symptoms due to hormonal decline can be closely related to sleep disturbances. Therefore, menopausal hormone therapy (MHT) should be considered as the treatment of choice among pharmacological treatments following cognitive behavioral therapy, which is suggested as the first-line treatment in the general population insomnia treatment guidelines. Additionally, melatonin and 5HT-based drugs, which have fewer side effects, along with MHT should be preferentially recommended in menopausal women.
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Vasomotor symptoms (VMS) are characteristic of menopause experienced by over 75% of postmenopausal women with significant health and socioeconomic implications. Although the average duration of symptoms is seven years, 10% of women experience symptoms for more than a decade. Although menopausal hormone therapy (MHT) remains an efficacious and cost-effective treatment, its use may not be suitable in all women, such as those at an increased risk of breast cancer or gynaecological malignancy. The neurokinin B (NKB) signaling pathway, together with its intricate connection to the median preoptic nucleus (MnPO), has been postulated to provide integrated reproductive and thermoregulatory responses, with a central role in mediating postmenopausal VMS. This review describes the physiological hypothalamo-pituitary-ovary (HPO) axis, and subsequently the neuroendocrine changes that occur with menopause using evidence derived from animal and human studies. Finally, data from the latest clinical trials using novel therapeutic agents that antagonise NKB signaling are reviewed.
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Fogachos , Menopausa , Animais , Feminino , Humanos , Fogachos/tratamento farmacológico , Fogachos/etiologia , Fogachos/metabolismo , Menopausa/fisiologia , Neurocinina B/metabolismo , Terapia de Reposição Hormonal , Transdução de SinaisRESUMO
Vasomotor symptoms (VMS) are often considered the classic menopausal symptom and are experienced by most women during the menopause transition. VMS are well established to be associated with decrements in quality of life during the menopause. More recent research also links VMS to poorer cardiovascular health. This review summarizes key insights about links between VMS and cardiovascular disease (CVD) risk that come from the Study of Women's Health Across the Nation (SWAN), a longitudinal epidemiologic cohort study of the menopause transition, as well as from the MsHeart/MsBrain studies, clinical studies that leverage vascular imaging and brain imaging as well as wearable technologies that provide objective indicators of VMS. Using a range of methodologies and extensive consideration of confounders, these studies have shown that frequent and/or persistent VMS are associated with adverse CVD risk factor profiles, poorer underlying peripheral vascular and cerebrovascular health, and elevated risk for clinical CVD events. Collectively, the SWAN and MsHeart/MsBrain studies form complementary epidemiologic and clinical studies that point to the importance of VMS to women's cardiovascular health during the menopause transition and beyond.
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Doenças Cardiovasculares , Fogachos , Feminino , Humanos , Estudos de Coortes , Fogachos/epidemiologia , Fogachos/etiologia , Qualidade de Vida , Menopausa , Saúde da Mulher , Estudos Longitudinais , Doenças Cardiovasculares/diagnóstico , Sistema Vasomotor , SudoreseRESUMO
Estrogen is a key regulatory hormone in the functioning of a female reproductive system. Estrogen hormone regulates many complex physiological processes, which has its role in reproduction and skeletal and cardiovascular systems by acting on estrogen receptors alpha (ERα) and beta (ERß), which are nuclear transcription factors. Selective estrogen receptor modulators (SERMs) are now being used to treat bone loss, breast carcinoma, and menopausal symptoms, metabolic neurodegenerative because of their characteristics that allow them to function as both estrogen agonists and antagonists, depending on the target tissue. First-generation SERMs, such as Tamoxifen, are used in the management protocol for breast cancer, which is estrogen receptor (ER-positive). Raloxifene is a second-generation SERM that is a valuable adjunct used to treat and prevent osteoporosis in postmenopausal women and prevent compression fractures of the vertebral column. Novel SERM molecules are on the horizon, proven more potent and efficacious in preventing and treating osteoporosis. These include Ospemifene, lasofoxifene, bazedoxifene and arzoxifene. The benefits of Raloxifene versus that of Bazedoxifene are under trial. Despite their therapeutic benefits and actions, these medications are not without adverse effects, such as thromboembolic disorders. Increased risk of uterine cancer has been linked to Tamoxifen. This article delves into the world of SERMs, including their development and discovery. The newer SERMs in late development, ospemifene, lasofoxifene, bazedoxifene, and arzoxifene, are described in detail.
