Menopause

What was reviewed?

This editorial summarizes and contextualizes the 2017 National Institute for Health and Care Excellence (NICE) guidelines and quality standards regarding the diagnosis of menopause and premature ovarian insufficiency (POI). The guidance, based on systematic reviews, critically evaluates the diagnostic utility of clinical indicators, ultrasound, and biochemical tests (particularly FSH, AMH, oestrogen, inhibin A and B), emphasizing appropriate diagnostic strategies for different age groups and clinical scenarios. The article also discusses the cost-saving implications and practical recommendations for clinical biochemistry laboratories in the UK, focusing on reducing unnecessary biochemical testing and streamlining diagnostic pathways.

Who was reviewed?

The review draws on evidence synthesized for NICE guideline development, including systematic reviews of studies involving perimenopausal and menopausal women, as well as those at risk for or suspected of POI. The population includes women over 45 presenting with menopausal symptoms, women aged 40–45 with possible menopausal features, and women under 40 with suspected POI, such as those with a history of cancer treatment or genetic syndromes like Turner syndrome. The referenced studies include a range of clinical cohorts and laboratory assessments across these age groups.

Most important findings

The NICE guideline, as summarized in this editorial, asserts that menopause in women over 45 should be diagnosed clinically—based on symptoms like vasomotor instability and menstrual irregularity—without reliance on laboratory or imaging tests. The evidence indicates that no single symptom or biochemical marker (including FSH, AMH, oestrogen, or inhibins) is sufficiently reliable in isolation for diagnosing menopause in this group. FSH is particularly unreliable due to its physiological fluctuations and interference from hormonal therapies. However, FSH measurement retains a role in diagnosing POI in women under 40, where elevated levels (>30 mIU/mL on two occasions) support the diagnosis, though a single test is inadequate due to hormonal variability. The review also emphasizes that AMH, despite its use as a marker of ovarian reserve, is not recommended for routine POI diagnosis due to assay variability and insufficient evidence for its diagnostic accuracy in this context.

Key implications

For clinical practice, the NICE guidance recommends diagnosing menopause in women over 45 based on symptoms alone, which reduces unnecessary and uninformative laboratory testing. This has significant resource-saving implications for healthcare systems. In women under 40 with suspected POI, FSH testing is appropriate, but diagnosis should be based on persistent elevations in FSH and compatible symptoms. Laboratories and clinicians should align their practice with these guidelines, minimizing inappropriate FSH testing in older women and focusing resources where diagnostic yield is greatest. This approach is expected to improve patient care, expedite appropriate referrals, and enhance long-term health outcomes while maximizing cost-effectiveness. The editorial provides actionable advice for laboratories, including audit and educational interventions to reduce unwarranted testing.

What was reviewed?

This article presents a comprehensive review of the effects of menopause on the female microbiome, with a specific focus on the genitourinary microbiome, encompassing the gut, vaginal, and urinary microbial communities. The review synthesizes evidence from recent clinical studies, observational data, and randomized controlled trials to elucidate the interplay between hormonal changes during menopause and alterations in these microbiomes. It particularly emphasizes the urinary microbiome, a relatively underexplored area, and its potential associations with common postmenopausal conditions such as genitourinary syndrome of menopause (GSM), recurrent urinary tract infections (rUTI), and lower urinary tract symptoms.

Who was reviewed?

The review includes data and findings from studies involving premenopausal and postmenopausal women of varying ages and ethnic backgrounds. The populations studied encompass healthy women, women with menopause-related symptoms, and those with urinary tract disorders, including rUTI, overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and GSM. Subjects in the included studies range from healthy controls to those receiving hormone therapy, probiotics, or other microbiome-targeted interventions. The review draws on both cross-sectional and longitudinal analyses, as well as clinical trials from diverse geographic locations.

Most important findings

Menopause induces significant shifts in the gut, vaginal, and urinary microbiomes, largely driven by estrogen decline. In the gut, although phylum-level changes are inconsistent, postmenopausal women show increased Firmicutes/Bacteroidetes ratios, higher abundance of genera like Lachnospira, Roseburia, and Bilophila, and changes in short-chain fatty acid (SCFA) profiles. The vaginal microbiome becomes less dominated by Lactobacillus species post-menopause, with increased prevalence of anaerobes such as Gardnerella, Prevotella, Atopobium, and Finegoldia. Notably, hormone therapy and probiotic interventions can partially restore Lactobacillus dominance and lower vaginal pH—benefits linked to symptom improvement.

The urinary microbiome also undergoes notable changes: postmenopausal women exhibit increased alpha diversity and reduced Lactobacillus abundance, with more Gardnerella, Prevotella, and Mobiluncus. The review highlights a substantial overlap between vaginal and urinary microbiomes, underscoring the interconnectedness of these sites. Both local estrogen therapy and specific probiotic administration have shown promise in restoring a healthier microbiome and reducing infection risk.

Key implications

Understanding menopause-related microbiome alterations is critical for developing targeted strategies to manage genitourinary health in postmenopausal women. The decline in Lactobacillus and increased diversity in the urinary and vaginal niches underpin higher rates of GSM, rUTI, and urinary symptoms. Interventions such as hormone therapy and probiotics can beneficially modulate the microbiome, alleviate symptoms, and lower infection risk. Clinicians should recognize the interdependence of the gut, vaginal, and urinary microbiomes in postmenopausal women and consider microbiome-focused therapies as adjuncts to conventional management. Further research into the urinary microbiome’s role in disease and its manipulation remains an urgent clinical need.

What was studied?

This large prospective cohort study investigated predictors of the onset of natural menopause among African American women, with particular attention to the potential role of perceived experiences of racism. The researchers aimed to clarify how demographic, reproductive, lifestyle, and psychosocial factors, including experiences of racism, affect the timing of natural menopause. Data were drawn from the Black Women’s Health Study, with baseline and follow-up information (including exposures and outcomes) collected by mailed questionnaires between 1995 and 1999. Using Cox proportional hazards regression, the study evaluated associations between various risk factors (smoking, body mass index [BMI], oral contraceptive use, parity, education, physical activity, age at menarche, unilateral oophorectomy, and perceived racism) and the incidence of natural menopause over a four-year period.

Who was studied?

The analytic sample included 17,070 African American women in the United States who were aged 35 to 55 years and premenopausal at baseline in 1995. Participants were drawn from the broader Black Women’s Health Study, which initially enrolled 64,500 women via mailed questionnaires. Inclusion criteria for this analysis required premenopausal status at baseline and completion of at least one follow-up questionnaire in 1997 or 1999. The cohort was well-educated, with the majority having completed high school or higher education, making the results particularly applicable to similarly educated African American women in the U.S. Generalizability to women with less education or lower socioeconomic status may be limited.

Most important findings

The study found that current smoking was the strongest predictor of earlier natural menopause, with a hazard ratio of 1.43 for current smokers and 1.21 for ex-smokers compared to never smokers. There was a clear dose-response relationship between smoking intensity (pack years) and risk of earlier menopause. Higher BMI was inversely associated with risk: women with a BMI ≥30 had a 22% lower risk compared to those with a BMI of 20–24. Use of oral contraceptives for at least one year also delayed menopause. Other reproductive factors and education were not significantly associated with menopause onset. Unilateral oophorectomy was associated with earlier menopause only among younger women. For perceived racism, most hazard ratios were elevated, but few reached statistical significance. The most notable was a 32% increased risk for women who experienced being treated as "not intelligent" monthly and a 23% increased risk for those thinking about their race daily.

Key implications

This study underscores that similar to White women, smoking is the most consistent and modifiable risk factor for earlier menopause among African American women, with implications for counseling and preventive health. Higher BMI and oral contraceptive use appear protective against early menopause. The findings regarding racism are suggestive but not definitive; while some associations were present, they were generally modest and inconsistent, indicating a need for further research on psychosocial stressors and reproductive aging in this population. Clinicians should be aware of these factors when discussing reproductive health and menopause timing with African American women but should recognize that current evidence does not support strong, actionable links between perceived racism and menopause onset.

What was reviewed?

This comprehensive review article explores the interplay between the gut and vaginal microbiome and menopause, focusing on implications for healthy aging in women. The authors synthesize recent research, highlighting how hormonal changes during menopause reshape the vaginal ecosystem, particularly through the decline of Lactobacillus dominance and increased prevalence of anaerobes and pathobionts. The review examines clinical and mechanistic studies addressing the association between microbial shifts and menopausal symptoms, such as genitourinary syndrome of menopause (GSM), recurrent urinary tract infections (UTIs), and vasomotor and neuropsychiatric symptoms. The authors also discuss the potential for microbiome-targeting interventions, including hormone replacement, probiotics, and emerging interventions like vaginal microbiota transplantation, summarizing evidence for their safety, efficacy, and effects on the vaginal microbiota during and after menopause.

Who was reviewed?

The review encompasses research conducted predominantly on peri- and postmenopausal women, with most clinical studies involving primarily Caucasian populations. The included studies span a range of sample sizes, from small longitudinal cohorts to larger randomized controlled trials, as well as cross-sectional analyses. The authors note a significant gap in research involving women of diverse racial, ethnic, and socioeconomic backgrounds, despite evidence that these factors influence microbiome composition. The reviewed literature also references women receiving various menopausal therapies (e.g., hormone replacement, DHEA, ospemifene) and those experiencing surgical or therapy-induced menopause (e.g., after oophorectomy or aromatase inhibitor use).

Most important findings

A key finding is the strong correlation between declining estrogen levels during menopause and a shift from a Lactobacillus-dominated vaginal microbiome to one characterized by increased diversity, including anaerobes (Gardnerella, Prevotella, Anaerococcus, Peptoniphilus, Peptostreptococcus) and pathobionts (Escherichia, Enterococcus, Streptococcus, Corynebacterium, Staphylococcus). This microbial shift is linked to elevated vaginal pH, atrophic changes, and increased susceptibility to GSM and UTIs. While some studies show that Lactobacillus depletion correlates with more severe genitourinary symptoms, others find no such association, underscoring the need for further research. Therapeutic interventions, such as local estrogen therapy, DHEA, and ospemifene, generally restore Lactobacillus dominance and lower vaginal pH, improving symptoms. Probiotics and live biotherapeutics show promise but lack robust data in postmenopausal women. Emerging concepts like precision probiotics and vaginal microbiota transplantation represent future avenues for tailored microbiome restoration.

