Menopausal Symptoms Research Articles

Beneficial Effects of Probiotics Derived from Inonotus Obliquus on Menopausal Symptoms in Ovariectomized Mice

Physical debilitation and other health risks such as cardiovascular disease and osteoporosis often accompany decreased estrogen production in postmenopausal women. Phytoestrogens, natural compounds that functionally mimic estrogens, have emerged as a potential treatment method for hormonal dysregulation during menopause. Among these, chaga (Inonotus obliquus) extract has gained attention for its various health benefits, including anti-cancer and antioxidant properties. The aim of this study was to investigate the bone metabolic efficacy of lactic acid bacteria derived from I. obliquusin ovariectomized C57BL/6J female mice. The results demonstrated the estrogenic activity of probiotics derived from I. obliquus and its potential to alleviate osteoporosis symptoms by improving bone microstructure and density. Furthermore, probiotics derived from I. obliquus favored biochemical markers associated with a reduction in bone resorption. Additionally, effects on brain neurotransmitters and serum estradiol levels suggested its regulatory role in estrogen mimicry. These findings underscore the therapeutic potential of probiotics derived from I. obliquus in managing menopausal symptoms and thus warrant potential human investigation in improving bone health in postmenopausal women.

Tokishakuyakusan alleviates ultraviolet-induced skin pigmentation by decreasing the expression of melanogenesis-related enzymes

Ethnopharmacological relevanceTokishakuyakusan (TSS), a traditional Kampo medicine, can effectively alleviate symptoms unique to women, such as menstrual pain and menopausal symptoms, and this effect is believed to be related to its ability to increase the secretion of female hormones. TSS is also believed to be effective against skin pigmentation. However, no studies have examined the effect of TSS on pigmentation. Aim of the studyIn this study, we conducted basic research to determine the effects of TSS on pigmentation. Materials and methodsFemale HRM-2 mice were given free access to a normal diet or a TSS-containing diet for 7 weeks. For 3 weeks starting from the 4th week of treatment, the back of the skin was irradiated with ultraviolet (UV) light, and the melanin level was measured. The expression levels of melanogenesis-related genes and inflammatory markers in the skin were analyzed. ResultsThe melanin level in the skin of the mice exposed to UV radiation was approximately three times greater than that in the skin of the mice in the non-UV-irradiated group, confirming pigmentation due to UV irradiation. The protein expression levels of tyrosinase (Tyr), tyrosinase-related protein-1 (Tyrp1), and dopachrome tautomerase (Dct), which are important for melanin production, were significantly greater in the UV irradiation group than in the non-UV irradiation group. In contrast, the amount of skin melanin in the mice treated with TSS was significantly lower than that in the UV-irradiated group, and the expression levels of melanogenesis-related enzymes were also lower. Furthermore, TSS significantly decreased the expression of microphthalmia transcription factor (Mitf), a transcription factor for melanogenesis-related enzymes, and the inflammatory cytokines interleukin-1β and interleukin-6. ConclusionsTSS inhibits melanin production in melanocytes by suppressing the increase in the expression of melanogenesis-related enzymes caused by UV irradiation. These findings suggested that this effect of TSS is exerted through the combined regulation of MITF expression and anti-inflammatory responses.

Beneficial Effects of Probiotics Derived from Inonotus Obliquus on Menopausal Symptoms in Ovariectomized Mice

Physical debilitation and other health risks such as cardiovascular disease and osteoporosis often accompany decreased estrogen production in postmenopausal women. Phytoestrogens, natural compounds that functionally mimic estrogens, have emerged as a potential treatment method for hormonal dysregulation during menopause. Among these, chaga (Inonotus obliquus) extract has gained attention for its various health benefits, including anti-cancer and antioxidant properties. The aim of this study was to investigate the bone metabolic efficacy of lactic acid bacteria derived from I. obliquusin ovariectomized C57BL/6J female mice. The results demonstrated the estrogenic activity of probiotics derived from I. obliquus and its potential to alleviate osteoporosis symptoms by improving bone microstructure and density. Furthermore, probiotics derived from I. obliquus favored biochemical markers associated with a reduction in bone resorption. Additionally, effects on brain neurotransmitters and serum estradiol levels suggested its regulatory role in estrogen mimicry. These findings underscore the therapeutic potential of probiotics derived from I. obliquus in managing menopausal symptoms and thus warrant potential human investigation in improving bone health in postmenopausal women.

Cardiovascular and physiological risk factors in women at mid-life and beyond.

