Severity Of Hot Flashes Research Articles

The influence of phytoestrogens on alleviating symptoms associated with menopause

Introduction and purpose. Menopause causes complaints such as hot flashes, night sweats, sleep problems and vaginal dryness. Hormone replacement therapy (HRT) is an effective treatment option for women with moderate to severe symptoms. In women who are unable to undergo HRT, plant-based preparations containing phytoestrogens can be used as an alternative. The purpose of this paper is to summarize the effectiveness of phytoestrogen supplementation.
 State of knowledge. Phytoestrogens are natural compounds structurally similar to estrogens, such as estradiol. They are divided into different classes, including isoflavones and lignans. Isoflavones, including genistein, found in soy products, cause a significant reduction in the severity of hot flashes, as well as improvements in vaginal dryness and sexual function. Lignans, found in flaxseed, sesame seeds and whole grains, have effects similar to endogenous estrogens, but studies to date have not shown significant efficacy of this group of substances in reducing menopausal symptoms. Resveratrol, a naturally occurring compound found in grapes and berries, has a weak estrogenic effect, whereby several clinical trials have demonstrated the effectiveness of resveratrol supplementation in alleviating menopausal symptoms.
 Conclusions. Phytoestrogens have been shown to alleviate some symptoms of menopause, such as hot flashes and night sweats, and may also have positive effects on bone density and cognitive abilities. Effects may vary depending on the source, dose and duration of treatment. There are also potential risks associated with their use, for which reason more research is needed to fully understand their effectiveness and safety.

Neurokinin 1/3 receptor antagonists for menopausal women: A current systematic review and insights into the investigational non-hormonal therapy.

Over 75% of menopausal women experience vasomotor symptoms (VMS), such as night sweats and hot flashes. Despite the prevalence of these symptoms, there is limited data on non-hormonal therapies to alleviate them. PubMed, Cochrane, Scopus, Ovid, Web of Science, and ClinicalTrials.Gov were searched for relevant studies. The search was performed using the following keywords, which were customized to suit the specific databases/registers: menopause, women, neurokinin 3, and/or Fezolinetant. The search was conducted until December 20, 2022. This systematic review was conducted in compliance with the PRISMA Statement 2020 guidelines. A total of 326 records were found, with 10 studies (enrolling 1993 women) selected for inclusion. The women received 40-mg doses of NK1/3 receptor antagonists twice daily, with follow-ups at 1 to 3 weeks. Moderately strong evidence was found suggesting that NK1/3 receptor antagonists can help limit the frequency and severity of hot flashes in menopausal women. While the results should be interpreted with caution until further clinical trials validate the efficacy and safety of NK1/3 receptor antagonists among menopausal women, these findings suggest that they are promising targets for future pharmacological and clinical studies in addressing vasomotor symptoms.

The severity of hot flashes is associated with the risk for incident metabolic syndrome and new-onset hypertension after the menopause

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Association of Migraine and Vasomotor Symptoms

ObjectiveTo further examine a potential link between migraine and vasomotor symptoms as well as hypertension as a cardiovascular disease risk factor, potentially explaining the association in midlife women. Patients and MethodsWe conducted a cross-sectional analysis from the Data Registry on Experiences of Aging, Menopause, and Sexuality using questionnaire data from women aged 45 to 60 years seen in women’s clinics at a tertiary care center from May 15, 2015, through January 31, 2022. A history of migraine was self-reported; menopause symptoms were assessed with the Menopause Rating Scale. Associations between migraine and vasomotor symptoms were evaluated utilizing multivariable logistic regression models adjusting for multiple factors. ResultsOf 5708 women included in the analysis, 1354 (23.7%) reported a migraine history. The total cohort had a mean age of 52.8 years, most (5184 [90.8%]) were White, and 3348 (58.7%) were postmenopausal. In adjusted analysis, women with migraine were significantly more likely to have severe/very severe hot flashes vs no hot flashes compared with women without migraine (odds ratio, 1.34; 95% CI, 1.08 to 1.66; P=.007). Migraine was associated with a diagnosis of hypertension in adjusted analysis (odds ratio, 1.31; 95% CI, 1.11 to 1.55; P=.002). ConclusionThis large cross-sectional study confirms an association between migraine and vasomotor symptoms. Migraine also was associated with hypertension, potentially providing a link with cardiovascular disease risk. Given the high prevalence of migraine in women, this association may help identify those at risk for more severe menopause symptoms.

