Systematic review of neurokinin-3 receptor antagonists for the management of vasomotor symptoms of menopause.

IMPORTANCE: Vasomotor symptoms (VMS) affect many postmenopausal persons and impact sleep and quality of life. OBJECTIVE: This systematic review examines the literature describing the safety and efficacy of neurokinin-3 receptor antagonists approved and in development for postmenopausal persons with VMS. EVIDENCE REVIEW: A search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted using the search terms and permutations of neurokinin-3 receptor antagonist, elinzanetant, fezolinetant, and osanetant. Inclusion criteria of reporting on efficacy or safety of fezolinetant, elinzanetant, or osanetant; studies in participants identifying as female; full record in English; and primary literature were applied. Abstract-only records were excluded. Extracted data were synthesized to allow comparison of reported study characteristics, efficacy outcomes, and safety events. Eligible records were evaluated for risk of bias via the Cochrane Risk of Bias 2 tool for randomized studies and the Grading of Recommendations Assessment, Development and Evaluation system was used. This study was neither funded nor registered. FINDINGS: The search returned 191 records; 186 were screened after deduplication. Inclusion criteria were met by six randomized controlled trials (RCT), four reported on fezolinetant, and two reported on elinzanetant. One record was a post hoc analysis of a fezolinetant RCT. An additional study was identified outside the database search. Three fezolinetant RCT demonstrated a reduction in VMS frequency/severity, improvement in Menopause-Specific Quality of Life scores, and improvement in sleep quality at weeks 4 and 12 compared with placebo without serious adverse events. The two RCT on elinzanetant also showed improvements in VMS frequency and severity. All eight records evaluated safety through treatment-emergent adverse events; the most common adverse events were COVID-19, headache, somnolence, and gastrointestinal. Each record evaluated had a low risk of bias. There is a strong certainty of evidence as per the Grading of Recommendations Assessment, Development and Evaluation system. CONCLUSIONS AND RELEVANCE: Because of the high-quality evidence supporting the efficacy of fezolinetant and elinzanetant, these agents may be an effective option with mild adverse events for women seeking nonhormone treatment of VMS.

Efficacy and safety of traditional Chinese medicine in the treatment of menopause-like syndrome for breast cancer survivors: a systematic review and meta-analysis.

BACKGROUND: In recent years, breast cancer (BC) incidence and mortality have been the highest in females. Menopause-like syndrome (MLS), arising from hypoestrogenism caused by endocrine therapy, significantly affects the quality of life for females. Traditional Chinese Medicine (TCM) has advantages in ameliorating MLS, but the efficacy of TCM in patients with BC has not been systematically evaluated. METHODS: A comprehensive search was performed on PubMed, Web of Science, Embase, Ovid, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Clinical Trial Registry from inception to September 4, 2023. The Cochrane Risk of Bias assessment tool was used for the quality evaluation of the randomized controlled trials (RCTs). Review Manager 5.4 software was used for statistical analysis, and the Grading of Recommendations Assessment, Development, and Evaluation was used for quality evaluation of the synthesized evidence. RESULTS: This review included 42 studies involving 3112 female patients with BC. The results showed that the TCM group was better at decreasing the Kupperman Menopausal Index (KMI) scores (standardized MD, SMD = - 1.84, 95% confidence interval, CI [- 2.21--1.46], Z = 9.63, P < 0.00001). Regarding the main symptoms of MLS, the TCM groups could significantly decrease the scores of hot flashes and night sweats (SMD = - 0.68, 95% CI [- 1.1--0.27], Z = 3.24, P = 0.001), paraesthesia (SMD = - 0.48, 95% CI [- 0.74--0.21], Z = 3.53, P = 0.0004), osteoarthralgia (SMD = - 0.41, 95% CI [- 0.6-0.21], Z = 4.09, P < 0.0001), anxiety (MD = - 0.85, 95% CI [- 1.13, - 0.58], Z = 6.08, P < 0.00001) and insomnia (MD = - 0.61, 95% CI [- 0.8, - 0.43], Z = 6.51, P < 0.00001). TCM can effectively improve the symptoms of MLS in patients with BC. Moreover, TCM could improve the objective response rate (ORR) by 50% (RR = 1.5, 95% CI [1.37-1.64], Z = 9.01, P < 0.00001). Follicle-stimulating hormone (FSH) and oestradiol (E2) had no significant difference compared with the control group (p = 0.81 and p = 0.87), and luteinizing hormone (LH) in the TCM group decreased significantly (MD = - 0.99, 95% CI [- 1.38, - 0.5], Z = 5.01, P < 0.00001). This means that the use of TCM does not negatively affect endocrine therapy and may even have a synergistic effect. The incidence of adverse events (AEs) was lower in the TCM groups than in the control groups. CONCLUSIONS: The meta-analysis stated that TCM could better improve the MLS of patients, alleviate related symptoms, and did not increase adverse drug reactions in BC survivors. This review brings more attention to MLS, and the present findings shed light on the potential applications of TCM in the treatment of MLS in BC survivors.

