Menopausal Vasomotor Symptoms Research Articles

Kisspeptin and Neurokinin B: roles in reproductive health

Kisspeptin and neurokinin B (NKB) play a key role in several physiological processes including in puberty, adult reproductive function including the menstrual cycle, as well as mediating the symptoms of menopause. Infundibular kisspeptin neurons, which co-express NKB, regulate the activity of gonadotropin releasing hormone (GnRH) neurons, and thus the physiological pulsatile secretion of GnRH from the hypothalamus. Outside of their hypothalamic reproductive roles, these peptides are implicated in several physiological functions including sexual behavior and attraction, placental function, and bone health. Over the last two decades, research findings have considerably enhanced our understanding of the physiological regulation of the hypothalamic-pituitary-gonadal (HPG) axis and identified potential therapeutic applications. For example, recognition of the role of kisspeptin as the natural inductor of ovulation has led to research investigating its use as a safer, more physiological trigger of oocyte maturation in <em>in vitro</em> fertilization (IVF) treatment. Moreover, the key role of NKB in the pathophysiology of menopausal hot flashes has led to the development of pharmacological antagonism of this pathway. Indeed, Fezolinetant, a neurokinin 3 receptor antagonist, has recently received Food and Drug Administration (FDA) approval for clinical use to treat menopausal vasomotor symptoms. Herein, we discuss the roles of kisspeptin and NKB in human physiology, including in the regulation of puberty, menstrual cyclicity, reproductive behavior, pregnancy, menopause, and bone homeostasis. We describe how perturbations of these key physiological processes can result in disease states and consider how kisspeptin and NKB could be exploited diagnostically, as well as therapeutically to treat reproductive disorders.

Searching for an oasis from the vasomotor symptoms of menopause: Could elinzanetant be the answer?

In the OASIS 1 and 2 trials, elinzanetant, a selective neurokinin-1,3 receptor antagonist, was compared to placebo in women aged 40-65 with moderate to severe menopausal vasomotor symptoms (VMSs) at multiple sites over 26weeks. Elinzanetant significantly reduced VMS frequency and severity and improved sleep disturbance and menopause-related quality of life compared to placebo with few adverse side effects.1.

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

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

7497 Association between Plasma Prolactin Levels and Menopausal Vasomotor Symptoms

Abstract Disclosure: F. Galbiati: None. J. Kang: None. D.J. Cote: None. J.E. Manson: None. U.B. Kaiser: None. Background: High prolactin (PRL) levels inhibit gonadotropin-releasing hormone (GnRH), causing hypogonadism. GnRH release is regulated by neurokinin B (NKB) and kisspeptin. NKB antagonists are used in treatment of menopausal hot flashes and vasomotor symptoms (VMS). In mice and humans with hyperprolactinemic anovulation, kisspeptin restored ovarian cyclicity and LH pulsatility. However, the interplay between kisspeptin and PRL is not fully understood. In two menopausal women with hyperprolactinemia and central hypogonadism, treatment with bromocriptine led to PRL normalization and new-onset VMS, suggesting that hyperprolactinemia inhibited VMS associated with hypogonadism. We aimed to investigate the association between PRL and menopausal VMS in women from the Nurses’ Health Study I and II (NHS, NHSII). We hypothesized that women with higher PRL levels would have a lower frequency/severity of menopausal VMS. Methods: We conducted a cohort study of 2618 females enrolled in NHS (n=1692) and NHSII (n=926) in whom blood samples were collected between 1989-99, were not pregnant or on hormonal therapy, and were either pre or post-menopausal as of blood draw. Subjects were free of breast, ovarian and other cancers, and provided complete data on VMS at menopause as well as in the past 4 weeks (assessed in 2008 in NHS and 2009, 2013, 2017 in NHSII). Plasma PRL was measured as part of 28 case-control studies of various health outcomes. We evaluated the presence and severity of VMS at menopause and 4 weeks prior to the questionnaire, as well as duration (in years) of VMS. We used multiple logistic regression, adjusting for covariates to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). Results: Women were aged 33-65 years at blood draw; range for years from blood draw to menopause was -10 to 10 (median=1.8) years; range for years from blood draw to report of VMS (both at menopause and current VMS) was 9.8 to 22 years. Mean PRL (SD; range) was 14.7ng/mL (10.1; 0.08-246). Women with the highest PRL levels were likely to be younger and less likely to be current smokers or obese. 77.4% of women reported VMS at menopause and 47.6% in recent 4 weeks; 52.3% reported moderate-to-severe VMS at menopause and 32.0% reported VMS in recent 4 weeks. Overall, PRL was not associated with duration of VMS or moderate-to-severe VMS at menopause or in the past 4 weeks; compared to the lowest quintile (≤8.0ng/mL), those in the highest PRL quintile (≥18.2ng/mL) had MVRR of 1.23(95%CI=0.94,1.60) for moderate-to-severe menopausal VMS and 1.03(95%CI=0.67,1.59) for recent VMS. Menopausal status did not affect the association between prolactin levels and VMS. Conclusion: PRL levels were not associated with occurrence, severity, or duration of menopausal VMS in a large cohort of women. Presentation: 6/1/2024