Adverse childhood experiences and sexual dysfunction in midlife women: Is there a link?

One in 3 children has had at least 1 adverse childhood experience (ACE), and ACEs have been associated with multiple medical and psychiatric morbidities in women later in life, including greater menopause symptom burden. To evaluate the association between ACEs and female sexual dysfunction (FSD) in midlife women. A cross-sectional analysis from DREAMS-the Data Registry on Experiences of Aging, Menopause, and Sexuality-was conducted with questionnaires completed by women aged 40 to 65years who presented to a women's health clinic at Mayo Clinic in Rochester, Minnesota, from May 2015 to December 2016. History of ACEs was obtained with the validated ACE questionnaire. FSD was assessed by the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. The association between ACEs and FSD (defined as Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11) was evaluated via a multivariable logistic regression model, adjusting for age, menopause status, hormone therapy use, anxiety, depression, relationship satisfaction, hot flash severity, and history of abuse in the past year. Women (N = 1572) had a mean age of 53.2years. Overall 59% reported having at least 1 ACE. When compared with no ACEs, a history of ≥4 ACEs significantly increased the odds of not being sexually active (odds ratio, 1.83; 95% CI, 1.30-2.57; P < .001). Among sexually active women, the proportion of women with FSD increased sequentially as the number of ACEs increased. In the univariate analysis, a history of ≥4 ACEs significantly increased the odds of FSD as compared with no ACEs (odds ratio, 2.12; 95% CI, 1.50-2.99; P < .001). The association remained statistically significant in the multivariable analysis after adjusting for confounders (odds ratio, 1.75; 95% CI, 1.15-2.68; P = .009). The findings highlight an opportunity for clinicians to screen for ACEs in women with sexual dysfunction and offer appropriate treatment and counseling as indicated. Strengths of the study include the large cohort, the use of validated tools for assessment of ACEs and FSD, and the adjustment for multiple potential confounding factors. Limitations include the cross-sectional study design, recall bias in reporting ACEs and recent abuse, and the low representation of racially and ethnically diverse women in the cohort. The study demonstrates an increased risk of sexual inactivity and sexual dysfunction in midlife women who experienced childhood adversity. The sexual dysfunction in women with ACEs seems to be independent of other factors that potentially affect female sexual function in midlife.

The effect of whole-body vibration training on selected breast cancer risk factors in obese postmenopausal women: A randomized controlled trial

Menopause is associated with various hormonal changes leading to many complications such as obesity, hot flashes and increased liability for breast cancer, that intractably alter female quality of life. This study was conducted to determine the effect of whole-body vibration training (WBVT) on body mass index and serum prolactin concentration, as risk factors for breast cancer and severity of hot flashes in obese postmenopausal women. A prospective, randomized, parallel group, active controlled study with a 1:1 allocation ratio was carried out. A total of 40 obese postmenopausal women (aged 50 to 60 years, postmenopausal for at least 3 years, with a body mass index BMI between 30-39.9 kg/m2) were randomly assigned into two equal groups (group A and B). Group A (WBVT, n = 20) received WBVT, 3 sessions per week for 3 months, while group B (control group, n = 20) was asked to retrain their usual lifestyle pattern. They were all instructed about healthy dieting. Statistical analysis was performed utilizing SPSS for windows, version 18 (SPSS, Inc., Chicago, IL). The results of our study showed that there was a statistically significant reduction in all measured variables in group A in post-study (p &lt; 0.05), while the control group (B) showed a non-statistically significant decrease in these variables in comparison to the pre-study (p &gt; 0.05). Comparison of the two groups after treatment showed a statistically significant decrease in the measured variables, in favor of the study group A (p &lt; 0.05). From the obtained results, it was concluded that whole body vibration is effective in decreasing BMI and waist circumference, in addition to reducing serum prolactin concentration and the severity of hot flashes in obese postmenopausal women. Therefore, it could be used to decrease the risk of breast cancer in obese postmenopausal women.