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The huge impact of climate change on humankind is multidimensional, and includes direct and indirect challenges to the physical, psychological and socio-cultural wellbeing. Women may be more vulnerable to climate-sensitive diseases, but little attention has been paid to specific needs and challenges associated with the menopause transition. The increase in average and extreme temperatures may modulate the manifestation of vasomotor symptoms; in particular, environmental temperature and seasonality may affect hot flushes and night sweats. However, more research is needed to define the impact of climate-related factors among the determinants influencing the individual experience of menopause. In addition, increased exposure to environmental pollution and toxins may also have a role in the modulation of ovarian aging mechanisms, possibly influencing timing of menopause. Finally, both air pollution and menopause transition are associated with unfavorable modifications of cardio-metabolic, bone and cognitive health, and account should be taken of these in the evaluation of the individual woman's health vulnerabilities. Overall, the evidence reported in this narrative review supports the need for specific strategies aimed at reducing the burden of climate and environmental change on menopausal women. Healthcare providers should promote behavioral measures that reduce anthropogenic climate change and at the same time have a beneficial role on several domains of physical and psychological wellbeing. From this perspective, menopause represents a golden moment to implement virtuous behaviors that will benefit at the same time women's longevity and the planet.
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Fogachos , Menopausa , Feminino , Humanos , Menopausa/psicologia , Fogachos/etiologia , Fogachos/psicologia , Saúde da Mulher , SudoreseRESUMO
BACKGROUND: Androgen deprivation therapy (ADT) is prescribed to almost half of all men diagnosed with prostate cancer. Although ADT is effective treatment, with virtually all men with advanced disease showing initial clinical response, it is associated with troublesome side effects including hot flushes and night sweats (HFNS). HFNS can be both frequent and severe and can have a significant impact on quality of life (QoL). They can occasionally be so debilitating that patients stop ADT altogether, despite the increased risk of disease relapse or death. Previous research has found that guided self-help cognitive behavioural therapy (CBT) can be effective in reducing HFNS due to ADT when delivered by a clinical psychologist. MANCAN2 aims test whether we can train the existing NHS Prostate Cancer Nurse Specialist (CNS) team to deliver guided self-help CBT and whether it is effective in reducing the impact of HFNS in men undergoing ADT. METHODS: MANCAN2 is a phase III multicentre randomised controlled trial and process evaluation. Between 144 and 196 men with prostate cancer who are currently receiving ADT and are experiencing problematic HFNS will be individually randomised in a 1:1 ratio in groups of 6-8 participants to either treatment as usual (TAU) or participation in the guided self-help CBT intervention plus TAU. A process evaluation using the normalisation process theory (NPT) framework will be conducted, to understand the CNS team's experiences of delivering the intervention and to establish the key influencers to its implementation as a routine practice service. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost-effectiveness of the intervention and participant adherence to the trial intervention will also be assessed. DISCUSSION: MANCAN2 will advance the program of work already conducted in development of management strategies for HFNS. This research will determine whether the severity of ADT-induced HFNS in men with prostate cancer can be reduced by a guided self-help CBT intervention, delivered by the existing NHS prostate cancer CNS team, within a multicentre study. The emphasis on this existing team, if successful, should facilitate translation through to implementation in routine practice. TRIAL REGISTRATION: ISRCTN reference 58720120 . Registered 13 December 2022.
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Terapia Cognitivo-Comportamental , Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/efeitos adversos , Androgênios , Qualidade de Vida , Neoplasias da Próstata/tratamento farmacológico , Suor , Recidiva Local de Neoplasia , Fogachos/terapiaRESUMO
OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP). METHODS: A total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points. RESULTS: In premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased. CONCLUSIONS: Seven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO.