Key implications

The review underscores the clinical relevance of the microbiome in menopausal health, advocating for more inclusive, mechanistic, and longitudinal research to clarify microbial contributions to symptoms and treatment responses. Restoration of Lactobacillus dominance in the vaginal niche—via hormone therapy, novel probiotics, or microbiota transplantation—may directly impact genitourinary and systemic health in menopausal women. The authors call for precision approaches and greater representation of diverse populations in future studies. Ultimately, microbiome-informed interventions could improve quality of life, reduce adverse health outcomes post-menopause, and move toward personalized medicine in women’s health.

What was reviewed?

This narrative review comprehensively examines how the menopausal transition in women, marked by a decline in estrogen and other sex hormones, leads to profound changes in the microbiome across key body sites: oral, intestinal (gut), and urogenital (vaginal and urinary). The review reveals the bidirectional interplay between hormonal shifts and the microbiome, illustrating how menopause-induced hormonal changes alter the composition, richness, and function of microbial communities. Key topics include the impact of estrogen and progesterone fluctuations on microbial diversity, the concept of the “menopause paradox” (where dominance of protective microbes decreases while overall diversity increases), and the role of the microbiome in mediating disease risk and symptomatology during menopause. The review further discusses the microbial metabolism of sex hormones, highlighting how certain microbes can influence hormone availability and, in turn, host physiology and health outcomes.

Who was reviewed?

The reviewed literature encompasses studies of women across the menopausal transition, including premenopausal, perimenopausal, and postmenopausal women, with particular focus on changes in oral, gut, and vaginal microbial communities. The review references diverse cohorts and methodologies, with most primary data derived from studies of women aged 40–59 (the typical age range for menopause). However, the authors note a significant overrepresentation of Western populations in existing research, with limited inclusion of non-Western, African, Asian, or Latin American cohorts, which may affect global generalizability of findings. The review also considers relevant animal models and in vitro studies that inform understanding of hormone-microbe interactions.

Most important findings

The review highlights that menopause is associated with a marked reduction in estrogen and progesterone, which drives systemic changes in multiple mucosal tissues and their resident microbiota. In the oral cavity, menopause can lead to decreased salivary flow and pH, increased risk of periodontal disease, and shifts in microbial composition, such as increased Prevotella copri and reduced Veillonella tobetsuensis. Periodontal pathogens like Porphyromonas gingivalis and Tannerella forsythia become more prominent, while certain commensals (e.g., Bifidobacterium dentium) may offer protective effects. Fungal dysbiosis, particularly candidiasis, is also more common. In the gut, menopause is linked to reduced microbial diversity and altered abundance of taxa, including increased Bacteroides, Prevotella, Veillonella, and Sutterella, and decreased Ruminococcus (a beneficial butyrate-producer). The gut microbiome’s ability to metabolize estrogens (the “estrobolome”) becomes especially relevant, influencing circulating hormone levels and potentially affecting cardiovascular, metabolic, and autoimmune risk.

The vaginal microbiome undergoes the “menopause paradox”: a decrease in Lactobacillus dominance and a rise in overall microbial richness, favoring colonization by anaerobic taxa such as Prevotella, Gardnerella, and Atopobium. This microbial shift is associated with increased vaginal pH, atrophy, dryness, and susceptibility to infections (bacterial vaginosis, candidiasis) and may contribute to higher risk of malignancy and urogenital symptoms. The review also describes the capacity of some oral and gut microbes to metabolize sex steroids, thus influencing systemic hormone availability and potentially modulating menopause-related symptoms.

Key implications

For clinicians, this review underscores the importance of considering the menopause-induced microbiome shift as a significant factor in women’s health, beyond hormonal changes alone. The interplay between declining estrogen/progesterone and microbial community structure increases the risk for oral disease, gut dysbiosis, and urogenital infections. Microbial signatures such as reduced Lactobacillus in the vagina or increased periodontal pathogens could inform risk stratification, early detection, and the development of targeted interventions. Personalized therapies incorporating diet, probiotics, hormone replacement, or microbiome-targeted interventions may help restore microbial balance, alleviate symptoms, and reduce disease risk in menopausal women. Importantly, the review calls for more geographically and ethnically diverse research to ensure findings are globally applicable.

This review article synthesized the current evidence on the interplay between menopause, female sex hormones, and the gut microbiome in humans. The authors critically examined studies addressing how menopause, a period marked by drastic declines in estrogen and progesterone, affects gut microbiome diversity, composition, and function. Focus was given to the bi-directional relationship between sex hormones and the gut microbiota, including the concept of the “estrobolome” (the collection of microbial genes capable of metabolizing estrogens). The review also explored how menopause-associated hormonal changes may impact gut barrier integrity, increase microbial translocation, and potentially influence the risk of chronic diseases common in postmenopausal women, such as cardiovascular disease, metabolic syndrome, and osteoporosis. The article further discussed gaps in knowledge, including the influence of hormone therapy on the gut microbiome and the need for future longitudinal and mechanistic studies.

Who was reviewed?

The review encompassed human studies that compared premenopausal and postmenopausal women, often with age and BMI-matched men as additional comparison groups. Study populations varied in geography (including the US, Spain, China, Korea, and Austria), ethnicity (with some large studies focusing on Hispanic/Latino women), and health status (including women with and without HIV, and women with premature ovarian insufficiency). Sample sizes ranged from small (n<20 per group) to large-scale cohorts exceeding 1,000 participants. some studies also included measurements of circulating sex hormones (estrogens and progesterone), allowing more direct assessment hormonal-microbiome relationships.< p>

Most important findings

Menopause is consistently associated with decreased gut microbiome diversity and a compositional shift that makes the microbiome of postmenopausal women more similar to that of men. Across studies, taxa such as Firmicutes (including Ruminococcus), Akkermansia muciniphila, and [Clostridium] lactatifermentans tend to decrease post-menopause, while Bacteroides, Prevotella, Dorea, Sutterella, and Butyricimonas often increase. Several studies link lower estrogen and progesterone levels with reduced microbial diversity and lower abundance of beneficial short-chain fatty acid-producing genera, while higher diversity and certain taxa (e.g., Ruminococcus, Clostridia) are associated with higher urinary or plasma estrogens. Moreover, the gut microbiome’s estrobolome potential is reduced after menopause, potentially limiting enterohepatic recycling of estrogens and progestins. Experimental and limited clinical data suggest declines in sex hormones may also impair gut barrier function, facilitating microbial translocation and systemic inflammation. However, findings are sometimes inconsistent, likely due to differences in study design, population, and sample size.

Key implications

This review highlights that menopause-induced hormonal changes are linked to reduced gut microbiome diversity, altered microbial composition, and lower estrobolome activity, collectively reflecting a shift toward a more “male-like” microbiome. These changes may contribute to increased risk of metabolic, cardiovascular, and bone diseases in postmenopausal women, although causality and underlying mechanisms remain to be clarified. The modifiable nature of the gut microbiome makes it a promising target for interventions aimed at improving menopause-related health outcomes. There is a pressing need for larger, longitudinal studies, and for research into the effects of menopausal hormone therapy on the gut microbiome. Understanding these relationships could open new avenues for personalized medicine in peri- and postmenopausal women.

What was reviewed?

This systematic review and meta-analysis synthesized data from 46 community-based studies across 24 countries, assessing the influence of socioeconomic position (SEP) and lifestyle factors on age at natural menopause (ANM). The review sought to determine overall mean ANM globally, compare regional differences, and quantify the impact of SEP (education, occupation, income) and modifiable lifestyle factors (smoking, body mass index [BMI], and physical activity) on menopausal timing. The meta-analyses incorporated both published and previously unpublished results from the Australian Longitudinal Study on Women’s Health (ALSWH), applying rigorous inclusion criteria and harmonizing variable definitions to maximize comparability.

Who was reviewed?

The review included a diverse range of women from 46 population-based cohorts across six continents, with total sample sizes in the tens of thousands. Study populations varied in age, ethnicity, and region (Africa, Asia, Australia, Europe, Latin America, Middle East, USA). All included studies excluded women with surgical menopause and largely defined natural menopause according to World Health Organization criteria. Most studies were cross-sectional, with some prospective cohorts; ethnic details were inconsistently reported. The ALSWH sample (n≈7,500) contributed prospective, nationally representative data from Australia.

Most important findings

The pooled mean age at natural menopause was 48.8 years, but substantial regional variation was noted: ANM was lowest in African, Latin American, Asian, and Middle Eastern countries, and highest in Europe, Australia, and the USA. Socioeconomic indicators showed a clear, dose-response association with ANM. Higher education and occupation levels were significantly associated with later menopause, and these effects were more pronounced in developed regions. Smoking was robustly associated with earlier menopause, advancing ANM by nearly one year, with a stronger effect in developed regions. Overweight status and moderate to high physical activity were weakly associated with later ANM, but findings were inconsistent and attenuated after adjustment for confounders. No consistent association was observed between income and ANM. Importantly, the review highlights that region, SEP, and lifestyle factors together explained a substantial portion of the observed heterogeneity in menopausal timing.

Key implications

This review confirms that ANM is not only regionally variable but also socially and behaviorally patterned. Lower education and occupation levels and smoking are associated with earlier menopause, suggesting that modifiable social and lifestyle factors substantially influence reproductive aging and may affect long-term health risks (e.g., osteoporosis, cardiovascular disease). These findings underscore the importance of incorporating SEP and lifestyle factors in clinical risk stratification for postmenopausal health. For microbiome research and clinical databases, the strong associations of SEP and smoking with ANM suggest these variables should be considered key contextual factors when interpreting or designing studies on menopausal microbiome signatures. The inconclusive associations for BMI and physical activity highlight the need for further, harmonized investigations, ideally using pooled individual-level data from prospective cohorts.

What was studied?

This research article investigated how the gut microbiome is altered in postmenopausal women with osteoporosis and osteopenia compared to healthy controls. The study aimed to characterize microbial diversity, taxonomic composition, and functional gene potential using shotgun metagenomic sequencing of fecal samples. Researchers sought to identify specific microbial taxa and metabolic pathways associated with bone health status, focusing on elucidating microbial signatures and potential mechanisms linking gut microbiota with bone metabolism in postmenopausal women.

Who was studied?

The study cohort consisted of 86 postmenopausal women aged 54 to 81 years, all at least 5 years post-menopause, recruited from the "Bugs’n’Bones" study at Massey University, New Zealand. Exclusion criteria included any systemic disease, gut-impacting food intolerances, smoking, high alcohol intake, recent antibiotic use, or significant weight change in the prior year. None were receiving medical treatment for osteoporosis or osteopenia. Based on WHO bone mineral density (BMD) T-score criteria, participants were classified as healthy (n=26), osteopenic (n=42), or osteoporotic (n=18).

