Severity Of Hot Flashes Research Articles

Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial.

To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms. A randomized, single blind, four arm, parallel assignment study was conducted in VMMC and SJH, New Delhi, India. 200 Indian menopausal women were recruited and assigned into four treatment groups viz., estradiol valerate (E2V), conjugated equine estrogen (CEE), isoflavones and Placebo group. The statistical significance of categorical variables was determined by Chi-square, Fisher's exact test. In case of quantitative variable parametric test Student's t test was used. In case of quantitative variables where data are not normally distributed, Kruskal-wallis test and Wilcoxon Mann-Whitney test were used. Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups. Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes. 91.9% decrease was observed in mean hot flash score in the E2V group after 24weeks of treatment, 89.2% in the CEE group, 60.42% decrease in the isoflavones group. While placebo led to 47.9% decrease in mean hot flash score. After 24weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group. No serious side effect was reported in any of the groups. Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24weeks. However, it seems more reasonable to replenish with less costly and bio-identical hormone, i.e. micronized estradiol valerate which is equally effective. The trial was registered under Clinical trial registry of India prospectively (number: CTRI/2012/04/002566).

Symptom clusters among MsFLASH clinical trial participants.

Our objective was to identify symptom clusters using standardized measures completed by participants in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health clinical trial at baseline, including hot flash interference, and sleep, depressive, anxiety, and pain symptoms. Data from all women randomized to interventions and controls from Menopausal Strategies: Finding Lasting Answers to Symptoms and Health studies 1, 2, and 3 (N = 899) were included; 797 with complete data were used in the analyses. Scores from standardized measures obtained at baseline included the following: Hot Flash-Related Daily Interference Scale, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9 measure of depressed mood, Generalized Anxiety Disorder, and Brief Pain Inventory PEG scores (pain intensity [P], interference with enjoyment of life [E], and interference with daily activity [G]). Latent class analysis was used to identify symptom clusters using standardized scale scores and their established cut points. We identified five classes using the Bayesian Information Criterion and the Akaike Information Criterion. Women in classes 1 and 2 had high hot flash interference levels relative to the others, and class 1 (10.5% of total) included severe hot flash interference, severe sleep symptoms, and moderately severe pain symptoms (hot flash, sleep, pain). In class 2 (14.1%), severe hot flash interference was paired with the severe sleep symptoms, and moderate to severe depressed and anxious mood symptoms and pain (hot flash, sleep, mood, pain). In class 3 (39.6%), women reported moderately severe sleep symptoms with moderate hot flash interference, and low severity mood and pain symptoms (hot flash, sleep). Those in class 4 (7.0%) reported moderate hot flash interference with severe levels of anxiety and depressed mood symptoms, but low levels of other symptoms (hot flash, mood). Women in class 5 (28.7%) reported the lowest levels of all the five symptoms (low severity symptoms). Women meeting hot flash frequency criteria for inclusion in clinical trials exhibited multiple co-occurring symptoms that clustered into identifiable groups according to symptom interference and severity. Variability of symptom profiles between the classes was evident, indicating that the classes were composed of differing symptom types and not simply differing severity levels. These symptom clusters may be useful phenotypes for differentiating treatment effects or evaluating associations with biomarkers or genes.

Impact of Adjuvant Endocrine Therapy on Quality of Life and Symptoms: Observational Data Over 12 Months From the Mind-Body Study.

To examine patterns of health and symptoms associated with the initiation of adjuvant endocrine therapy (ET) for primary breast cancer treatment. The mind-body study (MBS) observational cohort participants provided self-reported data on physical and mental health, ET-related symptoms, as well as depression, fatigue, and sleep obtained at enrollment (after primary treatment, prior to initiation of ET) and 6 and 12 months later. Longitudinal trajectories of outcome variables among three patient groups (no ET, aromatase inhibitor [AI], or tamoxifen) were compared by using linear mixed models. Two-thirds of the 186 women initiated ET, which was evenly split between AI and tamoxifen, and no significant differences were observed in self-reported measures among the groups at baseline or in covariate-adjusted analyses. Physical health scores were below normative levels initially and improved over time, but the AI group had a significantly lower score at 12 months (P = .05); mental health scores were within the normal range, were similar in each group, and did not change over time. The no-ET group showed either stable or declining symptom severity, whereas the ET groups often showed increased severity over time, and the AI group reported more severe musculoskeletal (P = .02), hot flash (P = .02), and cognitive problems (P = .006) at one or both of the follow-up time points compared with the no-ET group. The tamoxifen group had higher levels of hot flashes (P = .002), cognitive problems (P = .016), and bladder problems (P = .02) than the no-ET group. Attention should be given to the increased symptom burden associated with ET, and better efforts should be made to address patient-reported outcomes.

