Hot Flash-Related Daily Interference Research Articles

The Effects of Diaphragmatic Breathing Exercise on Hot Flashes in Menopausal Women during the COVID-19 Pandemic Period:

Vasomotor symptoms are the most common problem during the menopausal period. This study investigated the effects of diaphragmatic breathing exercises on hot flashes in menopausal Turkish women during the COVID-19 pandemic period. The study was carried out as a randomized controlled trial with the participation of menopausal women aged 45-60 years in eastern Turkey. A total of 68 women formed two groups, 34 in each group. A Descriptive Characteristics Form and the Hot Flash-Related Daily Interference Scale were used to collect study data.The results of the study showed that the menopause period in most women was between one and five years. The participants stated that the COVID-19 pandemic period increased the frequency of their menopausal hot flashes to a statistically significant extent. While there was a statistically significant difference (p0.05).The diaphragmatic breathing exercises in this study were found to reduce hot flashes complaints during the menopausal period.

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 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.

Effects of forehead cooling and supportive care on menopause-related sleep difficulties, hot flashes and menopausal symptoms: a pilot study

ABSTRACT Objective/Background This pilot study explored the efficacy of a novel forehead cooling device for perceived sleep difficulties and hot flashes in menopausal-age women. Participants 20 women (55.1 ± 4.2 years; 19 post-menopausal) with insomnia symptoms and self-reported two or more hot flashes per day. Methods Participants completed daily assessments of sleep and hot flashes (via diaries) across 1 baseline week and 4 weeks of open-label, in-home, nightly treatment with a forehead cooling device (15–18°C) along with sleep hygiene instructions. They also completed ratings of insomnia and menopausal symptoms using standardized questionnaires. Results Women reported reductions in sleep onset latency (SOL), wakefulness after sleep onset (WASO), and nocturnal hot flash severity during the first week of treatment (SOL: 25.7 ± 18.4 min; WASO: 36.3 ± 27.3 min; hot flash severity: 3.0 ± 2.8) compared with baseline (SOL: 38 ± 26.3 min; WASO: 52.2 ± 35.6 min; hot flash severity: 6.8 ± 3.7), with further improvements after 2–4 weeks of use (p < .001). There were also clinically meaningful reductions in insomnia severity and hot flash-related daily interference and lower psychological and physical symptom scores on the Greene climacteric scale after treatment (all p’s<0.001). Conclusions This exploratory, naturalistic, pilot study shows that nightly use of a forehead cooling device produces improvements in self-reported sleep and reductions in insomnia, hot flash, and other menopausal, symptoms. Controlled studies are warranted to determine the role of this therapy in the management of sleep difficulties and menopausal symptoms in women. Further mechanistic studies are needed to understand the physiological impact of forehead cooling on sleep and menopausal symptoms.

0482 A Preliminary Study on the Efficacy of Forehead-Cooling for Relieving Menopausal Sleep Difficulties and Hot Flashes

Abstract Introduction Many women experience sleep difficulties in the approach to menopause and post-menopause, with about 25% experiencing severe symptoms that impact daytime functioning and quality of life. Hot flashes contribute to these sleep difficulties, being associated with nocturnal awakenings, poorer sleep quality, and chronic insomnia. New non-pharmacological sleep solutions have become available, including a forehead cooling device designed to target elevated brain metabolism in insomnia sufferers. Here, we explored whether this device was effective in improving subjective sleep and hot flashes in menopausal-age women with insomnia symptoms. Methods This study was an open-label, in-home investigation of the efficacy of nightly treatment with a forehead cooling device in 20 women (55.1 ± 4.2 years) with insomnia symptoms and daily hot flashes. Participants completed daily diaries assessing sleep quality and hot flashes across a baseline week (no treatment) followed by 4 weeks of treatment. They also completed questionnaires before and after treatment including the insomnia severity index and the hot flash related daily interference scale. Results Women reported better sleep quality with a shorter sleep onset latency and fewer awakenings (between 14-30% improvement) during the first week of device use, with further improvements over time, relative to baseline (p &amp;lt;0.001). Women also reported fewer nocturnal hot flashes that were less severe during treatment (p&amp;lt;0.001). They had lower insomnia severity scores post-treatment (9.3±5.8) compared to pre-treatment (20.0±5.7) (p&amp;lt;0.001), with 17 participants showing a reduction of 6 points or greater on the insomnia severity index. There was also a significant reduction in hot flash related daily interference post-treatment (p&amp;lt;0.001). Conclusion Use of a forehead cooling device during the night improved subjective sleep quality and reduced insomnia symptoms and hot flash frequency and severity in this preliminary study of menopausal-age women. Further large scale randomized controlled trials are required to determine efficacy. Support Ebb Therapeutics

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.