Most important findings

The study found that both osteoporotic and osteopenic women had significantly different gut microbial taxonomic compositions compared to healthy controls, although their alpha diversity (Shannon and Simpson indices) did not differ. Beta diversity analyses and PERMANOVA confirmed significant community composition differences between healthy and diseased groups. Notably, healthy women showed higher abundances of unclassified Clostridia and methanogenic archaea (Methanobacteriaceae), including Methanobrevibacter smithii, while Bacteroides was more prevalent in osteoporotic and osteopenic groups. Other taxa such as Parabacteroides distasonis, Bacteroides uniformis, and Roseburia intestinalis were more abundant in osteopenic women, while Betaproteobacteria, Bacteroides stercoris, and Adlercreutzia were elevated in osteoporosis. Functional metagenomic analysis revealed that pathways related to carbohydrate metabolism, biosynthesis of secondary metabolites, phenylpropanoid and cyanoamino acid metabolism were enriched in osteoporotic and osteopenic groups, whereas replication and repair pathways were more prominent in healthy women. These results suggest a shift in the gut microbiome from health to osteopenia and osteoporosis, with specific microbial and functional signatures.

Key implications

This study provides the first shotgun metagenomic evidence that osteoporosis and osteopenia in postmenopausal women are associated with distinct gut microbiome signatures, both taxonomically and functionally. The findings highlight increased Bacteroides and decreased Clostridia and methanogenic archaea as potential microbial markers of bone loss, with functional shifts toward increased carbohydrate metabolism and secondary metabolite biosynthesis. These alterations may influence bone metabolism through mechanisms involving immune modulation, estrogen metabolism, and short-chain fatty acid production. The results underscore the potential for developing microbiome-based biomarkers and microbiome-targeted interventions targeting gut microbial communities to support bone health in postmenopausal women.

What was reviewed?

This comprehensive review synthesizes the current understanding of the mechanisms, endocrinology, and treatment options for menopausal hot flashes (HFs), emphasizing their physiological, neuroendocrine, and thermoregulatory underpinnings. The review details the characteristic clinical features of HFs, sudden intense warmth, sweating, and peripheral vasodilation, and investigates their temporal association with small core body temperature (Tc) elevations within a markedly narrowed thermoneutral zone. Freedman discusses the role of estrogen withdrawal, central sympathetic activation (particularly through α2-adrenergic receptors), and the complex neuroendocrine interactions involving norepinephrine (NE), serotonin (5-HT), and other neurotransmitters. The review also evaluates objective measurement techniques for HFs, including skin conductance and ambulatory monitors, and synthesizes findings from imaging studies exploring brain activation patterns during HFs. Treatment modalities, both hormonal and nonhormonal, including behavioral interventions, clonidine, serotonergic agents, isoflavones, and gabapentin, are critically reviewed in terms of efficacy and underlying mechanisms.

Who was reviewed?

The review encompasses findings from diverse populations: primarily peri- and postmenopausal women experiencing natural or surgical menopause, with some comparisons to asymptomatic women and men undergoing androgen deprivation for prostate cancer. Epidemiological data highlight racial and ethnic differences in HF prevalence (Caucasian women highest, Japanese and Chinese women lowest). Key physiological, endocrinological, and neuroimaging studies included both symptomatic and asymptomatic women, as well as breast cancer survivors who often experience treatment-induced HFs. Clinical trials of various treatments involved postmenopausal women with frequent HFs, including those with sleep complaints, and studies of objective HF measurement extended to men receiving GnRH agonists. The review thus offers a broad perspective, integrating findings from clinical, laboratory, and ambulatory settings across multiple demographic groups.

Most important findings

Menopausal hot flashes are characterized by a rapid, exaggerated heat dissipation response, sweating, vasodilation, and a feeling of internal heat, triggered by minimal Tc elevations within a greatly reduced thermoneutral zone. This narrowing is not solely attributable to estrogen depletion: while estrogen therapy effectively eliminates HFs, estrogen levels do not robustly correlate with HF presence or frequency, and additional factors must contribute. Elevated central sympathetic activity, mediated by α2-adrenergic receptors, appears critical in narrowing the thermoneutral zone; pharmacologic manipulation directly affects HF incidence. Objective monitoring via skin conductance and novel ambulatory devices provides reliable HF measurement, overcoming biases of self-reporting. Imaging studies demonstrate that the insular cortex, anterior cingulate, and brainstem are sequentially activated during HFs, linking physiological events to subjective experience. Treatment reviews show hormone therapy as the most effective, but nonhormonal options like paced respiration and clonidine are substantiated; SSRIs/SNRIs have mixed efficacy, and the role of serotonin is increasingly questioned. Botanical therapies show inconsistent benefit. Gabapentin exhibits moderate efficacy with known side effects. The review does not identify direct microbial associations or microbiome signatures related to HFs, and the role of the microbiome remains unaddressed in this context.

Key implications

For clinicians, this review underscores the multifactorial etiology of menopausal hot flashes, with central neuroregulatory dysfunction, rather than estrogen deficiency alone, being paramount. Treatments targeting central sympathetic tone (e.g., clonidine, behavioral relaxation) are rational, especially for women unwilling or unable to use hormone therapy. Objective monitoring methods, including skin conductance and ambulatory devices, may improve both diagnosis and evaluation of treatment response. The findings support individualized treatment, emphasize the need for thorough sleep disorder assessment in symptomatic women, and highlight areas for future research, particularly regarding central neuroregulatory pathways and novel therapeutic targets.

What was studied?

This original research investigated the gut microbiota signatures and fecal metabolite profiles in postmenopausal women with and without osteoporosis (PMO and non-PMO, respectively). The study aimed to elucidate the specific changes in both bacterial and fungal components of the intestinal microbiota, as well as associated fecal metabolites, that correlate with bone mineral density (BMD) in this population. Using 16S rRNA gene sequencing for bacteria, ITS sequencing for fungi, and LC-MS for metabolomics, the study comprehensively evaluated the compositional and functional alterations in the gut ecosystem of postmenopausal women stratified by osteoporosis status. The researchers also applied machine learning models to assess whether these microbial and metabolic signatures could serve as early diagnostic indicators for PMO.

Who was studied?

A total of 98 postmenopausal women aged 50–70 years were enrolled, divided into two groups based on BMD: 40 women with postmenopausal osteoporosis (PMO) and 58 women without osteoporosis (non-PMO). All participants were recruited from Zhongshan Hospital of Xiamen University, with strict inclusion and exclusion criteria to eliminate confounding factors such as organ dysfunction, recent antibiotic use, gastrointestinal diseases, and secondary causes of osteoporosis. For model validation, an independent cohort of 23 women (10 non-PMO, 13 PMO) from Xinyu People’s Hospital was included. Clinical data, serological markers, and BMD measurements were obtained alongside fecal samples for multi-omics analysis.

Most important findings

The study revealed marked differences in both bacterial and fungal gut communities between PMO and non-PMO women. Bacterial α-diversity (measured by Chao1, ACE, and Shannon indices) was significantly reduced in the PMO group, while fungal diversity changes were even more pronounced at the β-diversity level, indicating a distinct fungal signature in osteoporosis. Key bacterial genera enriched in PMO included Veillonella, Parabacteroides, and Harryflintia, while Prevotella and Enterobacterium were more abundant in non-PMO. Fungal genera such as Eurotium and Penicillium were elevated in PMO, whereas Pichia and Auricularia were enriched in non-PMO. Metabolomics identified higher levels of metabolites like levulinic acid and N-acetylneuraminic acid in PMO, with significant pathway alterations including alpha-linolenic acid and selenocompound metabolism. Correlation analysis showed that specific bacteria (e.g., Fusobacterium), fungi (e.g., Devriesia), and metabolites (e.g., L-pipecolic acid) were significantly associated with BMD. Machine learning models based on these microbial signatures distinguished PMO from non-PMO with high accuracy, underscoring their diagnostic potential.

Key implications

This study provides compelling evidence that gut microbial and metabolic profiles are closely tied to bone health in postmenopausal women. The identification of distinct bacterial, fungal, and metabolite signatures associated with osteoporosis advances our understanding of the gut-bone axis, suggesting potential mechanisms involving immune modulation and metabolic pathways. The robust diagnostic models highlight the clinical utility of gut microbiota analysis as a non-invasive tool for early PMO detection. The findings suggest that microbiome-targeted interventions, such as probiotics or dietary modifications, could be developed to prevent or mitigate osteoporosis in at-risk women, paving the way for personalized therapeutic strategies.

What was reviewed?

This narrative review critically examines the conventional framing of hot flashes and night sweats, collectively termed vasomotor symptoms (VMS), as mere symptoms of menopause. The authors argue for a paradigm shift, proposing that these phenomena are better understood as manifestations of underlying autonomic neurovascular dysregulation. The review synthesizes epidemiological, genetic, and mechanistic evidence to explore the etiological complexity of VMS, emphasizing associations with neurological (sleep, mood, cognition) and cardiovascular conditions. Drawing on large-scale longitudinal studies from Australia, the UK, and the US, the authors identify four consistent patterns of vasomotor disturbances and discuss their possible biological and genetic bases, independent of cultural or socioeconomic factors. The review also addresses the limitations of current research, including the lack of objective monitoring tools and standard terminology, and highlights emerging insights from genetic studies and neurobiological pathways (notably the hypothalamic KNDy neurons and neurokinin B signaling). The authors call for robust mechanistic research and advocate for the reclassification of VMS to better inform clinical practice and research strategies.

Who was reviewed?

The review considers data from diverse populations of women undergoing the menopausal transition, as reported in prominent longitudinal cohort studies such as the Australian Longitudinal Study of Women’s Health (ALSWH), the 1946 British birth cohort, and the Study of Women Across the Nation (SWAN, USA). These cohorts encompass women from multiple geographic, cultural, and socioeconomic backgrounds, allowing the review to draw generalizable conclusions about the universality of VMS patterns. The reviewed studies include women experiencing natural or surgical menopause (e.g., following bilateral oophorectomy), and incorporate genetic sub-studies examining variants related to estrogen metabolism, estrogen receptors, and neurotransmitter pathways. The focus is on midlife and older women, typically in the peri- and postmenopausal stages, and the analysis extends to those with and without VMS, as well as those with related comorbidities such as sleep disorders and cardiovascular disease.