Cardiovascular disease (CVD) is the leading cause of death in women. After menopause, sex-specific and gender-specific factors may play an important role in increasing CVD risk, with changes in sex hormones, body fat distribution, lipid and metabolic profile, and structural and functional vascular modifications. Premature and early-onset menopause are detrimental to cardiovascular health due to the early cessation of the protective effect of endogenous estrogen. An independent association of menopause with an increased risk of CVD has been documented in early menopause (<45 years). Sex-related differences are relevant in pharmacokinetics and pharmacodynamics; different enzyme formations, drug compatibility, efficacy, and side effects vary for different sexes. Despite some progress in sex and gender research in CVD, disparities remain. Menopausal hormone therapy (MHT) is available at mid-life for symptoms of menopause and may impact cardiovascular risk. Taken early, MHT may reduce CVD morbimortality. However, this is balanced against the risk of increased thrombosis. This paper reviews physiologic changes that contribute to cardiovascular risk in postmenopausal women and discusses clinical implications. Specifically, it explores the atheroprotective effects of estrogen and MHT and the associations between menopause with lipid levels, hypertension, body composition, and diabetes for women at mid-life and beyond.

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

Breast cancer risk assessment for prescription of menopausal hormone therapy in women with a family history of breast cancer: an epidemiological modelling study.

Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking. To quantify the risks associated with MHT use in women with varying breast cancer family histories of developing and dying from breast cancer. An epidemiological modelling study for women in England using the BOADICEA breast cancer prediction model and data relating to MHT use and breast cancer risk taken from research by the Collaborative Group on Hormonal Factors in Breast Cancer. The risk of developing and dying from breast cancer between the ages of 50 and 80 years was modelled in women with four different breast cancer family history profiles: 'average', 'modest', 'intermediate', and 'strong' by using 1) background risks of breast cancer by age and family history, 2) relative risks for breast cancer associated with MHT use, and 3) 10-year breast cancer-specific net mortality rates. This study modelled use of combined oestrogen-progestogen MHT (cyclical or continuous) and oestrogen-only MHT. For a woman of 'average' family history taking no MHT, the cumulative breast cancer risk (age 50-80 years) is 9.8%, and the risk of dying from the breast cancer is 1.7%. In this model, 5 years' exposure to combined-cyclical MHT (age 50-55 years) was calculated to increase these risks to 11.0% and 1.8%, respectively. For a woman with a 'strong' family history taking no MHT, the cumulative breast cancer risk is 19.6% (age 50-80 years), and the risk of dying from the breast cancer is 3.2%. With 5 years' exposure to MHT (age 50-55 years), this model showed that these risks increase to 22.4% and 3.5%, respectively. In this model, both family history and MHT are associated with increased risk of breast cancer. Estimates of the risks of breast cancer associated with MHT for women with different family histories can be used to support decision making around MHT prescription for women experiencing menopausal symptoms.

Cognitive shadows in perimenopause: linking subjective cognitive decline (SCD) to menopausal symptom severity.

As women approach perimenopause, the incidence of Subjective Cognitive Decline (SCD) rises. This study aims to investigate the association between SCD and the severity of perimenopausal symptoms. Conducted at The Affiliated Hospital of Guizhou Medical University Menopause Clinic from November 2022 to June 2023. Participants, aged 40-55 years, were classified as perimenopausal using the STRAW + 10 criteria. SCD was assessed separately using the Chinese version of the SCD-Q9 scale and the SCD International Working Group (SCD-I) conceptual framework, while perimenopausal symptoms were evaluated with the Modified Kupperman Index (MKI). Linear relationships between MKI scores and SCD-Q9 scores were clarified using both univariate and multivariate linear regression analyses. Additionally, a multivariate Logistic regression analysis was conducted to examine the association between MKI scores and SCD classification based on SCD-I criteria. The primary outcomes were the Modified Kupperman Index scores, SCD-Q9 questionnaire scores, and the diagnosis of SCD based on SCD-I criteria. Among 101 participants, the average MKI score was 18.90 ± 9.74, and the average SCD-Q9 score was 4.57 ± 2.29. Both univariate and multivariate linear regressions demonstrated a positive correlation between these scores. A multivariate Logistic regression analysis, using MKI as the independent variable and SCD-I criteria classification as the dependent variable, revealed a significant positive association. A notable association exists between SCD and perimenopausal symptoms severity. This underscores the potential clinical importance of addressing perimenopausal symptoms to mitigate SCD risks in women. Further studies should focus on clarifying the causality between these factors.

An influence of menopausal symptoms on mental health, emotion perception, and quality of life: a multi-faceted approach.

