Frequency Of Hot Flushes Research Articles

A survey of women diagnosed with breast cancer experiencing oncology treatment-induced hot flushes: identification of specific characteristics as predictors of hot flush occurrence, frequency, and severity.

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. 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. 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). 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. HFs continue across the BC treatment trajectory with women >5-year survivorship still reporting life impacts, with premenopausal women at the time ofBCdiagnosis at higher risk of experiencing severe and more frequentoncology treatment-induced HFs than postmenopausal women. Women at high risk require information on methods to moderate HF potential life impacts and maintain treatment compliance.

Effect of Serelys Homme on the Incidence and Severity of Vasomotor Symptoms and Quality-of-Life Impairments in Patients Receiving Hormone Therapy and Radiation for Localized Prostate Cancer: Results of the ESCULAPE Phase 2 Prospective Study

Androgen deprivation therapy (ADT) may cause vasomotor symptoms (VMS) including hot flushes and sweats, which affect quality of life (QoL). Serelys Homme is a nonhormonal and a natural origin product that could affect VMS in men undergoing ADT. We evaluated effectiveness and tolerance of Serelys Homme administration on VMS and QoL of patients undergoing combined ADT and radiation therapy for prostate cancer. Between April 2017 and July 2019, 103 patients were screened, and 53 patients refused to participate in the study. Serelys Homme therapy consisted of a daily administration of 2 tablets for 6 months. Patients were evaluated with 4 questionnaires including the adapted Modified Rankin Scale (adapted-MRS), European Quality of Life 5 Dimensions 3 Level Version (EQ 5D3L), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Hot Flash Related Daily Interference Scale (HFRDIS) at day 0, day 90 (D90), and day 180 (D180). Statistical evaluation was performed using the Wilcoxon rank sign test. A 2-sided P < .05 was considered statistically significant. Among the 50 patients, 4 withdrew after inclusion. All patients (n=46) received either postoperative or definitive radiation therapy combined with a short (n=15) or long course (n=31) of ADT. Serelys Homme administration significantly decreased the rate of patients who had ≥7 VMS and 3 to 6 VMS per day. The number of patients presenting with moderate or severe VMS was decreased at D90 (P=.005) and at D180 (P=.005). In addition, VMS duration was reduced at D90 (P=.002) and D180 (P < .001). Finally, at D90 and D180, 11.1% and 16.0% of patients, respectively, with initial severe or moderate VMS had a complete response without further symptoms. Among QoL parameters, fatigue decreased significantly. Effectiveness evaluated by doctors was rated as moderate or good to excellent VMS control in 20% and 60% of the patients, respectively. No side effects were recorded in the whole population. This study demonstrated effectiveness and excellent tolerance of Serelys Homme. We observed a significant reduction of the frequency, duration, and intensity of hot flushes and sweats induced by ADT. Serelys Homme increased QoL scores. These encouraging results open the prospect to further studies and Serelys Homme use in patients undergoing ADT for prostate cancer.

The effect of oral vitamin E and omega-3 alone and in combination on menopausal hot flushes: A systematic review and meta-analysis.

This systematic review was conducted to investigate the effects of vitamin E and omega-3 used alone and in combination on the frequency and intensity of hot flushes (primary outcomes) and adverse effects (secondary outcome) in menopausal women. English and Persian databases were searched until March 18, 2021. The quality of the published papers was evaluated using Cochrane Handbook and the meta-analysis was conducted in RevMan 5.3. Heterogeneity was assessed using I2. In cases with substantial heterogeneity, a random effects model was used instead of a fixed effects model. A total of 387 papers were obtained from the databases. Finally, 10 papers with a sample size of 1100 participants entered the systematic review and a meta-analysis was conducted on nine of them. The results of the meta-analysis of two studies indicated that using vitamin E and omega-3 in combination significantly reduced the intensity of hot flushes compared to the placebo (mean difference (MD): -0.35; 95% CI: -0.48 to -0.21). The mean frequency (MD: -0.50; 95% CI: -1.58 to 0.58) and intensity (SMD: -0.61; 95% CI: -1.50 to 0.29) of hot flushes in the omega-3 group and the frequency of hot flushes (SMD: -0.21; 95% CI: -0.47 to 0.04) in the vitamin E group showed no significant differences with the placebo. No serious adverse effects were reported in the studies. Given the low number of RCTs, more clinical trials with larger sample size are required.