Phase 2A Efficacy, Safety, and Tolerability Study of PH80 Nasal Spray for Acute Management of Menopausal Vasomotor Symptoms (Hot Flashes) in Women

Phase 2A Efficacy, Safety, and Tolerability Study of PH80 Nasal Spray for Acute Management of Menopausal Vasomotor Symptoms (Hot Flashes) in Women

Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause

Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed. To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms. Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023). Once daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks. Primary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12. Eligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: -3.3 [95% CI, -4.5 to -2.1], P < .001; OASIS 2: -3.0 [95% CI, -4.4 to -1.7], P < .001) and at week 12 (OASIS 1: -3.2 [95% CI, -4.8 to -1.6], P < .001; OASIS 2: -3.2 [95% CI, -4.6 to -1.9], P < .001). Elinzanetant also improved VMS severity at week 4 (OASIS 1: -0.3 [95% CI, -0.4 to -0.2], P < .001; OASIS 2: -0.2 [95 CI, -0.3 to -0.1], P < .001) and week 12 (OASIS 1: -0.4 [95% CI, -0.5 to -0.3], P < .001; OASIS 2: -0.3 [95% CI, -0.4 to -0.1], P < .001). Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable. Elinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS. ClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159.

Menopausal Vasomotor Symptoms and Subclinical Atherosclerotic Cardiovascular Disease: A Population-Based Study.

Menopausal vasomotor symptoms (VMS) are increasingly emphasized as a potentially important cardiovascular risk factor, but their role is still unclear. We assessed the association between VMS and subclinical atherosclerotic cardiovascular disease in peri- and postmenopausal women. Using a cross-sectional study design, questionnaire data were collected from a population-based sample of women aged 50 to 64. The questionnaire asked whether menopause was/is associated with bothersome VMS. A 4-point severity scale was used: (1) never, (2) mild, (3) moderate, and (4) severe. The VMS duration and time of onset were also assessed. Associations with subclinical atherosclerotic cardiovascular disease, detected via coronary computed tomography angiography, coronary artery calcium score, and carotid ultrasound were assessed using the outcome variables "any coronary atherosclerosis," "segmental involvement score >3," "coronary artery calcium score >100," and "any carotid plaque," using logistic regression. Covariate adjustments included socioeconomic, lifestyle, and clinical factors. Of 2995 women, 14.2% reported ever severe, 18.1% ever moderate, and 67.7% ever mild/never VMS. Using the latter as reference, ever severe VMS were significantly associated with coronary computed tomography angiography-detected coronary atherosclerosis (multivariable adjusted odds ratio, 1.33 [95% CI, 1.02-1.72]). Corresponding results for ever severe VMS persisting >5 years or beginning before the final menstrual period were 1.50 (95% CI, 1.07-2.11) and 1.66 (95% CI, 1.10-2.50), respectively. No significant association was observed with segmental involvement score >3, coronary artery calcium score >100, or with any carotid plaque. Ever occurring severe, but not moderate, VMS were significantly associated with subclinical coronary computed tomography angiography-detected atherosclerosis, independent of a broad range of cardiovascular risk factors and especially in case of long durations or early onset.