Dietary advanced glycation end-products and postmenopausal hot flashes: A post-hoc analysis of a 12-week randomized clinical trial

ObjectivePostmenopausal hot flashes are associated with an increased risk of cardiovascular disease and diabetes. Because dietary advanced glycation end-products (AGEs) may act as endocrine disruptors, this study examined the potential association of modifications to the intake of dietary AGEs with the frequency and severity of postmenopausal hot flashes. MethodsPostmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned to either the intervention group or the control group. The former were asked to follow a low-fat, vegan diet, including cooked soybeans (1/2 cup [86 g]/day) for 12 weeks, and the latter continued their usual diets for 12 weeks. Frequency and severity of hot flashes were recorded with a mobile application. Three-day diet records were analyzed using the Nutrition Data System for Research software and dietary AGEs were estimated, using a database. Seventy-one participants completed the whole study and 63 provided complete hot flash and dietary data for the AGEs analysis (n = 31 in the intervention and n = 24 in the control group). Pearson correlations were used to assess the association between changes in hot flashes and dietary AGEs. ResultsDietary AGEs decreased in the intervention group by 73 %, that is by 5509 ku/day on average (95 % −7009 to −4009; p < 0.001), compared with the control group (+458; 95 % CI −835 to +1751; p = 0.47; treatment effect −5968 ku/day [95 % CI −7945 to −3991]; Gxt, p < 0.001). Severe hot flashes decreased by 92 % (p < 0.001) and moderate-to-severe hot flashes decreased by 88 % in the intervention group (p < 0.001). Changes in dietary AGEs correlated with changes in severe (r = +0.39; p = 0.002) and moderate hot flashes (r = +0.34; p = 0.009) and remained significant after adjustment for changes in energy intake (r = +0.45; p < 0.001; and r = +0.37; p = 0.004, respectively) and changes in body mass index (r = +0.37; p = 0.004; and r = +0.27; p = 0.04, respectively). The reduction in dietary AGEs required to achieve a predicted reduction in hot flashes by 1/day was 6933 ku/day for severe and 4366 ku/day for moderate-to-severe hot flashes. ConclusionsThe reduction in dietary AGEs with a low-fat plant-based diet was associated with a significant reduction in the frequency of severe and moderate-to-severe postmenopausal hot flashes, independent of changes in energy intake and weight loss. Plant-based diets could be used not only to alleviate vasomotor symptoms in postmenopausal women, but also to reduce other health risks associated with AGEs. Trial registrationClinicalTrials.gov, NCT04587154.

Associations of fat mass index with hot flashes and lean mass index with insomnia in middle-aged women

Objective This cross-sectional study examined the relationship between body composition and physical and mental symptom severity in middle-aged women. Methods The first-visit records of 554 women aged 40–64 years were examined. The fat mass index (FMI) and lean mass index (LMI) were defined as fat mass and lean mass divided by the height squared, respectively. The participants were divided into two groups according to their median values. Results The only menopausal symptom with significantly different severity between the high and low FMI groups was hot flashes (HF) on the Menopausal Health-Related Quality of Life Questionnaire. The factors associated with severe HF were investigated using multiple logistic regression analysis. After adjusting, the FMI (kg/m2) was independently positively associated with severe HF (odds ratio, 1.08; 95% confidence interval, 1.02–1.15). Insomnia was the only menopausal symptom with significantly different severity between the LMI groups (defined as Athens Insomnia Scale score ≥10 points). The factors associated with moderate-to-severe insomnia were investigated using multiple logistic regression analysis. After adjusting, the LMI (kg/m2) was independently negatively associated with moderate-to-severe insomnia (odds ratio, 0.72; 95% confidence interval, 0.55–0.94). Conclusions The FMI was positively associated with severe HF, whereas the LMI was negatively associated with moderate-to-severe insomnia in middle-aged women.

Effect of Fennel-Valerian Extract on Hot Flashes and Sleep Disorders in Postmenopausal Women: A Randomized Trial.