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.

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.

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.

Clinical hypnosis in the treatment of postmenopausal hot flashes

The use of estrogen and progesterone to manage vasomotor symptoms (ie, hot flashes and night sweats) has declined because of concerns about their risks, and there is an increased interest in alternate, effective, and low-risk treatments. This study reports the results of a randomized controlled trial of clinical hypnosis for treating vasomotor symptoms among postmenopausal women. This is a randomized, single-blind, controlled, clinical trial involving 187 postmenopausal women reporting a minimum of seven hot flashes per day (or at least 50 hot flashes a week) at baseline between December 2008 and April 2012. Eligible participants received five weekly sessions of either clinical hypnosis or structured-attention control. Primary outcomes were hot flash frequency (subjectively and physiologically recorded) and hot flash score assessed by daily diaries on weeks 2 to 6 and week 12. Secondary outcomes included measures of hot flash-related daily interference, sleep quality, and treatment satisfaction. In a modified intent-to-treat analysis that included all randomized participants who provided data, reported subjective hot flash frequency from baseline to week 12 showed a mean reduction of 55.82 (74.16%) hot flashes for the clinical hypnosis intervention versus a mean reduction of 12.89 (17.13%) hot flashes for controls (P < 0.001; 95% CI, 36.15-49.67). The mean reduction in hot flash score was 18.83 (80.32%) for the clinical hypnosis intervention as compared with 3.53 (15.38%) for controls (P < 0.001; 95% CI, 12.60-17.54). At 12-week follow-up, the mean reduction in physiologically monitored hot flashes was 5.92 (56.86%) for clinical hypnosis and 0.88 (9.94%) for controls (P < 0.001; 95% CI, 2.00-5.46). Secondary outcomes were significantly improved compared with controls at 12-week follow-up: hot flash-related interference (P < 0.001; 95% CI, 2.74-4.02), sleep quality (P < 0.001; 95% CI, 3.65-5.84), and treatment satisfaction (P < 0.001; 95% CI, 7.79-8.59). Compared with structured-attention control, clinical hypnosis results in significant reductions in self-reported and physiologically measured hot flashes and hot flash scores in postmenopausal women.

A Pilot, 8-Week, Placebo Lead-In Trial of Quetiapine Extended Release for Depression in Midlife Women

Perimenopausal and early postmenopausal women have shown an increased risk for developing depression (new onset or recurrent); concomitant vasomotor and other menopause-related complaints significantly affect quality of life and overall functioning. This study examined the effects of quetiapine extended release (XR) in midlife women with major depressive disorder who also reported significant menopause-related symptoms. Forty eligible women with major depressive disorder entered a 2-week, placebo lead-in phase, followed by an 8-week open trial with quetiapine XR, flexible dose, 150-300 mg/d. The primary outcome measure (depressive symptoms) was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Other measures included menopause symptoms (Greene Climacteric Scale total scores and subscores) and the impact of hot flashes on functioning (Hot Flash-Related Daily Interference Scale). Weight, cholesterol, triglycerides, and glucose levels were monitored. Data from 24 subjects (modified intent-to-treat, last observation carried forward; quetiapine XR mean dose, 191 [SD, 55] mg/d) showed improvement in depressive and menopause-related symptoms, that is, reduction in MADRS, GCS, and Hot Flash-Related Daily Interference Scale scores (P < 0.01 for all comparisons). Seventeen subjects were considered responders (>50% reduction in MADRS scores); 15 achieved remission (MADRS<10). Main adverse effects included drowsiness and dry mouth. Based on these preliminary results, quetiapine XR should be further examined in larger, controlled trials for the management of depressed, symptomatic midlife women.