Management of the Vasomotor Symptoms of Menopause: Twofers in Your Clinical Toolbox.

The number of midlife women transitioning into menopause is substantial, with more than 1 million women in the United States entering menopause each year. Vasomotor symptoms (VMS), mood and sleep disturbances, and sexual problems are common during the menopause transition yet often go untreated. Menopausal hormone therapy is the most effective treatment of VMS, and the benefits typically outweigh the risks for women without contraindications who are younger than 60 years or within 10 years from menopause onset. For women who cannot or choose not to use hormone therapy, nonhormone prescription options exist to treat VMS. Many of these therapies have secondary benefits beyond VMS relief. For example, whereas paroxetine is Food and Drug Administration approved to treat VMS, it can also help with depressive and anxiety symptoms. The aim of this paper is to summarize prescription treatments of VMS and their secondary benefits for other common symptoms experienced by midlife women. The tools presented will help clinicians caring for midlife women provide individualized, comprehensive care with the goal of improving their quality of life during the menopause transition and beyond.

Short- and long-term impact by vasomotor symptoms in menopause and modern approaches to their correction

The importance of management in women in menopause and postmenopause is not diminishing, but only gaining relevance. It is estimated that by 2050, more than 1.6 billion women worldwide will reach this age, compared to 1 billion in 2020. Vasomotor symptoms (VMS) are the most common symptoms of menopause and affect more than 70% of women. They are diagnosed in 35-50% of women in perimenopause and 30-80% women in postmenopause. Most of these symptoms persist less than 7 years after the last menstrual period, but one in four women may experience them up to 10 years, and one in ten women may experience them after 10 years. They are based on complex endocrine, neuroendocrine and epigenetic mechanisms. This article is a review of scientific literature publications aimed at determining the impact of VMSs on women’s future life based on the analysis of published modern studies.VMSs not only have a negative impact on a woman’s quality of life, but also have potential importance for cardiovascular health. The increased risk of cardiovascular diseases (CVD) after menopause is attributed to a sharp decrease of endogenous estrogen levels, which indicates its potential cardioprotective effect in premenopausal women. It has been established that VMSs are a risk factor for coronary heart disease and diabetes mellitus. The presence of non-alcoholic fatty liver disease is also significantly associated with an increased risk of early and severe forms of VMSs among perimenopausal women.Taking into account that women spend a third of their lives in the postmenopausal period, it is important to analyze the experience of their management during this difficult period. It is based on focusing on a healthy lifestyle as part of primary prevention, including regular physical activity, calcium/vitamin D intake, maintaining an optimal body weight, avoiding stress, etc. Menopausal hormone therapy (MHT) is considered as a first-line treatment for VMSs in menopause and perimenopause. Its use should be individualized, and initiation and discontinuation should not be based only on a woman’s age. Assessment of baseline CVD risk, age and period since menopause are important. It is considered a priority for women with menopause before 10 years or under 60 years of age who have no contraindications to MHT. Hormone therapy is not indicated only for the prevention of CVD. However, it has the potential to improve cardiovascular risk profile due to its beneficial effects on vascular function, lipid levels, glucose metabolism, and reduction of diabetes mellitus.Non-hormonal VMS treatment has sufficient experience of use when there are medical contraindications to hormonal therapy or a woman’s personal choice. However, MHT remains the most effective for VMS treatment.

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.

Estetrol for the Treatment for Menopausal Vasomotor Symptoms: Phase 2 and Phase 3 Efficacy Results

Estetrol for the Treatment for Menopausal Vasomotor Symptoms: Phase 2 and Phase 3 Efficacy Results

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

The effect of black cohosh extract and risedronate coadministration on bone health in an ovariectomized rat model.