Effect of acupuncture on menopausal hot flushes and serum hormone levels: a systematic review and meta-analysis.

To evaluate the efficacy/effectiveness and safety of acupuncture for the treatment of hot flushes and its impact on serum hormone levels in menopausal women. A total of 10 databases were searched from their inception to August 2018. Reference lists of reviews and included articles were also hand-searched. Randomized controlled trials (RCTs) comparing the effect of acupuncture versus sham acupuncture, or acupuncture versus hormone therapy (HT), as treatment for menopausal hot flushes were included. Outcomes included hot flush frequency, hot flush severity and serum hormone levels of estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Meta-analyses were performed using Review Manager 5.3 software. Thirteen RCTs including 1784 patients were selected, seven of which were available for meta-analysis. Compared with sham acupuncture, acupuncture significantly decreased hot flush frequency (mean difference (MD) -0.84, 95% confidence interval (CI) [-1.64, -0.05], I2 = 54%) from baseline to the end of study, but did not impact end scores of hot flush frequency (MD 0.19, 95% CI [-0.61, 0.99], I2 = 0%) or severity (MD 0.02, 95% CI [-0.13, 0.17], I2 = 0%). No differences were found between acupuncture and HT in serum levels of E2 (MD 6.56, 95% CI [-3.77, 16.89], I2 = 76%), FSH (MD 1.06, 95% CI [-1.44, 3.56], I2 = 0%) or LH (MD -3.36, 95% CI [-13.37, 6.65], I2 = 89%). Acupuncture may not decrease hot flush frequency, but yet appears to have similar effects on serum hormone levels as HT, that is, increased E2 and decreased FSH and LH. Considering that no firm conclusions could be drawn due to the low quality and limited number of included trials included, further high-quality RCTs need to be conducted.

Maca's therapeutic effects

The maca plant (Lepidium meyenii), native to the Andes of central Peru, has traditionally been used as a staple crop as one of the few plants that successfully grow in that harsh climate. But over the last decade, interest in maca has increased worldwide and it has been advertised as a superfood with the ability to balance hormones, improve concentration, enhance fertility, and increase energy and stamina. Maca is a cruciferous vegetable related to broccoli, cauliflower, turnip, and cabbage that is rich in protein and fiber as well as many essential amino acids. Maca boasts high amounts of vitamin C, iron, calcium, and copper, and various plant compounds believed to be the source of maca's beneficial effects on vigor. Maca's glucosinolates have an antibiotic-like effect and help ward off bacterial, viral, and fungal infection in the intestines. Maca's polyphenols are considered the source of improved digestion, brain function, and blood sugar levels, and offer protection against blood clots, heart disease, and certain cancers. The antifungal action of maca extract is thought to be related to the presence of imidazole alkaloids chemically similar to antifungal azoles. There are many studies assessing maca's medicinal benefits regarding sexual dysfunction regulation; neuroprotective effects; memory enhancement; and the root's antidepressant, antioxidant, anti-cancer, and anti-inflammatory properties. A 2012 review by Gonzales in Evidence Based Complementary Alternative Medicine assessed evidence from 75 clinical studies for the effectiveness of maca. The authors found that though further research is required, available data suggest that maca shows significant positive effects on fertility, mood, memory, osteoporosis, metabolism, and the treatment of some tumors. Most studies of maca focus on fertility and libido, and have shown there is some evidence that maca root affects men's fertility. A small number of studies have shown an improvement in some menopausal symptoms. A systematic review of randomized controlled trials published in Maturitas in 2011 found that maca eased menopausal symptoms including hot flashes and interrupted sleep. A highly cited 2006 clinical study by Meissner et al. in International Journal of Biomedical Science evaluated the therapeutic effects of maca as a non-hormonal alternative to hormone replacement therapy in perimenopausal women. Results revealed that in addition to reduction in body weight and blood pressure and an increase in serum high-density lipoprotein and iron, maca balanced levels of follicle-stimulating hormone, estradiol, prostaglandin, and adrenocorticotropic hormones. The researchers reported that maca significantly reduced frequency of hot flushes, incidence in night sweating, interrupted sleep pattern, anxiety, irritability, depression, and heart palpitations. Peruvians in the central Andes dry maca root and consume 20 g to 100 g maca powder daily in porridge or a sweet drink. Doses up to 3 g daily for up to 4 months have been found to be safe in clinical trials. Maca is generally sold as a powder, in capsules, or liquid extract, available from health food stores and online markets. The taste and aroma of maca is reminiscent of caramel or butterscotch. Maca is often included in smoothies, sprinkled on oatmeal, or included in no-bake desserts. In general, maca is considered safe and there is some evidence for beneficial pharmacological effects, but more studies presenting robust data are needed as the overall evidence is too limited to draw firm conclusions. There are no reports of adverse reactions after consuming maca. Maca has a high vitamin K content. Patients who take warfarin should be informed that more frequent INR monitoring may be required when taking maca.

