Hot Flash Related Daily Interference Scale Research Articles

Efficacy and safety of fezolinetant, a neurokinin-3 antagonist, in treating vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis.

Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile. To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile. A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant. There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group. Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration.

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.

Psychometric properties of the French Hot Flash Related Daily Interference Scale (HFRDIS)

Objective Hot flashes are one of the major symptoms of climacteric syndrome. Despite the high prevalence of these symptoms, few questionnaires assessing the impact of hot flashes on quality of life have been validated. The aim of this study was to validate a French version of the Hot Flash Related Daily Interference Scale (HFRDIS) in a sample of French women. Methods In this prospective study, data were obtained from two groups of women aged between 40 and 60 years from both women without breast cancer and women under hormone therapy for breast cancer between March 2021 and February 2022. Translation was made by an official English–French translator using the forward–backward method. Results One hundred and sixty-seven women completed the HFRDIS questionnaire. The scree plots confirmed unidimensional structure. Cronbach’s α coefficient was 0.92 [0.90–0.94] similar to the original version. The intra-class correlation coefficients of each item ranged between 0.58 and 0.71 Concordance of the scores of each item with those obtained during the validation of the original version of the HFRDIS was confirmed. Conclusion The validation results show that the French version of the HFRDIS questionnaire is a valid tool to evaluate the impact of hot flashes on the daily life activities of patients.

A Telehealth-Delivered Tai Chi Intervention (TaiChi4Joint) for Managing Aromatase Inhibitor-Induced Arthralgia in Patients With Breast Cancer During COVID-19: Longitudinal Pilot Study.

BackgroundEstrogen receptor–positive breast cancer is the most common type of breast cancer in postmenopausal women. Aromatase inhibitors (AIs) are the endocrine therapy of choice recommended for these patients. Up to 50% of those treated with an AI develop arthralgia, often resulting in poor adherence and decreased quality of life.ObjectiveThe study is a single-arm longitudinal pilot study aiming to evaluate the safety, feasibility, acceptability, and potential efficacy of TaiChi4Joint, a remotely delivered 12-week tai chi intervention designed to relieve AI-induced joint pain.MethodsWomen diagnosed with stage 0-III breast cancer who received an AI for at least 2 months and reported arthralgia with a ≥4 score on a 0 to 10 scale for joint pain were eligible for study enrollment. Participants were encouraged to join tai chi classes delivered over Zoom three times a week for 12 weeks. Program engagement strategies included using a private Facebook study group and a Box cloud for archiving live class recordings. The program uses SMS text messaging and emails with periodic positive quotes and evidence-based information on tai chi for facilitating community bonding and class attendance. Participants were invited to complete the following assessments at baseline and at 1-, 2-, and 3-month intervals from study enrollment: Brief Pain Inventory, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), The Australian Canadian Osteoarthritis Hand Index (AUSCAN), Fatigue Symptom Inventory, Hot Flash Related Daily Interference Scale (HFRDIS), Pittsburgh Sleep Quality Index (PSQI), and Center for Epidemiological Studies–Depression (CES-D).ResultsA total of 55 eligible patients were invited to participate, and 39 (71%) consented and completed the baseline assessments. Participants attended 61% (median) of the suggested classes, with no tai chi–related adverse events reported. Of the 39 participants, 22 completed the 3-month follow-up assessment with a 56% retention rate. Study participants reported improvement from baseline compared to 3 months as follows (paired t test): Brief Pain Inventory (P<.001), AUSCAN pain subscale (P=.007), AUSCAN function subscale (P=.004), Fatigue Symptom Inventory (P=.004) and PSQI (P<.001), and HFRDIS (P=.02) and CES-D (P<.001). In particular, for our primary end point of interest, improvements in hip and knee symptoms, measured by WOMAC’s three subscales, were clinically meaningful and statistically significant when adjusted for multiple comparisons from baseline to 3 months post intervention.ConclusionsThe COVID-19 global pandemic has resulted in the need to rethink how mind-body therapies can be delivered. This study demonstrated the feasibility, acceptability, and potential efficacy of a telehealth-based tai chi intervention for reducing AI-induced arthralgia. The intervention decreased patient-reported pain and stiffness, and improved sleep quality and depressive symptoms. Fully powered, large, telehealth-based tai chi trials for AI-associated arthralgia are needed considering our promising findings.Trial RegistrationClinicalTrials.gov NCT04716920; https://www.clinicaltrials.gov/ct2/show/NCT04716920