Acupuncture for Menopausal Hot Flashes: A Randomized Trial.

Hot flashes (HFs) affect up to 75% of menopausal women and pose a considerable health and financial burden. Evidence of acupuncture efficacy as an HF treatment is conflicting. To assess the efficacy of Chinese medicine acupuncture against sham acupuncture for menopausal HFs. Stratified, blind (participants, outcome assessors, and investigators, but not treating acupuncturists), parallel, randomized, sham-controlled trial with equal allocation. (Australia New Zealand Clinical Trials Registry: ACTRN12611000393954). Community in Australia. Women older than 40 years in the late menopausal transition or postmenopause with at least 7 moderate HFs daily, meeting criteria for Chinese medicine diagnosis of kidney yin deficiency. 10 treatments over 8 weeks of either standardized Chinese medicine needle acupuncture designed to treat kidney yin deficiency or noninsertive sham acupuncture. The primary outcome was HF score at the end of treatment. Secondary outcomes included quality of life, anxiety, depression, and adverse events. Participants were assessed at 4 weeks, the end of treatment, and then 3 and 6 months after the end of treatment. Intention-to-treat analysis was conducted with linear mixed-effects models. 327 women were randomly assigned to acupuncture (n=163) or sham acupuncture (n=164). At the end of treatment, 16% of participants in the acupuncture group and 13% in the sham group were lost to follow-up. Mean HF scores at the end of treatment were 15.36 in the acupuncture group and 15.04 in the sham group (mean difference, 0.33 [95% CI, -1.87 to 2.52]; P=0.77). No serious adverse events were reported. Participants were predominantly Caucasian and did not have breast cancer or surgical menopause. Chinese medicine acupuncture was not superior to noninsertive sham acupuncture for women with moderately severe menopausal HFs. National Health and Medical Research Council.

Индивидуальный выбор менопаузальной гормональной терапии

The goal of anti-aging menopausal hormone therapy (MHT) lies in maintenance and restoration of the major organs and body systems, thus achieving two main effects: increasing life expectancy and improving its quality, which is fully consistent with the desires of women in perimenopausal and postmenopausal women. MHT started in the menopausal transition period is not only the treatment of early symptoms of menopause, but menopause itself and prevention of late complications. The article discusses the possibility and efficacy of Angeliq® Micro containing reduced doses of estrogen and progestogen (17β-estradiol 0.5 mg + drospirenone 0.25 mg). Indications for its purpose is to maintain moderate to severe hot flashes in postmenopausal women with an intact uterus.

Hypothalamic orexin’s role in exacerbated cutaneous vasodilation responses to an anxiogenic stimulus in a surgical menopause model

Distressing symptoms such as hot flashes and sleep disturbances affect over 70% of women approaching menopause for an average of 4–7 years, and recent large cohort studies have shown that anxiety and stress are strongly associated with more severe and persistent hot flashes and can induce hot flashes. Although high estrogen doses alleviate symptoms, extended use increases health risks, and current non-hormonal therapies are marginally better than placebo. The lack of effective non-hormonal treatments is largely due to the limited understanding of the mechanisms that underlie menopausal symptoms. One mechanistic pathway that has not been explored is the wake-promoting orexin neuropeptide system. Orexin is exclusively synthesized in the estrogen receptor rich perifornical hypothalamic region, and has an emerging role in anxiety and thermoregulation. In female rodents, estrogens tonically inhibit expression of orexin, and estrogen replacement normalizes severely elevated central orexin levels in postmenopausal women. Using an ovariectomy menopause model, we demonstrated that an anxiogenic compound elicited exacerbated hot flash-associated increases in tail skin temperature (TST, that is blocked with estrogen), and cellular responses in orexin neurons and efferent targets. Furthermore, systemic administration of centrally active, selective orexin 1 or 2 and dual receptor antagonists attenuated or blocked TST responses, respectively. This included the reformulated Suvorexant, which was recently FDA-approved for treating insomnia. Collectively, our data support the hypothesis that dramatic loss of estrogen tone during menopausal states leads to a hyperactive orexin system that contributes to symptoms such as anxiety, insomnia, and more severe hot flashes. Additionally, orexin receptor antagonists may represent a novel non-hormonal therapy for treating menopausal symptoms, with minimal side effects.

