Hot Flashes Research Articles

Evaluation of the Usefulness of Byakkokaninjinto for Hot Flushes Caused by Rosacea

Evaluation of the Usefulness of Byakkokaninjinto for Hot Flushes Caused by Rosacea

КЛИНИЧЕСКАЯ ЭФФЕКТИВНОСТЬ НЕГОРМОНАЛЬНЫХ МЕТОДОВ ТЕРАПИИ ПАТАЛОГИЧЕСКОГО КЛИМАКТЕРИЧЕСКОГО СИНДРОМА У ЖЕНЩИН

The purpose of the study is to study the clinical effectiveness of the dietary supplement "Menophen" in comparison with β-alanine in the treatment of menopausal symptoms in women in the perimenopausal, menopausal and postmenopausal periods. Menopausal syndrome is a complex of vegetative-vascular, psycho-emotional, metabolic-endocrine, vaginal, sexual and other disorders. According to domestic authors, vasomotor disorders such as hot flashes, lability of blood pressure and pulse, increased sweating, chills, which significantly reduce the quality of life of patients and disrupt the circadian sleep-wake rhythm, come to the fore. Today, menopausal women continue to work actively, but hot flashes and sleep disturbances significantly reduce their level of performance and increase the number of absences from sick leave by 82%, compared to women without hot flashes. At the same time, 87.5% of women refuse to use and prescribe MHT, expressing doubts about the safety of their use; the main fears of patients are weight gain and the development of oncological pathology. Treatment with the dietary supplement Menofen leads to a decrease in the number and severity of psycho-emotional, metabolic-endocrine and neurovegetative disorders in menopausal women.

Estimation of Subfatin, Fetuin-A and other Parameters in Obese Menopause Women

Background: Menopause is an aging in women, it begins in most of them at 45 years old, the main reason of menopause is the decline of the Estrogen result from decline of ovaries function, it’s include many of symptoms such as nocturnal sweats, hot flashes, depression, elevated of anxiety, insomnia, sleep disturbance, genitalia include inflammation, dryness, urinary tract infections, painful urination, gaining weight, usually in the abdomen, hips and joint pain. Menopause leads to many disease include insulin resistance, atherosclerosis, chronic hearts disease, obesity, osteoporosis. The adipose tissue it's secretes active proteins such as subfatin which is adipocytokines regulates food intake. Fetuin-A is adipokines and hepatokiens that generated mainly by liver it serves to act as carrier of free fatty acid in circulation. Materials& Methods: Ninety women ages (50-65) participated in the study. (45) non-obese menopausal women with BMI (22.08±3.39) Kg/m2 as a control group. (45) obese women in the menopause with a BMI (35.38±2.52) Kg/m2 as the second group. أعلى النموذجResults: The results showed that there was a significant decrease at (P≤ 0.01) in the level of Subfatin and increase at (P≤ 0.01) in Fetuin-A in the second group compared to the control group. Conclusion: This study found significant negative correlation between Subfatin and lipid profile and significant positive correlation between Fetuin-A and lipid profile.

Beyond the Hot Flashes: Exploring the Holistic Approaches to Menopause Management – A Review

Beyond the Hot Flashes: Exploring the Holistic Approaches to Menopause Management – A Review

Managing Menopause: The Evolving Role of Estrogens, Selective Serotonin Reuptake Inhibitors, and Phytoestrogens in Balancing Hormonal Fluctuations.

Menopause is characterized by the cessation of menstruation for 12 consecutive months. In this narrative review, we describe the transitional stages of menopause, clinical presentation, pharmacological management of symptoms, and effects on fluctuating hormone levels. To standardize the stages of menopause, the Stages of Reproductive Aging Workshop + 10 (STRAW+10) system was designed with five distinct categories corresponding to symptom presentation and numerical years. Common clinical presentations consist of vasomotor hot flashes, mood changes, decreased libido, osteoporosis, and genitourinary changes, all of which are associated with changes in hormone levels.Because hormones play a major role in the mechanism of menopause, hormone replacement therapy with estrogen, progesterone, or a combination is explored and shown to demonstrate symptom reduction in a large percentage of women. Nonhormonal treatment and alternative therapies are used to treat vasomotor symptoms if contraindications present to hormone therapy or for those who prefer fewer side effects. Thus, many women experience uncomfortable symptoms during menopause, some of which cause significant changes in quality of life. In this regard, understanding the pathophysiology, symptomatology, and current treatment options with side effect profiles allows for continued research and discovery of advanced therapy for treating symptoms to ameliorate discomfort and pain in menopausal women.

