A Systematic Literature Review of the Impact of Climate Change on Menopause: Altering the Age, Severity of Symptoms and Long-Term Effects

Objective: This systematic review investigates the impact of climate change on menopause, focusing on the correlation between geographical location—considering altitude, temperature, humidity, and annual temperature range—and women’s menopausal experiences. This study aims to interpret how these environmental factors influence the age of onset, severity of symptoms such as hot flushes and night sweats, and other long-term effects of menopause. Understanding these relationships addresses a significant gap in current knowledge and could guide future public health strategies. Methods: Through a comprehensive analysis of three cross-continental studies involving 1500 postmenopausal women from Spain, South American countries (Ecuador, Panama, Chile), various climates in Türkiye (Black Sea, Mediterranean, Continental), and the United Arab Emirates (UAE), this review evaluates diverse environmental impacts. Studies were selected based on their methodological rigor, geographical diversity, and focus on the unique and personal experiences of menopause. Data was collected via questionnaires and routine medical checkups, analyzing demographic, lifestyle, mood, symptom severity, and onset age variables. Results: Preliminary analysis indicates that 52.5% of participants from Spanish-speaking countries and the UAE reported vasomotor symptoms, with those in higher temperatures and lower altitudes experiencing exacerbated symptoms. Notably, Mediterranean climates were associated with an earlier menopause onset. Seasonal changes had minimal impact across all regions, suggesting lifestyle and other environmental factors play a more significant role. Conclusions: The findings highlight a clear link between climate-related geographical factors and the menopausal experience. Women in warmer, lower-altitude regions suffer more severe symptoms, while those in Mediterranean climates face earlier onset. The absence of significant seasonal variations across the studies underscores the predominance of lifestyle and environmental factors over purely climatic conditions. These insights pave the way for targeted interventions and support the need for further public health research into the complex interactions between climate change and menopause.

Efficacy evaluation of standardized Rheum rhaponticum root extract(ERr 731®)on symptoms of menopause:A systematic review and meta-analysis study

Menopause is characterized by various physical,mental and emotional symptoms.ERr 731®is a standardized extract from Rheum rhaponticum root and has been clinically studied for its role in reducing menopausal symptoms.The current systematic review and meta-analysis aimed to evaluate the efficacy of ERr 731®supplementation in alleviating the severity of menopausal symptoms.In this review,we searched across three online databases up to March 2023,evaluated the quality of the included studies by the Physiotherapy Evidence Database scale,and assessed the risk of bias by the Cochrane Risk of Bias tool.We then performed a metaanalysis using RevMan software to estimate the pooled mean difference(MD).The study protocol was registered in the Prospective Register of Systematic Reviews(CRD42023416808).After screening and evaluation,we included four high-quality studies(a total of 390 participants;the ERr 731®group:193 participants;the control group:197 participants)in the meta-analysis.The results showed that ERr 731®supplementation significantly reduced the Menopause Rating Scale score(MD:–15.12;P<0.001),compared with control therapy.Sensitivity analysis revealed no effect of individual studies on the overall pooled estimate or overall observed heterogeneity.The current review provides evidence that ERr 731®supplementation is effective in reducing menopause symptoms.Potential bias and high heterogeneity in the results warrant further clinical studies.

Exploring the Mechanism of Action of Glyasperin A in Intervening Menopause Based on Network Pharmacology and Molecular Docking Technology

[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were screened using TCMSP,3D model molecules converted into SMILES online tool,Swiss target prediction and literature search.The relevant target genes corresponding to menopause were identified using the Genecards database.Venn 2.1.0 was then used to generate the corresponding Venn diagram.Finally,the protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1 software.The core targets that were screened underwent enrichment and analysis using the Gene Ontology(GO)biological process and KEGG pathways with the assistance of the DAVID database and bioinformatics.The molecular docking was then verified using AutoDock and Pymol software on the core targets.[Results]This study screened 100 target genes of active ingredients.In the PPI network,ESR1 and AKT1 were found to have a higher degree.The GO and KEGG enrichment analyses revealed that the biological processes primarily involved platelet activation,regulation of circadian rhythms,and regulation of mRNA stability.The signalling pathways included hepatitis B,cytotoxicity,and gastric cancer.The molecular docking results indicated that the key active ingredients and proteins bound well,as evidenced by their small binding energies.[Conclusions]Using a systematic network pharmacology approach,this study predicts the basic pharmacological effects and potential mechanisms of GAA in intervening menopause,which provides a foundation for further research on its pharmacological mechanisms.