κ Agonists as a novel therapy for menopausal hot flashes.

The etiology of postmenopausal hot flashes is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing kisspeptin, neurokinin B and dynorphin-called KNDy neurons-are located adjacent to the thermoregulatory center. KNDy neurons regulate pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Dynorphin may inhibit this system by binding κ opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. A double-blind, cross-over, placebo-controlled pilot study evaluated the effects of a κ agonist. Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate to severe hot flashes (aged 48-60 y) were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all three interventions: placebo, standard-dose pentazocine/naloxone (50/0.5 mg), or low-dose pentazocine/naloxone (25/0.25 mg). In an inpatient research setting, each participant received the three interventions, in randomized order, on three separate days. On each day, an intravenous catheter was inserted for LH blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. The mean (SEM) hot flash frequency 2 to 7 hours after therapy initiation was lower than that for placebo (standard-dose κ agonist, 4.75 [0.67] hot flashes per 5 h; low-dose κ agonist, 4.50 [0.57] hot flashes per 5 h; placebo, 5.94 [0.78] hot flashes per 5 h; P = 0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some--but not all--women. This pilot study suggests that κ agonists may affect menopausal vasomotor symptoms.

Comparison of citalopram and venlafaxine's role in treating sleep disturbances in menopausal women, a randomized, double-blind, placebo-controlled trial.

Sleep disturbance is a common complaint in postmenopausal women. Few studies compared symptom improvement taking antidepressants versus placebo. This study aims to evaluate the efficacy of venlafaxine and Citalopram compared to placebo in treatment of sleep disturbance in healthy postmenopausal women. This randomized, double-blind, placebo-controlled clinical trial was conducted in three groups of 20 postmenopausal women. The patients took venlafaxine 75 mg/daily (group I) or citalopram 20 mg/d (group II) or placebo (group III). Each patient filled Pittsburgh sleep quality index (PSQI) and Pittsburgh and Beck depression questionnaires. The frequency of hot flashes in a day and its severity were measured through diaries. Somatic symptoms and adverse side effects were evaluated. Follow-up visit was conducted after 3 months. The prior and the later results were compared. The PSQI scores in three placebo, venlafaxine, and citalopram groups before treatment were 14.25 ± 3.85, 11.55 ± 3.96, and 13.50 ± 3.56, respectively (p = 0.076). These values after treatment reached 9.95 ± 5.07, 8 ± 3.06, and 6.95 ± 1.84, respectively. PSQI score in citalopram and venlafaxine group was not significantly different (p = 0.19) but the score in both groups was significantly lower compared with placebo group after treatment (p = 0.01). The frequency of hot flashes in a day was reduced significantly by both citalopram and venlafaxine (p < 0.05), although it was more reduced by citalopram than venlafaxine (p = 0.03). Severity of hot flashes in both venlafaxine and citalopram was significantly lower in comparison with placebo group (p = 0.02), and there was no significant difference between two drugs, though (p = 0.84). Beck score decreased more in venlafaxine group in comparison with other groups but it did not reach significant (p = 0.06). Citalopram and venlafaxine are equally more effective than placebo in reducing sleep disturbance and severity of hot flashes, while citalopram is more effective in reducing frequency of hot flashes than venlafaxine. Meanwhile, venlafaxine is more effective than citalopram in treatment of depression in postmenopausal women. Iranian Registry of Clinical Trials 201210152576N6.

295 - Oxidative Stress Is Increased with the Severity of Hot Flashes in Postmenopausal Women

295 - Oxidative Stress Is Increased with the Severity of Hot Flashes in Postmenopausal Women

Results of a phase Ib study of Q-122 treatment of vasomotor symptoms in breast cancer patients.