This study aims to evaluate the effect of a mixture of fennel and valerian extracts on hot flashes and sleep disorders of postmenopausal women in Iran. A randomized trial was conducted. A total of 76 postmenopausal women were randomly assigned to either of the two groups: fennel-valerian extract or control. One 500 mg fennel-valerian extract capsule was given twice, daily for 8 weeks. The 500 mg oral placebo capsule (starch) was given the same way. The mean duration of hot flashes increased in both the groups over time (P < 0.001). The mean frequency and severity of hot flashes in the intervention group were significantly lower than in the control group, in the first and second months after intervention (P < 0.050). Women in the fennel-valerian extract group had a significantly lower Pittsburgh Sleep Quality Index score than the control group 2 months after intervention (P = 0.030). This study found that fennel-valerian extract was effective for relieving sleep disorders as well as the severity and frequency of hot flashes compared with a placebo.

Impact of Adjuvant Hormone Therapy on Sleep, Physical Activity, and Quality of Life in Premenopausal Breast Cancer: 12-Month Observational Study.

This study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies ("tamoxifen plus ovarian function suppression group [T+OFS group]" versus "tamoxifen group [T group]") and the chronological changes in sleep disturbances in each group. Premenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT. Among the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA; however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2-5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes. Unlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period. ClinicalTrials.gov Identifier: NCT04116827.

The relationship between hot flashes and fatty acid binding protein 2 in postmenopausal women.

Hot flashes, the most bothering symptom of menopause, are linked to a metabolic inflammation. Due to estrogen deficiency in menopause, dysbiosis is observed. The intestinal barrier affects the interaction of microbiota in healthy or unhealthy individuals. This study investigates the relationship between hot flashes and gut permeability in postmenopausal women. In this cross-sectional study, we divided 289 women, aged 40-65 years, into four groups based on their hot-flash severity: HF0: never experienced hot flashes; HFm: mild hot flashes; HFM: moderate hot flashes; HFS: severe hot flashes. The measured variables included the clinical parameters; hot flashes experience; fasting plasma levels of zonulin, fatty acid binding protein 2 (FABP2), endotoxin, and cytokines/chemokines. We used multiple linear regression analysis to evaluate the relationship between hot flashes and the previously mentioned gut barrier proteins. The study was performed in a hospital medical center. The hot flashes had a positive tendency toward increased levels of circulating FABP2 (P-trend = 0.001), endotoxin (P-trend = 0.031), high-sensitivity C-reactive protein (hs-CRP) (P-trend = 0.033), tumor necrosis factor alpha (TNF-α) (P-trend = 0.017), and interferon-inducible protein-10 (IP10) (P-trend = 0.021). Spearman's correlation analysis revealed significant correlations of FABP2 with endotoxin, TNF-α, monocyte chemoattractant protein-1, IP10, and hs-CRP in the 289 postmenopausal women included in this study. Linear regression analysis revealed that hot-flash severity had significant assoiciations with FABP2 (P-trend = 0.002), but not with zonulin. After adjusting for body mass index, age, and menopause duration, multivariate linear regression analysis revealed the differences between HFs (% difference (95% confidence interval), 22.36 (8.04, 38.59), P = 0.01) and HF0 groups in terms of FABP2 levels. This study shows that hot flashes are significantly associated with FABP2 levels in postmenopausal women. It suggests that severe hot flashes are linked to an increase in intestinal barrier permeability and low-grade systemic inflammation.

Acupuncture for hot flashes in hormone receptor-positive breast cancer, a coordinated multinational study: Rationale and design of the study protocol