The menopausal transition brings with it many physical, cognitive, and affective changes in a woman's life, impacting quality of life. Whereas prior work has examined impact on general mental health and cognitive function, research on basic affective processing during menopause remains scarce. Using a median-split procedure, this pre-registered study examined the impact of stronger (N = 46 women) vs. milder (N = 47 women) menopausal symptoms using a behavioural task of subjective emotion perception (embody) and a passive eye tracking viewing task of emotional faces in addition to self-report questionnaires. After 3 months, participants completed the questionnaires again to examine whether objective measures of emotion perception (eye tracking) might predict mental health at follow-up. As anticipated, women with stronger vs. milder menopausal symptoms reported increased symptoms of anxiety, depression, stress, emotion regulation difficulties, and lower quality of life during both time points. While no evidence was found in the behavioural task, eye tracking data indicated blunted emotion perception in women with high menopausal symptoms, while women with low symptoms spent more time looking at happy faces relative to fearful or surprised faces. Although eye tracking or hormonal data did not predict mental health at follow-up, a higher estradiol/FSH ratio indicated a higher quality of life. This study documented an impact of the menopausal transition and strength of menopausal symptoms in particular on objective emotion perception as well as mental health and quality of life in women suffering from stronger vs. milder menopausal symptoms. Clinical implications are discussed.

Abstract PO3-01-08: Interaction of Prior Chemotherapy and Addition of Ovarian Function Suppression on Menopausal Symptoms in Tamoxifen-Treated Breast Cancer Patient: A prospective, Observational study

Abstract Background: Adjuvant endocrine therapy (AET) is commonly used for hormone receptor-positive breast cancer patients. Combining ovarian function suppression (OFS) with tamoxifen improves survival outcomes, but is associated with menopausal symptom-related issues and treatment discontinuation. This study aimed to compare menopausal symptoms between tamoxifen alone and tamoxifen plus OFS over 12 months and identify related factors. Methods: This prospective study included 209 premenopausal breast cancer patients on tamoxifen. Menopausal symptoms were assessed using the Menopausal Rating Scale (MRS) at baseline, 3, 6, and 12 months. Statistical analysis involved linear regression and generalized estimating equations. Results: Of the participants, 27.8% received tamoxifen plus OFS and were younger and more likely to be unmarried. The tamoxifen plus OFS group had lower baseline MRS scores, but higher scores at 6 and 12 months compared to tamoxifen alone. MRS scores increased significantly in both groups, plateauing at 6 months with tamoxifen alone and at 12 months with tamoxifen plus OFS. Factors associated with higher MRS scores at 6 months were baseline MRS scores and addition of OFS. Impact of OFS on MRS scores varied with prior chemotherapy status, being significant in patients without prior chemotherapy. Conclusion: Adding OFS to tamoxifen in premenopausal breast cancer patients was associated with a higher burden of menopausal symptoms compared to tamoxifen alone, particularly in patients who have not undergone prior chemotherapy. Therefore, careful consideration and decision-making regarding this issue are crucial in terms of both treatment outcomes and quality of life. Table 1. Baseline characteristics, Overall and According to adjuvant endocrine therapy, tamoxifen alone versus tamoxifen plus ovarian function suppression (OFS) Table 2. Multivariable linear regression about MRS scores from the baseline to 6 months, and with interaction between addition of OFS and prior chemotherapy effect Table 3. Interaction effect of additional OFS depending on prior chemotherapy; (a) without prior chemotherapy, (b) with prior chemotherapy Citation Format: Youngwon Lee, Jong Won Lee, Sae Byul Lee, Byung Ho Son, Hee Jeong Kim, Beom Seok Ko, Jisun Kim, Il-Yong Chung, Tae-Kyung Yoo. Interaction of Prior Chemotherapy and Addition of Ovarian Function Suppression on Menopausal Symptoms in Tamoxifen-Treated Breast Cancer Patient: A prospective, Observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-08.