Evaluación del impacto, los patrones de tratamiento y las percepciones de pacientes y clínicos de los síntomas vasomotores moderado-graves asociados a la menopausia en España / Analysis of the impact, patterns of care, and perspectives of patients and physicians about moderate-to-severe menopausal vasomotor symptoms in Spain

Introducción: La menopausia puede originar distintos síntomas, siendo los vasomotores especialmente prevalentes y molestos. Este trabajo pretende conocer su impacto y los patrones/percepciones sobre el tratamiento en España, para lo que se han analizado las opiniones de clínicos y pacientes con síntomas vasomotores moderado-graves (SVM-MG). Métodos: Estudio transversal descriptivo de la subpoblación española del Programa de Enfermedades Específicas de Adelphi-VMS™. Médicos de atención primaria y de Ginecología y Obstetricia seleccionaron las pacientes. Estas fueron invitadas a rellenar una encuesta y los cuestionarios MENQOL y WPAI:SHP. Los datos se han presentado como porcentaje o media±desviación estándar. Resultados: Un total de 32 médicos de Atención Primaria y Ginecología y Obstetricia completaron los formularios de registro para 241 mujeres, de las cuales 143 experimentaban SVM-MG. A pesar del impacto global reportado en el trabajo (24,84%±17,49 presentismo) y en la calidad de vida (3,37±1,52 MENQOL), solo el 53,85% de las mujeres eran tratadas. El tratamiento hormonal de la menopausia era el más prescrito (77,92%), seguido de los inhibidores de la recaptación de serotonina (32,47%). El 59% de los clínicos estaba muy o completamente satisfecho con el tratamiento hormonal de la menopausia, mientras que solo el 19% lo estaba con los inhibidores de la recaptación de serotonina. Pacientes y especialistas indicaron un nivel de satisfacción inferior al 38% en el control de los SVM. Conclusiones: Los SVM-MG asociados a la menopausia tienen un importante impacto sobre la calidad de vida. Una mayor sensibilización en su manejo y mejores opciones terapéuticas contribuirían significativamente a mejorar la salud y bienestar de la mujer durante el climaterio.(AU)

Introduction: Menopause generates different symptoms, among which vasomotor symptoms are especially prevalent and bothersome. The aim of this work was to determine their impact and the treatment patterns and perceptions in Spain by analyzing the opinions of physicians and patients with moderate-to-severe vasomotor symptoms (MS-VMS). Methods: Descriptive cross-sectional study of the Spanish subpopulation from the Adelphi-VMS™ Disease-Specific Program. Primary Care and Gynecology and Obstetrics physicians selected the patients. These patients were invited to complete a survey and the MENQOL and WPAI:SHP questionnaires. Data are presented as percentage or mean±standard deviation. Results: Overall 32 Primary Care and Gynecology and Obstetrics physicians participated in the study, enrolling 241 women, of whom 143 experienced MS-VMS. Despite the reported impact on global work (24.84%±17.49 presentism) and quality of life (3.37±1.52 MENQOL score), only 53.85% of women with MS-VMS were treated. Menopausal hormone treatment was the most prescribed (77.92%), followed by serotonin reuptake inhibitors (32.47%). Fifty-nine percent of clinicians were very or completely satisfied with hormone treatment, whereas only 19% had this level of satisfaction with selective serotonin reuptake inhibitors. Less than 38% of patients and physicians were satisfied with the control of VMS. Conclusions: Menopause-associated MS-VMS have an important impact on quality of life. Increased awareness about their management and better therapeutic options would significantly contribute to improving women's health and well-being during their climacteric period.(AU)