Preparations of black cohosh extract are sold as dietary supplements marketed to relieve the vasomotor symptoms of menopause, and some studies suggest it may protect against postmenopausal bone loss. Postmenopausal women are also frequently prescribed bisphosphonates, such as risedronate, to prevent osteoporotic bone loss. However, the pharmacodynamic interactions between these compounds when taken together is not known. To investigate possible interactions, 6-month-old, female Sprague-Dawley rats underwent bilateral ovariectomy or sham surgery and were treated for 24weeks with either vehicle, ethinyl estradiol, risedronate, black cohosh extract or coadministration of risedronate and black cohosh extract, at low or high doses. Bone mineral density (BMD) of the femur, tibia, and lumbar vertebrae was then measured by dual-energy X-ray absorptiometry (DEXA) at weeks 0, 8, 16, and 24. A high dose of risedronate significantly increased BMD of the femur and vertebrae, while black cohosh extract had no significant effect on BMD individually and minimal effects upon coadministration with risedronate. Under these experimental conditions, black cohosh extract alone had no effect on BMD, nor did it negatively impact the BMD-enhancing properties of risedronate.

Top studies of 2023 relevant to primary care: From the PEER team.

To provide a summary of the noteworthy medical articles published in 2023 that are relevant to family physicians. Articles were chosen and ranked by the PEER (Patients, Experience, Evidence, Research) team, a group of primary care health professionals focused on evidence-based medicine. The selection process involved routine surveillance of tables of contents in high-impact medical journals and continuous monitoring of EvidenceAlerts. Articles were prioritized based on their direct applicability to and potential to influence primary care practice. Selected articles addressed various clinical areas of primary care. The topics included a comparison of a treat-to-target approach versus a high-intensity statins prescription for lipid management; semaglutide and its impact on cardiovascular outcomes; respiratory syncytial virus vaccine for older adults; chlorthalidone versus hydrochlorothiazide in preventing cardiovascular events; amitriptyline for irritable bowel syndrome; the role of opioids in acute back pain; safety of oral penicillin challenges in patients allergic to penicillin; spironolactone for facial acne; strategies to reverse frailty in older adults; and identifying the provider of chronic disease management. Two "up and coming" medications are also mentioned: retatrutide for weight loss and fezolinetant for vasomotor symptoms of menopause. Research published in 2023 yielded several high-quality articles with topics relevant to primary care, including cardiovascular care, irritable bowel syndrome, care of the elderly, and acne management.

Nonhormone therapies for vasomotor symptom management.

Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.

FDA approved fezolinetant (Veozah): a critical evaluation of its efficacy and safety for menopausal vasomotor symptoms, calling for prospective research.

Women going through menopause frequently experience vasomotor symptoms such as hot flashes, night sweats, and sleep disturbances, significantly influencing their quality of life. Hormonal therapy has been demonstrated to be beneficial in treating VMS. However, due to specific restrictions, it is not recommended for every woman. Fezolinetant, a neurokinin 3 antagonist and non-hormonal treatment for severe to moderate VMS, functions by inhibiting neuronal impulses originating from the hypothalamic thermoregulatory center. Current Skylight 2 and 4 trials statistically demonstrate the safety and acceptability of fezolinetant, with relatively few adverse effects reported. Fezolinetant has been shown great potential for treating menopausal-related VMS, supporting its further advancement. However, further investigation is required to thoroughly evaluate its safety, effectiveness, and its impact on sleep patterns.

Kisspeptin and neurokinin B neuroendocrine pathways in the control of human ovulation.