Abstract PO3-12-06: The pilot study for a mobile-based monitoring solution to manage menopausal symptoms of premenopausal breast cancer patients with endocrine therapy

Abstract Background Endocrine therapy (ET) is the most important treatment for hormone receptor (HR)-positive breast cancer (BC) patients. Each of the endocrine medications, such as aromatase inhibitors (AIs), luteinizing hormone-releasing hormone (LHRH) analogs, and selective estrogen receptor modulators, has its own set of side effects, and these might lead to poor drug adherence and eventual discontinuation. There are few systematic monitoring systems for menopausal symptoms of patients on ET. We conducted a prospective, pilot study through the mobile platform-based monitoring solution which contains a questionnaire about menopausal symptoms to assess the feasibility of the solution. Methods We screened and collected data from HR-positive BC patients who underwent surgery at a single institution from May 2022, until recruiting a total of 20 patients. Patients scheduled for postoperative ET at age 50 or younger were included. Preoperatively confirmed metastatic BC patients were excluded. A total of 19 patients were enrolled, excluding one patient who self-discontinued medication. Menopause Rating Scale (MRS) surveys were periodically administered to the patients using a mobile platform-based solution to collect responses during first 3 months of ET. The primary endpoint of this study was the response rate of the patients, and the second endpoint was MRS scores and patient satisfaction. At the time of initial enrollment before the start of ET, MRS was collected using a paper questionnaire. The concordance rate of MRS response using a paper questionnaire and this solution was compared. We also conducted a user evaluation at the end of the third month of ET to determine satisfaction. The data collected from the solution were used by physicians to assist in patient care for clinical use. Results The median age of the cohort was 39 (range 29-47). Six patients were treated with Tamoxifen alone, Tamoxifen with LHRH analog in 12 patients, and AI with LHRH analog in 1 patient. There were 3 (15.8%) of pTis, 13 (68.4%) of pT1, and 3 (15.8%) of pT2, as well as 18 (94.7%) of pN0 and 1 (5.3%) patients of pN1. The total response rate of patients to the solution during the study period was 84.5%. Each symptom has different response rates and MRS scores, from 70.2% for sex-related symptoms to 95.4% for joint pain, and from 1.24 out of 4 for sleep disturbances to 0.45 out of 4 for vaginal dryness. The match rate between mobile and paper surveys was 90.0%. The overall satisfaction score for the solution of patients was 8.06 out of 10, with the highest score (8.79 out of 10) given in terms of using patients’ responses in outpatient appointments with the physician. Conclusion The analysis of MRS using this mobile solution in premenopausal BC patients undergoing postoperative ET is expected to be feasible for clinical use and should be analyzed in a large-scale study in the future. Citation Format: Dong Seung Shin, Jai Min Ryu, Byung Joo Chae, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jonghan Yu. The pilot study for a mobile-based monitoring solution to manage menopausal symptoms of premenopausal breast cancer patients with endocrine therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-06.

Abstract PO5-12-05: A Retrospective Study of the Rate of Cognitive Impairment and Influencing Factors during Postoperative Endocrine Therapy for Breast Cancer

Abstract Background Although cancer-related cognitive impairment (CRCI) has been gradually recognized, general cognitive function tests such as the MMSE are not sensitive enough to diagnose CRCI. There is also a lack of evidence on the incidence and its response. However, even mild cognitive impairment can have a significant impact on quality of life. In this study, we retrospectively analyzed the prevalence of cognitive impairment in patients undergoing endocrine therapy at our hospital and the factors influencing the symptoms. Subjects 349 patients who continued single-agent postoperative endocrine therapy for at least 6 months between January 1 and October 31, 2022, and who responded to the cognitive dysfunction questionnaire at least once. Data from the cognitive dysfunction items of the endocrine therapy questionnaire administered during the period were used to retrospectively examine the CRCI awareness rate and factors involved. Results and Discussion The patients who were aware of cognitive dysfunction was 170, or 49% of all patients, and univariate analysis showed that age was significantly higher in the group with CRCI, but there were no significant differences in type of endocrine therapy or history of chemotherapy between the groups with and without CRCI. Physical symptoms such as menopausal symptoms (hot flashes and sweats), arthralgia, myalgia, fatigue, depressed mood, and malaise were significantly more frequent in patients with CRCI, which could be considered side effects of endocrine therapy. Risk factors such as low cognitive reserve, low level of education, advanced age, race, depression, fatigue, and anxiety have been reported in the past, and in this study, fatigue, depressed mood, and malaise were found significantly more frequently in patients with cognitive dysfunction. However, the diagnosis of depression and dementia may also be important.Non-pharmacological interventions, especially cognitive rehabilitation and exercise, are expected to be effective in improving symptoms, but there is no certain opinion yet. The limitation of this study is that it was a single-center, retrospective analysis. In addition, it was difficult to evaluate the results over time, including before the start of oral medication, so we are considering conducting a prospective data collection study so that comparisons can be made in the future. Conclusion: This study was a simple screening, based only on subjective symptoms. In recent years, postoperative endocrine therapy has been prolonged to 10 years, and there is a possibility to improve the quality of life of patients by recognizing the possibility of cognitive dysfunction in both providers and patients, and by taking measures that include multiple factors. Citation Format: Akari Murakami, Mayuko Aono, Kaho Utsunomiya, Kumiko Okujima, Kana Takemoto, Megumi Takaoka, Erina Kusakabe, Kana Taguchi, Kanako Nishiyama, Yoshiaki Kamei, Yasutsugu Takada, Hitoshi Tanimukai. A Retrospective Study of the Rate of Cognitive Impairment and Influencing Factors during Postoperative Endocrine Therapy for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-05.