BackgroundAcupuncture has been reported to reduce hot flashes in patients with breast cancer undergoing adjuvant hormonal therapy. Although hot flashes are common, the prevalence varies among cultures, races, and ethnicities; the efficacy of acupuncture across cultures has not been investigated. MethodsThis is a coordinated multinational study, including three parallel randomized trials with a planned analysis of individual patient data, to test the effectiveness of acupuncture on hot flash-related symptoms in hormone receptor-positive breast cancer patients on adjuvant endocrine therapy. Using a standardized acupuncture protocol (total across all three studies of n = 80) versus usual care (total n = 80), symptoms are assessed using changes in the Endocrine Symptom Subscale of Functional Assessment of Cancer Therapy-Endocrine Symptoms. Secondary outcomes include hot flash severity, quality of life, and sleep quality. Differences in response to acupuncture between participants in the three countries will also be explored. DiscussionHere we describe the design of a protocol for a coordinated multinational study, with attention to the complex considerations in developing a multinational research effort testing a non-pharmacologic intervention. This protocol and approach provide guidance for future efforts to evaluate and test non-pharmacologic interventions across multinational populations. Trial registrationclinicaltrials.gov (Identifier: NCT00797732, registered on December 21, 2018), Chinese Clinical Trial Registry (ChiCTR2100045888), and The Clinical Research Information Service (CRIS) of Korea (Registration number: KCT0003618).

Shortening the baseline period in hot flash symptom control trials: Comparison of a one-day versus seven-day baseline hot flash diary.

e24094 Background: Hundreds, if not thousands, of participants are enrolled hot flash trials each year given the magnitude of the problem for breast and prostate cancer survivors. Classically, these studies have included a baseline period of 1-week, or longer, to understand the frequency and severity of hot flashes before starting a new treatment. The objective of the current study was to compare the accuracy of a 1-day baseline hot flash diary to a more traditional 1-week dairy. A shorter baseline period would be more convenient for patients and provide a more efficient study design. Methods: Raw data from 5 pilot studies and 15 phase III randomized, controlled trials (RCTs), all of which used a one-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p-values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. Results: A total of 2,573 participants were included. On average, participants had 8.5 hot flashes per day on Day 1. Mean hot flash frequencies and scores on subsequent days (Days 2-7) were within 6% of Day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Re-analysis for each pilot study revealed that no individual study conclusions would have been meaningfully altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. Conclusions: A 1-day hot flash diary appears to accurately reflect true frequency and severity of baseline hot flash symptoms in appropriately sized cohorts. Results support a shorter baseline period for pilot studies and RCTs.

Adjuvant Hormone Therapy-Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis.

Clinical trials have shown that adjuvant hormone therapy (AHT)-related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11-2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21-1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41-2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39-2.35) or died from cancer (HR, 1.71; 95% CI, 1.37-2.12). AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.

Acupuncture for hot flashes in hormone receptor-positive breast cancer, a pooled analysis of individual patient data from parallel randomized trials.

12124 Background: Hot flashes are a common side effect of endocrine therapy in breast cancer patients (pts). In a coordinated multinational study, we evaluated the impact of acupuncture on hot flashes and related symptoms in hormone receptor-positive breast cancer pts undergoing adjuvant endocrine therapy in the USA, China, and South Korea. Methods: Parallel randomized trials were conducted at three sites: Dana-Farber Cancer Institute, USA; Jiangsu Hospital of Traditional Chinese Medicine, China; and Daegu Catholic University Medical Center, Republic of Korea, using the same inclusion/exclusion criteria, randomization, and measures. Breast cancer pts receiving adjuvant endocrine therapy and having ≥14 hot flashes per week were randomized equally to acupuncture (A) or usual care (UC); randomization was stratified by number of hot flashes per day (2-6 or 7+). Pts in arm A received a standardized acupuncture protocol twice per week for 10 weeks; pts in the UC arm received usual care. Symptoms were assessed at baseline and week 10. The primary endpoint was change in the Endocrine Symptom Subscale (ESS) of the Functional Assessment of Cancer Therapy-Endocrine Systems (FACT-ES). Secondary endpoints included changes in the FACT-Breast (FACT-B) and Daily Hot Flash Score (DHFS), a measure incorporating hot flash frequency and severity. Target enrollment was 160 pts (USA 80, China 40, Korea 40) providing 84% power to detect a clinically meaningful change in the ESS. Analyses were intention-to-treat. A pooled analysis of individual patient data was performed using linear models adjusted for site and baseline number of hot flashes. Results: Between Jan. 2019 and June 2021, 158 female pts with stage 0-III breast cancer were randomized from the USA (n=78), China (n=40), and South Korea (n=40). Median age was 48 years (range: 25 to 73). At baseline, pts reported similar numbers of hot flashes between study arms (6.2± 4.3 vs. 6.5± 3.8 per day). At week 10, pts in arm A reported statistically significant improvements in ESS score, FACT-B total score and DHFS compared with the UC arm (Table). The reduction in the DHFS from baseline in arm A was 53%. There were no serious adverse events. Conclusions: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing adjuvant hormonal therapy for breast cancer in the USA, China and South Korea. Clinical trial information: NCT00797732, ChiCTR2100045888, KCT0003618. [Table: see text]