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Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Salpingo-Ooforectomia/efeitos adversos , Hemoglobinas Glicadas , Proteína BRCA1/genética , Proteína C-Reativa , Proteína BRCA2/genética , Colesterol , Triglicerídeos , Lipídeos , Neoplasias Ovarianas/genética , Ovariectomia , Mutação , Neoplasias da Mama/etiologiaRESUMO
Hot flashes and night sweats, also known as vasomotor symptoms (VMS), are common and bothersome symptoms of the menopause transition. In addition to negatively impacting quality of life, VMS have been associated with multiple indicators of cardiovascular disease (CVD) risk, including an unfavorable CVD risk factor profile, increased subclinical CVD, and elevated risk of CVD events. Several facets of VMS have been associated with CVD risk, including the frequency, timing, duration, and severity of VMS. VMS may signify poor or degrading cardiovascular health among midlife women and indicate women who warrant focused CVD prevention efforts.
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Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.
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Neoplasias Ovarianas , Salpingo-Ooforectomia , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Qualidade de Vida , Consenso , Pré-Menopausa , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Ovariectomia , Predisposição Genética para DoençaRESUMO
OBJECTIVES: With poor sleep highly prevalent during the menopause transition, there is a need to better understand modifiable psychological resources that may be associated with improved sleep. Hence, we investigated whether self-compassion can explain variance in self-reported sleep quality in midlife women, over and above vasomotor symptoms. METHODS: This cross-sectional study (N = 274) used questionnaire data from self-report measures of sleep, hot flushes and night sweats, hot flush interference, and self-compassion, with analyses conducted using sequential (hierarchical) regression. RESULTS: Poor sleep, as measured by the Pittsburgh Sleep Quality Index, was prevalent and significantly worse in the subsample of women with hot flushes and night sweats, g = 0.28, 95 % CI [0.04, 0.53]. The interference of hot flushes in everyday life (ß = 0.35, p < .01), but not their frequency, predicted self-reported sleep quality. Once self-compassion was added to the model it was the only predictor of poor sleep (ß = -0.32, p < .01). When positive self-compassion and self-coldness were considered separately, the effect on sleep quality appeared to be attributable to self-coldness scores alone (ß = 0.29, p < .05). CONCLUSIONS: Self-compassion may have a stronger relationship with self-reported sleep quality in midlife women than vasomotor symptoms. Future intervention-based research could test the efficacy of self-compassion training for midlife women experiencing sleep disturbances, as this may be an important and modifiable psychological resilience factor.
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Autocompaixão , Qualidade do Sono , Feminino , Humanos , Estudos Transversais , Sudorese , Fogachos/complicações , Fogachos/psicologia , Menopausa/psicologiaRESUMO
Background: Tibolone is an alternative to conventional estrogen and progesterone in relieving post-menopausal symptoms in Indian women. Material and Methods: A prospective short-term observational study was done at a tertiary care teaching hospital in New Delhi from November 2019 to September 2021. Fifty-three women, less than 60 years of age, presenting with moderate to severe intensity of menopausal symptoms as assessed by measuring menopausal rating score (MRS > 8) were enrolled and given Tibolone 2.5 mg daily for 3 months. Improvements in symptoms were seen at 1 month and 3 months. Side effects were also noted. Results: Marked improvement was seen as reduction in scores of psychological, somatic and genitourinary symptoms was noted. The psychological symptoms reduced from 8.92 ± 1.959 to 2.905 ± 1.042, the somatic symptoms decreased from 8.33 ± 2.299 to 3.4 ± 1.167, and genitourinary symptoms decreased from 3.64 ± 1.42 to 2.150 ± 0.948 after 3 months of treatment with Tibolone. Only 3 patients (5.6%) experienced vaginal spotting with no major side effects. Conclusions: Tibolone is a highly effective and well accepted drug to reduce moderate to severe menopausal symptoms, especially psychological symptoms including depression.