Telehealth delivered Tai Chi intervention for managing aromatase inhibitor-induced arthralgia in breast cancer patients: TaiChi4Joint during the COVID-19 pandemic a Pilot study.

e12523 Background: Estrogen receptor positive breast cancer (BC) is the most common type of breast cancer in postmenopausal women and aromatase inhibitors (AI) are the endocrine therapy of choice recommended for these patients. Up to 50% of those treated with an AI develop Arthralgia often resulting in poor adherence and decreased quality of life. Methods: This is a single arm longitudinal pilot study aiming to evaluate the safety, feasibility, acceptability and potential efficacy of TaiChi4Joint, a remotely-delivered 12-week Tai Chi intervention designed for the relief of AI-induced joint pain. Women diagnosed with stage 0-III BC who have been receiving an AI for at least 2 months and reporting arthralgia with a ≥ 4 score on a 0-10 scale for joint pain were eligible for study enrollment. Participants were encouraged to join Tai Chi classes delivered over ZOOM three times a week for 12 weeks. Program engagement strategies include the use of a private Facebook study group and box.com cloud for archiving live class recordings. The program utilizes Text messaging and emails with periodic positive quotes and evidence based information on Tai Chi for facilitating community bonding and class attendance. Participants were invited to complete the following assessments online at baseline, 1, 2 and 3 months intervals from study enrollment: Brief Pain Inventory (BPI), Western Ontario and McMaster University Osteoarthritis index (WOMAC), The Australian Canadian Osteoarthritis Hand Index (AUSCAN), Fatigue Symptom Inventory (FSI), Hot Flash Related Daily Interference Scale (HFRDIS), Pittsburg Sleep Quality Index (PSQI) and Center for Epidemiological Studies Depression (CES-D). Results: 55 eligible patients were invited to participate and 39 consented and completed the baseline assessments. 61% (median) Participants attended the classes, with no Tai Chi related adverse events reported. 22 of the 39 participants completed the 3-month follow up assessments with a 56% retention rate. Study participants reported improvement from baseline compared to 3 month as follows: For BPI ( P = .000), AUSCAN pain subscale ( P =.000), AUSCAN function subscale for 35 patients ( P = .000), WOMAC ( P = .000), CES-D ( P = 0.001), FSI ( P = 0.00) and PSQI ( P = .000). However HFRDIS improved in 11 patients ( P = 0.00) for the other 22 patients (P = 0.154). Conclusions: The COVID-19 global pandemic has resulted in the need to rethink how mind-body therapies can be delivered. This study demonstrated the feasibility, acceptability, and potential efficacy of a Telehealth based Tai Chi intervention for reducing AI-induced arthralgia. The intervention decreased patient reported pain, stiffness and improved sleep quality and depressive symptoms. With our promising findings, larger telehealth based trials of Tai Chi for AI-associated arthralgia are needed. Clinical trial information: NCT04716920.

Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA).

Objective:In the primary analysis of the phase 2b VESTA study, oral fezolinetant reduced frequency and severity of menopausal vasomotor symptoms (VMS) compared with placebo. This secondary analysis evaluates effects of fezolinetant on responder rates and patient-reported outcomes (PROs).Methods:In this 12-week, double-blind study, postmenopausal women with moderate/severe VMS were randomized to fezolinetant 15, 30, 60, or 90 mg BID or 30, 60, or 120 mg QD or placebo. Proportion of responders was based on reductions in VMS from daily diary records. P values for comparisons between active treatment and placebo were calculated using logistic regression. Changes from baseline in PROs (Menopause-Specific Quality of Life questionnaire, Hot Flash-Related Daily Interference Scale, Greene Climacteric Scale) were conducted using a mixed model for repeated measurements and compared post hoc with published minimally important differences (MIDs).Results:Of 356 women randomized, 352 were treated and analyzed. A greater proportion of women receiving fezolinetant versus placebo met definitions of response at week 12. For all doses, mean changes from baseline in Menopause-Specific Quality of Life questionnaire VMS scores exceeded the MID (1.2) at weeks 4 (placebo: −1.8; fezolinetant: range, −1.9 to −3.6) and 12 (placebo: −2.3; fezolinetant: range, −2.9 to −4.4). Mean changes in Hot Flash-Related Daily Interference Scale at weeks 4 (placebo: −2.2; fezolinetant: range, −2.5 to −3.8) and 12 (placebo: −2.9; fezolinetant: range, −3.3 to −4.3) exceeded the MID (1.76). Greene Climacteric Scale-VMS domain scores improved for most fezolinetant doses versus placebo (week 4, placebo: −1.7; fezolinetant: range, −2.1 to −3.3; week 12, placebo: −2.1; fezolinetant: range, −2.7 to −3.6).Conclusions:Oral fezolinetant was associated with higher responder rates than placebo and larger improvements in QoL and other PRO measures, including a reduction in VMS-related interference with daily life.