Complete Hydatidiform Mole at Menopause: A Case Report from Panzi Hospital, Bukavu, Democratic Republic of Congo

Gestational trophoblastic disease is an abnormal proliferation of trophoblastic tissue during pregnancy. It occurs in women of childbearing age, although a few cases have also been observed in post-menopausal women, although it is extremely rare in the latter. Here we describe a rare case of complete hydatidiform mole in a 56-year-old female patient who presented with genital bleeding combined with nausea and vomiting and a gravid uterus 16 cm in height. The ultrasound findings and the increase in serum β-HCG to 182566.00 mIU/ml suggested a diagnosis of complete hydatidiform mole. Given the post-menopausal state and the future risk of post-molar gestational trophoblastic neoplasia, we opted for total hysterectomy without preservation of the adnexa via a transabdominal approach, followed by antimitotic treatment with methotrexate. The uterus measured 18.45 cm × 11.18 cm with intra cavitary vesicles. Microscopic examination showed chorionic villi of variable size and shape, most of which were dilated and oedematous, associated with trophoblastic cell proliferation and haemorrhage suggestive of complete benign hydatidiform mole. Follow-up showed a consistent decrease in serum β-HCG levels and no evidence of residual disease. A suspicion of gestational trophoblastic disease should be borne in mind when evaluating a patient with peri- or post-menopausal bleeding to avoid delay in diagnosis and treatment.

Sociodemographic and Clinical Aspects of Climacteric Syndrome of Menopause in the City of Kati in Mali Involving 113 Women

Objective: This paper aims to study the sociodemographic and clinical aspects of menopausal climacteric syndrome in the city of Kati in Mali. Patients and Methods: This was a quantitative descriptive and cross-sectional study, conducted in the city of Kati from February 1 to July 31, 2021. We included 112 menopausal women. Women were selected from a household survey using the sampling step. We were interested in conjugal, family and professional life, self-esteem and the state of health of women in general. Results: More than half of the women in our study were already postmenopausal (52.2%);the mean age was 50.5 years with the extremes ranging from 41 to 62 years. The majority of them were married (69.9%), housewives (43.4%) and Bambara (53.1%). The most common climacteric syndromes were: joint pain (65.5%), hot flashes (62.8%) and night sweats (56.6%). Genital-urinary syndromes (42.5%) were dominated by decreased libido (41.7%), urinary disorder (23%) and vaginal dryness (14.6%). Genitalia-urinary syndromes increased the frequency of disagreements;Pearson’s Chi-square = 33.63;ddl = 1;P = 0.001. There was a statistically significant relationship between night sweat, genital-urinary syndromes, joint pain, and increased disease frequency with, respectively: Pearson’s chi-square = 4.660;ddl = 1;P = 0.031;Fisher’s exact test, P = 0.001, Pearson’s Chi-square = 8.434;ddl = 1;P = 0.004. There was no statistically significant relationship between climacteric syndrome and family life, work life and self-esteem. Changes in the professional relationship between women and their co-workers included, respectively: arguments (50%);disagreements (25%) and disobedience (25%). Conclusion: Menopause deteriorates the quality of life of women who suffer in silence, hence the need to pay special attention to them.

Correlation of Equol (7-Hydroxy-3-(4-Hydroxyphenyl)Chroman) in Woman Urine with the Symptoms of Menopause

Objective: In order to identify the correlation between equol excreted through human urine and the symptom of menopause. Methods: The method used is cross sectional study examined to 99 postmenopausal women fulfilling the inclusion criteria from February 2014 to July 2014. This research was taken in the Endocrinology Clinic, Department of Obstetrics and Gynecology, Hasan Sadikin Hospital and Unpad’s Pharmacokinetic Laboratory. All objects were interviewed using menopause rating scale (MRS) questionnaire. Their urine samples were analyzed using high performance liquid chromatography (HPLC). Then the results of questionnaire and HPLC test were evaluated. Results: The result is 97 objects (98%) detected having menopausal symptoms, produced equol. There is significant correlation between the level of equol in post-menopausal women that showed correlation (-0.71) which mean the higher the equol level, the lower the MRS score (p < 0.001) that mean the symptom is milder. Conclusion: Equol level in menopause women urine is a good predictor to identify the level of menopause symptoms.