Fezolinetant: un nuevo tratamiento en estudio para la menopausia / Fezolinetant: A new treatment being studied for menopause

La menopausia es el cese fisiológico de la menstruación que puede presentarse en las mujeres entre los 42 y 58 años con una sintomatología diversa. La clínica más frecuente es la vasomotora, que puede afectar en gran medida a la calidad de vida de las mujeres. Tradicionalmente se ha usado la terapia hormonal sustitutiva, que se considera el tratamiento más efectivo. Sin embargo, existe una serie de contraindicaciones por las que se debe plantear el uso de una terapia no hormonal. Actualmente estas opciones son subóptimas en efectividad y tolerancia, por lo que se está investigando acerca de nuevos tratamientos como el fezolinetant, un antagonista del receptor de neuroquinina 3. Para dilucidar dichas investigaciones se ha realizado una búsqueda bibliográfica en las principales bases de datos. Aunque aún queda por establecer su seguridad y efectos a largo plazo, la terapia con fezolinetant parece ser prometedora en pacientes en las que no se puede usar terapia hormonal. Disminuye la sintomatología vasomotora moderada o grave desde el primer día de tratamiento de manera estadísticamente significativa al compararla con placebo y con otros tratamientos no hormonales, con un buen perfil de tolerancia y escasos efectos secundarios. Sin embargo, este medicamento aún se encuentra en ensayos de fase III, por lo que se necesita continuar con su estudio.(AU)

Menopause is the physiological cessation of menstruation that can occur in women between 42 and 58 years of age with diverse symptoms. The most common clinic is vasomotor, which can greatly affect the quality of life of women. Traditionally, hormone replacement therapy has been used and is considered the most effective treatment. However, there are contraindications for which the use of non-hormonal therapy should be considered. Nowadays, these options are suboptimal in terms of effectiveness and tolerance, which is why research is being carried out on new treatments such as fezolinetant, a neurokinin 3 receptor antagonist. To elucidate these investigations a bibliographic search has been carried out in the main databases. Although its safety and long-term effects remain to be established, fezolinetant looks promising in patients for whom hormonal therapy cannot be used. It decreases statistically significant the moderate or severe vasomotor symptoms from the first day of treatment when compared with placebo and with other non-hormonal treatments with a good tolerance profile and few side effects. However, this drug is still in phase III trials, so it needs to continue with its study.(AU)

Management of Menopausal Symptoms: A Review.

Importance: Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]). Observations: Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene. Conclusions and Relevance: During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.

Gray matter differences associated with menopausal hormone therapy in menopausal women: a DARTEL-based VBM study.

Menopausal hormone therapy (MHT) in women can reduce troublesome menopause symptoms and prevent cognitive decline. This cross-sectional study investigated the MHT-related effect on brain morphology and its association with sex hormones in menopausal women by using an optimized diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL)-based voxel-based morphometry (VBM) method. Twenty-one menopausal women without MHT (noMHT) and 20 menopausal women with MHT were included in this study. Magnetic resonance imaging data were processed using SPM 12 with DARTEL-based VBM whole brain analysis approach. A 2-sample t-test and analysis of covariance (ANCOVA) adjusting for age and total intracranial volume were used to compare GM volume between noMHT and MHT women. The association between MHT (treatment period, hormones levels) and brain volume variations were analyzed by Spearman correlation. MHT women showed significantly larger volumes of the superior/middle/inferior frontal gyri, hypothalamus, inferior temporal gyrus, parahippocampal gyrus, hippocampus, cerebellar cortex, postcentral gyrus, precuneus, angular gyrus, supplementary motor area, superior occipital gyrus, and precentral gyrus compared to the noMHT women. The volumes of the angular gyrus and hypothalamus in MHT women positively correlated with treatment period. On the other hand, the hypothalamic volume negatively correlated with FSH and LH levels, and the volumes of the inferior frontal gyrus, and angular gyrus negatively correlated with progesterone levels, respectively. MHT-treated women showed larger GM volume than noMHT women. The anatomical structures that showed greater volume in association with MHT included the deep brain areas, frontal, temporal, parietal, and occipital gyri.