Styphnolobium japonicum Fruit and Germinated Soybean Embryo Complex Extract for Postmenopausal-Symptom Relief.

Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms. A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF-GSE complex extract at ratios of 1:1, 1:2, and 2:1. Treatment with the SJF-GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48-72 mg/g sophoricoside and 8-12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles. The SJF-GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause.

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.

Homoeopathic Management of Menopause: A Comprehensive Review

Background: Menopause signifies a crucial physiological shift in a woman's journey, denoting the halt of menstrual cycles caused by the gradual decline in ovarian activity. Conventional management options, such as Hormone Replacement Therapy (HRT), are effective but not devoid of risks and limitations. In contrast, homeopathy offers a holistic approach to symptom management, aiming to address the underlying cause of menopausal disturbances. Aim and Objective: By critically analyzing clinical studies, randomized controlled trials, and observational research, this paper seeks to elucidate the role of homeopathy as an alternative and complementary therapy for menopause. The objective is to provide insights into the potential benefits of homeopathy and contribute to the growing body of evidence supporting its use in menopausal care. Methodology: A comprehensive search strategy was done to identify relevant literatures from databases such as PubMed, SCOPUS, and Google Scholar. The selection of eligible studies was conducted according to predefined criteria for inclusion and exclusion. Results: Our findings resulted into nine studies that fulfilled the inclusion criteria, including randomized controlled trials, observational studies, and clinical trials. These studies collectively provided evidence of the efficacy of homeopathic medicines in managing various menopausal symptoms, including hot flushes, mood swings, and sleep disturbances. Conclusion: The reviewed literature suggests that homeopathy offers a promising avenue for managing menopausal symptoms, providing an alternative or complimentary approach to conventional therapies. Individualized treatment strategies tailored to each woman's unique symptomatology appear particularly beneficial. However, further clinical trials are needed to fully elucidate the efficacy and mechanisms of action of homeopathic interventions in menopausal care.

Population pharmacokinetic-pharmacodynamic model of elinzanetant based on integrated clinical phase I and II data.

Elinzanetant is a potent and selective dual neurokin-1 (NK-1) and -3 (NK-3) receptor antagonist that is currently developed for the treatment of women with moderate-to-severe vasomotor symptoms (VMS) associated with menopause. Here, we report the development of a population pharmacokinetic (popPK) model for elinzanetant and its principal metabolites based on an integrated dataset from 366 subjects (including 197 women with VMS) collected in 10 phase I or II studies. The pharmacokinetics of elinzanetant and its metabolites could be well described by the popPK model. Within the investigated dose range of 40-160 mg, the oral bioavailability of elinzanetant was dose independent and estimated to be 36.7%. The clearance of elinzanetant was estimated to be 7.26 L/h and the central and peripheral distribution volume were 23.7 and 168 L. No intrinsic or extrinsic influencing factors have been identified in the investigated population other than the effect of a high-fat breakfast on the oral absorption of elinzanetant. The popPK model was then coupled to a pharmacodynamic model to predict occupancies of the NK-1 and NK-3 receptors. After repeated once-daily administration of the anticipated therapeutic dose of 120 mg elinzanetant, the model-predicted median receptor occupancies are >99% for NK-1 and >94.8% for NK-3 during day and night-time, indicating sustained and near-complete inhibition of both target receptors during the dosing interval.