Estetrol Cotreatment of Androgen Deprivation Therapy in Infiltrating or Metastatic, Castration-sensitive Prostate Cancer: A Randomized, Double-blind, Phase II Trial (PCombi)

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved. ObjectiveTo assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose estetrol (HDE4) when combined with ADT. Design, setting and participantsA phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi study). InterventionPatients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 (n = 41) or placebo (n = 21) cotreatment for 24 wk. Outcome measurements and statistical analysisCoprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population. Results and limitationsOf 62 patients included in the study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo (p < 0.001). Daily HFs occurred in 5.9% versus 55%. Bone turnover parameters decreased significantly with HDE4 (p < 0.0001). Total and free T decreased earlier (p < 0.05), and free T was suppressed further (p < 0.05). PSA suppression was more profound and earlier (p < 0.005). FSH levels were suppressed by 98% versus 57% (p < 0.0001). Estrogenic side effects were nipple sensitivity (34%) and gynecomastia (17%). ConclusionsHDE4 cotreatment of ADT patients with advanced prostate cancer was well tolerated, and no treatment-related cardiovascular adverse events were observed at 24 wk. HFs and bone turnover were substantially reduced. Suppression of free T, PSA, and FSH was more rapid and profound, suggesting enhanced disease control by HDE4 cotreatment. Larger and longer-lasting studies are needed to confirm the results of the study reported here. Patient summaryCotreatment of androgen deprivation therapy with high-dose estetrol in advanced prostate cancer patients results in fewer occurrences of hot flushes, bone protection, and other antitumor benefits. Nipple sensitivity and gynecomastia may occur as side effects.

Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The meta-analysis presented in this article covered the efficacy of red clover isoflavones in relieving hot flushes and menopausal symptoms in perimenopausal and postmenopausal women. Studies were identified by MEDLINE (PubMed), Embase, and the Cochrane Library searches. The quality of the studies was evaluated according to Cochrane criteria. A meta-analysis of eight trials (ten comparisons) demonstrated a statistically significant reduction in the daily incidence of hot flushes in women receiving red clover compared to those receiving placebo: weighted mean difference (WMD—weighted mean difference) −1.73 hot flushes per day, 95% CI (confidence interval) −3.28 to −0.18; p = 0.0292. Due to 87.34% homogeneity, the performed analysis showed substantive difference in comparisons of postmenopausal women with ≥5 hot flushes per day, when the follow-up period was 12 weeks, with an isoflavone dose of ≥80 mg/day, and when the formulations contained a higher proportion of biochanin A. The meta-analysis of included studies assessing the effect of red clover isoflavone extract on menopausal symptoms showed a statistically moderate relationship with the reduction in the daily frequency of hot flushes. However, further well-designed studies are required to confirm the present findings and to finally determine the effects of red clover on the relief of flushing episodes.

Chapter 30 - The neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies

The preoptic area of the hypothalamus is the central hub of thermoregulation in mammals, coordinating autonomic heat-effector pathways in response to sensory information from the ambient and internal environment. This aims to maintain temperature homeostasis at a predetermined thermoregulatory set-point. However, hormonal and neuronal changes during the menopause, including estrogen deficiency, disrupt these normal thermoregulatory responses. This results in abnormal activation of heat dissipation effectors, manifesting clinically as hot flush symptoms. Neurokinin B (NKB) signaling via the neurokinin-3 receptor (NK3R) within the preoptic area is thought to play an important role in the pathophysiology of hot flushes. Therefore attenuation of the NKB/NK3R signaling pathway has garnered much interest as a novel therapeutic target for the amelioration of menopausal hot flushes. Recent clinical trials have demonstrated that NK3R antagonists can produce rapid and sustained improvements in hot flush frequency, severity, and quality of life, without the need for estrogen exposure. Therefore NK3R antagonists are fast emerging as a safe and efficacious alternative to hormone replacement therapy, the current gold standard of treatment.