Evaluation of the effect of Silybum marianum extract on menopausal symptoms: A randomized, double-blind placebo-controlled trial.

The tendency to use herbs to manage menopausal symptoms has increased in recent years. The purpose of this study was to evaluate the effect of Silybum marianum (L.) compared with placebo in women with hot flashes. Eighty women were randomly allocated into two equal groups (S. marianum extract [400 mg/d] or placebo capsules). Hot flashes frequency and severity were evaluated in 12 weeks with the Greene Climacteric Scale (GCS) and the Hot Flash Related Daily Interference Scale (HFRDIS). The data were analyzed in SPSS software using t-test, Mann-Whitney, chi-square test and repeated measure analysis. Hot flashes frequency and severity decreased from 4.32 ± 0.20/day to 1.31 ± 0.15/day and from 5.25 ± 0.22 to 1.62 ± 0.08, respectively, during the study in test group (p < .001) which were significantly better than effects of placebo in all steps of study (p < .001). Significant decreases in GCS and HFRDIS scores were also detected in S. marianum group compared with placebo after 4, 8 and 12 weeks (p < .001). The results showed that S. marianum can decrease frequency and severity of hot flashes significantly. Considering the safety and high consumption of this herbal medicine worldwide, its use in women with menopausal symptoms can be helpful.

Cognitive behavior therapy for menopausal symptoms (CBT-Meno): a randomized controlled trial.

To evaluate the effectiveness of cognitive behavioral therapy for menopausal symptoms (CBT-Meno) compared with a waitlist condition (no active intervention). A randomized controlled trial was conducted with 71 perimenopausal or postmenopausal women who were seeking treatment for menopausal symptoms. Blind assessments were conducted at baseline, 12 weeks postbaseline, and 3 months post-treatment. An intention-to-treat analysis was conducted. CBT-Meno sessions included psychoeducation, and cognitive and behavioral strategies for vasomotor and depressive symptoms, anxiety, sleep difficulties, and sexual concerns. Primary outcomes were scores on the Hot Flash Related Daily Interference Scale (HFRDIS) and Beck Depression Inventory (BDI-II). Secondary outcomes were scores assessing vasomotor and sexual concerns on the Greene Climacteric Scale (GCS-vm, GCS-sex), the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the Female Sexual Function Index (FSFI). There were significantly greater improvements in CBT-Meno compared with waitlist in vasomotor symptom interference (HFRDIS; P < 0.001, ηP = 0.21) and "bothersomeness" (GCS-vm; P = 0.04, ηP = 0.06), depressive symptoms (BDI-II; P = 0.001, ηP = 0.15), sleep difficulties (PSQI; P = 0.001, ηP = 0.17), and sexual concerns (GCS-sex; P = 0.03, ηP = 0.07). These results were found even when controlling for menopausal staging and medication use. Gains were maintained at 3 months post-treatment. CBT-Meno was particularly effective in improving self-reported vasomotor symptoms, depressive symptoms, sleep difficulties, and sexual concerns. Although future studies will be needed to confirm the impact of CBT-Meno on anxiety symptoms, these results suggest that this protocol is effective in targeting commonly reported menopausal symptoms. : Video Summary: Supplemental Digiatl Content 1, http://links.lww.com/MENO/A416.