Application of Medicinal Plants on Menopause Symptoms

Objectives:To relate the symptoms of menopause and the use of medicinal plants.Methods:it was carried out a study that applied the qualitative method,by means of a bibliographical and documental revision in sources of digital data of wide reach(Google,SciELO,DOAJ,Latindex and SCOPUS).It was kept in mind the quality and the present time.Conclusions:It was based on the search of articles in Virtual the Library in Health(Spanish:BVS)and using the key words:menopause,medicinal plants,phytotherapy,menopause symptoms.

Effect of Menopause on Gene Expression Profiles of Circu-lating Monocytes: A Pilot in vivo Microarray Study

Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can differentiate into various cell types and play an important role in tissue morphogenesis and immune response. We studied gene expression profiles of peripheral blood monocytes in healthy pre- and postmenopausal women using Affymetrix Human U133A GeneChip array that contains probes for -14,500 genes. Comparative analyses between the samples showed that 20 genes were up- and 20 were down-regulated. Of these genes, 28 were classified into six major GO categories relevant to such biological processes as the cell proliferation, immune response, cellular metabolism, and the others. The remaining 12 genes have yet unidentified biological functions. Our results support the hypothesis that functional state of circulating monocytes is indeed affected by menopause, and resulting changes may be determined through the genomewide gene expression profiling. Several differentially expressed genes identified in this study may be candidates for further studies of menopause-associated systemic autoimmune, neurodegenerative, and cardiovascular disorders. Our study is only the first attempt in this direction, but it lays a basis for further research.

Aging and menopause reprogram osteoclast precursors for aggressive bone resorption

Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing osteoporosis.The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes.However,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity.Therefore,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were collected.Using multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age.We conclude that monocytes are"reprogrammed"in vivo,allowing them to"remember"age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive osteoclasts.Our discovery suggests that this may be mediated through DNA methylation.We suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.

Menopause and cognitive impairment:A narrative review of current knowledge

A severe impairment of cognitive function characterizes dementia.Mild cognitive impairment represents a transition between normal cognition and dementia.The frequency of cognitive changes is higher in women than in men.Based on this fact,hormonal factors likely contribute to cognitive decline.In this sense,cognitive complaints are more common near menopause,a phase marked by a decrease in hormone levels,especially estrogen.Additionally,a tendency toward worsened cognitive performance has been reported in women during menopause.Vasomotor symptoms(hot flashes,sweating,and dizziness),vaginal dryness,irritability and forgetfulness are common and associated with a progressive decrease in ovarian function and a subsequent reduction in the serum estrogen concentration.Hormone therapy(HT),based on estrogen with or without progestogen,is the treatment of choice to relieve menopausal symptoms.The studies conducted to date have reported conflicting results regarding the effects of HT on cognition.This article reviews the main aspects of menopause and cognition,including the neuroprotective role of estrogen and the relationship between menopausal symptoms and cognitive function.We present and discuss the findings of the central observational and interventional studies on HT and cognition.

Liver disease in menopause

There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

Management of genitourinary syndrome of menopause in breast cancer survivors:An update

There is increasing attention about managing the adverse effects of adjuvant therapy(Chemotherapy and anti-estrogen treatment)for breast cancer survivors(BCSs).Vulvovaginal atrophy(VVA),caused by decreased levels of circulating estrogen to urogenital receptors,is commonly experienced by this patients.Women receiving antiestrogen therapy,specifically aromatase inhibitors,often suffer from vaginal dryness,itching,irritation,dyspareunia,and dysuria,collectively known as genitourinary syndrome of menopause(GSM),that it can in turn lead to pain,discomfort,impairment of sexual function and negatively impact on multiple domains of quality of life(QoL).The worsening of QoL in these patients due to GSM symptoms can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly.The diagnosis of VVA is confirmed through patient-reported symptoms and gynecological examination of external structures,introitus,and vaginal mucosa.Systemic estrogen treatment is contraindicated in BCSs.In these patients,GSM may be prevented,reduced and managed in most cases but this requires early recognition and appropriate treatment,but it is normally undertreated by oncologists because of fear of cancer recurrence,specifically when considering treatment with vaginal estrogen therapy(VET)because of unknown levels of systemic absorption of estradiol.Lifestyle modifications and nonhormonal treatments(vaginal moisturizers,lubricants,and gels)are the first-line treatment for GSM both in healthy women as BCSs,but when these are not effective for symptom relief,other options can be considered,such as VET,ospemifene,local androgens,intravaginal dehydroepiandrosterone(prasterone),or laser therapy(erbium or CO2 Laser).The present data suggest that these therapies are effective for VVA in BCSs;however,safety remains controversial and a there is a major concern with all of these treatments.We review current evidence for various nonpharmacologic and pharmacologic therapeutic modalities for GSM in BCSs and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research.We include recommendations for an approach to the management of GSM in women at high risk for breast cancer,women with estrogen-receptor positive breast cancers,women with triplenegative breast cancers,and women with metastatic disease.