Open-label placebos for menopausal hot flushes: a randomized controlled trial

This study investigated the efficacy of an open-label placebo (OLP) treatment for menopausal hot flushes. Women with at least five moderate or severe hot flushes per day were allocated to receive four weeks of OLP for twice a day or no-treatment. Intention-to-treat analyses included n = 100 women. In comparison to no-treatment, OLP reduced the log-transformed hot flush composite score (frequency × intensity) (mean difference in change: − 0.32, 95% CI [− 0.43; − 0.21], p < 0.001, Cohen’s d = 0.86), hot flush frequency (− 1.12 [− 1.81; − 0.43], p = 0.02, Cohen’s d = 0.51), and improved overall menopause-related quality of life (− 2.53 [− 4.17; − 0.89], p = 0.02, Cohen’s d = 0.49). Twelve (24%) (vs. three [6%]) patients had 50% lesser hot flushes. Problem rating of hot flushes and subdomains of quality of life did not improve. After four weeks, the OLP group was further divided via randomization to continue or discontinue the treatment. Benefits were maintained at week 8 (log-transformed score: − 0.04 [− 0.06; 0.14], p = 0.45). There was no difference between taking placebos for 8 or 4 weeks (log-transformed score: 0.04 [− 0.17; 0.25], p = 0.73). Results indicate that open-label placebos may be an effective, safe alternative for menopausal hot flushes.

Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study.

BackgroundInterest in herbal medicines and non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. Vasomotor symptoms are the most characteristic and notable symptoms of menopause.ObjectiveTo investigate the changes in the frequency and severity of hot flush and associated vasomotor symptoms experienced by peri-menopausal and menopausal women supplemented with the herbal formulation (Nu-femme™) comprising Labisia pumila (SLP+®) and Eurycoma longifolia (Physta®) or placebo.DesignRandomised, double-blind, placebo-controlled, 24-week study enrolled 119 healthy women aged 41–55 years experiencing peri-menopausal or menopausal symptoms and supplemented with Nu-femme™ or placebo. The primary endpoint was comparative changes between treatment groups in the change in the frequency and severity of hot flushes. The secondary objectives were to assess the changes in the frequency and severity of joint pain, Menopause Rating Scale (MRS) and Menopause-Specific Quality of Life (MENQOL) questionnaire domain scores. Concentrations of serum hormone, lipid profile, bone markers, sleep quality and vitality were also studied as secondary objectives.ResultsAt week 12, significant (P < 0.01) improvements in hot flush symptoms were observed in Nu-femme™ and placebo groups. Even though there was no significant difference between groups, higher percentage of improvement, 65%, was seen in Nu-femme™ compared to 60% in placebo. Significant improvements (P < 0.001) in MRS and MENQOL scores at weeks 12 and 24 were observed in both groups, respectively. Luteinising hormone and follicle-stimulating hormone levels were significantly reduced (P < 0.05) at weeks 12 and 24, respectively, compared to baseline in the Nu-femme™ group, with no significant changes observed in the placebo group. There were significant (P < 0.05) reductions in serum low-density lipid and triglycerides levels at week 12 in Nu-femme™ group, but no changes seen in placebo group. At the end of week 24, changes in haematology and clinical chemistry parameters remained within normal clinical ranges in both groups.ConclusionHerbal formulation consists of L. pumila and E. longifolia (Nu-femme™) may support reduction in hot flushes and improvements in hormone and lipid profile in healthy peri-menopausal and menopausal women.

The effects of a new, improved Chinese medicine, Gengnianchun formula granules, on hot flushes, depression, anxiety, and sleep in Chinese peri- and postmenopausal women: a randomized placebo-controlled trial.