Novel Evidence-Based Combination of Plant Extracts with Multitarget Mechanisms of Action for the Elimination of Hot Flashes during Menopause.

Hot flashes are considered the most bothersome complaint during menopause. Although hormone therapy is an effective option to relieve hot flashes, it has been associated with significant side effects. The aim of our study is to suggest a novel combination of different plant extracts with distinct mechanisms of action against hot flashes. We selected the rhizome of Glycyrrhiza glabra L. (Fabaceae), the rhizome of Actaea racemosa L. (Ranunculaceae), the aerial parts of Hypericum perforatum L. (Hypericaceae) to produce extracts rich in bioactive phytochemicals and the seed oil of Oenothera biennis L. (Onagraceae). We investigated their estrogenic and antioxidant potential and their inhibitory effect against prostaglandin D2 receptor 1 (DP1) as a novel mechanistic pathway for vasodilation in hot flashes, alone or in combination. The phytochemical footprint of the extracts was analyzed using HPLC-PDA and UPLC-HRMS. We observed that the tested extracts possess different mechanisms of action. A. racemosa exerts a beneficial activation of the estrogen receptor, H. perforatum possesses the highest antioxidant capacity and the seed oil of O. biennis inhibits the DP1 receptor. The triple combination in the optimal doses pertains to efficacy against all three mechanisms of action, serves as a multitarget plant-based therapy and could serve as a novel strategy for the alleviation of hot flashes in postmenopausal women.

Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics.

This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor ß((ERß) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics.

Moving beyond inclusion: Methodological considerations for the menstrual cycle and menopause in research evaluating effects of dietary nitrate on vascular function.

Recent reports have acknowledged the underrepresentation of women in the field of dietary nitrate (NO3-) research. Undoubtedly, greater participation from women is warranted to clarify potential sex differences in the responses to dietary NO3- interventions. However, careful consideration for the effects of sex hormones - principally 17ß-estradiol - on endogenous nitric oxide (NO) synthesis and dietary NO3- reductase capacity is necessary for improved interpretation and reproducibility of such investigations. From available literature, we present a narrative review describing how hormonal variations across the menstrual cycle, as well as with menopause, may impact NO biosynthesis catalyzed by NO synthase enzymes and NO3- reduction via the enterosalivary pathway. In doing so, we address methodological considerations related to the menstrual cycle and hormonal contraceptive use relevant for the inclusion of premenopausal women along with factors to consider when testing postmenopausal women. Adherence to such methodological practices may explicate the utility of dietary NO3- supplementation as a means to improve vascular function among women across the lifespan.

Estrogenic activity of Sage (Salvia officinalis L.) aerial parts and its isolated ferulic acid in immature ovariectomized female rats.

ETNOPHARMACOLOGICAL RELEVANCE: Common sage (Salvia officinalis L., Lamiaceae), a medicinal plant of Mediterranean origin, has been traditionally applied in cases of excessive sweating, and in menopausal complaints, including hot flushes. AIM OF THE STUDY: This study aims to study the possible estrogenic effect of the aerial parts of S. officinalis ethanolic extract in immature ovariectomized female rats. MATERIALS AND METHODS: The ethanolic extract was subjected to qualitative and quantitative HPLC analysis and phytochemical isolation. The estrogenic activity of S. officinalis ethanolic extract at oral doses of 50, 100 and 200 mg/kg b.wt. and its isolated ferulic acid at a dose of 50 mg/kg b.wt. for a week, was assessed on ovariectomized immature Wistar rats. The experiment was confirmed by luteinizing hormone (LH) and follicle stimulating hormone (FSH) serum levels determination, a histopathological examination and a histomorphometrical study. RESULTS: HPLC/PDA analysis revealed fourteen phenolic compounds the major constituents were methyl rosmarinate (24.86 mg/100 g) and ferulic acid (6.06 mg/100 g) together with five flavonoids where the major constituents were rutin, naringenin and quercetin. Two compounds were isolated from the polar fraction and identified as methyl rosmarinate (1) and ferulic acid (2). Oral administration of sage ethanolic extract and ferulic acid revealed a significant increase in the uterine weight compared to ovariectomized control rats. Moreover, S. officinalis and ferulic acid showed different phases of estrus cycle denoting estrogenic activity, and significantly decreased the serum levels of FSH and LH. CONCLUSION: From these results it could be concluded that S. officinalis ethanolic extract and its content of ferulic acid could be useful as a safe natural source for estrogenic activity, supporting its traditional use to improve postmenopausal symptoms.