Abstract PO2-19-02: NRG-BR009: Phase III Trial Evaluating Addition of Adjuvant Chemotherapy to Ovarian Function Suppression + Endocrine Therapy in Premenopausal Women with pN0-1, HR+/HER2- Breast Cancer and Oncotype Recurrence Score ≤25 (OFSET)

Abstract Background: Identifying pts with HR-positive/HER2-negative breast cancer (BC) who benefit from adjuvant chemotherapy (ACT) has been a major research focus over the past 20 years. Development and clinical application of genomic classifiers such as the 21-gene recurrence score (RS) has contributed to the biologic understanding of BC and has refined pt selection for ACT. The TAILORx and RxPONDER clinical trials demonstrated that RS identifies many postmenopausal pts with node-negative and node-positive BC and RS &amp;lt; 25, who do not benefit from the addition of ACT to endocrine therapy (ET). However, both trials also showed that certain subsets of premenopausal pts (node-negative/high clinical risk/RS 16-20, node-negative/RS 21-25, and node-positive/RS &amp;lt; 25) benefited from the addition of ACT to ET. Most premenopausal pts in these two trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR-positive/HER2-negative BC in the SOFT and TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, OFSET is a Phase III, multicenter clinical trial evaluating the addition of ACT to OFS+ET vs. OFS+ET alone. Methods: We hypothesize that the addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR-positive/HER2-negative tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival (IDFS), overall survival (OS), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and health-related quality of life (HRQOL). Eligible pts must be node-negative with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS &amp;lt; 25. Stratification is by nodal status/RS status (pN0 RS 16-25 vs pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 vs ≥40). Pts are randomized after surgery to either OFS+ET or ACT followed by OFS+ET. ET is an aromatase inhibitor per investigator discretion, but tamoxifen is allowed if pts do not tolerate the AI or if OFS is incomplete. Radiation therapy will be administered per investigator discretion according to protocol guidelines. The HRQOL sub-study will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score, between the arms, as well as increased pain severity (PROMIS) during ACT+OFS+ET compared to OFS+ET. Blood and tumor specimens will be collected for future research. The accrual of 3,960 pts is anticipated to be completed in seven years and seven mos. Based on data from NSABP B-28 and RxPONDER, the 5-year IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on data from TAILORx, the 5-year IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of the pts to be pN0 and 44% pN1, a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET vs. OFS+ET, with one-sided alpha of 0.025 and 80% power will require 380 IBCFS events, which are expected to occur ~11 years after study initiation. The OFSET study is expected to be activated in the third quarter of 2023. Current accrual (06-19-2023) is 0/3,960 Support: U10CA180868, U10CA180822, UG1CA189867, U24CA196067. NCT05879926. Citation Format: Eleftherios Mamounas, Gong Tang, Shannon Puhalla, Sandra Swain, Patricia Ganz, N. Lynn Henry, Reena Cecchini, Sonya Reid, Priya Rastogi, Charles Geyer, Julia White, Amy Clark, Tufia Haddad, Gregory Vidal, Norman Wolmark. NRG-BR009: Phase III Trial Evaluating Addition of Adjuvant Chemotherapy to Ovarian Function Suppression + Endocrine Therapy in Premenopausal Women with pN0-1, HR+/HER2- Breast Cancer and Oncotype Recurrence Score ≤25 (OFSET) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-02.