The aim of the study was to investigate the effectiveness and safety of a new, improved herbal formula of a traditional Chinese medicine, improved Gengnianchun (I-GNC), on hot flushes, depression, anxiety, and sleep in peri- and postmenopausal women in China. A randomized, single-blind, placebo-controlled trial of peri- and postmenopausal women with Kupperman Index (KMI) scores of 15 or higher was conducted for 12 weeks. Hot flush frequencies, KMI scores, Hamilton depression scale scores, Hamilton anxiety scale scores, and Pittsburgh Sleep Quality Index scores were evaluated. Each outcome was evaluated every 4 weeks. Ninety-eight participants completed the study. The I-GNC formula significantly reduced the mean (SD) frequency of hot flushes from 7 (4.554) to 1.2 (1.675) in the I-GNC group and from 6.74 (3.43) to 3.66 (2.635) in the placebo group (P < 0.01). The KMI (P < 0.01), Hamilton depression scale (P < 0.01), and Hamilton anxiety scale (P < 0.01) scores decreased in both groups after treatment, and significant differences were observed between the two groups (P < 0.01); however, no significant difference in the Pittsburgh Sleep Quality Index score was observed. I-GNC had no effect on serum follicle-stimulating hormone or E2 levels. There were no obvious adverse effects. The traditional Chinese medicine herbal formula I-GNC can alleviate the symptoms of menopausal syndrome and improve quality of life among peri- and postmenopausal women. I-GNC is safe and has no notable adverse effects.

A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety.

Objective:The aim of this study was to select the minimum effective dose of estetrol (E4) for the treatment of vasomotor symptoms in postmenopausal women.Methods:This was a multicenter, randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 257, of whom 32 were hysterectomized) aged 40 to 65 years, with ≥7 moderate to severe hot flushes (HFs) per day, or 50 or more moderate to severe HFs weekly, received 2.5, 5, 10, or 15 mg E4, or placebo once-daily for a period of 12 weeks. Efficacy was assessed by recording the frequency and severity of HFs. Overall safety was assessed by recording adverse events, measuring endometrial thickness, and monitoring bleeding patterns. Treatment groups were compared using analysis of covariance.Results:The frequency of moderate to severe HFs decreased with all E4 doses. The difference in the percentage change of weekly HF frequency was significant for 15 mg E4 versus placebo at both W4 (−66% vs −49%, P = 0.032) and W12 (−82% vs −65%, P = 0.022). The decrease in severity of HFs was significantly more pronounced for 15 mg E4 than for placebo at both W4 (−0.59 vs −0.33, P = 0.049) and W12 (−1.04 vs −0.66, P = 0.049); the other doses failed to achieve statistical significance. In nonhysterectomized women, endometrial thickness increased during treatment and normalized following progestin treatment at study completion. No endometrial hyperplasia was observed.Conclusions:Estetrol 15 mg is considered to be the minimum effective daily oral dose for treatment of vasomotor symptoms. Its current seemingly favorable safety profile is further to be confirmed in phase 3 clinical development.Video Summary:.

Manualized cognitive behavioral group therapy to treat vasomotor symptoms for women diagnosed with mood disorders

ObjectiveThis 6-week, prospective, single-arm study examined the feasibility, acceptability, and preliminary efficacy of cognitive behavioral group therapy in peri- and postmenopausal women with mood disorders (major depression or bipolar) and problematic vasomotor menopausal symptoms. Methods59 participants from an outpatient clinic with mood disorders and problematic vasomotor symptoms were enrolled. The primary outcomes were change from baseline to 6 weeks in Hot Flush Night Sweat Problem Rating, Hot Flash Related Daily Interference, and Quality of Life. Secondary outcomes were change in Hot Flush Frequency, depression, anxiety, perceived stress, anhedonia, beliefs and cognitive appraisals of menopause. ClinicalTrials.gov [identifier: NCT02860910]. ResultsOn the Hot Flush Night Sweat Problem Rating, 39.3% improved 2 or more points, which was clinically relevant. Changes in Quality of Life (p = .001) and the Hot Flash Related Daily Interference Scale were also significant (p < .001). Significant results were found on most secondary outcomes (hot flush frequency on the Hot Flush Daily Diary, depression, anxiety, perceived stress (p < .001) and anhedonia (p = .001). One of six subscales (control subscale) on the cognitive appraisal of menopause significantly improved (p < .001). Three subscales on the beliefs measure did not change significantly (p = .05, p = .91, and p = .14). Six-week study retention was robust (N = 55, 93%) and 94.2% of individuals reported that cognitive behavioral group therapy sessions were useful. ConclusionThis exploratory study suggests that CBGT is acceptable, feasible, and efficacious in women with mood disorders and problematic menopause vasomotor symptoms. Further studies are needed using more rigorous and controlled methods.