Elucidating the estrogen-like effects and biocompatibility of the herbal components in the Qing' E formula.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qing' E Formula (QEF) is a compound preparation that was originally recorded in the 'Prescriptions of the Bureau of Taiping People's Welfare Pharmacy' during the Song Dynasty (10th century CE). It consists of four Chinese medicinal herbs, Eucommiae Cortex (Eucommia ulmoides), Psoraleae Fructus (Psoralea corylifolium), Juglandis Semen (Juglans regia), and Garlic Rhizoma. According to traditional Chinese medicine (TCM), QEF has the ability to tonify the kidney and strengthen muscle and bone. According to the 'kidney governing bone' theory in TCM, QEF is also used to treat the symptoms of climacteric syndrome, especially osteoporosis caused by reduced production of estrogen during the perimenopausal period; however, the therapeutic roles of the individual components of the QEF and their compatibility within the formula has not been investigated. AIM OF THE STUDY: In this study, the compatibility mechanism and estrogen-like action properties of the four herbal components in the QEF was elucidated according to the organizing principle of Chinese medicine formulas using both in vitro and in vivo models. MATERIALS AND METHODS: The estrogen-like effects of QEF and its herbal components were investigated in MCF7 and HEK293 cells as well as ovariectomized (OVX) rats. The estrogen-like effects of the QEF and its components were analyzed in vitro using Cell Counting Kit-8 and Luciferase reporter gene assays. In the in vivo studies, the blood plasma levels of hormones, lipids, neurotransmitters, aromatase, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured through enzyme-linked immunosorbent assays (ELISAs). The histological morphologies of the target organs after exposure to QEF were investigated by HE staining and immunohistochemical methods. The expression levels of estrogen pathway-related proteins and genes in the OVX rats were measured by Western blotting and real time quantitative PCR (RT-qPCR), respectively. RESULTS: The in vitro results showed that the QEF, Eucommia (EC) and Psoralea (PF) promoted the proliferation of MCF-7 cells and upregulated the expression of ERα, ERß and pS2 genes in the MCF-7 cells. Notably, the QEF demonstrated the most active estrogen-like effects compared to the individual ingredients. The in vivo results showed that the QEF, EC, and PF increased the uterine coefficient, upregulated the expression of both ERs (ERα and ERß) in the uterus, and increased blood serum hormone levels. QEF and its individual components ameliorated menopausal-derived lipid metabolism dysfunction, increased neurotransmitter production by stimulating the adrenal glands, enhanced the antioxidant activity in the serum by increasing the concentration of SOD, reversed ovariectomy-derived atrophy in the uterus, and reduced the weight gain associated with estrogen reduction in the OVX rats. The QEF also antagonize the loss of appetite of OVX animals caused by feeding Psoralea alone, which could explain the compatibility mechanism of Qing' E Formula with reducing toxicity and increasing efficiency. CONCLUSIONS: The estrogen-like effects of Eucommia and Psoralea were mainly mediated through activation of ERα and ERß. The phytoestrogen components regulated hormone production and the expression of related proteins and genes, which indicated that these components exhibited estrogen-like therapeutic effects. However, the QEF showed the greatest estrogen-like effects compared to the individual components. Overall, this corroborated the therapeutic prowess of the QEF and clarified the pharmacodynamic interactions between the different components extracts in the QEF.

Herbal Products Used in Menopause and for Gynecological Disorders.

Herbal products are often used as an alternative to pharmacological therapy. Menopausal symptoms and gynecological disorders (such as premenstrual syndrome and dysmenorrhea) are the indications where pharmacological therapy may have serious adverse events, hence many women prefer to use herbal products to help with these symptoms. Here, we reviewed plants and derived products, which are commonly used for the abovementioned indications, focusing on clinical data, safely profile and whether or not their use is justified. We noted that limited data are available on the use of some plants for alleviating the symptoms of menopause and gynecological disorders. While black cohosh (Cimicifuga racemose) and red clover (Trifolium pretense) were consistently shown to help reduce menopausal symptoms in clinical studies, currently available data do not fully support the use of fenugreek (Trigonella foenum-graecum), hops (Humulus lupulus), valerian (Valeriana officinalis), and soybean (Glycine max and Glycine soja) for this indication. For premenstrual syndrome and premenstrual dysphoric disorder, chaste tree (Vitex agnus-castus) shows effectiveness, but more clinical studies are needed to confirm such effect upon the use of evening primrose (Oenothera biennis).