Mugwort (<i>Artemisia vulgaris</i>, <i>Artemisia douglasiana</i>, <i>Artemisia argyi</i>) in the Treatment of Menopause, Premenstrual Syndrome, Dysmenorrhea and Attention Deficit Hyperactivity Disorder

Mugwort has many traditional uses around the world. The Chumash Indians of California use it to treat imbalances that women may suffer such as premenstrual syndrome, dysmenorrhea and menopausal symptoms. The plant contains a sesquiterpene that appears to work through a serotonergic mechanism and may be beneficial for women. Mugwort therapy is safer for menopausal women than hormone replacement therapy. Children affected by attention deficit hyperactivity disorder benefit from mugwort therapy. There is no doubt that mugwort therapy is safer for these children than methylphenidate or amphetamine.

Effect of Conjugated Estrogen in Stress Urinary Incontinence in Women with Menopause

Menopause is one of the natural stages of life of women that is associated with instability of vasomotor, flushing, sweating, anxiety and depression, urogenital atrophy and urinary problems. The age range of physiological event is between 48 - 55 years old. With regard to the role of genetics, nutrition and geographical conditions of the age of menopause in Iranian women is lower than and among 46 - 53 years. With the increase in life expectancy in recent decades, duration of menopause is increased and almost involved a third of the life of women so special issues of this era have had more attention. Since menopause is not the end of the life of a woman and keep her physical and mental health and problems resulting from the process of menopause such as urinary problems and incontinence will lead to improve the quality of life in this period. Many studies have tried to find a therapy for postmenopausal women with stress urinary incontinence using hormone. So this article seeks to examine the effect of conjugated estrogen in stress urinary incontinence of menopausal women with using the library method. The survey showed that by starting menopause, decreasing estrogen causes atrophy of mucosa of urogenital and the lining of the urethra and bladder, estrogen causes to maintain muscle tonicity. Also sacral nerves are also rich in estrogen receptors and by estrogen deficiency, elasticity of the urinary system decreases. Estrogen deficiency causes excitability of nerves and frequency of urine. So estrogen can increase the resistance of the urethra, bladder sensory threshold and sensitivity in Adorno in smooth muscles of the urethra and the rest of detrusor.

Physiotherapy as a Way to Maintain Vaginal Health during Menopause

The majority of women will experience some or most of the menopause symptoms in their life. Thais time in women’s life is associated with a reduction in estrogen levels which leads to physiological changes that affect different organ systems. In the urogenital tract, these changes usually cause vulvar and vaginal atrophy, affecting a vaginal health of women and decreasing their quality of life. Also, there is a reduction in vaginal moisture and loss of tissue elasticity. Besides, other organ systems are involved and they can also negatively impact normal vaginal physiology. These evolutional changes frequently lead to bothersome symptoms that can negatively impact a woman’s vaginal health and the quality of life. The role of pelvic floor physiotherapy is to improve the tone and strength of the muscle fibres in order to achieve the increase of motor units, improve muscle elasticity and to increase the muscle mass which will help to alleviate menopause symptoms.

Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit （BMU） activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced signi-ficantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mecha-nical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.