Non-concealed placebo treatment for menopausal hot flushes: Study protocol of a randomized-controlled trial

BackgroundBeneficial effects of placebos are high in double-blind hot flush trials. Studies in various conditions suggest that honestly prescribed placebos may elicit symptom improvement.ObjectiveTo determine whether open label placebo (OLP) treatment is efficacious in alleviating hot flushes among peri- and postmenopausal women.Methods/designIn this assessor-blinded, randomized-controlled trial, n = 100 women experiencing five or more daily hot flushes of at least moderate severity and bothersomeness are assigned 1:1 to a 4-week OLP treatment or no treatment. To explore the duration and maintenance of placebo effects, the OLP group is randomized a second time to either discontinue or continue the OLP treatment for another 4 weeks. All participants receive a briefing about placebo effects and study visits at baseline, post-treatment (4 weeks), and follow-up (8 weeks, OLP group only). Qualitative interviews about subjective experiences with the OLP treatment are conducted.Primary outcomes are differences between the OLP and the no-treatment group in the hot flush composite score (frequency × severity), and bothersomeness of hot flushes as assessed with the Hot Flush Rating Scale at post-treatment. Secondary outcomes include hot flush frequency, health-related quality of life, global improvement, and the number of responders at post-treatment. Data are analyzed by fitting (generalized) linear mixed models. An exploratory analysis of maintenance and duration is performed including follow-up data.DiscussionThis trial will contribute to the evaluation of OLP treatments in clinical practice and further our understanding about the magnitude of placebo effects in hot flush treatments.Trial registrationClinicaltrials.gov, NCT03838523. Retrospectively registered on February 12th, 2019. The first patient was enrolled on October 10th, 2018.

Complementary and Alternative Medicine for Breast Cancer Patients: An Overview of Systematic Reviews

The application of systematic review (SR) has been increased rapidly in the field of cancer treatment. Complementary and alternative medicine (CAM) for cancer is no exception. The aim of this review is to evaluate and summarize systematic reviews on the CAM use in breast cancer patients. Search sources were Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR), and PubMed. In addition, we assessed the quality of SR with the Assessing the Methodological Quality of Systematic Reviews (AMSTAR). This review did not consider control groups and outcomes. Thirty-four SRs met a set of criteria. According to interventions, there were twenty SRs which included yoga, acupuncture, and herbal medicines. Meta-analysis of 19 out of 34 reviews showed the followings: (1) acupuncture had a beneficial effect on the frequency of hot flushes, (2) yoga had a beneficial effect on depression and health-related QOL, (3) mindfulness-based stress reduction (MBSR) had a beneficial effect on anxiety and depression, (4) combination of herbal medicine and chemotherapy synergistically improved clinical outcomes, (5) acupuncture did not show significant effect on the severity of hot flushes and cancer-related pain, (6) yoga was unable to be confirmed as having an effect on cancer-related pain and physical well-being. Given the results of AMSTAR, 9 out of 34 reviews were of high quality and 3 reviews were deemed to be of low quality. In conclusion, since most SRs were at moderate or high quality levels, CAM could be helpful for treating specific symptoms related to breast cancer.

Resistance training for hot flushes in postmenopausal women: A randomised controlled trial

ObjectivesTo investigate the effect of 15 weeks of resistance training on the frequency of moderate to severe hot flushes in postmenopausal women. Study designPostmenopausal women with at least 4 moderate or severe hot flushes or night sweats per day day were randomized to a 15-week resistance training intervention or unchanged physical activity. Participants did not exercise regularly at baseline and had not used any therapy for hot flushes two months prior to study entry. The resistance training was performed three times per week and the program contained 8 exercises performed with 8–12 repetitions in 2 sets. Loads were set individually from eight-repetition maximum-strength tests and increased progressively. Main outcome measuresThe primary outcome was change in mean moderate or severe hot flushes per day from baseline to week 15, assessed with symptom diaries. Secondary outcomes included change in hot flush score and time spent on physical activity. ResultsBetween November 19, 2013, and October 26, 2016, 65 women were enrolled; 58 completed the trial and were included in the analyses. The mean age was 55 and the mean number of moderate or severe hot flushes per day at baseline was 7.1; there were no baseline differences between groups. The frequency of hot flushes decreased more in the intervention group than in the control group (mean difference −2.7, 95% CI −4.2 to −1.3). The mean percentage change was -43.6% (−56.0 to −31.3) in the intervention group and −2.0% (−16.4–12.4) in the control group. ConclusionA 15-week resistance-training program decreased the frequency of moderate and severe hot flushes among postmenopausal women and could be an effective and safe treatment option to alleviate vasomotor symptoms.