Real-world clinical evaluation of natural and induced vasomotor symptoms in the USA and Europe

Objective This study aimed to examine physicians’ and patients’ perceptions regarding symptom burden and impact in women experiencing natural vasomotor symptoms (nVMS) or vasomotor symptoms induced by endocrine therapy for breast cancer (iVMS). Methods The cross-sectional survey based on real-world clinical consultations was conducted in the USA and five European countries. Obstetrician–gynecologists, primary-care physicians and oncologists provided demographic and symptom data for patients experiencing VMS; patients optionally self-reported their experiences via questionnaires, including their symptom profile and work/activity burden through the Menopause Quality of Life (MENQOL) and Work Productivity and Activity Impairment (WPAI) tools. Results Physicians completed survey forms on 2451 consulting patients; patients completed 1029 questionnaires. nVMS and iVMS severity was significantly associated with the severity of mood symptoms and sleep disturbances (p < 0.0001). However, around half of the patients with mild nVMS/iVMS also experienced moderate–severe mood changes (55.4%/43.7%) or sleep disturbances (42.4%/40.4%). Presence of mood/sleep disturbances alongside nVMS increased MENQOL vasomotor scores (p = 0.004/p < 0.001). Presence of sleep disturbances increased WPAI activity impairment (p < 0.001) but mood changes did not. Similar findings were reported for iVMS patients. Conclusion Significant burden from the triad of natural or induced menopausal symptoms, sleep disturbances and mood changes affected women’s daily activities, work and quality of life more than vasomotor symptoms alone.

The association of sociodemographic factors and history of chronic diseases on menopausal symptoms: A cross-sectional study.

Menopausal symptoms are very diverse in terms of prevalence and severity, and this difference is due to various factors such as psychological factors, sociocultural status, lifestyle, geographical location, and other factors. This study aimed to assess the prevalence of menopausal symptoms and evaluate the predictive factors related to the prevalence and severity of menopausal symptoms. This was a cross-sectional analytical study that was performed on 214 women aged 35-65 years old who were referred to Alzahra Educational, Research and Treatment Center in Rasht, Iran. The data collection tool was a valid and reliable questionnaire, using the list of menopausal symptoms and a checklist of subjects' general characteristics. 16.8% of postmenopausal women in our study had at least one menopausal symptom. Using multiple linear regression, race (p = 0.02), history of chronic diseases (p = 0.04), place of residence (p = 0.02), and marital satisfaction (p = 0.02) were associated with menopausal symptoms. Nineteen percentof the covariates related to the logistics function were explained by the predictor variables in the model. Evaluation of menopausal symptoms showed that the severity of menopausal symptoms was related to factors such as body mass index(BMI), ethnicity, place of residence, marital satisfaction, and history of chronic diseases, and need to address BMI, psychological issues, and chronic illness.

A fNIRS investigation of menopausal-related symptoms and brain cortical activity in menopause.

This study aimed to delineate the association between menopausal-related symptoms and brain cortical hemodynamics in peri-postmenopause women. Cross-sectional data from a total of 358 Han-Chinese women who visited the Menopause Clinic in the Shanghai Sixth People's Hospital from August 2019 to August 2022. Menopausal-related symptoms were analyzed through Kupperman index (KMI) scale and PSQI scale, while cerebral blood flow was measured using a functional near-infrared spectroscopy (fNIRS). Multiple linear regression model was used to assess the risk factors for subregions of brain hemodynamic response. After adjusting for confounding factors, we identified that menopausal symptom (B=-1.575, 95% CI (-2.661, -0.488), p=0.005) and duration of menopause (B=-14.583, 95% CI (-26.753, -4.192), p=0.007) were independently associated with the lower brain hemodynamic response in the prefrontal lobe, while in the temporal lobe, overweight (BMI≥24kg/m2) was negatively associated with the lower brain cortical activity (B=-36.882, 95% CI (-72.708, -1.056), p=0.044) after adjusting for other confounding variables. Our findings proposed that menopausal symptom and overweight should be attached great importance to the postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as menopausal hormone therapy (MHT) of brain health in postmenopausal women.

The Effect of Yoga on Menopause Symptoms: A Randomized Controlled Trial.

The research was conducted as a randomized controlled study with the aim of determining the effect of yoga on menopause symptoms. Menopausal women between the ages of 40 and 60 years were included in the research. There were 31 menopausal women in each of 2 groups, making a total of 62. A Descriptive Characteristics Form and the Menopause Rating Scale (MRS) were used to collect data. In the research, the yoga group practiced yoga for 60 minutes twice a week for 10 weeks. In the final lesson of the 10 weeks of yoga training, the women were again given the MRS. No intervention was performed on the control group. The median score on the MRS of the women in the yoga group was 16 (11-21) in the pretest, and 5 (3-9) in the posttest (P < .05). The median score on the subscale of psychological complaints of the women in the yoga group was 6 (3-8) in the pretest, and 1 (1-2) in the posttest (P < .05). The median score on the subscale of urogenital complaints of the women in the yoga group was 3 (3-5) in the pretest, and 1 (0-2) in the posttest (P < .05). The median score on the subscale of somatic complaints of the women in the yoga group was 7 (4-10) in the pretest, and 1 (1-3) in the posttest (P < .05). It was concluded from the research that 60 minutes of yoga 2 days a week for 10 weeks may reduce the psychological, somatic, and urogenital symptoms experienced in menopause.