99 Background: Breast cancer patients taking tamoxifen (TAM) or an aromatase inhibitor (AI) often develop severe vasomotor symptoms (VMS) yet the only FDA approved non-hormonal treatment for VMS, 7.5 mg paroxetine, has a warning against concomitant use with TAM. Q-122, an orally-available small molecule, is being developed to address this unmet medical need. Results from the Phase 1b study, Q-1001, are presented. Methods: Q-1001 was a Phase 1 open-label, two-dose, dose-escalation study of the safety and preliminary effectiveness of Q-122 in females with breast cancer currently taking TAM or an AI and experiencing an average of at least 7-8 moderate to severe hot flashes per day. Key exclusion criteria included significant renal or hepatic disease, untreated hyperthyroidism and clinically significant abnormal laboratory findings. The study period included a 2 week drug-free screening phase, 28 day treatment phase, and 2 week drug-free follow-up period. Subjects were initially enrolled into Group 1 (100 mg Q-122) followed by Group 2 (200 mg Q-122). Safety was assessed by review of adverse events (AEs), physical findings and laboratory values. The primary efficacy endpoints were mean changes in frequency and severity (hot flash severity score, HFSS) of moderate and severe hot flashes from baseline to Week 4. Menopausal symptoms were assessed using the Greene Climacteric Scale (GCS). Results: 10 and 11 subjects received 100 and 200 mg Q-122 respectively; 8 subjects in each group completed the study. At the end of treatment for groups 1 and 2 respectively, the daily average frequency of hot flashes was reduced from 9.9 to 4.1 and from 8.6 to 3.2, and the mean HFSS was reduced by 62% and 68% from baseline values. Menopausal symptoms assessed using the GCS were significantly reduced from baseline (psychological: -82%; somatic: -65%; vasomotor: -65%). All AEs (n = 29) were either mild (79%) or moderate (21%) in severity and only 3 (all in one subject) were considered possibly related to study drug. Conclusions: Treatment with Q-122 resulted in significant reduction in the frequency and severity of VMS and improvement in menopausal symptoms as assessed by the GCS. No safety issues associated with the use of Q-122 were identified in this study.

Risk factors for hot flashes among women undergoing the menopausal transition: baseline results from the Midlife Women's Health Study.

The aim of this study was to examine the associations of demographic characteristics, health behaviors, and hormone concentrations with the experience of any, current, more severe, and more frequent midlife hot flashes. Baseline data from 732 women aged 45 to 54 years who were enrolled in the Midlife Women's Health Study were analyzed. A clinic visit was conducted to collect blood samples for hormone assays and to measure ovarian volume using transvaginal ultrasound. A self-administered questionnaire ascertained information on demographic factors, health habits, and hot flash history. Multivariable logistic regression was conducted to examine associations between potential risk factors and hot flash outcomes. Approximately 45% of participants reported experiencing midlife hot flashes. In covariate-adjusted models, older age, perimenopause status, current and past cigarette smoking, and depressive symptoms were significantly associated with increased odds of all of the hot flash outcomes. In addition, history of oral contraceptive use was associated with increased odds of any hot flashes. In contrast, higher current alcohol intake was significantly associated with decreased odds of any, current, and more severe hot flashes. Higher estradiol and progesterone concentrations were significantly associated with decreased odds of all hot flash outcomes. Although the temporality of such associations is not known because of the cross-sectional nature of the data, these observed relationships can help to identify women at risk for hot flashes.

Comparison of physical interventions, behavioral interventions, natural health products, and pharmacologics to manage hot flashes in patients with breast or prostate cancer: protocol for a systematic review incorporating network meta-analyses.

