Hot Flashes Research Articles

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear. Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database. Eligible CVAEs were extracted from the ClinicalTrials.gov registry. A systematic search of electronic databases (PubMed, Embase, Cochrane Library, and important meetings) until 3 September 2023 was conducted. A disproportionality analysis was performed from the first quarter (Q1) of 2013 to Q1 of 2023 using data from the FAERS database. Study heterogeneity was assessed using the I2 statistic. Using Peto odds ratio (Peto OR) and inverse variance methods to calculate the risk and incidence of CVAEs associated with CDK4/6 inhibitors. In total, 17 RCTs with 23,437 patients were included in our meta-analysis. During the follow-up period of 8.4-34.0 months, CDK4/6 inhibitors significantly increased the risk of CVAEs (Peto OR, 1.86, 95% confidence interval, 1.30-2.68, P < 0.01). The rates of hypertension and QT prolongation were 68.07 (62.87-73.27) and 57.15 (50.83-63.48) per 1000 patients, respectively. Moreover, we identified nine CVAEs that were not reported in RCTs. These included acute coronary syndrome, arrhythmia, lymphoedema, hot flush, vein rupture, thrombophlebitis migrans, embolism venous, angiopathy and intracardiac thrombus, which were found to be strongly correlated with CDK4/6 inhibitors. Furthermore, the risk of CVAEs varied depending on the specific CDK4/6 inhibitors used, its combination with different endocrine therapies, and the patient's treatment stage. CDK4/6 inhibitors increase the risk of CVAEs, some of which may lead to serious consequences. Early recognition and management of CVAEs is of great importance in clinical practice. PROSPERO registration number CRD42023462059.

A real‑world pharmacovigilance study of raloxifene based on the FDA adverse event reporting system (FAERS)

ABSTRACT Background Raloxifene was approved for the treatment of postmenopausal osteoporosis; however, its safety profile remains inadequately understood. This study aimed to evaluate the safety signals associated with raloxifene. Research design and methods Adverse events (AEs) related to raloxifene, spanning from the first quarter of 2004 to the fourth quarter of 2023, were extracted from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was conducted using several methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Results The analysis yielded 7 229 reports related to raloxifene across 19 277 AEs. A total of 217 significantly disproportionate signals were identified, including muscle spasms and hot flashes. Notably, the study also uncovered novel AEs, including eye conditions like cataracts and macular degeneration, as well as gynecological issues like uterine polyps and hemorrhage. Additionally, the analysis confirmed that pulmonary embolism and deep vein thrombosis were the two most prevalent thromboembolic AEs. Conclusion Our study reaffirmed some existing safety information regarding raloxifene while also unveiling novel risk signals. The findings provided crucial insights to enhance the rational use of the drug and inform safety regulatory strategies.

The association between metabolic dysfunction-associated steatotic liver disease diagnosis and vasomotor symptoms in midlife women.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and vasomotor symptoms (VMS) are associated with increased cardiovascular disease risk. Although visceral adiposity has been linked to MASLD and VMS independently, this study aimed to evaluate associations between the two in midlife women. A cross-sectional study of women aged 45-60 years receiving primary care at one of four sites was conducted from March 1 through June 30, 2021. MASLD diagnosis was obtained utilizing the International Classification of Diseases, Ninth Revision and Tenth Revision codes. VMS burden was evaluated with the Menopause Rating Scale and categorized as severe/very severe versus none/mild/moderate. Logistic regression models were used to assess the association between VMS and diagnosed MASLD both univariately and after individually adjusting for several risk factors. A total of 4,599 women were included in the final analysis, 304 (7%) of whom had an MASLD diagnosis. On univariate analysis, women with an MASLD diagnosis were more likely to have severe/very severe VMS (odds ratio [OR], 1.50; 95% CI, 1.08-2.08; P = 0.015). However, the association between MASLD diagnosis and severe/very severe VMS was no longer statistically significant after individually adjusting for body mass index (adjusted OR, 1.36; 95% CI, 0.97-1.92) and hypertension (adjusted OR, 1.38; 95% CI, 0.99-1.93). The relationship between MASLD and VMS appears to be best explained by other variables including BMI and hypertension. Although they do not appear to be directly linked, given the prevalence of bothersome VMS in midlife women, addressing VMS may enable greater adherence to lifestyle modifications as part of MASLD management.