Most important findings

The review’s central finding is that VMS, hot flashes, and night sweats are likely not merely transient symptoms of hormonal withdrawal, but rather indicators of underlying neurovascular dysregulation that may predispose women to chronic conditions of aging. Across countries, four distinct patterns of VMS (varying by onset, severity, and duration) recur, suggesting a biological underpinning rather than cultural artifacts. Notably, severe or persistent VMS are associated with increased risks for sleep disturbances (e.g., insomnia, obstructive sleep apnea), mood and cognitive disorders, and cardiovascular conditions such as endothelial dysfunction and coronary artery calcification. Genetic studies implicate variants in genes governing estrogen synthesis, metabolism, and signaling, as well as noradrenergic and serotonergic pathways, as contributors to individual susceptibility and symptom patterns. Evidence points toward disruption in hypothalamic KNDy neuron signaling and altered autonomic outflow (both sympathetic and parasympathetic) as mechanistic drivers. Pharmacological interventions targeting neurokinin B receptors, and established therapies such as menopausal hormone therapy (MHT), show variable efficacy depending on individual neurovascular profiles. The review highlights the limitations of self-reported symptom scales and the need for objective, standardized assessment tools.

Key implications

Reframing VMS as signs of autonomic neurovascular dysregulation rather than simply menopausal symptoms has pivotal clinical and research implications. It advocates for a more nuanced, mechanism-based approach to assessing and managing midlife women, particularly in stratifying risk for chronic diseases like cardiovascular disease, dementia, and osteoporosis. This perspective supports the development of personalized interventions, potentially informed by genetic and autonomic profiling, and underscores the need for investment in objective monitoring technologies and longitudinal studies.

What was reviewed?

This review article comprehensively addresses the diagnosis, evaluation, and management of osteoporosis in premenopausal women, emphasizing the unique considerations in this population compared to postmenopausal women. The authors discuss the significance of low-trauma fractures and low bone mineral density (BMD) in premenopausal women, the limitations of using standard BMD diagnostic thresholds (T-scores), and recommend the use of age-matched Z-scores for assessment. The review explores special circumstances, such as pregnancy- and lactation-associated osteoporosis, and highlights the rarity but clinical importance of idiopathic osteoporosis (IOP) in younger women. The article also provides an extensive overview of secondary causes of osteoporosis in this population, including endocrine disorders, inflammatory diseases, nutritional deficiencies, and medication effects, as well as detailing appropriate laboratory evaluations and management strategies, both non-pharmacological and pharmacological.

Who was reviewed?

The review covers premenopausal women, particularly those presenting with low-trauma fractures and/or low BMD, as well as subgroups affected by unique physiological states like pregnancy and lactation. The article references studies involving diverse cohorts of premenopausal women, including those with idiopathic osteoporosis, women with secondary causes of bone loss (such as glucocorticoid excess, anorexia nervosa, estrogen deficiency, and celiac disease), and women exposed to risk-modifying medications. Certain referenced studies focus on women with specific conditions, but the review synthesizes findings broadly applicable to the general premenopausal female population at risk for or diagnosed with osteoporosis.

Most important findings

The review underscores that osteoporosis in premenopausal women is uncommon and often secondary to underlying conditions rather than being primary. The most frequent secondary causes include glucocorticoid excess, anorexia nervosa, estrogen deficiency, and celiac disease, all of which can disrupt bone formation and turnover through mechanisms such as chronic inflammation, malnutrition, hormonal derangements, and malabsorption. The article notes that low-trauma fractures in premenopausal women are strong predictors of future fracture risk, but the direct relationship between BMD (measured by DXA) and fracture risk in this group is less clear than in postmenopausal women. For diagnosis, the review recommends using Z-scores (not T-scores), with a Z-score below −2.0 indicating bone density below the expected range for age. Management should focus on treating underlying causes, optimizing nutrition and lifestyle, and reserving pharmacological therapy for women with major or multiple fractures or ongoing bone loss. Limited data support the use of bisphosphonates and teriparatide in select high-risk cases, but caution is warranted due to potential risks, especially regarding future pregnancies. The review also lists a broad array of secondary causes and outlines a structured laboratory assessment to identify them.

Key implications

For clinicians, the review highlights the importance of a thorough diagnostic workup to uncover secondary causes of osteoporosis in premenopausal women, as management often hinges on addressing these root issues. The findings justify a conservative approach to pharmacotherapy in most cases, with primary reliance on lifestyle modification, nutritional support, and targeted treatment of underlying conditions. The recommendations emphasize individualized care and caution regarding medication use in women of childbearing potential, given the possible long-term skeletal and fetal risks. Recognizing and managing secondary causes not only improves bone health but may also address broader metabolic and reproductive health concerns. The review provides practical guidance for clinical evaluation, risk stratification, and safe management, bridging the gap between research findings and day-to-day clinical practice.

What was studied?

This research investigated the interplay between gut microbiota composition, fecal metabolites, and clinical symptoms in perimenopausal women, with a particular focus on the influence of follicle-stimulating hormone (FSH) levels. Using 16S rRNA gene sequencing and untargeted metabolomic profiling, the study analyzed stool samples from 44 women experiencing perimenopausal symptoms to determine differences in microbial diversity, specific microbial taxa, and metabolic pathways associated with varying FSH levels. The research aimed to elucidate how fluctuations in reproductive hormones, particularly FSH, are linked with changes in the gut microbiome and metabolic signatures, and how these biological variations correspond to clinical manifestations such as hot flashes, bone pain, and mental disturbances.

Who was studied?

The study cohort comprised 44 outpatient perimenopausal women, divided into two groups based on FSH levels: Group 1 (G1, n=16) had FSH <40 iu l (indicative of declining ovarian reserve), and group 2 (g2, n=28) had fsh>40 IU/L (indicative of premature ovarian failure). Demographic and hormonal profiles were similar between groups except for differences in FSH, LH, E2, and progesterone levels. Symptoms were categorized and quantified using the K-score. The G1 group experienced more mental disorders (anxiety, insomnia, depression), while the G2 group had a higher prevalence of hot flashes and bone pain. Age, testosterone, and prolactin did not differ significantly between the groups, minimizing confounding effects from these variables.

Most important findings

The study found no significant difference in overall microbial diversity (alpha or beta diversity) between the two FSH-defined groups. However, there were notable shifts in the relative abundance of specific bacterial taxa. At the genus level, Faecalibacterium, Subdoligranulum, Agathobacter, and Roseburia were more abundant in G1, while Bacteroides, Escherichia-Shigella, Bifidobacterium, and Blautia were more abundant in G2. Importantly, Bacteroides implicated in bone health was higher in G2, which also had a greater prevalence of bone pain. Bifidobacterium, associated with mitigating mental disorders, was also elevated in G2, where mental symptoms were less common. Spearman correlation analyses revealed that FSH was negatively correlated with Subdoligranulum and Agathobacter, while estradiol was positively correlated with Faecalibacterium and unclassified Lachnospiraceae. Metabolomic analysis revealed significant upregulation of metabolites involved in tyrosine metabolism, alpha-linolenic acid metabolism, and other lipid pathways in G2, which aligns with emerging evidence linking lipid metabolism disorders to postmenopausal osteoporosis. Several metabolites showed strong correlations with specific bacterial genera, highlighting potential microbiome-metabolite axes relevant to symptomatology.

Key implications

This study adds to the growing evidence linking perimenopausal hormonal changes, particularly elevated FSH, with specific alterations in the gut microbiome and fecal metabolome. The observed associations between certain bacterial taxa (e.g., Bacteroides, Bifidobacterium, Faecalibacterium, Blautia) and clinical symptoms suggest that the gut microbiota may modulate the risk or severity of common perimenopausal manifestations such as bone pain, hot flashes, and mental disorders. The enrichment of lipid and amino acid metabolism pathways in women with higher FSH and more pronounced bone pain supports the potential utility of microbiome and metabolome profiling in risk stratification and therapeutic targeting. While the study is limited by its small sample size, the findings indicate that microbiome signatures could serve as biomarkers for symptom phenotyping and inspire novel interventions, such as targeted probiotics or dietary modifications, to improve quality of life in perimenopausal women.

What was studied?

This original research article investigated the relationship between menopausal syndrome (MPS) and gut microbiota in women. Specifically, the study compared the gut microbial composition and predicted microbial functions between women experiencing MPS and healthy menopausal women. The research utilized 16S rRNA gene sequencing to profile gut microbiota from fecal samples, assessed clinical and hormonal parameters (including estradiol, FSH, and LH), and applied bioinformatics tools to characterize microbial signatures and pathway enrichment associated with MPS.

Who was studied?

The study enrolled 101 women aged 40–60 years from Guangzhou, China, between June 2020 and October 2021. Of these, 77 women were diagnosed with menopausal syndrome (MPS group), and 24 were healthy menopausal controls (H group). Diagnosis of MPS required the presence of menopausal symptoms, menstrual irregularities, and a modified Kupperman index (KI) score >15, while controls had a KI score <15 and no hot flashes. exclusion criteria included recent use of sex hormones or antibiotics, severe chronic disease, age outside the 40–60-year range. groups were matched for age, bmi, metabolic comorbidities to minimize confounding factors.< p>

Most important findings

The study identified significant gut microbiota dysbiosis in women with MPS compared to healthy controls. While overall microbial diversity did not differ significantly, 14 microbial species showed differential abundance. Notably, Aggregatibacter segnis, Bifidobacterium animalis, and Acinetobacter guillouiae were enriched in healthy controls and positively correlated with estradiol levels, while their abundance was reduced in MPS and inversely correlated with FSH and LH. Bifidobacterium animalis, known for its probiotic and metabolic benefits, was highlighted as particularly depleted in MPS. Functional prediction analysis revealed that women with MPS had gut microbiota enriched in pathways related to cardiovascular disease and carbohydrate metabolism, suggesting a microbiota-mediated predisposition to metabolic and cardiovascular risk post-menopause.

Key implications

These findings underscore the existence of distinct gut microbiota signatures associated with MPS and hormonal status in menopausal women. The depletion of beneficial species, especially Bifidobacterium animalis, and enrichment of pathways linked to metabolic and cardiovascular diseases suggest that gut microbiota may modulate both menopausal symptoms and long-term health risks. Clinically, the results support the potential for microbiome-targeted interventions (MBTIs) (e.g., probiotics, dietary modulation) to alleviate MPS symptoms and reduce comorbidities. However, the study’s cross-sectional design and modest sample size warrant further longitudinal and interventional research to clarify causality and therapeutic potential.

What was studied?

This original research article investigated the relationship between the diversity and composition of the fecal microbiome and urinary estrogen profiles in postmenopausal women. The study specifically aimed to determine whether urinary concentrations of estrogens and their metabolites, which are known to influence breast cancer risk, were associated with measures of gut microbial diversity and the relative abundance of specific microbial taxa. The researchers used 16S rRNA gene pyrosequencing to profile the fecal microbiome and liquid chromatography-tandem mass spectrometry to quantify urinary estrone, estradiol, and 13 hydroxylated estrogen metabolites. Statistical analyses assessed associations between microbiome diversity metrics, microbial taxa, and various estrogen metabolite ratios that have been linked to breast cancer risk in prior studies, adjusting for confounders such as age, body mass index (BMI), and study design factors.