Association of Climacteric and Vasomotor Symptoms With Quality of Life in Postmenopausal Women

Background: Menopause is associated with various symptoms, including climacteric and vasomotor symptoms, which may impact the quality of life in postmenopausal women.Objective: The study aimed to determine the association between climacteric and vasomotor symptoms with quality of life in postmenopausal women, and to explore the influence of BMI and the number of children on this relationship.Methods: This cross-sectional analytical study included 368 postmenopausal women aged 40-55 years, selected through non-probability convenient sampling from DHQ Hospital Mianwali. Data were collected using the Menopause Rating Scale (MRS), Hot Flash Related Interference Scale (HFRDIS), and Menopause-Specific Quality of Life (MENQOL) questionnaire. Descriptive statistics and Pearson’s correlation were used for analysis via SPSS version 25, with statistical significance set at p < 0.05.Results: The study found no significant correlation between climacteric symptoms and quality of life (r = 0.076, p = 0.148) or vasomotor symptoms and quality of life (r = -0.28, p = 0.591). However, a significant negative correlation was observed between BMI and quality of life (r = -1.70, p = 0.001), and the number of children and quality of life (r = -0.102, p = 0.05).Conclusion: Climacteric and vasomotor symptoms were not associated with quality of life, but higher BMI and more children negatively impacted quality of life in postmenopausal women.

Menopausal symptoms and utilization of menopausal hormone therapy among women aged 40–60 years in Addis Ababa, Ethiopia: a cross-sectional study

BackgroundThe onset of menopause leads to diminished estrogen exposure, resulting in a high morbidity burden related to menopausal symptoms. Menopausal hormonal therapy is an effective therapy that offers more advantages than disadvantages for women aged less than 60 years or who have had menopause for less than 10 years.ObjectiveThis study aimed to assess the prevalence of menopausal symptoms, identify factors associated with menopausal symptoms, and assess the use of menopausal hormone therapy among women aged 40–60 who visited the gynecological clinics of three hospitals in Addis Ababa, Ethiopia.MethodsA facility-based cross-sectional study was conducted from January 2022 to June 2022 at Gandhi Memorial Hospital, Tikur Anbessa Hospital, and Zewditu Memorial Hospital on 296 middle-aged women. Data were collected using an interviewer-administered structured questionnaire and analyzed for sociodemographic factors, utilization of menopausal hormone therapy, and prevalence of menopausal symptoms using the menopause rating scale. Data were analyzed using SPSS version 25. Bivariate and multivariate logistic regression analyses were performed to identify independent predictors of each subscale of menopausal symptoms. The strength of the association was measured using odds ratios with 95% confidence intervals, and statistical significance was set at a value of P < 0.05.ResultThe prevalence of menopausal symptoms was 89.9%. According to the menopausal rating scale, the frequency of reported symptoms was hot flushes (54.7%), muscle and joint pain (32.1%) on the somatic subscale; physical and mental exhaustion (55.1%), irritability (48.6%) on psychological subscale; and sexual problems (41.3%), bladder problems (39.2%) on urogenital subscale. This study also showed that the age of women [aOR: 0.317, 95%CI (0.102, 0.990)], and monthly family income [aOR = 0.182, 95% CI (0.041, 0.912)] were significantly associated with somatic menopausal symptoms. There was no utilization of menopausal hormonal therapy to treat menopausal symptoms and to prevent complications.ConclusionThe prevalence of menopausal symptoms is high; however, the utilization of individualized administration of menopausal hormone therapy according to symptoms is negligible. It appears essential for these institutions to work on service availability and delivery of menopausal hormone therapy for those in need of wider benefits for their clients.

A 2-year follow-up to a randomized controlled trial on resistance training in postmenopausal women: vasomotor symptoms, quality of life and cardiovascular risk markers

BackgroundMost women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women.MethodsThis observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT.ResultsAlthough all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p < 0.001 and p = 0.006, respectively) regarding MS-VMS. The IG maintained a significantly lower MS-VMS frequency than the CG at the 6-month follow-up. At the 2-year follow-up, there was no significant difference between the original RCT groups. No significant changes over time or differences between groups were found in HRQoL or cardiovascular risk markers. However, significant interactions between original RCT groups and time were found for visceral adipose tissue (p = 0.041), ferritin (p = 0.045), and testosterone (p = 0.010).ConclusionsA 15-week resistance training intervention reduced MS-VMS frequency up to six months post-intervention compared to a CG, but the effect was not maintained after two years. The RTI did neither contribute to preserved improvements of cardiovascular risk markers nor improved HRQoL after two years compared to a CG.Trial registrationClinical trials.gov registered ID: NCT01987778, trial registration date 2013–11-19.