Application of Chaihu-Guizhi-Longgu-Muli decoction combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality.

To explore the application of Chaihu-Guizhi-Longgu-Muli decoction (CGLM) combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality. The data of 120 menopausal insomnia patients admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were equally divided into the experimental group (n=60) and the control group (n=60) according to the order of admission. All patients were treated with Liuwei Dihuang Pills, and the experimental group was additionally given CGLM. The Pittsburgh Sleep Quality Index (PSQI), estrogen level, negative emotion score, quality of life score, serum ß-endorphin (ß-EP) level, serotonin level (5-HT) and treatment effective rate were compared between the two groups of patients. After treatment, the experimental group obtained markedly lower PSQI scores and negative emotion scores than the control group (P<0.001). The estrogen levels, ß-EP levels and 5-HT levels of the experimental group after treatment were significantly better than those of the control group (P<0.001). Higher quality of life scores and treatment effective rates were observed in the experimental group after treatment than the control group (P<0.001). CGLM combined with Liuwei Dihuang Pills can regulate the serum hormone levels of patients with menopausal insomnia, reduce negative emotions and improve sleep quality and quality of life, which merits clinical promotion.

Climacteric symptoms more severe in 2010 than in 2000 - experience of Finnish women aged 52-56 years not now or previously on menopausal hormone therapy.

OBJECTIVES: To analyze and compare the experience of climacteric symptoms and their associations with sociodemographic and health-related characteristics in two cohorts of Finnish women aged 52-56 years, born ten years apart and not now or previously on menopausal hormone therapy (MHT). STUDY DESIGN: Nationwide population-based time-trend study with a large number of participants (n = 1986 + 1988). MAIN OUTCOME MEASURES: The experience of climacteric symptoms was assessed by 12 commonly used menopause-related symptoms. RESULTS: Women aged 52-56 experienced more moderate or severe symptoms and fewer mild symptoms in 2010 than in 2000. Being unemployed or inactive was associated with more severe symptoms (P = 0.007), but employment status had no effect on the relative odds estimates. CONCLUSIONS: The influence of the birth cohort and time-period effects as well as work-related factors on the experience of climacteric symptoms in women not now or previously on MHT needs further research, particularly since the change in the experience of symptoms found in this study occurred within only ten years.

Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause.

Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor; thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.

Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

Changes in Bone Metabolism and Antioxidant Defense Systems in Menopause-Induced Rats Fed Bran Extract from Dark Purple Rice (Oryza sativa L. Cv. Superjami).

Menopause is a matter of concern for women's health due to a deficiency of female hormones; additionally, reactive oxygen species and aging can cause osteoporosis. Food becomes increasingly interesting as a menopausal woman's alternative to hormone therapy. The effects of ethanol extracts from dark purple Superjami rice bran on bone metabolism and antioxidant defense systems in menopause-induced animal models were evaluated. Female rats underwent sham surgery or were ovariectomized to induce a menopause-like state. Rats were divided into a sham control group (SHAM), an ovariectomized control group (OVX), and an ovariectomized grou supplemented with Superjami rice bran extract group (OVX-S) and fed for 8 weeks. The OVX groups exhibited significantly more weight gain, amounts of bone turnover biochemical markers (alkaline phosphatase, osteocalcin, and C-terminal telopeptide), bone loss, lipid-peroxidation and oxidative stress than the SHAM group. However, Superjami bran extract added to the diet resulted in a significant reduction in body weight and lipid peroxidation, as well as enhanced bone metabolism and antioxidant enzyme activities, in ovariectomized rats. These results propound that extracts from Superjami rice bran have therapeutic potentiality against bone loss and oxidative stress in menopause-induced states and will be useful in preventing postmenopausal osteoporosis and oxidative damage.