Surgical menopause enhances hippocampal amyloidogenesis following global cerebral ischemia

Background： Prematurely menopausal women have a doubled lifetime risk of dementia and a 5-fold increased risk of mortality from neuro- logical disorders, but the molecular mechanisms underlying these risks remain unclear. We hypothesized that ischemia-induced amyloidogenesis may be enhanced in the hippocampus following prolonged loss of ovarian 17β-estradiol （E2）, which could contribute to these phenomena. Methods： The current study used a rat model of premature surgical menopause （10-week bilateral ovariectomy） with E2 therapy either initiated immediately （short-term E2 deprivation （STED）） or delayed to the end of the ovariectomy period （long-term E2 deprivation （LTED））. One week after continuous, subcutaneous E2 therapy, we subjected animals to 10-min global cerebral ischemia （GCI） to assess the effect of LTED on ischemia-induced amyloidogenesis in the hippocampal CA1. Results： The present study revealed that while hippocampal β-amyloid （Aβ） is not typically enhanced following GCI, there is a rapid, robust elevation of endogenous Aβ in LTED females after GCI. In STED females, we observed that GCI attenuates and E2 maintains A Disintegrin and Metalloprotease 10 （ADAM 10） expression in the hippocampal CA1, and concurrently, GCI increases and E2 decreases BACE1 levels in the same region. Intriguingly, however, we observed a loss of E2 regulation of ADAM 10, ADAM 17, and BACE 1 levels in the hippocampal CA I of LTED females, which provides mechanistic evidence for the enhanced post-ischemic Aβ load following LTED. We also observed loss of E2 regulation of tau hyperphosphorylation in LTED females subjected to GCI. Conclusion： Collectively, these studies partially explain the enhanced risk of dementia and mortality from neurological disorders seen in prematurely menopausal women and support timely initiation of E2 therapy to yield maximum neurological benefit.

Sleep Disorders in Menopause: Review of the Literature and Occurrence through Menopausal Stages

We here review principal literature data about sleep disorders in menopause and we compared it with data obtained from a systematical screening of a sample of 161 menopausal women through questionnaires and clinical evaluation. Our data reveal high occurrence of sleep disorders in this group of women if compared to literature data about general population, in the absence of statistically significant differences among the three menopausal stages: we find only a trend toward a higher risk of OSAS (Obstructive Sleep Apnea Syndrome) in PM versus early PM and MT. However, none of women in our survey underwent PSG (polysomnography), essential to confirm the diagnosis of OSAS and none was diagnosed with RLS (Restless Legs Syndrome) (prior to our survey) by the Gynecologist or General Pratictioner: these data reveal the issue of too low attention towards sleep disorders in this contest. Generic “sleep complaints” are clearly associated with depressed mood and worse-quality life along the menopausal process. In our sample, a non-specific definition of insomnia shows a peculiar relationship with a mood disorder: it is only variable not associated with higher BDI and KI scores, in fact. This might suggest that the conditions linked to depression of these women could be more specific sleep disturbances, such as RLS and OSAS.

The age at natural menopause and the frequency of climacteric symptoms in Chinese women

Objectives: To estimate the age at natural menopause and the frequency of climacteric symptoms in Chinese women.Design: A cross-sectional study of randomly recruited 788 women, aged 45 to 55 years in Beijing.Results: The mean age at natural menopause was 48. 2 years. there was a trend that women with more parities, more babies breast fed or longer duration of breastfeeding had a delayed age at natural menopause. Higher socio-economic status was related to a later cessetion of menstruation. Vasomotor and psychological symptoms increased during menopause transition. However, psychological disorders tended to decrease after the menopause. Bone-joint problems were inversely associated with daily activi-ty or physical exercise. Perimenopausal women experienced the most frequent climacteric symptoms.Conclusion: The menopausal age was influenced by reproductive factors and socio-economic status-Vasomotor and psychological symptoms were associated with the menopausal status. However, bone-joint problems was not.

Serum 17β-estradiol and oral dryness feeling in menopause

The aim of this study was to compare serum 17β-estradiol of menopausal women with/without Oral Dryness (OD) feeling, and evaluate the re-lationship between serum 17β-estradiol and severity of OD feeling. A case-control study was carried out on 70 selected menopausal women aged 40 - 77 years with or without OD feeling (35 as case, 35 as control) conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. Xerostomia inventory (XI) score was used as an index of OD feeling severity. The serum 17β-estradiol concentration was measured by an enzyme immunoassay kit (ELISA). Statistical analysis of Student’s t-test and Spearman correlation coefficient was used. The mean serum concentration of 17β-estradiol was significantly lower in case than control. There was a significant negative correlation between XI score and concentration of 17β-estradiol in menopausal women (r = –0.311, P = 0.004). It seems that there is a negatively slight correlation between OD feeling severity and serum 17β-estradiol in menopausal women.