Survey of patient experience and management of vasomotor symptoms due to menopause from the PatientsLikeMe community.

This study aimed to describe menopause and treatment experiences of women with vasomotor symptoms due to menopause in the United States. A cross-sectional survey was administered to women 40-65 years of age recruited from PatientsLikeMe, a dedicated online platform for patients. A total of 196 women (mean age 55.7 years; 81.2% White) completed the survey and were included in the analyses. The majority (87.2%) reported experiencing bothersome symptoms; 54.3% (100/184) had daytime hot flashes, and 59.2% (109/184) had nighttime sweats and hot flashes, up to 5 times per day on average. Mean postmenopause duration was 10.8 years. Although most (68.5%, 126/184) reported having vasomotor symptoms for less than 5 years, some (14.1%, 26/184) had symptoms for more than a decade. Only 35.2% (69/196) were treated for their symptoms; the most frequently reported prescription treatment was hormone therapy (58%; 40/69), which was administered for less than 3 years in most cases (67.5%, 27/40). Although women were generally satisfied with their interactions with healthcare providers, 23.0% reported inadequate support. Sleep, personal relationships, and physical, emotional, and mental well-being were the most affected by vasomotor symptoms. Healthcare professionals with training in women's health were the most valued resource for dealing with the symptoms associated with menopause. Not all women with symptoms were treated. In those whose concerns were addressed by providers, a reluctance to pursue treatment was still observed. A need persists to ensure that this population has the resources and support needed to effectively manage symptoms.

Mental disorders of the depressive and anxiety spectrum in neuroendocrine tumors: prevalence, pathogenesis, clinical particulars

Neuroendocrine tumors (NETs) are a heterogeneous group of slowly progressing tumors from neuroendocrine cells able to secrete biologically active substances. The most striking clinical manifestation of functioning NETs is the carcinoid syndrome, which is caused by serotonin overproduction and is most often associated with hot flashes, diarrhea, and abdominal pain. The prevalence of depressive and anxiety spectrum disorders in NETs patients can amount to 30–50%. The development of depressive and anxiety spectrum disorders in NETs can occur both through a nosogenic mechanism facilitated by a long pre-diagnostic stage, the presence of a serious disease with severe somatic symptoms and resulting significant decrease in quality of life. The mental disorders may be a result of somatogenic factors, which include an imbalance of significant mediators in the central nervous system (in particular, serotonin), as well as chronic inflammation and abnormalities of the body's immune defense. In the treatment of patients with NETs and verified anxiety and depressive disorders, special attention is paid to the safety of prescribing the first-line therapy, the selective serotonin reuptake inhibitors. The side effects of these agents are related to the activity of serotonin receptor agonists in the gut, which results in diarrhea and increased gastrointestinal motility, the symptoms similar to the carcinoid syndrome manifestations. The accumulated evidence allows concluding on the relative safety of serotoninergic antidepressants in NETs patients, but does not exclude some groups of patients with an increased risk of complications related to an additional effect on serotonin metabolism. Current knowledge on the prevalence, pathogenesis and treatment of depressive and anxiety spectrum disorders, comorbid to NETs, are limited and contradictory. Therefore, further studies with a larger patient samples are required to identify key factors of the pathophysiology and manifestation of mental disorders in NETs patients, which would generally facilitate the optimization of their treatment.

Effectiveness of Commercial Red Clover (Trifolium pratense L.) Products for the Treatment of Symptoms in Menopausal Women—A Narrative Review