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Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is accompanied by side effects affecting health-related quality of life (HRQL). Objective: To assess the effects of the fetal estrogen estetrol (E4) on symptoms related to estrogen and androgen deficiency, and on HRQL measured using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Design setting and participants: This was a phase 2, double-blind, randomized, placebo-controlled study in patients with advanced PCa. Intervention: Patients receiving ADT were randomly assigned at a 2:1 ratio to daily treatment with a high dose of E4 (HDE4; n = 41) or placebo (n = 21) for 24 wk. Outcome measurements and statistical analysis: The primary outcome was the effect of HDE4 cotreatment on hot flushes (HFs). Secondary outcomes were the Q-Man questionnaire for evaluation of the effect on estrogen and androgen deficiency symptoms, and the FACT-P questionnaire for evaluating HRQL. Results and limitations: At 24 wk, the number of patients experiencing HFs was significantly lower in the HDE4 group than in the placebo group (14.3% vs 60.0%; p < 0.001). HDE4 treatment was associated with lower incidence of night sweats, arthralgia, and fatigue, but more nipple tenderness and gynecomastia. At 24 wk, the mean HRQL score favored HDE4 over placebo for the FACT-P total score (122.2 ± 12.3 vs 118.7 ± 19.7) and for several other FACT subscales. Conclusions: Daily HDE4 coadministration almost completely prevented HFs in patients with advanced PCa treated with ADT. HDE4 also had positive effects on HRQL and counteracted other estrogen deficiency symptoms caused by ADT. These data support the dual efficacy concept of ADT and HDE4 to improve HRQL and increase the antitumor effect of ADT. Patient summary: For patients on androgen deprivation therapy for advanced prostate cancer, cotreatment with a high dose of estetrol almost completely prevents the occurrence of hot flushes and improves quality of life and well-being, but nipple sensitivity and an increase in breast size may occur.
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Cardiovascular disease (CVD), the leading cause of death among US adults, is more prevalent in menopausal females compared with age-matched males. Vasomotor symptoms of menopause (VMS; hot flashes/flushes and night sweats) are common among females undergoing menopausal transition and have been associated with elevated blood pressure (BP) and increased CVD risk. Autonomic dysregulation of BP has been posited as a contributing factor to the elevated CVD risk in menopausal females with VMS. This review includes 1) a brief overview of the relationship between VMS and CVD, 2) mechanisms of hot flushes and their potential impact on short- and long-term BP regulation, and 3) how the disruption of autonomic function associated with VMS might provide a mechanistic pathway to CVD development. Finally, this review will highlight knowledge gaps and future directions toward better understanding of hot flush physiology and VMS contributions to CVD.
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Doenças do Sistema Nervoso Autônomo , Doenças Cardiovasculares , Adulto , Feminino , Humanos , Sudorese , Menopausa/fisiologia , Fogachos/complicações , Sistema VasomotorRESUMO
This study compared the effects of aerobic physical training and estradiol (E2) replacement on central pathways involved with thermoregulation in ovariectomized rats. Rats were assigned to untrained ovariectomized treated with placebo (UN-OVX), untrained ovariectomized treated with E2 (E2-OVX), and trained ovariectomized (TR-OVX) groups. Tail skin temperature (TST), internal temperature (Tint), and basal oxygen consumption (VO2) were recorded. Neuronal activity, brain expression of Kiss1, NKB and Prodyn, and central norepinephrine (NE) levels were measured. UN-OVX had the highest TST. Compared to UN-OVX rats, TR-OVX and E2-OVX had lower Fos expression in the paraventricular and arcuate (ARC) nuclei, and lower double labeling for Tyrosine Hydroxylase and Fos in the brainstem. Compared to UN-OVX, only TR-OVX group exhibited lower kisspeptin (Kiss1), neurokinin B (NKB), and prodynorphin expression in the ARC and higher central NE levels. Aerobic physical training before menopause may prevent the heat dissipation imbalance induced by reduction of E2, through central NE release, modulation of Kiss1, NKB and prodynorphin expression in neurons from ARC nucleus.