Fezolinetant Compared With Placebo for Vasomotor Symptoms in Menopause: A Systematic Review and Meta-Analysis [ID 2683665

INTRODUCTION: Although menopausal hormone therapy is the most effective choice for vasomotor symptoms (VMS), it is not appropriate for everyone. Therefore, fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist has been proposed as an alternative therapy. We aimed to perform a meta-analysis of the clinical outcomes comparing fezolinetant and placebo for vasomotor symptoms in menopause. METHODS: PubMed, Embase, and Cochrane databases were searched for studies comparing 30 mg of fezolinetant with placebo in menopausal women. Outcomes assessed were frequency of moderate/severe VMS and change from baseline to week 12 in total VMS score. Our secondary outcomes were headache, bone fracture, and treatment-emergent adverse events (TEAEs) leading to discontinuation of the drug and TEAEs leading to death. We only included randomize control trials. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics and random-risk effect was used if 𝐼2&gt;50%. RESULTS: Seven studies met inclusion criteria, with 3,678 patients included, of whom 1,067 were randomized to fenzolinetant. No statistical difference was found in frequency of moderate/severe VMS or TEAEs leading to death, TEAEs leading to drug discontinuation. However, severity of moderate and severe VMS comparing to baseline VMS (MPR) was significantly lower with fezolinetant 30 mg BID (odds ratio [OR] −0.22; 95% CI, −0.30, −0.13; P=.00001; I 2=89%). In addition, headache and bone fractures (OR −6.98; 95% CI, −6.98 to −6.73; P=.03; I 2=100%) were lower with fezolinetant compared to placebo. CONCLUSION: Our findings suggest that 30 mg of fezolinetant is a well-tolerated nonhormone therapy that improves vasomotor symptoms with menopause. The safety and efficacy demonstrated in our study support the potential use of fezolinetant as an effective nonhormonal treatment option and may reduce bone fractures and headaches in menopausal women.

Effects of mind-body exercise on perimenopausal and postmenopausal women: a systematic review and meta-analysis.

The increasing attention to the management of perimenopausal and postmenopausal women parallels the growth of the aging population. Although hormone therapy is commonly used to alleviate menopausal symptoms, it carries a potential risk of cancer. Recently, mind-body exercises have emerged as innovative approaches for improving menopausal symptoms and bone health. However, research findings have needed to be more consistent, highlighting the significance of this study's systematic review of mind-body exercise effects on perimenopausal and postmenopausal women. This study aims to evaluate the impact of mind-body exercises, including tai chi, yoga, Pilates, qigong, baduanjin, and mindfulness-based stress reduction, on bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women. Four electronic databases-PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science-were systematically searched from inception until July 2023. The search focused exclusively on randomized controlled trials to examine the impact of mind-body exercise interventions on perimenopausal and postmenopausal women. The methodological quality of the included studies was evaluated using the Cochrane Bias Risk Assessment tool. A total of 11 randomized controlled trials, comprising 1,005 participants, were included in the analysis. Traditional meta-analysis indicated that mind-body exercise significantly enhanced bone mineral density in perimenopausal and postmenopausal women compared with control groups, with a standardized mean difference (SMD) of 0.41 (95% CI, 0.17 to 0.66; P = 0.001, I2 = 7%). In addition, significant improvements were observed in sleep quality (SMD, -0.48; 95% CI, -0.78 to -0.17; P = 0.002, I2 = 76%), anxiety reduction (SMD, -0.80; 95% CI, -1.23 to -0.38; P = 0.0002, I2 = 84%), depressive mood (SMD, -0.80; 95% CI, -1.17 to -0.44; P < 0.0001, I2 = 79%), and fatigue (SMD, -0.67; 95% CI, -0.97 to -0.37; P < 0.0001, I2 = 0%). The findings of this meta-analysis demonstrate that mind-body exercise positively influences bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women.

Effects of herbal compounds on various aspects of endometriosis treatment: a systematic review.