BackgroundBreast and prostate cancers are the most commonly diagnosed non-dermatologic malignancies in Canada. Agents including endocrine therapies (e.g., aromatase inhibitors, gonadotrophin-releasing hormone analogs, anti-androgens, tamoxifen) and chemotherapy have improved survival for both conditions. As endocrine manipulation is a mainstay of treatment, it is not surprising that hot flashes are a common and troublesome adverse effect. Hot flashes can cause chills, night sweats, anxiety, and insomnia, lessening patients’ quality of life. These symptoms impact treatment adherence, worsening prognosis. While short-term estrogen replacement therapy is frequently used to manage hot flashes in healthy menopausal women, its use is contraindicated in breast cancer. Similarly, testosterone replacement therapy is contraindicated in prostate cancer. It is therefore not surprising that non-hormonal pharmacological treatments (anti-depressants, anti-epilectics, anti-hypertensives), physical/behavioral treatments (e.g., acupuncture, yoga/exercise, relaxation techniques, cognitive behavioral therapy), and natural health products (e.g., black cohosh, flax, vitamin E, ginseng) have been studied for control of hot flashes. There is a need to identify which interventions minimize the frequency and severity of hot flashes and their impact on quality of life. This systematic review and network meta-analysis of randomized studies will synthesize available evidence addressing this knowledge gap.Methods/designAn electronic search of Medline, Embase, AMED, PsycINFO, and the Cochrane Register of Controlled Trials has been designed by an information specialist and peer reviewed by a second information specialist. Study selection and data collection will be performed by two reviewers independently. Risk of bias assessments will be completed using the Cochrane Risk of Bias Scale. Outcomes of interest will include validated measures of hot flash severity, hot flash frequency, quality of life, and harms. Bayesian network meta-analyses will be performed where judged appropriate based on review of clinical and methodologic features of included studies.DiscussionOur review will include a broad range of interventions that patients with breast and prostate cancer have attempted to use to manage hot flashes. Our work will establish the extent of evidence underlying these interventions and will employ an inclusive approach to analysis to inform comparisons between them. Our findings will be shared with Cancer Care Ontario for consideration in the development of guidance related to supportive care in these patients.Systematic review registrationPROSPERO: CRD42015024286Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0099-y) contains supplementary material, which is available to authorized users.

Is anxiety associated with hot flashes in women with breast cancer?

Women with breast cancer are at higher risk for experiencing hot flashes (HFs), which is attributable, in large part, to systemic cancer treatments and their effects on estrogen levels. However, other factors, such as anxiety, could also play a role. This study aimed to assess the cross-sectional and temporal relationships between anxiety and HFs among women treated for breast cancer and to clarify the direction of these relationships. Fifty-six women recently treated for breast cancer were assessed prospectively using a 14-day Hot Flashes and Anxiety Diary (HFAD). Anxiety and HFs were also assessed using the Hospital Anxiety and Depression Scale-anxiety subscale and the Menopause-Specific Quality of Life Questionnaire-vasomotor subscale. In addition, HFs were objectively recorded for a continuous 24-hour period using home-based sternal skin conductance. No cross-sectional relationship was found between anxiety and subjectively assessed HFs, or between anxiety and the frequency and intensity of objectively assessed HFs. However, a greater anxiety level on the HFAD was significantly associated with a shorter time to reach the HF peak, as assessed with sternal skin conductance (partial Spearman correlation coefficient rsp = -0.44). Moreover, greater anxiety predicted more severe self-reported HFs on the following night, both assessed with the HFAD (rsp = 0.13). Conversely, self-reported diurnal and nocturnal HFs on the HFAD did not predict next-day anxiety level. This study reveals a significant relationship between anxiety and faster-developing objectively measured HFs. Furthermore, anxiety has been found to significantly predict subsequent increases in self-reported HFs, suggesting that strategies that target anxiety could potentially have a beneficial effect on HFs in women with breast cancer.