Menopause symptom burden and management across rural, suburban, and urban settings in a US population.

The aim of this study was to compare menopause experience in rural, suburban, and urban-residing women. A 2019 online survey of US females queried respondents on menopause symptoms, resources, and treatments. Those ≥45 years of age and in late menopause transition or postmenopause were included in the analysis. Late menopause transition and postmenopause subgroups were stratified by rural, suburban, and urban residence, and age-weighted proportions for menopause symptoms and treatments were calculated and compared using chi-square tests. A total of 1,531 respondents, 45% (n = 686) late menopause transition, mean age of 50.7 (SD 3.9) and 55% (n = 845) postmenopause, and mean age of 65.1 (SD 8.5) were included. More prevalent symptoms in late menopause transition rural residents were as follows: muscle aches and pains (urban: 49%, suburban: 49%, rural: 65%, P = 0.003), and panic attacks (urban: 18%, suburban: 24%, rural: 30%, P = 0.04). More prevalent symptoms in postmenopause rural residents were as follows: mood swings (urban: 18%, suburban: 14%, rural: 23%, P = 0.02), urinary incontinence (urban: 19%, suburban: 14%, rural: 23%, P = 0.02), and vaginal dryness (urban: 22%, suburban: 29%, rural: 37%, P = 0.004). Vasomotor symptom prevalence was high (71% late menopause transition, 20% postmeopause), but current menopause hormone therapy use was low (11% late menopause transition, 11% postmenopause) and did not differ by residence, despite differences in menopausal resources used. Rural women may experience greater burden of psychological and somatic menopause symptoms but not vasomotor symptoms. Overall low rates of menopause hormone therapy use suggest a need for education regarding hormone therapy, tailored to residential groups who rely on different resources on healthy aging.

A study on anxiety and depression symptoms among menopausal women: a web based cross sectional survey

BackgroundAn essential part of aging is menopause, which indicates the final phase of the female reproductive cycle. The objective of this research was to assess anxiety and depressive symptoms among menopausal women in Asir region, Saudi Arabia.MethodsThe cross-sectional survey was carried out in February to June 2024, using a random sampling procedure, study participants were selected. All menopausal women including &amp;lt;50 and ≥60 years old, were included, and symptoms of depression and anxiety were collected using Patient Health Questionnaire-9 (PHQ-9) Generalized Anxiety Disorder-7 (GAD-7) respectively.ResultsOf the 396 menopausal women, the majority 170 (42.9%) were &amp;lt;50 years old and 92 (23.2%) were between 50 and 54 years old. Two hundred eighty-one were married (71%) and 273 (68.9%) were literate. Most of them, 229 (57.8%) got married at &amp;lt;18 years and 196 (49.5%) have a parity of 3–5 and 189 (47.7%) women attained menopause at &amp;lt;50 years old. In terms of menopausal symptoms, 268 (67.7%) women experienced hot flushes; 252 (63.6%) had night sweats and were more irritable 256 (64.6%) followed by 244 (61.6%) had decreased sexual desire. In general, 258 (65.2%) and 206 (52.02%) menopausal women reported having depression and anxiety symptoms, respectively. Married (OR = 0.317; 95% CI = 0.182–0.551, p = 0.000) and literate (OR = 0.518; 95% CI = 0.309–0.868, p = 0.013) are less likely to be in depression compared to widowed/separated individuals. Literates (OR = 0.271; 95% CI = 0.165–0.443, p = 0.000), are less likely to have anxiety compared to illiterates.ConclusionThe study found that a significant percentage of menopausal women had depression and anxiety symptoms. These results emphasize the significance of screening and assessing women experiencing anxiety and depression symptoms throughout the menopausal transition. To alleviate menopausal symptoms, it is also suggested to conduct activities to educate menopausal women, such as a health awareness program in shopping centers and other public places, etc.

Engaging survivor and oncologist stakeholders to develop a patient-reported outcome assessment to use as a component of survivorship care.