Predictors of Frequency and Severity of Vasomotor Symptoms: Results from the REPLENISH Trial [19M

INTRODUCTION: The objective of this analysis was to determine whether baseline characteristics can predict the frequency and severity of hot flushes (HF) in postmenopausal women. METHODS: REPLENISH was a phase 3, randomized, double-blind, placebo-controlled trial that evaluated the safety and efficacy of TX-001HR (17β-estradiol/progesterone oral capsule) in 767 postmenopausal women, who had ≥50 moderate to severe HF/week at baseline. Post hoc associations of baseline characteristics (age, race, BMI, smoking, time since last menstrual period [LMP], age at LMP, tubal ligation, parity, estradiol levels, and menopause-specific quality of life [MENQOL] total and vasomotor domain scores) with frequency and severity of hot flushes were evaluated. RESULTS: Baseline predictors for having ≥50 moderate to severe HF/week were BMI (P=.0299), MENQOL total score (P<.0001), and MENQOL Vasomotor domain score (P<.0001). For every unit increase in BMI, the odds of having ≥50 moderate to severe HF decreased by 12.6% while a one-point increase in MENQOL total and vasomotor scores increased the odds by 20.9% and 110.9%, respectively. Baseline predictors for HF severity were current smoking (P=.0042), and MENQOL overall (P<.0001) and vasomotor (P<.0001) scores. Multiple regression analyses showed that the MENQOL vasomotor score was the best predictor of severity (R2=0.1876; P<.0001), followed by MENQOL total score + smoking (R2=0.0325; P<.0001). Other baseline characteristics evaluated were not predictors of HF frequency and/or severity. CONCLUSION: In REPLENISH, baseline BMI, smoking, and MENQOL total and vasomotor scores were predictors for moderate to severe HF frequency and/or severity. These characteristics could potentially be used to predict women's HF frequency and severity at menopause.

Neurokinin B and Neurokinin-3 Receptor Signaling: Promising Developments in the Management of Menopausal Hot Flushes.

Vasomotor symptoms, including hot flushes and night sweats, pose a significant symptomatic burden to women undergoing menopause, and negatively impact on both their physical and psychological well-being. Management of these symptoms can be challenging, with the use of conventional hormone replacement therapy limited by duration of treatment and clinical contraindications. Recent advances in our understanding of the neuroendocrine regulation of the reproductive axis and thermoregulation postmenopause has helped identify a promising new therapeutic target to ameliorate hot flushes. Antagonism of the neurokinin B/neurokinin-3 receptor (NK3R) signaling pathway has emerged as an efficacious treatment in managing vasomotor symptoms, with evidence of rapid and sustained reduction in hot flush frequency and severity and improvements in secondary quality-of-life measures such as sleep. Within this review, we will explore the growing body of evidence supporting the use of NK3R antagonists in the management of vasomotor symptoms, and the possible utility in managing dysfunctional sex-hormone-dependent disorders and glycolipid metabolism disorders such as polycystic ovarian syndrome.

SAT-239 Bioidentical Estradiol and Progesterone Improved Hot Flushes, Night Sweats and Sweating