Who was studied?

The study population comprised 60 healthy postmenopausal women aged 55–69 years, randomly selected from members of Kaiser Permanente Colorado. Key exclusion criteria included current or recent use of antibiotics or hormone therapy, and any history of cancer or gastrointestinal disease. The participants were predominantly white (91%) and non-Hispanic (95%), with a median age of 64 years and a median BMI of 27, reflecting an overweight to obese cohort. All had received a recent normal screening mammogram and had not taken medications or had conditions likely to impact gut microbiota or systemic hormone levels. Fecal and urine samples were collected, shipped, and analyzed under standardized conditions.

Most important findings

The study found a statistically significant positive association between whole-tree phylogenetic diversity of the fecal microbiome and the urinary ratio of estrogen metabolites to parent estrogens. This ratio, as well as pathway-specific ratios, has been previously associated with a reduced risk of postmenopausal breast cancer. The relative abundance of the order Clostridiales (especially the family Ruminococcaceae) was directly correlated with the metabolites-to-parent estrogen ratio, while the genus Bacteroides was inversely correlated. These associations persisted after adjusting for age, BMI, sample collection variables, and study design. Notably, overall measures of microbial diversity, rather than the abundance of dominant phyla (Firmicutes or Bacteroidetes), were most strongly linked to favorable estrogen metabolite profiles.

Key implications

This study provides evidence that greater gut microbial diversity is associated with estrogen metabolite profiles considered protective against breast cancer in postmenopausal women. The findings suggest that the gut microbiota, particularly the diversity and specific taxa such as Clostridiales and Ruminococcaceae, may modulate systemic estrogen metabolism, possibly through deconjugation and enterohepatic recycling of estrogens. These data support the hypothesis that manipulation of the gut microbiome could influence estrogen homeostasis and, by extension, breast cancer risk. However, due to the cross-sectional design and small sample size, causality cannot be established, and findings regarding specific microbial associations should be considered exploratory. Further research with larger cohorts and longitudinal designs is warranted to confirm these associations and elucidate underlying mechanisms.

What was studied?

The study explored how menopause affects the gut microbiome and estrobolome (the subset of gut bacteria involved in metabolizing sex hormones), and how these changes may relate to cardiometabolic risk factors. Using a large, well-characterized sample from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), researchers performed shotgun metagenomic sequencing on stool samples from about 2300 participants, including premenopausal women, postmenopausal women, and age-matched men. A subset also underwent serum metabolomics to assess sex hormone metabolites. The primary aims were to assess whether menopause alters gut microbiome diversity and composition, to identify specific microbial taxa and functions associated with menopausal status, and to investigate the relationship between these microbiome features, circulating sex hormone metabolites, and cardiometabolic risk profiles.

Who was studied?

Participants were drawn from the HCHS/SOL, a large, diverse cohort of Hispanic/Latino adults in the US. The analytic sample included 295 premenopausal women, 1,027 postmenopausal women, and 978 men (divided into groups age-matched to pre-and postmenopausal women). Exclusion criteria included cancer and insufficient sequencing data. Menopausal status was based on self-report and further refined to exclude women with surgical menopause, hormone therapy, or ambiguous menopausal status. Men were matched to women by age, BMI, Hispanic/Latino background, and nativity to control for confounders. Cardiometabolic risk factors and detailed demographic and lifestyle data were collected for all participants. Serum metabolomics data were available for a subset of 346 women.

Most important findings

Postmenopausal women exhibited lower gut microbiome diversity and a composition more similar to men than to premenopausal women, even after adjusting for age and confounders. Specific taxa enriched in postmenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis, while Escherichia coli-Shigella spp., Oscillibacter sp., Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis were depleted. Functionally, postmenopausal women had increased microbial sulfate transport systems and decreased abundance of β-glucuronidase, a key estrobolome enzyme, suggesting reduced microbial deconjugation of sex steroid hormones. Correlations between gut microbial features and serum progestin metabolites in postmenopausal women indicate active microbial participation in sex hormone retention. Menopause-related microbiome changes, especially the loss of beneficial species like C. lactatifermentans, were associated with adverse cardiometabolic profiles, including higher waist circumference, lower HDL, and higher blood pressure.

Key implications

The findings suggest that menopause-induced hormonal changes drive a shift in the gut microbiome toward a less diverse, more male-like composition, with reductions in both beneficial bacteria and estrobolome activity. These microbial shifts may reduce the potential for microbial reactivation of sex steroid hormones, potentially exacerbating the hormonal deficiency of menopause. The observed associations between menopause-related microbiome alterations and adverse cardiometabolic risk factors underscore the gut microbiome’s potential role in mediating increased metabolic risk after menopause. These results highlight the need for further research on microbiome-targeted interventions or hormone therapies to mitigate postmenopausal metabolic risk and suggest that microbiome signatures could be useful biomarkers for menopausal status and related health risks.

What was studied?

This original research article investigated compositional and functional differences in the gut microbiota between premenopausal and postmenopausal women using a metagenome-wide association study (MWAS). Shotgun metagenomic sequencing of fecal samples enabled the authors to compare not only the taxonomic diversity and abundance of gut microbes but also the metabolic modules and biochemical pathways associated with the gut microbiome in each group. The study aimed to clarify how menopause and the associated decline in endogenous estrogen affect the gut microbiome and its potential implications for metabolic and immune health risks in postmenopausal women. The research also explored how specific microbial taxa and their metabolic activities might contribute to disease risk profiles characteristic of postmenopausal status.

Who was studied?

The study cohort comprised 24 premenopausal and 24 postmenopausal women, carefully matched for age and body mass index (BMI) to control for confounding variables. All postmenopausal individuals experienced natural menopause and had not used antibiotics for at least one month prior to sample collection. Additional exclusion criteria included a history of chronic or current infection, malignancy, or recent antibiotic use. Clinical data collected included bone mineral density (BMD), blood lipid profiles, lifestyle, diet, and exercise habits. No significant differences were observed between the groups in these clinical and lifestyle factors, ensuring that the observed microbiome differences could be attributed primarily to menopausal status.

Most important findings

Postmenopausal women exhibited significantly reduced gut microbiome richness and diversity at the gene, species, and genus levels, as measured by Shannon index and taxon counts. Taxonomic shifts included depletion of Firmicutes and Roseburia species and enrichment of Bacteroidetes and the toluene-producing genus Tolumonas in postmenopausal women. Functionally, the pentose phosphate pathway, a key source of cellular antioxidant capacity, was more prevalent in premenopausal women, while metabolic modules involved in homocysteine and cysteine biosynthesis, glycolysis, and amino acid degradation were enriched in postmenopausal women. Notably, Tolumonas negatively correlated with BMD, suggesting a potential link with osteoporosis risk. The study also highlighted that higher homocysteine biosynthesis in the postmenopausal gut microbiome may contribute to increased cardiovascular risk. These compositional and functional shifts suggest that menopause leads to a gut microbial environment less supportive of antioxidant defense and potentially more conducive to metabolic and immune dysfunction.

Key implications

The findings underscore menopause-associated gut microbiome alterations as potential contributors to increased risks of metabolic, cardiovascular, and bone diseases in postmenopausal women. Reduced microbial diversity and depletion of beneficial taxa such as Roseburia may compromise host metabolism and immune function, while enrichment of taxa and pathways linked to harmful metabolites (e.g., homocysteine, toluene) may exacerbate disease risk. These insights suggest that the gut microbiome represents a promising therapeutic target for interventions (e.g., specific probiotics, dietary modulation, or fecal microbiota transplantation) aimed at improving metabolic and immune health outcomes in postmenopausal women. Moreover, identified microbial and functional signatures may serve as valuable biomarkers for risk stratification or monitoring of menopause-related disease progression.

What was studied?

The study focused on the impact of menopause on metabolic changes, particularly the effects of menopause on lipid and amino acid profiles, and their contribution to future cardiovascular and metabolic risks. It analyzed the metabolomic data from 26,065 individuals of Northern European ancestry, examining how menopause alters a broad spectrum of 135 serum metabolites, including lipoproteins, fatty acids, amino acids, and small molecules related to energy metabolism. The study aimed to assess the systemic metabolic shifts associated with menopause, considering not only traditional lipid measures but also detailed lipid subclass measurements and amino acid concentrations, which are emerging as key players in cardiovascular disease (CVD) and metabolic disorders.

Who was studied?

The study involved a large cohort of 26,065 participants, consisting of 16,107 Finnish individuals and 9,958 Estonian individuals. Participants were from a range of ages, predominantly from 40 to 75 years, with the analysis particularly focused on women in the menopausal transition (ages 40-55 years). The study excluded individuals using hormone replacement therapy (HRT), those with diabetes or on lipid-lowering medications, and pregnant women, to focus on natural metabolic shifts associated with menopause. The cohort was racially and ethnically homogenous, primarily consisting of individuals of Northern European descent, which may limit generalizability to other populations.

Most important findings

Postmenopausal women showed significantly higher concentrations of total cholesterol, esterified cholesterol, and lipoprotein subclasses, alongside higher concentrations of apoB and smaller, denser HDL particles. These changes align with increased cardiovascular risk. Higher levels of amino acids such as glutamine, tyrosine, and isoleucine were observed in postmenopausal women, which are linked to increased risk for metabolic diseases like Type 2 diabetes and cardiovascular diseases. Postmenopausal women exhibited increased levels of monounsaturated fatty acids and omega-7 and omega-9 fatty acids, which are associated with lipid metabolism and may influence CVD risk pathways. The study also found that a rapid increase in atherogenic lipid measures occurred between the ages of 45 and 50, coinciding with the onset of menopause, highlighting menopause's role in altering lipid metabolism and contributing to long-term metabolic and cardiovascular risks.

Key implications

The findings from this study underline menopause as a pivotal factor influencing metabolic shifts that increase the risk of cardiovascular and metabolic diseases. The changes in lipid and amino acid profiles suggest that menopause accelerates a shift towards a pro-atherogenic state, which can predispose women to conditions like heart disease and type 2 diabetes. These insights are crucial for clinicians as they highlight the need for early monitoring of metabolic health during the menopausal transition. The study also emphasizes the importance of considering metabolic profiling, including lipoprotein subclass and amino acid measures, as potential biomarkers for future cardiovascular risk in postmenopausal women. Additionally, the role of menopause in influencing fatty acid metabolism suggests that interventions targeting diet and lifestyle may be necessary to mitigate these risks.