Incorporating patient-reported outcomes (PROs) into survivorship care may improve the comprehensiveness of follow-up. The objective was to engage stakeholders to develop a PRO assessment of survivors' symptoms and concerns for use during breast cancer follow-up. We convened patient and oncologist stakeholder advisory groups to develop an initial PRO assessment including survivorship domains of importance, measurement instruments, and clinically significant thresholds, and revise the assessment based on feedback from community focus groups and two rounds of iterative pilot testing with survivors. Stakeholders identified key domains and measurement instruments, including recurrence symptoms, treatment side effects, adherence, mental health, and sexual health. Ninety-four survivors completed the PRO assessment in the initial pilot test (median age 62years, median 2years from diagnosis). Most (89/93) reported questions were easy to understand. The level of missingness was low. The most common threshold-level symptoms/concerns were hot flashes (46%), fatigue (35%), back pain (31%), joint pain (31%), and anxiety (30%). The PRO assessment was revised to clarify symptom causality and desire to discuss with a provider. In a follow-up pilot study with 20 survivors, the most common symptoms were chest/breast discomfort (50%) and anxiety (25%). We leveraged stakeholder input to develop a comprehensive PRO assessment to use to assess breast cancer survivors' well-being. Our PRO assessment is acceptable to survivors. Future research will focus on the integration of the PRO assessment into clinical care.

Exploring heterogeneity of perimenopause with application of multivariable analysis approaches

ObjectivesHeterogeneity of clinical appearance had made it a challenge to make individualized and comprehensive management of perimenopause. This study aimed to estimate the profiles over heterogenous appearances of perimenopause with application of latent variable analysis methods over an optimized multidimensional assessing framework.MethodsA two-phase clinical study was designed and advanced in the research center in Guangzhou, China. The assessing framework was developed over the initial item pool as integration of 4 scales including Insomnia severity index, Modified Kupperman index, Self-rating anxiety scale, and Self-rating depression scale. Validity and reliability of the instrument were evaluated and the psychometric properties of the items were estimated with multidimensional item response theory(MIRT). And then computer adaptive testing(CAT) was developed with the estimated model. We used latent profile analysis (LPA) to cluster patients into subgroups as patterns characterized by multidimensional latent trait scores. Finally, interpretability and efficiency were analyzed via comparison between the two assessing strategies.ResultThere were in total 336 patients diagnosed with perimenopause enrolled for the assessment. A conceptual framework was estimated consisting of 6 factors including sleep disturbance, mood swings, vasomotor symptoms, positive attitude towards life, multisystem abnormality, and fatigue. The construct validity was evaluated as optimized with CMIN/df = 1.814, GFI = 0.619, CFI = 0.721, TLI = 0.707 and RMSEA = 0.075. With scores in the simulated CAT, the 4 latent profiles model was estimated indicating the heterogeneity of perimenopause characterized by different severity of psychological and physical discomforts in the LPA.ConclusionThe quantitative paradigm raised in this study revealed the potential patterns presenting heterogeneity of perimenopause offering better interpretation for clinical assessment.

Samelisant (SUVN-G3031), A Histamine 3 Receptor Inverse Agonist: Results from The Phase 2 Double-Blind Randomized Placebo-Controlled Study for The Treatment of Excessive Daytime Sleepiness in Adult Patients with Narcolepsy

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5% patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

Basics of vasomotor symptoms.

Basics of vasomotor symptoms.

Actigraphy-derived multidimensional sleep health among breast cancer survivors and controls: Pink SWAN.

To compare breast cancer survivors (BCS) to women without breast cancer (controls) on sleep health risk factors and actigraphy-derived dimensions of sleep (duration, maintenance, timing, and regularity) and examine whether the effect of breast cancer on sleep differs by time since diagnosis. Analyses included data from 68 BCS and 1042 controls who participated in actigraphy and Pink SWAN sub-studies within the Study of Women's Health Across the Nation. BCS and control characteristics were compared using chi-square, Fisher's exact, and Wilcoxon rank sum tests. Sleep measures were regressed onto breast cancer status using binomial logistic and linear regression. The interaction between BCS status and years since diagnosis (< 5; ≥ 5) was tested in these models before and after covariate adjustment. There were no overall sleep differences between BCS and controls; both groups experienced poor sleep health on average across multiple dimensions. Physical inactivity, sleep apnea, and vasomotor and depressive symptoms were associated with worse sleep in both groups. Total sleep time was lower among BCS than controls within 5years of diagnosis (6.13 vs. 6.57h; p = .03) but did not differ at > 5years post-diagnosis (6.59 vs. 6.45h; p = .32). BCS reported greater use of exogenous hormones (p < .0001) and were twice as likely to have initiated anxiolytic use post-diagnosis (p = .03). BCS within 5years of diagnosis experienced shorter sleep duration than controls but did not differ on other sleep parameters. Both groups experienced poor sleep health. BCS and similarly-aged women experience poor sleep health requiring assessment and treatment.