Abstract 5044: Reducing breast cancer risk with hormone replacement therapy

Abstract Menopause occurs in women between the ages of 45 and 55 and often results in symptoms that can be alleviated with hormone replacement therapy (HRT). HRT improves the symptoms associated with menopause that negatively affect quality of life, such as hot flashes, difficulty sleeping, fatigue, and vaginal atrophy. HRT also prevents osteoporosis. A current HRT formulation, which includes conjugated equine estrogens (CE) and medroxyprogesterone acetate, unfortunately increases the risk of breast cancer. Over the years, the number of women taking HRT has decreased due to this perceived increased risk. A new form of HRT, which contains CE and bazedoxifene (BZA), a selective estrogen receptor modulator, has recently been approved by the FDA for treatment of moderate to severe hot flashes and for the reduction of osteoporosis development. The CE/BZA mixture has been shown to not only relieve symptoms associated with menopause, but also does not stimulate the breast or uterus. Various studies show that CE/BZA may be protective in the breast. Currently, the mechanism of action of this new combination therapy is not known. Our goal is to identify the molecular mechanism of action of CE/BZA through transcriptome and whole genome occupancy analysis in breast cancer cell lines. In addition, we are determining the effects of the combination therapy on breast cancer progression in a transgenic mouse model. The overall hypothesis of our project is that the ability of CE/BZA to delay the onset of mammary tumors and decrease the number of lesions in the polyoma middle T antigen transgenic mouse model is due to its action as an estrogen receptor α antagonist in the mammary gland. We have determined that CE stimulates gene expression in MCF7 cells at a similar rate to 17β-estradiol, and that BZA is able to decrease this stimulation. Similarly, we have found that CE increases ERα occupancy at promoters of some estrogen target genes, while a combination of CE and BZA decreases this occupancy. Through understanding the molecular mechanism of CE/BZA and by determining whether it reduces the incidence of invasive breast cancer in a transgenic mouse model, we will be able to improve quality of life for many women by relieving menopausal symptoms in a safe manner. Citation Format: Anna Dembo, Geoffrey Greene. Reducing breast cancer risk with hormone replacement therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5044. doi:10.1158/1538-7445.AM2015-5044

Does quitting smoking decrease the risk of midlife hot flashes? A longitudinal analysis

Epidemiological studies have shown that cigarette smoking is associated with an increased risk of midlife hot flashes; however, the effect of quitting smoking on this risk is unclear. The purpose of this study was to examine the effect of quitting smoking on hot flashes using data from 761 women aged 45 to 54 years of age at baseline followed for 1 to 7 years. Results showed that women who quit smoking were less likely to suffer from hot flashes, less likely to have severe hot flashes, and less likely to have frequent hot flashes than women who continued to smoke (OR=0.55, 0.80, 0.76), but were more likely to suffer from any hot flashes, more severe hot flashes, and more frequent hot flashes than women who never smoked (OR=2.55, 1.68, 1.46). Subset analysis of the 353 women who had ever smoked found that women who had quit smoking for longer than 5 years had significantly lower odds, severity, and frequency of hot flashes than women who had continued smoking (OR=0.36, 0.62, 0.63) or women who had quit in the previous 5 years (OR=0.66, 0.77, 0.69). These findings suggest that that early smoking cessation programs may improve women's well-being during the menopausal transition.

Venlafaxine in management of hot flashes in women with breast cancer: a systematic review and meta-analysis

Toxicity due to treatment causes a negative impact on quality of life in breast cancer survivors. Hot flash symptoms, described as intense sensations of heat, sweating and flushing occur in more than 50 % of breast cancer patients taking tamoxifen. We hypothesized that venlafaxine, a selective-norepinephrine reuptake inhibitor drug, was effective for reducing patient-reported hot flash scores among women treated for breast cancer compared to other non-hormonal treatments. We searched Medline, Scopus, and Cochrane Central Register of Controlled Trials from inception till May 2015 for venlafaxine (75 mg once daily or greater) with non-hormonal comparators for the treatment of hot flashes in female breast cancer patients. The primary outcome was hot flash score (derived from patient-reported hot flash severity and frequency) in randomized controlled trials. Standardized mean differences (SMD) were calculated for each study due to variation in the outcome measures. Heterogeneity was determined using I (2) statistics, and publication bias was assessed using a contour funnel plot and Egger's tests. Pooled analyses demonstrated that venlafaxine significantly reduced hot flash scores compared to the trial comparators (overall SMD 2.06; 95% confidence interval (CI) [0.40, 3.72]). There was significant heterogeneity among these studies (I (2) = 98.7%, P < 0.001). Asymmetry in the contour funnel plot suggests the presence of publication bias and a trend towards small study effects (Egger's test, P = 0.096). Venlafaxine is efficacious in managing hot flashes among women with breast cancer. This review highlights methodological issues that arise from eligible trials and recommends a collaborative approach in survivorship studies.

Critical appraisal of paroxetine for the treatment of vasomotor symptoms.