Red clover (Trifolium pratense L.) is found in southeast Europe and Anatolia. Its primary traditional medicinal use includes the treatment of various conditions of the upper respiratory tract. In recent years, its isoflavones have become the focus of research aimed at developing treatments to alleviate menopausal symptoms. Reduced levels of circulating estrogen due to reduced ovarian function can cause short-term symptoms such as hot flashes, palpitations, difficulty sleeping, headaches, fatigue, mood disorders and reduced concentration but also long-term chronic conditions, such as cardiovascular disease, accelerated weight and bone mass loss, atrophic vaginitis, osteoporosis, and cognitive impairment. The aim of this narrative review was to analyze the effects of commercially available and standardized red clover extracts on menopausal women. Eight randomized controlled trials on a total of 8769 menopausal women (aged 40 to 65 years) evaluated the effect of red clover isoflavone extract on menopausal symptoms. In all studies, isoflavone extract treatment showed improvement in all menopausal symptoms, including some common comorbidities, namely, hot flashes (1487 women, 25%), blood lipids (1155 women, 19%), atherosclerosis (6938 women, 79%), risk of breast cancer and endometrial cancer (428 women, 5%), osteoporosis and osteopenia (555 women, 6%), and menopause-related cognitive impairment (3530 women, 40%).

Brown Adipose Tissue Activity and Childhood Exposure to Cold Are Associated With Hot Flashes at Menopause.

Hot flashes (HFs) are experienced as sudden sensations of heat. We hypothesized that brown adipose tissue (BAT) activation could increase the likelihood of HFs in winter. The aim of this study was to test whether women with more BAT activity were more likely to experience self-reported or biometrically measured HFs. Women aged 45-55 years (n = 270) participated in face-to-face interviews and anthropometric and ambulatory measures. Level of BAT activity was estimated from the difference in supraclavicular skin temperature measured by infrared thermography before and after cooling. Logistic regressions were applied to examine whether bothersome HFs (yes/no) during the past 2 weeks were associated with BAT activity, adjusting for menopausal status, childhood exposure to cold, waist/hip ratio, and self-reported health. Linear regressions were used to examine the frequency of self-reported and biometrically measured HFs during the study period and BAT activity, adjusting for potential confounders. Menopausal status, childhood exposure to cold, waist-to-hip ratio (WHR), and self-reported health were associated with both BAT activity and HFs. After adjusting for potential confounders, an increase in BAT activity almost tripled the likelihood of bothersome HFs (OR 2.84, 95% CI 1.26-6.43). In linear regressions, BAT activity was not associated with frequency of subjective or objective HFs during the study period, but childhood exposure to cold was associated with subjective HF report (β = 0.163, p = 0.010). To our knowledge, this is the first study of BAT activation and HFs. Our results support a role for BAT activity in HF experience. Therefore, we encourage further examination of the role of BAT, as well as childhood exposure to cold, in HFs.

Strategies for coping with postmenopausal health problems among women in Egbu Community Owerri North Imo State

This study explores the strategies used by postmenopausal women in Egbu Community, Owerri North, Imo State, Nigeria, to cope with health problems associated with menopause. Menopause, a significant life stage, is often accompanied by various physical, emotional, and mental health challenges, such as hot flashes, painful sexual intercourse, depression, and memory loss. These challenges are exacerbated by socio-cultural factors, limited healthcare infrastructure, and a lack of awareness and education about menopause, particularly in rural communities like Egbu. The study adopts a descriptive cross-sectional design and utilizes a self-structured questionnaire to collect data from 150 postmenopausal women. The findings reveal that the most common physical problem is painful sexual intercourse, while mental depression is the predominant emotional and mental issue. Coping strategies employed by these women include engaging in moderate exercise, seeking medical advice, and maintaining adequate rest and sleep. However, poor education, lifestyle factors, and religious beliefs significantly influence the effectiveness of these coping strategies.The study concludes that while some coping strategies are effective, there is a need for targeted interventions to improve awareness, education, and access to healthcare services. These interventions should be culturally sensitive and designed to empower women, enhance their quality of life, and reduce the stigma surrounding menopause. The study's findings are crucial for informing community health planning and policy development to better support postmenopausal women in rural areas.

Treatment satisfaction, unmet needs, and new treatment expectations for vasomotor symptoms due to menopause: women's and physicians' opinions.