Associations of social vulnerability index with patient-reported outcomes in women treated with chemotherapy for early-stage breast cancer.

In a convenience sample of women scheduled for chemotherapy for early-stage breast cancer, we investigated associations of the Center for Disease Control and Prevention's neighborhood-level social vulnerability index (SVI) with pretreatment demographics and patient-reported outcome (PRO) measures (health behavior, function and quality of life, treatment toxicities during chemotherapy). The SVI Overall score is comprised of 4 themes: socioeconomic, household composition, minority status/language, and household type/transportation, with scores ranging from 0 = lowest to 1 = highest vulnerability neighborhoods. Participant SVI scores were derived from zip codes listed in the patient's address within the electronic medical record (EMR). Associations of study variables with SVI were evaluated using Spearman correlation for continuous variables and Kruskal-Wallis tests for categorical variables. In a sample of 309 women, the mean age was 56 years (range 23-83) and 75% White. Greater vulnerability SVI Overall score was associated with lower education (P =.02), nonmarriage (P ≤.0001), higher body mass index (P =.03), and prechemotherapy PRO measures such as fewer self-reported walking minutes/week (P ≤.001), history of smoking (P =.02) and alcohol use (P < .001), depression (P =.01), and lower emotional social support (P =.008). During chemotherapy, moderate, severe, or very severe symptoms were associated with greater vulnerability SVI Overall scores for hot flashes (P =.03), arthralgia (P =.02), myalgia (P =.02), peripheral neuropathy (P =.01), edema of limbs (P =.04), and nausea (P <.001). SVI scores derived from addresses in the patient's EMR can be used to generate information that adds to the patient's social history in ways that are informative for anticipating and monitoring chemotherapy-related toxicities.

Dienogest versus gonadotropin-releasing hormone analogues for the clinical treatment of endometriosis: an updated meta-analysis

Endometriosis is a chronic gynecological condition where endometrial-like tissue grows outside the uterus, leading to persistent pelvic pain, dysmenorrhea, dyspareunia, and infertility. The objective of the systematic review was to examine the efficacy and safety of Dienogest, which is a synthetic, orally active 19-nortestosterone derivative, in the treatment of women with endometriosis compared to GnRH-a, which is commonly used to treat conditions like endometriosis. We conducted a search of PubMed, Google Scholar, and Cochrane Library databases from inception until August 2024 for clinical studies, using the following keywords: ("Dienogest") and ("gonadotropin-releasing hormone analogue" or GnRH Analogues OR GnRH agonist) and (Endometriosis). Relevant randomized control trials were identified. Pooled effect estimates were calculated using a random effect model. This meta-analysis included eight randomized controlled trials (RCTs) with 1,219 patients, 602 in the dienogest group and 617 in the GnRH analogue group. Both treatments were equally effective in controlling pain, dysmenorrhea, and dyspareunia, but dienogest offered advantages. Dienogest significantly reduced the recurrence rate (RR: 0.37, 95% CI [0.15, 0.91]; p=0.03) and hot flushes (RR: 0.24, 95% CI [0.10, 0.59]; p=0.002) and protected against bone mineral density (BMD) loss. However, it increased the risk of irregular vaginal bleeding (RR: 3.61, 95% CI [1.09, 11.97]; p=0.04). Other side effects, such as headache, vaginal dryness, spotting, and alopecia, were not statistically significant. It concluded that Dienogest has comparatively fewer side effects than GnRH analogue, making it a considerably safer option for treating endometriosis.

Menopause knowledge, attitudes and experiences of women in Saudi Arabia: a qualitative study