Abstract P4-16-01: A randomized, double-blind, placebo-controlled trial of testosterone (T) for aromatase inhibitor-induced arthralgias (AIA) in postmenopausal women: Alliance A221102

Abstract Background: Aromatase inhibitors are a mainstay hormone receptor-positive breast cancer treatment. AIA occur in up to 50% of patients (pts), adversely affecting quality of life and treatment compliance. A small phase II clinical trial of oral testosterone unedeconate appeared to improve AIA over placebo (P), with no significant androgenic side effects. The current study was performed to confirm these findings. Methods: This randomized P-controlled trial enrolled postmenopausal women on adjuvant anastrozole or letrozole and experiencing moderate-to-severe AIA (≥5 on 0-10 scale). Pts were initially randomized to receive a subcutaneous pellet containing T 120 mg + anastrozole 8 mg (T+AIpellet) or P at the end of the first week on study (after obtaining baseline hot flash data) and at 3 months (mo). Due to slow accrual, the protocol was amended to change the route of delivery to topical T or P applied to the skin once daily for 6 mo. Baseline and monthly questionnaires were administered, including: Modified Brief Pain Inventory for aromatase arthralgia (BPI-AIA), prolife of mood states (POMS), the menopause specific quality of life questionnaire (MENQOL), a hot flash diary, the hot flash related daily interference scale (HFRDIS) and a symptom experience questionnaire. The primary endpoint was intra-patient change in joint pain at 3 mo, compared using a two-sample t-test. Results: 227 pts were accrued between 9/1/2013-11/29/2017. 55 pts were randomized prior to the protocol amendment and received T+AIpellet or P. Baseline characteristics were balanced between arms, with the exceptions of median weight, BMI, hemoglobin (all higher in T arm), and breast tenderness, dissatisfaction with personal life/depression, and skin changes (all higher in P arm). Compared to baseline, there were no significant differences between T and P in average pain or joint stiffness at 3 (p=0.483) or 6 mo (p=0.573). Average pain was significantly lower each month compared to baseline, irrespective of treatment arm. There were no significant differences in any other items evaluated by BPI-AIA, POMS, MENQOL, hot flash diary or HFRDIS. Similarly, there were no substantial differences in toxicity. A subset analysis of the 55 pts randomized to receive T+AIpellet or P identified significant reductions in average pain scores with T+AIpellet during the first month (p=0.038), but not thereafter. T+AIpellet pts had significantly more reduction in reported % of baseline hot flash frequency (p=0.034) and score (p=0.031), nausea (p=0.019), fatigue (p=0.042), mood swings (p=0.026), hand/feet swelling (p=0.009), stress urinary incontinence (p=0.039) and changes in appearance, texture or tone of their skin (p=0.0083), than pts on P. Conclusions: Overall, T did not improve AIA or menopausal symptoms compared to P. While there was significant improvement in AIA over the study period, T did not facilitate this process. However, T+AIpellet was associated with improvement in short-term AIA and several menopausal symptoms compared to P, suggesting that subcutaneous T combined with anastrozole may be superior to transdermal T alone. Support: UG1CA189823, U10CA180820, U10CA189809; ClinicalTrials.gov Identifier: NCT01573442 Citation Format: Leon-Ferre RA, Le-Rademacher J, Terstriep S, Glaser R, Novotni P, Giuliano A, Copur MS, Jones C, Page S, Mitchell W, Birrell SN, Loprinzi CL. A randomized, double-blind, placebo-controlled trial of testosterone (T) for aromatase inhibitor-induced arthralgias (AIA) in postmenopausal women: Alliance A221102 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-01.

Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial.

Due to concerns regarding the side effects of hormone therapy, many studies have focused on the development of non-hormonal agents for treatment of hot flashes. The aim of this study was to evaluate the efficacy and safety of saffron (stigma of Crocus sativus) in treatment of major depressive disorder associated with post-menopausal hot flashes. Sixty women with post-menopausal hot flashes participated in this study. The patients randomly received either saffron (30mg/day, 15mg twice per day) or placebo for 6 weeks. The patients were assessed using the Hot Flash-Related Daily Interference Scale (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and also at the second, fourth, and sixth weeks of the study. Fifty-six patients completed the trial. Baseline characteristics of the participants did not differ significantly between the two groups. General linear model repeated measures demonstrated significant effect for time×treatment interaction on the HFRDIS score [F (3, 162)=10.41, p=0.0001] and HDRS score [F (3, 162)=5.48, p=0.001]. Frequency of adverse events was not significantly different between the two groups. Results from this study revealed that saffron is a safe and effective treatment in improving hot flashes and depressive symptoms in post-menopausal healthy women. On the other hand, saffron, with fewer side effects, may provide a non-hormonal and alternative herbal medicine option in treatment of women with hot flashes.