The roles of initially kisspeptin and subsequently neurokinin B pathways in the regulation of human reproduction through the control of GnRH secretion were first identified 20 years ago, as essential for the onset of puberty in both boys and girls. Within that short time we already now have the first licence for clinical use for a neurokinin antagonist in a related indication, for menopausal vasomotor symptoms. Between these two markers of the start and end of the reproductive lifespan, it is clear that these pathways underlie many of the aspects of the hypothalamic regulation of reproduction which had hitherto been enigmatic. In this review, we describe the data currently available from studies designed to elucidate the roles of kisspeptin and neurokinin B in human ovarian function, specifically the regulation of follicle development leading up to ovulation, and in the control of the mid-cycle GnRH/LH surge that triggers ovulation. These studies, undertaken with only very limited pharmacological tools, provide evidence that the neurokinin B pathway is important in controlling the hypothalamic contribution to the precise gonadotropic drive to the ovary that is necessary for mono-ovulation, whereas the switch from negative to positive estrogenic feedback results in kisspeptin-mediated increased GnRH secretion. Potential therapeutic opportunities in conditions characterised by disordered hypothalamic/pituitary function, polycystic ovary syndrome, and functional hypothalamic amenorrhoea, and in the induced LH surge that is a necessary part of IVF treatment are discussed.

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms: A Meta-analysis.

To evaluate the efficacy and adverse events of fezolinetant for treating vasomotor symptoms (VMS) of menopause. PubMed/MEDLINE, ClinicalTrials.gov , EMBASE, Cochrane Database, Scopus, and WHO International Clinical Trials Registry Platform were searched through June 2023 for publications and randomized controlled trials on fezolinetant compared with placebo in menopausal women who experienced moderate-to-severe VMS. Our literature search identified 330 articles, of which five studies with six reports were included in our meta-analysis per our eligibility criteria. The risk of bias was evaluated using Cochrane's RoB 2 (Risk of Bias version 2) tool, quality of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, and outcome measures data for effect size were pooled in random-effects model and rated. A total of 2,168 participants from five randomized clinical trials (six reports) were included. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI, 1.84-3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was -0.60 (95% CI, -0.92 to -0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35-29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo. Fezolinetant is effective in lowering moderate-to-severe VMS frequency and sleep disturbances in postmenopausal women. PROSPERO, CRD42023427616.

The efficacy of purified pollen extract for reducing vasomotor symptoms in women: a systematic review and meta-analysis.

Menopause impacts the quality of life for women, with symptoms varying from hot flashes to night disturbances. When menopausal hormonal therapy is contraindicated or women refuse menopausal hormonal therapy, many consider alternatives such as pollen extract for treating vasomotor symptoms. This meta-analysis focuses on the impact of using purified pollen extract as a treatment option to reduce vasomotor symptoms in women, specifically focusing on symptoms such as hot flashes, night disturbances, myalgias, and depression. A comprehensive literature search was conducted using the following Boolean search string "women OR females" AND "purified pollen OR pollen extract OR cytoplasmic pollen OR Bonafide OR Femal OR Estroven OR Serelys" AND "menopausal symptoms OR vasomotor symptoms OR hot flashes OR night sweats OR sleep disturbance." Publications in English from 2003 to the present were included. To assess the risk of bias, authors used the Cochrane Risk-of-Bias 2 for a randomized controlled trial and Risk-of-Bias in Non-Randomized Studies of Interventions (ROBINS-I) for observational studies. Using ReviewManager, a Der Simonian-Laird random-effects model meta-analysis was conducted to determine the standardized mean differences (SMDs) in the outcomes for each study. Five articles were retained: one randomized controlled trial and four observational studies ( N = 420). An overall decrease in scores from the baseline of studies compared with a 3-month follow-up after purified cytoplasm of pollen (PCP) treatment was recognized when compiling the data. Overall, there was significant improvement across all outcomes at 3 months: hot flashes demonstrated an overall improvement in SMD of -1.66 ( P < 0.00001), night disturbance scores were improved with an SMD of -1.10 ( P < 0.0001), depression scores were improved with an SMD of -1.31 ( P < 0.0001), and myalgia had an improvement in SMD of -0.40 ( P < 0.00001). When controlled studies were pooled for meta-analysis, outcomes, however, were no longer statistically significant. Evaluating the risk-to-benefit ratio of alternative therapies, such as PCP extract, is important to care for women who cannot take traditional vasomotor symptom therapies. Pooled data from controlled studies evaluating PCP extract suggest that vasomotor symptom improvements seen in noncontrolled studies may have been due to the placebo effect; however, its use was not associated with significant adverse effects.