BackgroundMenopause can be seen as a complex phenomenon influenced by an individual’s cultural norms, belief systems, and lifestyle choices. In conservative societies such as Saudi Arabia, some women silently struggle with menopause due to cultural taboos and social stigma, making their experiences invisible and lowering their quality of life. The aim of this study was to explore in-depth the knowledge, attitudes, and experiences of middle-aged Saudi women with menopause.MethodsThe study employed qualitative methods using semi-structured interviews with middle-aged women undergoing menopause in Saudi Arabia from February to May 2023. The interviews were conducted online in Arabic, recorded and transcribed verbatim. The data were analysed inductively using thematic analysis.ResultsA total of twenty-nine women, aged 40–64 years, were interviewed. Three key themes were identified: mixed emotions towards menopause; experiencing biopsychosocial changes; and adapting to the transition. Overall, most participants had mixed perspectives on menopause. Negative aspects included feelings of uncertainty and the loss of fertility while positive aspects included a sense of relief from menstruation and the newfound freedom to engage in religious activities at any time. Notably, during the interviews, many participants reconsidered their initial negative views and voiced predominantly positive perspectives. Several women reported inconvenient menopausal symptoms, such as hot flashes, night sweats, disturbed sleep, and fatigue. Concerns about being perceived as less attractive led many to keep their symptoms private, and societal expectations played a significant role in influencing how women managed these symptoms and sought help. Many women opted to seek information discreetly online rather than seeking support from others. Self-care practices were favoured for managing menopause, with medical care being undervalued or at times deemed unsatisfactory.ConclusionIn Saudi Arabia, menopause is generally seen as a natural phase of life. Many women appreciate the positive aspects it brings, such as relief from menstrual pain and an enhanced ability to participate in religious practices. However, they also encounter challenges, including hot flashes and concerns about perceived decreases in attractiveness. A notable trend is the preference for self-care strategies over medical interventions or hormone replacement therapy (HRT). There is a need to raise awareness about menopausal symptoms to reduce negative perceptions and experiences and to develop health promotion and educational interventions to support and empower women during this transition. Future research with healthcare professionals would extend these findings.

Diet quality, body weight, and postmenopausal hot flashes: a secondary analysis of a randomized clinical trial

BackgroundA low-fat vegan diet, supplemented with soybeans, has been shown effective in reducing postmenopausal hot flashes. This secondary analysis assessed the association of a plant-based index (PDI), healthful (hPDI), and unhealthful (uPDI), with changes in hot flashes in postmenopausal women.MethodsParticipants (n = 84) were randomly assigned to a low-fat vegan diet supplemented with soybeans (n = 42) or a control group (n = 42) for 12 weeks. Three-day dietary records were analyzed and PDI indices were calculated. A repeated measures analysis of variance (ANOVA) was used for statistical analysis.ResultsAll three scores increased in the vegan group, compared with no change in the control group; the effect sizes were: PDI + 9.8 (95% CI + 5.8 to + 13.8; p < 0.001); hPDI + 10.9 (95% CI + 6.4 to + 15.3; p < 0.001); and uPDI + 3.6 (95% CI + 0.5 to + 6.6; p = 0.02). The change in all three scores negatively correlated with change in body weight (PDI: r=-0.48; p < 0.001; hPDI: r=-0.38; p = 0.002; and uPDI: r=-0.31; p = 0.01). The changes in PDI and uPDI were negatively associated with changes in severe hot flashes (r=-0.34; p = 0.009; and r=-0.43; p < 0.001, respectively), and associations remained significant after adjustment for changes in body mass index (r=-0.31; p = 0.02; and r=-0.41; p = 0.001, respectively).ConclusionsThese findings suggest that minimizing the consumption of animal products and oil may be an effective strategy to reduce hot flashes in postmenopausal women, and that categorization of plant foods as “healthful” or “unhealthful” may be unwarranted.Trial registrationClinicalTrials.gov, NCT04587154, registered on Oct 14, 2020.

The therapeutic role of exercise training during menopause for reducing vascular disease.

Menopause marks a major milestone in female reproductive ageing. It is characterized by the cessation of ovarian function and a concomitant decline in hormones such as oestradiol. Subsequently, females undergoing menopausal transition experience a progressive increase in cardiovascular and cerebrovascular disease risk. During menopause, reductions in nitric oxide (NO) bioavailability, endothelial dysfunction, increases in systemic inflammation, oxidative stress, and impaired vascular remodelling may contribute towards an accelerated decline in the function of cerebral and peripheral vascular systems. Historically, hormone therapy (HT) has been used as a means of managing vascular disease risk and reducing menopause-associated vasomotor symptoms such as hot flushes, though some studies suggest regular exercise has the potential to be a promising alternative. Regular aerobic exercise during early postmenopause may slow vascular decline by improving NO and oestradiol bioavailability, promoting positive vascular remodelling and lowering systemic inflammation. However, exercise-mediated improvements in markers of vascular function are not consistently observed in oestradiol-deficient postmenopausal women. Emerging evidence suggests that due to the greater oestradiol bioavailability during early postmenopause, vascular adaptations to exercise may be enhanced during this stage, as opposed to late postmenopause. Subsequently it may be important to begin regular exercise in the years preceding and immediately following the final menstrual period to slow the progression of vascular disease risk during perimenopause and beyond. The present review will provide a summary of our current understanding of how vascular function is affected during menopause and the role of regular aerobic and resistance exercise training in managing vascular disease risk.