Menopausal Hot Flashes and Renal Function

BackgroundDuring the menopause transition, women are at an increased risk of developing hypertension, which is a key marker of cardiovascular disease (CVD). Although historically hot flashes have been considered a quality‐of‐life issue, emerging data provides a link between hot flashes and risk of CVD. Poor renal function is suggested to be one of the key physiological contributors to increased risk of hypertension and CVD among women with hot flashes. Thus, the aim of this study was to characterize the relationship between hot flashes and renal function in peri‐ and post‐menopausal women using a retrospective chart review. We hypothesized that women with hot flashes would demonstrate reduced renal function compared to women without hot flashes.MethodsWe performed a chart review using serum creatinine and estimated glomerular filtration rate (eGFR) as proxies to assess renal function. Electronic health records for Mayo Clinic patients across multiple sites were abstracted for female patients who were diagnosed with peri‐ or post‐menopause between 2016 and 2020, between 45 and 55 years of age, and had available creatinine laboratory test results. Data regarding demographics, anthropometrics, systemic blood pressure, menopausal stage, occurrence of hot flashes, and comorbidities were extracted from electronic health records. Differences between women with and without hot flashes were evaluated using two‐tailed, independent samples t‐tests. We completed a univariate analysis of variance testing the main effects of menopausal status (peri‐ or post‐menopausal) and presence of hot flashes (yes or no). Given the potential modifying effects of menopause, analytical models were performed in duplicate with and without models separated by menopausal status (peri‐and post‐menopause).ResultsData from 83 medical charts were assessed, including 57 women with hot flashes and 26 women without hot flashes. Without separating by menopausal status, there were no hot flash‐related differences in age (51 ± 3 vs. 51 ± 3 years, P = 0.64) or body mass index (30 ± 7 vs. 33 ± 11, P = 0.19) between women with and without hot flashes. Additionally, there were no hot flash‐related differences in metrics of blood pressure, including systolic (120 ± 13 vs. 125 ± 20, P = 0.19), diastolic (75 ± 11 vs. 77 ± 13, P = 0.54), and mean arterial pressure (90 ± 11 vs. 92 ± 14, P = 0.62). There were also no hot flash‐related differences in indicators of renal function, including creatinine (0.8 ± 0.1 vs. 0.8 ± 0.2, P = 0.65) and eGFR (88 ± 11 vs. 85 ± 16, P = 0.36). The clinical characteristics of the perimenopausal versus postmenopausal women are summarized in Table 1by hot flash status. There were no main effects of hot flash or menopausal status on creatinine (menopausal stage: p=0.810, hot flash status: p=0.659, interaction effect: p=0.983) or eGFR (menopausal stage: p=0.508, hot flash status: p=0.405, interaction effect: p=0.834).ConclusionsIn this retrospective chart review of peri‐ and post‐menopausal women, there were no differences in systemic blood pressure or renal function between groups. Future investigations may include longitudinal markers of renal function and metrics describing frequency and severity of hot flashes.

The Efficacy and Safety of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors in the Treatment of Menopausal Hot Flashes: A Systematic Review of Clinical Trials.