What was studied?

The study focused on the metabolic changes associated with menopause, specifically the hormonal shifts that occur as women transition from perimenopause to early postmenopause. It explored the changes in the circulating metabolome, including alterations in lipoproteins, amino acids, and other metabolites, and examined the relationship between these changes and hormone levels, particularly estradiol (E2) and follicle-stimulating hormone (FSH). The research was conducted using longitudinal data collected from a cohort of Finnish women and utilized nuclear magnetic resonance (NMR) metabolomics to quantify a wide array of metabolites, providing insights into how menopause affects the broader metabolic profile and influences cardiovascular and metabolic health.

Who was studied?

The study involved 218 Finnish women, aged 47 to 55, who were followed longitudinally from perimenopause through early postmenopause. These women were part of the Estrogenic Regulation of Muscle Apoptosis (ERMA) cohort. Participants were assessed for menopausal status, hormonal changes, and their metabolic profiles over an average follow-up period of 14 months. A subset of the women (15%) began menopausal hormone therapy (MHT) during the follow-up. The cohort was selected to minimize the influence of aging and included only women without conditions affecting hormone profiles or metabolic health.

Most important findings

Postmenopausal women showed an increase in apoB-containing lipoprotein particles, and lipid levels such as triglycerides and cholesterol in these particles. This shift towards a proatherogenic lipid profile could increase cardiovascular disease risk. The study found increased levels of leucine, tyrosine, and other branched-chain amino acids, which are linked to insulin resistance and higher cardiovascular risk. A shift in fatty acid profile from polyunsaturated to saturated fats was observed, which may indicate an increased risk for type 2 diabetes. Glycerol levels increased, while ketone bodies like 3-hydroxybutyrate decreased, suggesting deteriorating insulin sensitivity. Decreased citrate levels were noted, which may be linked to reduced bone health in postmenopausal women.

Key implications

The findings highlight menopause as a critical period for cardiovascular and metabolic health, marked by significant alterations in the circulating metabolome. The observed shifts in lipoproteins, fatty acids, and amino acids suggest a proatherogenic and insulin-resistant state, which could predispose postmenopausal women to increased risks of cardiovascular diseases and type 2 diabetes. The study emphasizes the need for clinicians to monitor these metabolic markers in menopausal women and consider interventions, including lifestyle modifications or menopausal hormone therapy, to mitigate these risks. Further research on the specific molecular mechanisms underlying these metabolic shifts and their long-term effects on women’s health is also essential.

What was reviewed?

This comprehensive review examined the relationship between menopause-associated changes in lipid metabolism and the increased risk of metabolic disorders in postmenopausal women. It addressed the physiological changes underlying menopause and their impact on fat distribution, lipid profiles, and the development of metabolic syndrome, obesity, and cardiovascular disease (CVD). The authors also critically reviewed dietary recommendations and beneficial compounds, including vitamin D, omega-3 fatty acids, antioxidants, phytochemicals, and probiotics, that may help manage or mitigate abnormal lipid metabolism in this population.

Who was reviewed?

The review focused on postmenopausal women, typically aged 45–55 years and older, representing a significant and growing portion of the global female population. The authors synthesized data from a wide range of studies, including large cohort and longitudinal studies such as the Study of Women’s Health Across the Nation (SWAN), as well as clinical trials, animal models (notably ovariectomized mice), and cross-sectional analyses. The population included healthy women, as well as those with obesity, metabolic syndrome, and related comorbidities.

Most important findings

The review highlights important associations between estrogen deficiency and changes in adipokines, such as increased leptin and resistin and decreased adiponectin and ghrelin, which collectively exacerbate insulin resistance and metabolic dysfunction. Notably, the review discusses the role of gut microbiota and probiotics, referencing emerging evidence that multistrain probiotics improve endothelial function and insulin resistance in obese postmenopausal women. Dietary interventions were shown to be effective: higher protein intake helps preserve lean mass and prevent sarcopenia, traditional diets rich in fish, seaweeds, vegetables, and fruits lower triglycerides and improve HDL-C, and supplementation with vitamin D and omega-3 fatty acids is associated with lower adiposity, improved lipid profiles, and reduced inflammation. Antioxidants and phytochemicals from plant foods, as well as probiotics, provide additional cardiometabolic protection.

Key implications

Understanding the interplay between menopause, lipid metabolism, and metabolic disorders is essential for developing preventive and therapeutic strategies in clinical practice. The review underscores the importance of dietary patterns and nutrients, particularly vitamin D, omega-3 fatty acids, antioxidants, phytochemicals, and probiotics, in improving lipid profiles, reducing inflammation, and supporting metabolic health in postmenopausal women. From a microbiome perspective, the documented benefits of probiotics and dietary modulation of gut flora suggest a promising avenue for personalized interventions to mitigate menopause-associated metabolic risk.

What was studied?

The study examined the metabolic changes that occur during menopause, focusing on how menopause modulates circulating metabolites in midlife women. Researchers specifically analyzed 94 charged metabolites, including amino acids, fatty acids, and other small molecules, to assess how these metabolic changes correlate with the increased risk of chronic diseases, such as cardiovascular disease and diabetes, that affect postmenopausal women. The goal was to understand the broader metabolic shifts that occur during menopause and their potential implications for long-term health risks.

Who was studied?

The study involved 1,193 women from the Tsuruoka Metabolomics Cohort Study, a community-based cohort of Japanese women aged between 40 and 60 years. The participants were divided into three groups based on their menopausal status: premenopausal, menopausal transition, and postmenopausal. To ensure that the results were not influenced by factors such as hormone replacement therapy (HRT), participants with certain health conditions or who had recently used HRT were excluded. The cohort was selected from Tsuruoka City, Japan, and included a diverse group of women across various stages of menopause, allowing for a comprehensive analysis of the metabolic changes associated with this life stage.

Most important findings

The study revealed that menopause is associated with significant shifts in the metabolic profile of women, particularly in metabolites linked to cardiovascular and metabolic risks. As women transitioned from premenopausal to postmenopausal status, several metabolites, including those involved in the urea cycle, TCA cycle, and homocysteine metabolism, showed elevated levels. This included an increase in metabolites like ornithine, taurine, glutamine, and carnitine, which are connected to cardiovascular health risks, such as arteriosclerosis. These metabolic shifts could explain the heightened risk of cardiovascular diseases observed in postmenopausal women. Additionally, higher levels of amino acids such as glutamine and lysine were found, which are often associated with insulin resistance and increased risk for metabolic disorders like diabetes. The study also observed a shift in lipid metabolism, as certain lipid metabolites showed patterns similar to changes seen in traditional lipid markers like total cholesterol and LDL cholesterol, which also change during menopause. These findings suggest that menopause accelerates metabolic changes that may contribute to the development of chronic diseases.

Key implications

The implications of this study are significant for clinical practice, as they suggest that menopause is not only a time of hormonal changes but also a pivotal period for metabolic health. The findings highlight the need for clinicians to monitor metabolic markers in women during the menopausal transition, as these shifts may predict long-term health outcomes such as cardiovascular disease and diabetes. Clinicians should consider metabolic profiling as a tool for identifying women at higher risk for these conditions and may need to implement early interventions, such as lifestyle modifications, to mitigate these risks. Moreover, the results emphasize the importance of personalized prevention strategies, particularly in postmenopausal women, as metabolic changes become more pronounced during this stage.

What was reviewed?

This review article comprehensively examines the interplay between metal exposures, menopause, and COVID-19. The authors synthesize current evidence on how environmental and dietary exposure to metals, including heavy metals such as arsenic, cadmium, mercury, and lead, influences the onset and course of menopause and, in turn, how these factors may impact susceptibility to and outcomes from COVID-19. The review highlights the hormonal, metabolic, and immunological changes during menopause and how these are modulated by metal exposures, with a particular focus on trace minerals’ role in immune competence and the severity of SARS-CoV-2 infection.

Who was reviewed?

The review synthesizes data from epidemiological studies, clinical research, and mechanistic investigations involving women at various menopausal stages across diverse populations exposed to environmental metals. While some cited studies focus on the general female population, others investigate specific cohorts such as women in polluted regions, those with occupational metal exposure, or patients with COVID-19. Both human and relevant animal studies are included to elucidate pathogenic mechanisms, and supporting data from male and pediatric populations are referenced for context.

Most important findings

The review identifies several key microbiome-relevant associations and signatures. High blood levels of heavy metals, including arsenic, cadmium, lead, and mercury, are linked to disruptions in endocrine function, earlier or altered onset of menopause, and increased risk of age-related diseases such as osteoporosis and cardiovascular disease. For instance, arsenic exposure is associated with an earlier menopause, while cadmium can mimic estrogenic effects but also disrupt ovarian function and the timing of menopause. In postmenopausal women, mobilization of bone lead increases blood lead levels, potentially exacerbating toxic effects. Metal exposures are further implicated in modulating the immune response to SARS-CoV-2, with higher levels of toxic metals correlating with impaired respiratory function and more severe COVID-19 outcomes. Conversely, deficiencies in essential trace elements are associated with increased COVID-19 severity and poorer recovery. The review notes potential benefits of supplementation with zinc, magnesium, and selenium, especially in postmenopausal women, to support both immune function and mitigate the toxic effects of heavy metals.

Key implications

For clinicians, these findings underscore the importance of monitoring metal exposures and trace element status in menopausal and postmenopausal women, particularly in the context of the ongoing COVID-19 pandemic. Screening for and addressing deficiencies in zinc, selenium, and magnesium may be warranted to reduce vulnerability to severe COVID-19 and counteract the deleterious effects of heavy metals. The review also suggests that environmental and occupational history should be part of menopausal risk assessment, and that hormone replacement therapy may have added benefits in supporting immune resilience during viral infections. The need for further research into the interaction between environmental pollutants, metal metabolism, menopausal transition, and the gut microbiome is highlighted, especially for the development of personalized interventions and microbiome-informed risk stratification.

What was studied?

The study investigated the relationship between urinary metal concentrations and the timing of natural menopause in midlife women, using data from the Study of Women’s Health Across the Nation (SWAN). It specifically examined 15 urinary metals, including arsenic, lead, cadmium, copper, mercury, and zinc, to assess how these metals, both individually and in mixtures, influenced the onset of menopause. The research aimed to fill the knowledge gap regarding the impact of environmental metal exposure on ovarian aging and the timing of menopause, a critical factor linked to various long-term health risks.

Who was studied?