BackgroundVasomotor symptoms (VMS), characterized by hot flashes and night sweats, are the most commonly reported symptoms associated with estrogen deficiency during menopause and occur in up to 70% of women. The goal of treatment is to reduce the frequency and severity of symptoms. Although hormone therapy (HT) is generally recommended as first-line treatment, it is not appropriate for all patients. Antidepressants, specifically selective serotonin reuptake inhibitors, have been evaluated and utilized internationally for alternative treatment for VMS. In 2013, paroxetine mesylate (Brisdelle®) received a US Food and Drug Administration-labeled indication for moderate-to-severe hot flashes, making it the first nonhormonal treatment for VMS associated with menopause. The objective of this review is to critically evaluate available clinical data regarding the efficacy and safety of paroxetine for the treatment of VMS in menopausal women.MethodsMEDLINE, PubMed, and Google Scholar were searched using the keywords paroxetine, vasomotor symptoms, hot flashes, and menopause. Searches were limited to humans, English language, and clinical trial design with a primary outcome of hot flash/vasomotor changes.ResultsParoxetine (hydrochloride and mesylate) has been associated with a 33%–67% reduction in hot flash frequency with 6–12 weeks of treatment compared to 13.7%–37.8% reductions with placebo in patients both with and without a history of breast cancer. It was also associated with significant reductions in hot flash severity. Benefits of treatment persisted through 24 weeks in the study of the longest duration. Most adverse effects reported were of mild-to-moderate severity, with improved tolerability associated with lower doses (7.5–12.5 mg/day).ConclusionParoxetine is a safe and effective therapy for the treatment of VMS during menopause. Paroxetine (7.5–12.5 mg/day) should be considered a first-line therapy option for VMS in patients when HT is either inappropriate or intolerable.

Tamoxifen (TAM)-induced severe hot flashes (HF): Is dose reduction (DR) a safe and effective strategy?

557 Background: It is recognized that severe HF toxicity due to TAM can compromise compliance. We previously established that HF do not correlate with endoxifen level or CYP2D6genotype, though prio...

Alterations in adhesion molecules, pro-inflammatory cytokines and cell-derived microparticles contribute to intima-media thickness and symptoms in postmenopausal women.

Menopause, the cessation of menses, occurs with estrogens decline, low-grade inflammation, and impaired endothelial function, contributing to atherosclerotic risk. Intima-media thickness (IMT) is an early subclinical biomarker of atherosclerosis. Inflammation may have a role on symptoms: hot flashes, anxiety, and depressive mood, which also are related to endothelial dysfunction, increased IMT and cardiovascular risk. In this study we compared several inflammatory markers in early vs. late postmenopausal women and studied the association of IMT and symptoms with these markers in the full sample. In a cross-sectional design including 60 women (53.1±4.4 years old) at early and late postmenopause, we evaluated the expression of CD62L, ICAM-1, PSGL-1, CD11b, CD11c, and IL-8R on PBMC by flow cytometry. Serum soluble ICAM-1, sVCAM-1, sCD62E, sCD62P, CXCL8, IL-1β, IL-6, and TNF-α levels were quantified by ELISA. Plasma levels of microparticles (MPs) were determined by FACS. Finally, carotid intima-media thickness (IMT) was measured by ultrasound. We observed that ICAM-1 expression by lymphocytes and serum sVCAM-1 levels were augmented at late postmenopause. Late postmenopause women with severe hot flashes had increased expression of CD62L and IL-8R on neutrophils. By multivariate analysis, the carotid IMT was strongly associated with membrane-bound TNF-α, CD11b expression, Annexin V+ CD3+ MPs, LPS-induced NO production, HDL-cholesterol and age. Depressive mood was associated negatively with PSGL-1 and positively with LPS-induced NO. Finally, Log(AMH) levels were associated with carotid IMT, IL-8R expression and time since menopause. IMT and depressive mood were the main clinical features related to vascular inflammation. Aging, hormonal changes and obesity were also related to endothelial dysfunction. These findings provide further evidence for a link between estrogen deficiency and low-grade inflammation in endothelial impairment in mature women.

Improving Thermoregulatory Control And Vascular Function With Exercise Training Reduces The Frequency And Severity Of Menopausal Hot Flashes

Improving Thermoregulatory Control And Vascular Function With Exercise Training Reduces The Frequency And Severity Of Menopausal Hot Flashes