To assess treatment satisfaction, unmet treatment needs, and new vasomotor symptom (VMS) treatment expectations among women with moderate to severe VMS and physicians treating women with VMS. This noninterventional, nonrandomized survey included qualitative interviews and quantitative surveys of women and physicians in the US. Participating women had moderate to severe VMS in the past year and received ≥1 hormone therapy (HT), non-HT, or over-the-counter (OTC) treatment for VMS in the past 3 months. Participating physicians were obstetrician-gynecologists (OB-GYNs) and primary care physicians (PCPs) who treated ≥15 women with VMS in the past 3 months. Two online survey questionnaires were developed using insights from literature, qualitative interviews, and clinical experts. Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) measured treatment satisfaction. Results were summarized descriptively. Questionnaires were completed by 401 women with VMS and 207 physicians treating VMS. Among women, mean total MS-TSQ score ranges were 62.8-67.3 for HT, 59.8-69.7 for non-HT, and 58.0-64.9 for OTC treatments. Among physicians, mean total MS-TSQ scores were considerably higher for HT than for non-HT and OTC treatments (HT: 73.4-75.6; non-HT: 55.6-62.1; OTC: 49.2-54.7). Women reported "lack of effectiveness" (41.2%), and physicians reported "long-term safety concerns" (56.5%) as main features that do not meet their current treatment expectations. The majority of women and physicians would consider trying a new non-HT treatment for VMS (75.8 and 75.9%, respectively). Treatment satisfaction and new treatment expectations were similar but with some differences between women and physicians; the need for additional treatments for VMS was identified.

Biopsychosocial factors intersecting with weekly sleep difficulties in the menopause transition

ObjectivesSleep difficulties are common in the menopause transition and increase risk for a variety of physical and psychological problems. The current study investigated potential interactions between psychosocial variables and within-person changes in ovarian hormones in predicting perimenopausal sleep problems as well as the potential interactions between poor sleep and psychosocial factors in predicting worsened mood, affect, and attention. Study designThe sample included 101 perimenopausal individuals. Participants completed 12 weekly assessments of self-reported sleep outcomes, depressive mood and affect, and attention function, and of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) levels (urinary metabolites of estradiol and progesterone, respectively); they also had 24-h tracking of vasomotor symptoms. Other psychosocial variables such as trauma history and stressful life events were assessed at baseline. ResultsA history of depression, baseline depressive symptoms, trait anxiety, and more severe and bothersome vasomotor symptoms predicted worsened sleep outcomes. Recent stressful life events, trauma history, and person-centred E1G and PdG changes did not predict sleep outcomes. However, there was an interaction whereby person-centred E1G decreases predicted lower sleep efficiency in those with higher baseline depressive symptoms. Higher baseline depression and trauma history also amplified the effect of vasomotor symptoms on sleep outcomes. In evaluating the effect of poor sleep on psychological and cognitive outcomes, stressful life events emerged as a moderating factor. Finally, trauma history and poor sleep interacted to predict worsened attention function. ConclusionsThe current study suggests that certain individuals may be at greater risk of perimenopausal sleep problems and the resulting negative effects on mood and cognition.

Overcoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control

BackgroundThe combination of bazedoxifene 20 mg (BZA) and conjugated estrogens 0.45 mg (CE) marketed as Duavee® is approved for vasomotor symptom relief and osteoporosis prevention. Our pilot study suggested it had potential breast cancer risk reduction, and we proposed a multisite Phase IIB primary prevention trial assessing change in breast imaging and tissue risk biomarkers. By the time funding was acquired in February 2021, Duavee® was unavailable with an uncertain return date. A redesign was needed to salvage the study. MethodsThe basic trial design was minimally altered. Women age 45–64 at elevated risk for breast cancer with vasomotor symptoms and no menses for at least 2 months have mammography, phlebotomy, and benign breast tissue sampling before and after 6 months of intervention. However, instead of Duavee® (single pill) vs placebo, women are randomized to 6 months of BZA + CE vs Waitlist. Those initially randomized to Waitlist can receive BZA + CE after 6 months. The primary endpoint is between arm difference in change in a fully automated measure of mammographic density with blood and tissue-based secondary endpoints. OutcomesAccrual initiation was delayed due to contractual difficulties surrounding BZA importation during COVID-19 and deploying a fully automated method (Volpara®) to assess the primary endpoint. To accommodate this delay, a mid-grant no cost extension along with amended eligibility requirements were employed. 61/120 participants needed were entered in the initial 27 months of accrual and 37 months of funding. Despite a late start, accrual is likely to be completed within the funding period.