The study population consisted of 1,082 premenopausal women, aged 45–56, from multiple racial and ethnic groups, including White, Black, Chinese, and Japanese women. The participants were enrolled in the SWAN study, a large, community-based, prospective cohort. These women were followed for an average of 4.1 years, during which they provided regular urine samples for analysis of metal concentrations. The study aimed to explore how various environmental exposures, specifically metals, affect the timing of natural menopause and associated health risks.

Most important findings

The study found that higher urinary concentrations of arsenic and lead were significantly associated with earlier natural menopause. Specifically, women in the highest quartile of urinary arsenic had an average menopause age 1.6 years earlier compared to those in the lowest quartile. Similarly, higher lead concentrations also correlated with earlier menopause. This suggests that exposure to certain metals may accelerate ovarian aging. Additionally, the study used an Environmental Risk Score (ERS) to quantify the cumulative effect of multiple metal exposures, showing that women with higher ERS values experienced menopause earlier, further emphasizing the role of metal mixtures in accelerating the menopausal transition. The study also observed no significant association with other metals like cadmium or mercury but highlighted the potential cumulative effects of metal mixtures on menopause timing.

Key implications

The study's findings emphasize that environmental exposure to heavy metals, such as arsenic and lead, may have significant public health implications by influencing the timing of natural menopause. Since earlier menopause is linked to various health risks such as cardiovascular diseases, osteoporosis, and cognitive decline, understanding the role of environmental toxins in this process could inform public health interventions aimed at reducing exposure to harmful metals. This research underscores the importance of considering both individual and combined exposures to metals in future epidemiological studies and public health policies.

What was studied?

This study examined the associations between urinary heavy metals, including arsenic, cadmium, mercury, and lead, and the levels of key sex hormones (estradiol, follicle-stimulating hormone, testosterone, and sex hormone-binding globulin) in midlife women. The research used data from the Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of women aged 45-56 years, followed over several years. The focus was on understanding how environmental exposures to heavy metals might influence hormone profiles during the menopausal transition, a critical period of reproductive aging, which can have long-term health implications for women, including cardiovascular disease, osteoporosis, and metabolic disorders.

Who was studied?

The study included 1,355 women from the SWAN cohort, representing a diverse range of racial and ethnic groups, including White, Black, Chinese, and Japanese women. Participants were aged 45-56 years at baseline (1999-2000). The analysis focused on midlife women who were followed through their menopausal transition, with hormone levels repeatedly measured up until 2017. Urinary metal concentrations were assessed at baseline, and serum hormone levels were measured annually. The cohort included women from different geographic locations across the U.S., providing insights into how environmental exposures affect sex hormone levels across various populations.

Most important findings

The study found that exposure to heavy metals significantly influenced hormone levels in midlife women. Specifically, a doubling in urinary mercury and lead concentrations was associated with lower estradiol (E2) levels by 2.2% and 3.6%, respectively. Additionally, higher lead concentrations were associated with higher follicle-stimulating hormone (FSH) levels, by 3.4%. Cadmium exposure was linked to increased levels of sex hormone-binding globulin (SHBG) by 3.6%. However, no significant association was found between metals and testosterone levels. The joint effects of metal mixtures showed a negative association with E2 and a positive association with FSH. The study also noted that the associations were stronger in early and late perimenopausal stages.

Key implications

The findings of this study highlight the significant role that environmental heavy metals can play in altering sex hormone levels during midlife, a crucial period for women’s health. The associations between higher lead and mercury concentrations with reduced estradiol levels and increased follicle-stimulating hormone levels suggest that metal exposure may accelerate ovarian aging, a factor that could impact menopause timing and related health risks, such as cardiovascular diseases and osteoporosis. The study emphasizes the need for public health strategies to minimize heavy metal exposure and further underscores the importance of monitoring environmental toxins as part of women’s healthcare during midlife.

What was reviewed?

This comprehensive review synthesized current evidence on medicinal plants and natural compounds with estrogenic activity, focusing on their potential to prevent neurodegeneration, memory loss, and other menopause-related symptoms in women. The authors conducted an extensive literature search using SCOPUS, PubMed, and ScienceDirect, focusing on plants with established estrogenic activity. The paper details the pharmacological effects of these plants and their phytoestrogenic constituents, highlighting mechanisms involving estrogen receptor modulation, antioxidant, and anti-inflammatory actions. Special emphasis is placed on the potential of these compounds to alleviate cognitive deficits during menopause and aging, as well as their roles in preventing or treating neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Who was reviewed?

The review encompassed a wide range of studies, including preclinical research in cellular and animal models, as well as clinical trials and meta-analyses involving postmenopausal women. The included studies span healthy female and male subjects, women undergoing hormone replacement therapy (HRT), postmenopausal women, and patients with neurodegenerative conditions. The botanical scope was global, drawing on traditional medicinal plants from Europe, Asia, and the Americas, with particular focus on species commonly used in traditional Chinese medicine and Western herbalism.

Most important findings

The review identifies a diverse array of estrogenic plants, such as soy, red clover, black cohosh, sage (Salvia officinalis), ginger, and others, that contain phytoestrogens capable of binding to and modulating estrogen receptors. These plants offer cognitive and neuroprotective benefits through multiple mechanisms: selective estrogen receptor modulation, antioxidant effects, and anti-inflammatory actions. For instance, soy isoflavones, red clover, and Lespedeza bicolor have demonstrated memory-enhancing effects and reduction of amyloid-beta pathology in animal models of Alzheimer's disease. Some clinical trials report improvement in menopausal symptoms, quality of life, and cognitive performance with phytoestrogen supplementation, although results are sometimes inconsistent.

Key implications

The findings underscore the promise of estrogenic plants as safer, potentially effective alternatives to conventional HRT for managing menopausal symptoms and reducing neurodegenerative disease risk. Their selective activity on estrogen receptors, along with concurrent antioxidant and anti-inflammatory effects, positions them as multi-target interventions for aging-related cognitive decline. Importantly for clinical practice, these botanicals may offer neuroprotection without the increased risk of cancer and cardiovascular disease associated with conventional HRT, especially when used early in menopause. The review highlights the need for further high-quality, long-term clinical trials to clarify efficacy, optimal timing, and safety.

What was studied?

This study explored the potential of Rhodiola rosea (R. rosea), a natural selective estrogen receptor modulator (SERM), as a treatment for menopause symptoms and health risks. The authors reviewed molecular mechanisms by which R. rosea could mitigate cognitive decline, mood disturbances, cardiovascular disease, osteoporosis, and cancer associated with estrogen decline during menopause. Emphasis was placed on the neuroprotective, cardioprotective, anti-inflammatory, and anti-oxidative properties of R. rosea extracts, particularly focusing on the bioactive constituent salidroside and its interaction with estrogen receptors. The paper also presented a clinical case illustrating improvements in cognitive function and mood with R. rosea treatment in a menopausal woman.

Who was studied?

The study synthesized findings from in vitro, animal, and limited human clinical studies examining R. rosea extracts and salidroside effects on estrogen receptor modulation and menopause-related pathologies. These included ovariectomized rodent models simulating estrogen deficiency, human clinical trials assessing cognitive and mood improvements in stressed or fatigued adults, and case reports from menopausal women. The study focused on women in menopausal transition and postmenopause, at increased risk for neurocognitive, cardiovascular, and bone-related disorders due to estrogen decline.

Most important findings

Rhodiola rosea acts as a natural SERM with tissue-specific modulation of estrogen receptors, showing agonistic effects on brain, bone, and cardiovascular tissues while lacking uterotrophic or pro-carcinogenic activity. Salidroside demonstrated neuroprotective effects by enhancing synaptic function, memory, and executive function, partly via ERβ activation and anti-inflammatory pathways such as NF-κB inhibition. Cardiovascular benefits arose from improved endothelial nitric oxide synthase (eNOS) activity, enhanced nitric oxide production, and antioxidant protection reducing oxidative stress. Osteoprotective effects included inhibition of oxidative stress-induced osteoblast dysfunction, preventing bone loss in estrogen-deficient models. Importantly, R. rosea showed anti-cancer potential by inhibiting proliferation and inducing apoptosis in estrogen receptor-positive and -negative breast cancer cell lines without stimulating tumor growth. Clinically, R. rosea improved cognitive function, reduced anxiety, depression, and fatigue in menopausal and stressed individuals with minimal side effects, suggesting a favorable safety profile compared to synthetic SERMs and hormone replacement therapy (HRT).

Key implications

This review highlights Rhodiola rosea as a promising natural alternative to conventional HRT and synthetic SERMs for managing menopause-associated cognitive decline, mood disorders, cardiovascular risk, osteoporosis, and cancer risk. Its multi-targeted estrogen receptor modulation and anti-inflammatory, antioxidant mechanisms address critical pathways affected by estrogen loss. Unlike HRT, R. rosea may confer these benefits without increasing risks of cancer or thrombosis. However, clinical trials specifically in menopausal women are necessary to validate efficacy, optimal dosing, and long-term safety. The compound’s favorable side effect profile and neuroprotective properties make it a potential adjunct or alternative therapy, aligning well with growing patient interest in botanical and non-hormonal menopause treatments.

What was studied?

This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of a novel herbal preparation, Menopause Relief EP® (RR-BC), combining extracts of Actaea racemosa (black cohosh, BC) and Rhodiola rosea (RR), in relieving menopausal symptoms. The study compared this combination against two doses of black cohosh alone and placebo over 12 weeks. The primary outcomes were improvements in menopausal symptom severity assessed by the Kupperman Menopausal Index (KMI) and Menopause Rating Scale (MRS), with secondary endpoints including quality of life (QoL) measured by the Utian Quality of Life (UQOL) scale. Safety and adverse events (AEs) were also monitored.

Who was studied?

The study enrolled 220 menopausal women aged 40–82 years (median 52 years) diagnosed with menopausal complaints confirmed by elevated FSH and low estradiol levels. Participants were randomized evenly into four groups (RR-BC combination, low-dose BC, high-dose BC, and placebo). Patients had moderate menopausal symptoms as measured by baseline KMI and MRS scores. Women with hormone therapy, psychological disorders, or other conditions likely to interfere with outcomes were excluded. Ninety percent completed the study per protocol, with treatment compliance exceeding 90% across groups.

Most important findings

The RR-BC combination significantly reduced menopausal symptom severity, as shown by a 71.2% decrease in KMI scores after 12 weeks, outperforming both low-dose and high-dose BC groups and placebo. Similarly, MRS scores decreased by 67.7% with RR-BC versus 49.9% and 60.0% for the BC groups. Quality of life, particularly in emotional and physical health domains, improved significantly more with RR-BC than with BC or placebo. The RR-BC group also experienced significant improvements in sexual activity. Safety analysis showed no significant difference in adverse event frequency or severity between groups, with no serious adverse events reported. The data support a synergistic or additive effect of Rhodiola when combined with black cohosh, enhancing relief from psychological and somatic menopausal symptoms. Although the study did not directly assess microbiome changes, both plants have known adaptogenic and neuroprotective properties that may indirectly influence microbiome-associated inflammation and hormonal regulation, which are relevant to menopause symptomatology.