Background: Hot flashes (HF) are a common symptom during the menopausal transition. It is therefore important to identify effective drugs that can alleviate HF. This study aimed to systematically review published clinical trials on the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of HF in healthy menopausal womenMethods: In this systematic review, articles published during 2003-2019 in PubMed, MEDLINE, Web of Science, Scopus, Science Direct, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials, and Google Scholar as well as Iranian databases such as SID, and Magiran were searched. The quality of the selected articles was assessed using the Jadad score calculation.Results: Thirty-six articles on randomized controlled trials were included in this study, out of which 27 articles had acceptable, and nine had weak methodological quality. Findings on SSRIs class of drugs indicated that escitalopram, paroxetine, and fluoxetine have higher efficacy and safety in the treatment of menopausal HF than other drugs. Studies on the effectiveness of sertraline, citalopram, and fluvoxamine are limited in number or show inconsistent results. Therefore, further high-quality studies are required to confirm their effectiveness in alleviating HF. Within the SNRIs class, venlafaxine and desvenlafaxine showed significant efficacy in the treatment of menopausal HF. However, studies on the effectiveness of duloxetine are also limited, which requires further research.Conclusion: Most studies have indicated the efficacy and safety of some antidepressants, such as SSRIs and SNRIs, in decreasing the frequency and severity of HF. These drugs are therefore recommended for the treatment of menopausal HF.

The Effect of Pimpinella anisum on Treatment and Recurrence of Menopausal Hot Flashes: A Randomized, Controlled, Multicenter, Double-Blind, Parallel-Group Clinical Trial

Background: Considering the high prevalence of hot flashes and the controversies in its treatments, the present study evaluated the effect of Pimpinella anisum extract on the treatment and recurrence of hot flashes in women referred to the health centers of medical sciences universities in Tehran, Iran in 2019. Methods: The present double-blind controlled parallel-group clinical trial included 72 menopausal women with chief complaint of hot flashes. The participants were randomly assigned into two equal groups (n = 36 each) of experimental (receiving three P. anisum capsules) and control. The severity and frequency of hot flashes were measured by Visual Analogue Scale (VAS) before the treatment, eight weeks after the treatment, and four weeks after discontinuation of the medication. The data of patients, including their diet, were recorded in the questionnaires and information forms. The data were analyzed using SPSS 19, and the intra-group results were analyzed using the repeated measures analysis of variance (ANOVA). Also, to compare the scores between the groups, t-test, and Mann-Whitney-Wilcoxon (MWW) were used. Results: The frequency of hot flashes in the P. anisum group was 7.89 ± 5.67 before the treatment, 1.04 ± 1.24 eight weeks after the treatment, and 4.21 ± 2.03 in the four-week follow-up period. The severity of hot flashes among the P. anisum group was 11.50 ± 9.78, 1.90 ± 2.77, and 5.78 ± 1.92 before the treatment, eight weeks after the treatment, and four-week follow-up (P = 0.001), respectively. However, the severity and frequency of hot flashes did not change significantly in the placebo group (P = 0.75). No side effects were seen in any of the groups. Conclusions: Pimpinella anisum was effective in reducing the frequency and severity of hot flashes.

A Clinical Review on Paroxetine and Emerging Therapies for the Treatment of Vasomotor Symptoms.

Most women experience vasomotor symptoms (VMS) during their menopausal transition. Menopausal hormone therapy (HT) is the most effective treatment for VMS, but some women choose not to use HT or have contraindications to using HT. Non-hormonal treatment options should be offered to these symptomatic menopausal women. Multiple large randomized controlled trials have demonstrated statistically significant reductions in hot flash severity and/or frequency with the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). To date, paroxetine mesylate remains the only non-hormonal treatment that has been approved by the United States Food and Drug Administration (FDA) for the management of moderate to severe postmenopausal vasomotor symptoms. Lower doses are needed to reduce VMS than those used to treat anxiety or depression, which is beneficial since side effects are typically dose dependent. The recommended dosage is 7.5 mg once daily at bedtime. Dose dependent side effects include nausea, fatigue, and dizziness. Knowing potential medication interactions is critical such as with medications that can lead to serotonin syndrome, concomitant use with monoamine oxidase inhibitors and being aware of p450 drug metabolism is essential for patients taking drugs that utilize the CYP2D6 enzyme for metabolism including tamoxifen. This review discusses in detail the available data supporting the use of paroxetine for the treatment of VMS, including side effects and considerations regarding prescribing. A discussion of other emerging treatments is included as well, including estetrol, oxybutynin and neurokinin 3 (NK3) receptor antagonists.