In Vitro Evaluation of CYP-Mediated Metabolism of Fezolinetant and Pharmacokinetic Interaction Between Fezolinetant and Fluvoxamine in Healthy Postmenopausal Smokers and Nonsmokers.

Fezolinetant is an oral, nonhormonal, neurokinin 3 receptor antagonist treatment option for moderate to severe vasomotor symptoms associated with menopause. An in vitro study using human recombinant cytochrome P450 (CYP) enzymes and human liver microsomes showed that fezolinetant is metabolized to its major but inactive metabolite, ES259564, predominantly through CYP1A2, with minor contributions from CYP2C9 and CYP2C19. The clinical impact of CYP1A2 inhibition and induction on single-dose pharmacokinetics of fezolinetant was assessed in an open-label, single-sequence, phase 1 study in healthy postmenopausal women, where the impact of fluvoxamine, a strong CYP1A2 inhibitor, and smoking, a moderate CYP1A2 inducer, were evaluated. In total, 18 participants, 9 of whom were smokers, were enrolled. Fezolinetant pharmacokinetics were evaluated after a single 30-mg dose on Day 1 and Day 7. Fluvoxamine 50 mg was administered as a single dose on Days 3 and 10 and twice daily from Days 4 to 9. Fluvoxamine increased geometric mean ratio of fezolinetant maximum plasma concentrations (Cmax) and area under the curve from time of dosing extrapolated to infinity (AUCinf) to 182% and 939%, respectively, while ES259564 Cmax decreased to 20.1% with no significant change in AUC. In smokers versus nonsmokers, when fezolinetant was administered alone, fezolinetant Cmax and AUCinf decreased to 71.7% and 48.3%, respectively, while ES259564 Cmax increased to 130.2% and AUCinf decreased to 81.8%. A single oral 30-mg dose of fezolinetant was considered safe and well tolerated when co-administered with fluvoxamine in healthy postmenopausal women.

Evaluation of Peri Menopausal Syndrome at the Age Group of 43-48 Years. A Study from Tamilnadu, India

The perimenopause, sometimes referred to as the menopausal transition, is associated with significant changes in hormones and reproduction. Both these changes and the symptoms that go along with them have been well documented. The perimenopause is an ill- defined time frame that surrounds advancing years of a woman's reproductive life. The onset of irregular menstruation and its cessation after a year of amenorrhea constitute the final menstrual cycle. This study was conducted at the Sree Ramakrishna Medical College of Naturopathy and Yogic Sciences and Hospital in Kulasekharam, Tamil Nadu, India. The study's female participants were between the ages of 43 to 48. Following the description of the investigation's goals, vocal agreement was achieved. This survey had thirty responses. In this study the questionaire were consists of thirty questions such as hot flashes, thirst, pain, increased bleeding, and an unpleasant mood . Female participants who were unwilling or uncooperative were not included in the study. Many women find the menopausal transition to be a challenging time in their lives. If they lost any of their human potential, it would be catastrophic for both individuals and society. Therefore, it is essential to keep working to comprehend how perimenopause fits into women's lives and to predict and treat the common and uncommon symptoms that could lower their quality of life. Future health care initiatives should concentrate on these areas to enhance the general health and well-being of perimenopausal women.

Efficacy and safety of fezolinetant for moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy: phase 3b randomised controlled trial

ObjectivesTo assess the efficacy and safety of the non-hormonal, neurokinin 3 receptor antagonist, fezolinetant, to treat moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy.DesignPhase 3b randomised...

Study on gut microbiota and metabolomics in postmenopausal women

Menopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16 s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis.

Are neurokinin 3 receptor antagonists effective in treatment of menopausal vasomotor symptoms?

Are neurokinin 3 receptor antagonists effective in treatment of menopausal vasomotor symptoms?