A comparative study of menopausal hot flashes and their psychosocial correlates in Taiwan and the United States

Objective To compare the frequency, severity, and interference of menopause-related hot flashes and their psychosocial correlates in Taiwanese and U.S. women. Study design Cross-sectional study, using a convenience sample of 101 Taiwanese and 121 U.S. midlife women. Main outcome measures Hot-flash measures, including frequency, severity (Women's Health Initiative Symptom Scale), hot flash related daily interference; and psychosocial measures: Attitudes toward Menopause and Aging Scale, Coping Strategies Questionnaire, Sense of Coherence Questionnaire, Center for Epidemiological Studies-Depression Scale, Spielberger State-Trait Anxiety Inventory, and State-Trait Anger Scale. Results Using ANCOVA with demographic variables as covariates, U.S. women reported greater frequency and daily interference from hot flashes compared with Taiwanese women. Greater depression, greater catastrophizing about hot flashes, lower sense of coherence, lower state/trait anger, and more positive attitudes toward aging were reported in the U.S. cohort. The groups were similar in their frequency of specific coping strategies, and they did not differ significantly in menopause symptom severity, attitudes towards menopause, state/trait anxiety, or overall negative psychosocial characteristics. Hierarchical multiple regression analyses indicated that hot-flash related daily interference was predicted by marital status, frequency of hot flashes, and negative psychosocial characteristics among the U.S. women; and by frequency of hot flashes and negative psychosocial characteristics among the Taiwanese women. Conclusions Despite differences in the frequency and daily interference from hot flashes in the two samples, the predictors of interference were similar. Results highlight the importance of considering both psychosocial factors and cultural differences in providing guidance and treatment for women experiencing menopause-related hot flashes.

P01-292 Midlife women with major depressive disorder: Effects of quetiapine extended-release on mood, sleep and menopause-related symptoms

Background:Recent studies suggest that the menopausal transition may constitute a period of greater risk for the development of new onset/recurrent depressive episodes. In addition, the presence of vasomotor and other menopause-related complaints may adversely affect quality of life and overall functioning. With the long-term safety of hormone therapies being questioned, non-hormonal strategies are needed for the management of symptomatic midlife women. This report is a preliminary analysis of a study investigating the effects of quetiapine extended-release (Seroquel XR) in symptomatic perimenopausal and postmenopausal women with major depressive disorder (MDD).Methods:Peri and postmenopausal women, age 40 to 60 years, suffering from MDD and reporting menopause-related symptoms were recruited into a 2-week, placebo lead-in phase, followed by an open trial (8 weeks) with quetiapine extended-release, flexible dose, 150-300 mg/day. The primary outcome measure (i.e. changes in depressive symptoms) was assessed via Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Other measures included: Hamilton Depression Rating Scale (HAM-D), menopause-related symptoms (Greene Climacteric Scale - GCS), Clinical Global Impression (CGI-S), sleep characteristics (Pittsburgh Sleep Quality Index - PSQI) and the impact of hot flashes on daily functioning (Hot Flash-Related Daily Interference Scale (HFRDIS).Results:Thirty-nine women (mean age 49.3±4.3 years) were enrolled in the placebo lead-in phase. Of those, 25 were considered eligible for the 8-week trial with quetiapine extended-release. This interim analysis (LOCF) included 18 women who completed 4 to 8 weeks of treatment with quetiapine extended-release (median MADRS total scores at baseline = 28 ±6.1; median final dose of quetiapine extended-release=200 mg/day). At the end of the study, 13 out of 18 (72.2%) participants achieved remission (total MADRS scores &lt; 10). Overall, subjects showed significant reduction in total MADRS (p&lt; 0.001) and HAM-D scores (p&lt; 0.001). Treatment with quetiapine extended-release improved menopause-related symptoms, as shown by a decrease in Greene Climacteric Scale total scores (p&lt; 0.001) and sub-scores for psychological (p&lt; 0.001), vasomotor (p=0.001), and somatic (p=0.001) complaints (Wilcoxon tests). Quetiapine extended-release did affect menopause-related sexual dysfunction (changes in CGS sexual sub-scores, p=0.06). There was a substantial reduction in overall burden associated with vasomotor symptoms, i.e., decreased HFRDIS scores (p&lt; 0.001). Lastly, sleep efficiency, perceived sleep quality, and daily sleep disturbances improved significantly after treatment with quetiapine extended-release (p&lt; 0.001 for all PSQI sub-scores).Discussion:This is the first study examining the efficacy of Seroquel XR for the treatment of Major Depressive Disorder in a population of symptomatic peri and postmenopausal women. Treatment with Seroquel XR not only reduced depressive symptomatology but also improved vasomotor symptoms and sleep complaints. Larger randomized, placebo-controlled studies are warranted to better explore the efficacy and predictors of response with quetiapine extended-release for this specific population.