Abstract P1-09-04: Flaxseed &amp; breast cancer: A systematic review

Abstract Background: Flaxseed has been extensively studied in in vitro and in vivo models for possible association with reducing the risk of breast cancer. Clinical trials have been limited. There has been confusion regarding whether it is safe and beneficial for breast cancer survivors to take flaxseed. Therefore, we conducted a systematic review to evaluate the existing randomized controlled trial to understand the safety and efficacy of using flaxseed for symptom control and reducing the risk of recurrence among breast cancer survivors. Patients and Methods: We conducted a literature search of English language publications in MEDLINE, EMBASE, and Cochrane from the databases’ inception to May 2021 using the keywords flaxseed, breast cancer, randomized clinical trial, and human studies. Results: We identified three randomized controlled trials (RCT) that include patients with a history of breast cancer. Sample size ranged from 24 to 178 patients and treatment duration ranged from 13 to 42 days. The primary end points were hot flash severity (one study) and tumor biomarkers (two studies). There was no statistically significant reduction in mean hot flash score in the flaxseed group compared to the placebo group. One study showed a statistically significant reduction in Ki-67 (34.2%; P=0.001) and in c-erbB2 expression (71.0%; P=0.003), and an increase in apoptosis (30.7%; P=0.007) in the group that received flaxseed, but not in the placebo group. On the contrary, another study showed no difference in Ki-67, caspase, the Ki-67/caspase ratio, and Estrogen-receptor β. Two studies reported mild adverse events as shown in Table 1. None of the studies assessed the change in estrogen level. Risk of bias assessment showed that the overall risk of bias associated with the included studies is moderate to high. The high risk of bias originates from lack of blinding of participants and personnel. Conclusion: Current clinical research in breast cancer survivors is too limited to recommend flaxseed for cancer prevention. Flaxseed appears to be safe with mild side effects, however, the effect of flaxseed on estrogen concentration has not been established. Table 1.Characteristics of included studies and risk of bias assessmentIDBreast cancer participantsSample sizeExperimentalControlOutcomesAdverse eventsRisk of biasPruthi 2012(U.S.)With breast cancer: (Yes/No)Flaxseed: 44/88Placebo: 47/90Flaxseed: 88Placebo: 90Flaxseed bar: 7.5g of flaxseed, 200 calories, one bar daily, 6 weeksPlacebo bar: 2g protein, 20% fiber, 200 calories, one bar daily, 6 weeksFrequency and severity of hot flash; hot flash interference; the Profile of Mood States; the Menopause Quality of Life Scale; the Global Impression of BenefitAbdominal distension and pain, diarrhea, flatulence, nausea, pruritus, maculopapular rash, vomitingLowThompson 2005(Canada)Flaxseed: (ER+ &amp; PR+) 17/19; (ER- OR PR-) 2/19Placebo: (ER+ &amp; PR+) 11/13; (ER- OR PR-) 2/13Flaxseed: 19Placebo: 13Flaxseed muffin: 25g flaxseed + 20.7g white wheat flour, one daily, 32 daysPlacebo muffin: 20.7g whole wheat flour+10g canola oil, one daily, 39 daysBreast cancer biomarkers including Ki-67, apoptosis, C-erbB2, ER and PR scoresAbdominal fullness and increased bowel movementsSome concernMcCann 2014(Canada)Clinical stage: Flaxseed: I 4/6; IIA 1/6; IIB 1/6;Anastrozole: I 6/7; IIA 1/7;Flaxseed/Anastrozole: I 5/6; IIA 1/6;Placebo: I 3/5; IIA 2/5Flaxseed: 6;Anastrozole: 7;Flaxseed/Anastrozole: 6;Placebo: I5;Flaxseed: 25 g/d ground flaxseed + 1/d placebo pill, 13-16 daysAnastrozole: 1 mg/d;Flaxseed/Anastrazole: 25 g/d ground flaxseed + 1 mg/d Anastrozole;Placebo: 1/d; 13-16 daysBreast cancer biomarkers including Ki-67, caspase, the Ki-67/caspase ratio, and Estrogen-receptor βNot reportedHigh Citation Format: Rui Wang, Mingxiao Yang, Iris Zhi, Ting Bao. Flaxseed &amp; breast cancer: A systematic review [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-09-04.