In the phase 3 REPLENISH trial of postmenopausal women with a uterus, TX-001HR (TherapeuticsMD, Boca Raton, FL), an oral 17β-estradiol-progesterone (E2/P4) softgel capsule, reduced moderate to severe hot flush frequency and severity and improved quality of life outcomes, while protecting the endometrium. The objective of this analysis was to further determine the effects of the E2/P4 capsules versus placebo on vasomotor symptoms (VMS) as assessed by the menopause-specific quality of life (MENQOL) questionnaire. In the REPLENISH trial (NCT01942668), women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized 1:1:1:1:1 to daily E2/P4 (mg/mg) of 1/100 (FDA approved as BIJUVATM), 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy). Other women (with fewer VMS) were randomized 1:1:1:1 to active E2/P4 doses only. Three of the 29 items in the MENQOL questionnaire assess vasomotor symptoms: hot flushes, night sweats, and sweating. The symptoms, if experienced, were rated using a 7-item Likert scale ranging from “Not at all bothered” (score of 2) to “Extremely bothered” (score of 8); if not experienced, the score was 1. Changes from baseline to week 12, and months 6 and 12 in these 3 items were assessed in the overall efficacy population (MITT) and VMS (MITT-VMS) substudy population. Women were randomized to daily doses of E2/P4 (mg/mg) 1/100 (n=415), 0.5/100 (n=424), 0.5/50 (n=421), 0.25/50 (n=424) or placebo (n=151). Participants (mean age of 55 years and mean BMI of 27 kg/m2) were primarily white (65%) or black (32%). Mean baseline scores ranged from 6.7 to 7.4 for hot flushes, 6.1 to 7.1 for night sweats, and 6.0 to 6.9 for sweating. In the MITT population, women treated with all E2/P4 doses had significantly more favorable improvements from baseline in their hot flushes (range of significant mean changes with E2/P4 vs placebo, -2.9 to -4.3 vs -1.9 to -2.7), night sweats (-3.1 to -4.0 vs -2.4 to -3.0) and sweating (-2.8 to -3.6 vs -2.3 to -3.2) scores at week 12, and months 6 and 12 (all, P≤0.002). Similarly, significant improvements from baseline with E2/P4 vs placebo (all, P≤0.030) were observed in the MITT-VMS substudy population for hot flushes (-3.0 to -4.4 vs -1.9 to -2.7), night sweats (-3.3 to -4.4 vs -2.4 to -3.0), and sweating (-3.1 to -4.2 vs -2.3 to -3.2), except for those treated with the lowest E2/P4 dose (0.25 mg E2/50 mg P4) at months 6 and 12 for sweating. In the REPLENISH trial, compared with placebo, postmenopausal women treated with E2/P4 had significant improvements in their hot flushes, night sweats and sweating as assessed by MENQOL. Benefits continued for up to 12 months of treatment. These results with this first oral hormone therapy formulation combining bioidentical estradiol and progesterone in a single capsule are consistent with the primary REPLENISH results demonstrating efficacy for the treatment of moderate to severe vasomotor symptoms in menopausal women with a uterus.

SAT-237 Combined Bioidentical Estradiol and Progesterone Capsules Improved Quality of Sleep in Postmenopausal Women with Vasomotor Symptoms

Difficulty sleeping is a common complaint of postmenopausal women. In the REPLENISH trial, the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL), was shown to reduce moderate to severe hot flush frequency and severity and improve quality of life outcomes in menopausal women with a uterus, while protecting the endometrium. In this analysis, the effect of the E2/P4 capsules on “difficulty sleeping” in postmenopausal women experiencing hot flushes, was assessed by the menopause-specific quality of life (MENQOL) questionnaire and also analyzed by age. The phase 3 REPLENISH trial (NCT01942668), evaluated 4 daily doses of E2/P4 capsules in postmenopausal women (40-65 years, intact uterus) with vasomotor symptoms (VMS). Women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy); women with fewer/less severe VMS were randomized to active E2/P4 doses only for endometrial safety. MENQOL was administered at baseline, week 12, and months 6 and 12. The “difficulty sleeping” item was rated using a 7-item Likert scale ranging from “Not at all bothered” (analysis score of 2) to “Extremely bothered” (analysis score of 8) if difficulty sleeping was experienced, if not experienced, the score for the analysis was set to 1. Changes from baseline to week 12, and months 6 and 12 in all women (MITT population) were analyzed by ANCOVA between each E2/P4 groups vs placebo and stratified by age (pre-specified FDA subgroup; <55 and 55+). Treatment groups in the MITT population (n=1833) were E2/P4 1/100 (n=416), 0.5/100 (n=422), 0.5/50 (n=421), 0.25/50 (n=423) or placebo (n=151). The MITT population had a mean age of 55 years; in the <55-year group (n=927) mean age was 51.2 years and in the ≥55-year group (n=906) mean age was 58.1 years. Mean baseline scores for the “difficulty sleeping” item ranged from 5.1 to 5.8 points. In the MITT population, difficulty sleeping significantly improved from baseline with the three highest E2/P4 doses (1/100, 0.5/100, 0.5/50) compared with placebo at all timepoints (all, P<0.05), except for 0.5/50 at month 6. In women <55 years, the sleep difficulty item significantly improved from baseline at all timepoints with two E2/P4 doses (1/100 and 0.5/50) vs placebo. In women 55+ years, significant improvements from baseline were observed at week 12 with three E2/P4 doses (1/100, 0.5/100, 0.5/50) vs placebo. In REPLENISH, women treated with E2/P4 capsules containing 1 or 0.5 mg E2 demonstrated significant and sustained improvements in the MENQOL difficulty sleeping assessment, especially those <55 years. These data warrant further evaluation.