Endometriosis means the presence of tissue similar to normal endometrium outside the uterus. Although surgical, hormonal, and analgesic treatment relieves symptoms and improves fertility, it is associated with side effects and a high recurrence rate. Alternative medicines like medicinal plants have been used for the treatment of chronic diseases. Given the global importance of endometriosis as a chronic disease affecting over 15% of all women in their fertile period, this systematic review aimed to give a comprehensive view of research on medicinal plants. Comprehensive searches were performed on three databases, including PubMed/MEDLINE, Web of Science Core Collection (Indexes = SCI-EXPANDED, SSCI, A, and HCI Timespan), and Scopus, to identify papers published until June 2023. Keywords, such as "Endometriosis" and "Herbal Medicine", were used to search. A manual search of valid journals followed by a manual search of the references of the retrieved full-text articles was performed. All retrieved articles were imported into a database into Endnote X9. Articles that did not meet the inclusion criteria were excluded from the study, and the full texts of all the articles that met the inclusion criteria were assessed. Studies that evaluated the effects of herbal compounds on various aspects of endometriosis treatment were included in the review. In total, 11 studies were included in the present study. The evidence showed that in addition to safety, drugs available alongside treatments could play an effective role in improving the symptoms associated with endometriosis. In this study, the positive results of using Chinese treatments were reported in aspects such as fertility rate, pain, endometriosis recurrence rate, quality of life, sexual function, CA-125 level, and menopause symptoms. A wide range of preclinical and clinical studies evaluated the effectiveness and safety of medicinal plants in the treatment of endometriosis symptoms. Thus, alternative treatments for endometriosis with no or low side effects should be included in the holistic treatment of endometriosis upfront. However, there is still a need for well-designed trials to investigate standard interventions and specific and safe doses of herbal medicines.

Severity and frequency of menopausal hot flash symptoms are not associated with arterial stiffness in females

Background: Females who experience menopausal hot flashes ([MHF]; episodes of sudden warmth and sweating) have greater risk of developing hypertension than females without MHF. MHF symptom severity and frequency are positively associated with hypertension. Considering that augmented arterial stiffness contributes to hypertension, this work aimed to investigate the relations between MHF severity and frequency with arterial stiffness. We hypothesized that females with moderate to severe MHF symptoms would exhibit greater arterial stiffness compared to females without MHF symptoms. Further, we hypothesized that there would be a positive relation between MHF frequency and arterial stiffness. Methods: Twenty-five females (51±5 [SD] years) with no history of hypertension or cardiovascular disease participated. The Menopausal Rating Scale was used to categorize participants by symptom severity (None MHF: n=7, Mild MHF: n=9, Moderate/Severe MHF: n=9). Participants self-reported MHF frequency over three consecutive days in real time using a hot flash diary (4±5 MHF/day, Range: 0-16). After 15 minutes of supine rest, brachial cuff blood pressures (sphygmomanometer) and heart rate (electrocardiogram) were recorded. Arterial stiffness was measured as pulse wave velocity ([PWV]; SphygmoCor®). PWV was measured using a carotid tonometer simultaneously with a leg cuff to capture blood pressure waveforms at the carotid and femoral sites. Aortic systolic pressure, aortic diastolic pressure, and augmentation index (AIx) were measured via pulse wave analysis ([PWA]; SphygmoCor®) using a brachial cuff. Data were analyzed using one-way analysis of variance (ANOVA) and Spearman Rho (ρ). Results: Age, body mass index, resting mean blood pressure, and resting heart rate were not different among MHF severity groups (P&gt;0.05 for all). PWV was not different among severity groups (None: 6.2±0.67 vs. Mild: 6.4±1.0 vs. Moderate/Severe: 6.6±1.0 cm/s, P=0.72). MHF frequency did not correlate with PWV (P=0.42). Aortic systolic pressure (None: 110±6 vs. Mild: 114±5 vs. Moderate/Severe: 112±11 mmHg, P=0.66), aortic diastolic pressure (None: 76±9 vs. Mild: 77±6 vs. Moderate/Severe: 76±10 mmHg, P=0.93), and AIx (None: 31.9±9.0 vs. Mild: 38.7±11.1 vs. Moderate/Severe: 30.4±7.4 %, P=0.16) were not different among severity groups. MHF frequency did not correlate with metrics of PWA (Systolic: P=0.61; Diastolic: P=0.89, AIx: P=0.42). Conclusion: Arterial stiffness and metrics of PWA were not different among females with varying MHF symptom severity. MHF frequency was also not correlated with aortic stiffness and metrics of PWA. Other mechanisms of vascular function (e.g., autonomic function, vasodilation, and/or vasoconstriction) should be investigated to determine potential contributors of hypertension risk in females with MHF. AHA 898649, NIH T32 DK07352, K01 HL148144, NCATS UL1 TR002377. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.