Validity, cut-points, and minimally important differences for two hot flash-related daily interference scales.

To conduct psychometric analyses to condense the Hot Flash-Related Daily Interference Scale (HFRDIS) into a shorter form termed the Hot Flash Interference (HFI) scale; evaluate cut-points for both scales; and establish minimally important differences (MIDs) for both scales. We analyzed baseline and postrandomization patient-reported data pooled across three randomized trials aimed at reducing vasomotor symptoms (VMS) in 899 midlife women. Trials were conducted across five MsFLASH clinical sites between July 2009 and October 2012. We eliminated HFRDIS items based on experts' content validity ratings and confirmatory factor analysis, and evaluated cut-points and established MIDs by mapping HFRDIS and HFI to other measures. The three-item HFI (interference with sleep, mood, and concentration) demonstrated strong internal consistency (alphas of 0.830 and 0.856), showed good fit to the unidimensional "hot flash interference factor," and strong convergent validity with HFRDIS scores, diary VMS, and menopausal quality of life. For both scales, cut-points of mild (0-3.9), moderate (4-6.9), and severe (7-10) interference were associated with increasing diary VMS ratings, sleep, and anxiety. The average MID was 1.66 for the HFRDIS and 2.34 for the HFI. The HFI is a brief assessment of VMS interference and will be useful in busy clinics to standardize VMS assessment or in research studies where response burden may be an issue. The scale cut-points and MIDs should prove useful in targeting those most in need of treatment, monitoring treatment response, and interpreting existing and future research findings.

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.

Use of a levonorgestrel-containing intrauterine system with supplemental estrogen improves symptoms in perimenopausal women: a pilot study.

The aim of this study was to compare perimenopausal symptomatology using a levonorgestrel-containing intrauterine system (LNG-IUS) + low-dose transdermal estradiol (TDE) with LNG-IUS alone. The trial was a double-blind, randomized, controlled pilot trial. Regularly cycling women aged 38 to 52 years, with at least one self-reported symptom (hot flashes, bloating, headache, adverse mood, or poor sleep), were randomized to either LNG-IUS + low-dose TDE gel (intervention) or LNG-IUS alone (control). TDE was administered once daily as a 0.06% gel containing 0.75 mg of TDE for 50 days. LNG-IUS was placed at least 90 days before TDE or placebo gel treatment to assure stable circulating LNG. Participants completed the Center for Epidemiologic Studies Depression scale (CESD), Hot Flash Related Daily Interference scale (HFRDIS), Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) at the time of LNG-IUS placement, at 90 days (the time of randomization to TDE/placebo), and 140 days (end of study). TDE and placebo groups were compared using repeated-measures analysis of variance. Thirty-eight women aged 42.9 ± 2.7 years, with a mean BMI of 24.7 ± 3.3 kg/m², were enrolled; 20 were randomized to TDE. Women receiving TDE had significantly improved FSS scores between days 90 and 140 (mean difference TDE: -0.8 ± 1.2 vs placebo: 0.1 ± 0.7; P = 0.026) and borderline significant improvement in HFRDIS scores (mean difference TDE: -5.5 ± 15.3 vs placebo: 4.2 ± 13.1; P = 0.076). Women who reported hot flashes at baseline and who received TDE had a significant decrease in HFRDIS scores between days 90 and 140 (n = 9, P = 0.035). CESD and PSQI scores were not associated with TDE use. A brief, low-dose estrogen intervention, combined with a LNG-IUS, led to significant improvement of some common perimenopausal symptoms. Such a "minimalist" approach to management of the perimenopause holds promise for reducing common, bothersome perimenopausal symptoms while maintaining effective contraception.

Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause

Two phase 3, randomized, placebo-controlled trials demonstrated that low-dose paroxetine 7.5 mg reduced the frequency and severity of vasomotor symptoms (VMS) associated with menopause and had a favorable tolerability profile. The impact of paroxetine 7.5 mg on body weight and sexual function was evaluated in a pooled analysis. Postmenopausal women aged 40 years or older who had moderate to severe VMS were randomly assigned to receive paroxetine 7.5 mg or placebo once daily for 12 or 24 weeks. Assessments included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale score, Hot Flash-Related Daily Interference Scale sexuality subscore, and adverse events related to weight or sexual dysfunction. Pooled efficacy and safety populations comprised 1,174 and 1,175 participants, respectively. Baseline values were similar for median weight (∼75 kg), median BMI (∼28 kg/m), and the proportion of women with sexual dysfunction (∼58%). No clinically meaningful or statistically significant changes from baseline in weight or sexual function assessments occurred in the paroxetine 7.5 mg group. Small but statistically significant increases in weight and BMI were observed in the placebo group only on week 4. No significant difference between treatment groups was observed in the proportion of participants who had 7% or higher gain in body weight on week 4, 12, or 24. Rates of adverse events suggestive of sexual dysfunction were low and similar in both treatment groups. Paroxetine 7.5 mg does not cause weight gain or negative changes in libido when used to treat menopause-associated VMS in postmenopausal women.

Increased hot flash severity and related interference in perimenopausal human immunodeficiency virus–infected women

As women with human immunodeficiency virus (HIV) are living longer, more are entering perimenopause. Prior studies suggest that HIV-infected women are more likely to have hot flashes than non-HIV-infected women. However, little is known regarding hot flash severity and hot flash-related interference with daily function, mood, and quality of life in this population. Perimenopausal HIV-infected and non-HIV-infected women matched by age, race, and menstrual patterns completed the Menopause Rating Scale (to assess hot flash severity) and the Hot Flash Related Daily Interference Scale (HFRDIS). Menopause Rating Scale and HFRDIS scores and subscores were compared between the groups. Thirty-three HIV-infected women and 33 non-HIV-infected women who were similar in age (median [interquartile range], 47 [45-48] vs 47 [46-49] y), race (64% vs 52% nonwhite, P = 0.32), and menstrual patterns (number of periods in the past year; 5 [4-9] vs 6 [4-10], P = 0.53) were studied. Perimenopausal HIV-infected women reported greater hot flash severity (HIV vs non-HIV: 2 [1-3] vs 1 [0-3], P = 0.03) and hot flash-related interference (HFRDIS total score, 37 [10-60] vs 6 [0-20], P = 0.001). Perimenopausal HIV-infected women experience greater hot flash severity and related interference compared with non-HIV-infected perimenopausal women. Increased distress secondary to hot flashes may reduce quality of life and negatively impact important health-promoting behaviors, including adherence to antiretroviral therapy, in HIV-infected women.

Patient‐reported outcomes in women with breast cancer enrolled in a dual‐center, double‐blind, randomized controlled trial assessing the effect of acupuncture in reducing aromatase inhibitor‐induced musculoskeletal symptoms

Aromatase inhibitors (AIs) have been associated with decrements in patient-reported outcomes (PROs). The objective of this study was to assess whether real acupuncture (RA), compared with sham acupuncture (SA), improves PROs in patients with breast cancer who are receiving an adjuvant AI. Postmenopausal women with a stage 0 through III breast cancer who received an AI and had treatment-associated musculoskeletal symptoms were randomized to receive 8 weekly RA versus SA in a dual-center, randomized controlled trial. The National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal symptoms questionnaire, the Center for Epidemiological Studies Depression (CESD) scale, the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), the hot flash daily diary, the Hot Flash-Related Daily Interference Scale (HFRDI), and the European quality-of-life survey (EuroQol) were used to assess PROs at baseline and at 4weeks, 8 weeks, and 12 weeks. The intention-to-treat analysis included 23 patients in the RA arm and 24 patients in the SA arm. There were no significant differences in baseline characteristics between the 2 groups. Compared with baseline, scores in the RA arm improved significantly at week 8 on the CESD (P = .022), hot flash severity (P = .006), hot flash frequency (P = .011), the HFRDI (P = .014), and NSABP menopausal symptoms (P = .022); scores in the SA arm improved significantly on the EuroQol (P = .022),the HFRDI (P = .043), and NSABP menopausal symptoms (P = .005). Post-hoc analysis indicated that African American patients (n = 9) benefited more from RA than SA compared with non-African American patients (n = 38) in reducing hot flash severity (P < .001) and frequency (P < .001) scores. Both RA and SA were associated with improvement in PROs among patients with breast cancer who were receiving AIs, and no significant difference was detected between arms. Racial differences in response to acupuncture warrant further study.

Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study

ObjectivesTo compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a...

The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial

Hot flashes are common experience for menopausal women, and for many, are severe enough to significantly compromise their overall sense of well being and quality of life. The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. In a 6-week randomized clinical trial, a total of 56 menopausal women aged 45-59 years were participated in this study. The patients were asked for their hot flashes characteristics and responded to HFRDIS (hot flash related daily interference scale) questionnaire before and after the intervention. The participants were randomly assigned to take two capsules per day (totally 90 capsules for 6 weeks) of placebo or evening primrose (500 mg) for continuous 6 weeks. Then, the improvement in hot flashes was compared between two groups. The percent of improvement in hot flash frequency, severity and duration were 39, 42 and 19 %, in evening primrose group compared with 32, 32 and 18 % in placebo group, respectively. Although all three characters of hot flash was ameliorated in evening primrose arm, only its severity was significantly better in this arm compared with placebo group (P < 0.05). All HFRDIS score were significantly improved in two groups, but the percentage of improvement in social activities, relations with others, and sexuality was significantly superior to placebo group (P < 0.05). The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks as well as ameliorating the HFRDIS score.

Duloxetine for major depressive disorder and daytime and nighttime hot flashes associated with the menopausal transition

BackgroundWe sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety. MethodsAfter a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n=19) received eight weeks of open-label treatment with duloxetine (60mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7). ResultsOf 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for ≥1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14–18), and 6.5 (IQR 4–11.5), respectively, reflecting a significant decrease (p=.0006). The response and remission rates were 56.3% (all responders were also remitters, having ≥50% decrease in HAM-D scores and final scores ≤7). Anxiety improved with treatment (p=.012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p=.009 and p=.008, respectively). Daytime but not nighttime hot flashes improved significantly. ConclusionsThese data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition.

Efficacy of a Non-Hormonal Treatment, BRN-01, on Menopausal Hot Flashes

BackgroundHomeopathic medicines have a place among the non-hormonal therapies for the treatment of hot flashes during the menopause.ObjectiveThe objective of this study was to evaluate the efficacy of the non-hormonal treatment BRN-01 in reducing hot flashes in menopausal women.Study DesignThis was a multicenter, randomized, double-blind, placebo-controlled study carried out between June 2010 and July 2011.SettingThe study was conducted in 35 active centers in France (gynecologists in private practice).PatientsOne hundred and eight menopausal women, ≥50 years of age, were enrolled in the study. The eligibility criteria included menopause for <24 months and ≥5 hot flashes per day with a significant negative effect on the women’s professional and/or personal life.InterventionTreatment was either BRN-01 tablets, a registered homeopathic medicine containing Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH), or identical placebo tablets, prepared by Laboratoires Boiron according to European Pharmacopoeia standards. Oral treatment (2 to 4 tablets per day) was started on day 3 after study enrollment and was continued for 12 weeks.Main Outcome MeasureThe main outcome measure was the hot flash score (HFS) compared before, during, and after treatment. Secondary outcome criteria were the quality of life (QoL) [measured using the Hot Flash Related Daily Interference Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating Scale), evolution of the mean dosage, and compliance. All adverse events (AEs) were recorded.ResultsOne hundred and one women were included in the final analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted for baseline values, was significantly lower in the BRN-01 group than in the placebo group (mean ± SD 88.2 ± 6.5 versus 107.2 ± 6.4; p = 0.0411). BRN-01 was well tolerated; the frequency of AEs was similar in the two treatment groups, and no serious AEs were attributable to BRN-01.ConclusionBRN-01 seemed to have a significant effect on the HFS, compared with placebo. According to the results of this clinical trial, BRN-01 may be considered a new therapeutic option with a safe profile for hot flashes in menopausal women who do not want or are not able to take hormone replacement therapy or other recognized treatments for this indication.Trial registration number (EudraCT): 2009-016959–21.