Key implications

This trial demonstrates that combining Rhodiola rosea with Actaea racemosa provides superior symptom relief and quality of life improvements for menopausal women compared to black cohosh alone, with excellent safety and tolerability. The combination’s enhanced effect on emotional health and sexual function suggests it addresses neuropsychological symptoms effectively, likely via adaptogenic and estrogen-modulating mechanisms. These findings encourage further investigation of combined botanical therapies in menopause, including exploration of their impact on the microbiome and inflammatory pathways. This approach offers a promising alternative or adjunct to hormone replacement therapy, especially for women seeking non-hormonal, plant-based interventions with favorable safety profiles.

What was reviewed?

This Cochrane systematic review comprehensively assessed the clinical effectiveness and safety of black cohosh (Cimicifuga spp.) preparations for treating menopausal symptoms. The review synthesized data from randomized controlled trials comparing black cohosh to placebo, hormone therapy, red clover, fluoxetine, or other controls. It aimed to determine whether black cohosh reduces the frequency and severity of vasomotor symptoms (hot flushes, night sweats), vulvovaginal symptoms, and improves menopausal symptom scores, while evaluating its safety profile in perimenopausal and postmenopausal women.

Who was reviewed?

The review included sixteen randomized controlled trials involving a total of 2,027 women aged mostly between 50 and 56 years, all experiencing menopausal symptoms. Participants were perimenopausal or postmenopausal women recruited across various clinical and geographical settings, including the US, Germany, China, and Europe. Trials used oral monopreparations of black cohosh at doses ranging from 8 to 160 mg daily, over durations from 4 to 52 weeks. Control interventions included placebo, hormone therapy, red clover, fluoxetine, and other comparators.

Most important findings

Pooled evidence showed no statistically significant benefit of black cohosh over placebo in reducing the frequency or intensity of hot flushes or night sweats. Meta-analysis of five trials demonstrated a negligible mean difference in daily hot flush frequency and menopausal symptom scores. Comparisons of black cohosh with hormone therapy consistently favored hormone therapy, which significantly reduced vasomotor symptoms and menopausal scores. Trials comparing black cohosh to red clover or fluoxetine yielded inconclusive results due to limited data and heterogeneity. Safety data indicated no significant difference in adverse events between black cohosh and placebo, although reporting was incomplete. Data on secondary outcomes such as bone health, sexuality, quality of life, and cost-effectiveness were insufficient for conclusive analysis.

Key implications

Current evidence from randomized controlled trials does not support black cohosh as an effective treatment for menopausal vasomotor symptoms compared to placebo or hormone therapy. However, the overall quality of the evidence is moderate to low due to methodological limitations and heterogeneity among trials. Current safety data show that people generally tolerate black cohosh well, but researchers need to report findings more rigorously. Given the widespread use of black cohosh as a complementary therapy, researchers should conduct further high-quality, well-designed studies to clarify its efficacy, safety, and impact on quality of life and other clinically relevant outcomes. Understanding potential interactions with the microbiome and its influence on symptom modulation could enrich future investigations and help guide more targeted therapies for menopause.

What was reviewed?

This review article comprehensively evaluates the current pharmacological treatments for menopausal symptoms, focusing on hormone replacement therapy (HRT), non-hormonal options, and emerging therapies. It addresses the efficacy, safety, and mechanisms of various estrogen, progestogen, androgen, selective estrogen receptor modulators (SERMs), and alternative compounds used to manage vasomotor symptoms, urogenital atrophy, bone loss, mood disorders, and sexual dysfunction in perimenopausal and postmenopausal women.

Who was reviewed?

The review synthesizes evidence from randomized controlled trials, observational studies, and meta-analyses involving diverse populations of menopausal women across clinical settings globally. It includes women experiencing a spectrum of menopausal symptoms such as hot flushes, night sweats, sleep disturbance, mood changes, urogenital atrophy, and metabolic complications. The review integrates findings on standard populations as well as subgroups with comorbidities affecting treatment decisions and outcomes.

Most important findings

The review confirms that estrogen therapy remains the most effective treatment for vasomotor and urogenital symptoms associated with menopause. It emphasizes the differential pharmacokinetics and safety profiles of oral versus transdermal estrogen, highlighting that non-oral routes tend to have fewer thromboembolic risks and more physiological hormone metabolism. Progestogens are necessary alongside estrogen in women with an intact uterus to prevent endometrial hyperplasia, though choice of progestogen influences side effects and tolerability. Non-hormonal agents such as gabapentin, clonidine, and selective serotonin reuptake inhibitors (SSRIs) provide moderate relief for vasomotor symptoms, especially in women who cannot undergo HRT. Phytoestrogens and black cohosh lack consistent evidence for efficacy, and safety concerns remain, particularly hepatotoxicity with black cohosh. Newer therapies include tibolone, a synthetic steroid with tissue-selective effects, showing benefit for sexual function and bone health but with some cardiovascular risks in older women.

The review also touches on androgen therapy, particularly testosterone, which shows promise in treating hypoactive sexual desire disorder in surgically menopausal women, though concerns regarding breast cancer risk and cardiovascular effects necessitate cautious use. Emerging selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene offer fracture prevention and reduced breast cancer risk but may worsen vasomotor symptoms.

Key implications

Clinicians should tailor menopausal symptom management based on individual risk profiles, symptom severity, and patient preferences. Estrogen therapy remains first-line for significant symptoms but must be balanced against risks of thromboembolism and cancer, emphasizing the benefits of transdermal over oral routes when feasible. Non-hormonal alternatives offer options for those contraindicated for HRT but generally provide less symptom relief. The heterogeneity of menopause symptoms and comorbidities calls for personalized approaches, including consideration of novel SERMs and androgens. Further research into the interaction between menopausal therapies and the microbiome may enhance understanding of systemic effects and optimize treatment strategies. Safety monitoring, especially for long-term hormone use, remains paramount.

What was reviewed?

This review article explores the role of the gut microbiota in menopause and evaluates the potential of prebiotic and probiotic interventions as therapeutic strategies for managing menopausal symptoms. It summarizes current evidence on how the menopausal transition influences gut microbial diversity and composition, especially with sex hormone fluctuations, and how these microbial changes may contribute to common menopause-related conditions such as metabolic disorders, osteoporosis, inflammation, and cognitive decline.

Who was reviewed?

The review synthesizes data from a wide range of studies, including human observational cohorts, animal models, and clinical trials involving peri- and postmenopausal women. It covers studies investigating the gut microbiota composition across different menopausal stages and examines interventions with prebiotics and probiotics designed to modulate the microbiome in menopausal populations. Additionally, it includes mechanistic insights from rodent models and discusses potential translational applications for human health.

Most important findings

Menopause induces significant shifts in gut microbiota characterized by decreased diversity and a shift towards a composition resembling that of age-matched men, including reductions in beneficial bacteria like Roseburia and Lachnospira and increases in potentially detrimental taxa such as Bacteroidetes and Tolumonas. These microbial changes correlate with altered estrogen metabolism through the estrobolome, a collection of bacterial genes encoding β-glucuronidase and sulfatase enzymes that reactivate estrogens, impacting systemic estrogen levels and menopausal symptoms.

Emerging evidence indicates that gut dysbiosis during menopause may play a significant role in driving increased intestinal permeability, chronic systemic inflammation, and metabolic disturbances. Various prebiotic fibers, such as flaxseed and soybean fiber, and specific probiotic strains, including Lactobacillus acidophilus, L. gasseri, and L. rhamnosus, have demonstrated potential in alleviating menopausal symptoms. These interventions appear to work by enhancing gut microbial diversity, strengthening intestinal barrier function, modulating systemic inflammatory responses, and influencing estrogen metabolism. Collectively, these findings suggest that targeting the gut microbiota may offer a promising adjunct or alternative approach to managing menopause-associated health challenges.

Key implications

This review highlights the gut microbiota as an important and potentially modifiable factor influencing a wide range of menopause-associated health challenges. Accumulating evidence suggests that targeted modulation of the gut microbiome through prebiotic and probiotic interventions offers a promising non-hormonal therapeutic strategy to alleviate menopausal symptoms and manage related metabolic, inflammatory, and psychological conditions. However, to translate these findings into effective clinical practice, future research should prioritize elucidating the underlying causal mechanisms linking gut microbial alterations to menopausal health outcomes. In addition, there is a critical need to identify specific microbial strains, functional pathways, or metabolites that mediate these beneficial effects. Developing personalized, evidence-based microbiome-targeted therapies could ultimately enhance long-term health, reduce disease risk, and improve the overall quality of life for menopausal women.

What was reviewed?

This comprehensive critical review examined the effectiveness and safety of complementary and alternative medicine (CAM) interventions for managing menopausal symptoms. It focused on mind-body practices, natural products, and whole-system approaches such as traditional Chinese medicine and acupuncture. The review synthesized evidence from randomized controlled trials (RCTs) and systematic reviews published through early 2017, aiming to clarify CAM's role in alleviating vasomotor symptoms (VMS), mood disturbances, sexual dysfunction, sleep problems, and other common menopausal complaints.

Who was reviewed?

The review encompassed a diverse cohort of menopausal and postmenopausal women, including healthy individuals and breast cancer survivors, drawn from multiple RCTs across various countries. Participants typically experienced vasomotor symptoms, mood disorders, sleep disruption, and quality-of-life impairments. The literature included trials with sample sizes ranging from small pilot studies to larger RCTs, focusing on CAM modalities used either as standalone treatments or adjuncts to conventional therapies.

Most important findings

The review identified that mind-body interventions, particularly hypnosis, consistently demonstrated clinically significant reductions in hot flash frequency and severity, with some studies showing up to 74% reduction in subjective hot flashes. Cognitive behavioral therapy (CBT) and relaxation techniques showed potential benefits in reducing distress and improving quality of life but were less effective in decreasing hot flash frequency. Mindfulness-based stress reduction and yoga may alleviate psychological symptoms and improve sleep quality but lack strong evidence for vasomotor symptom reduction.

Among natural products, evidence was mixed and inconclusive. Black cohosh showed inconsistent benefits, with some studies indicating no significant effect on menopausal symptoms, while combined preparations with other herbs appeared more promising. Phytoestrogens (soy, red clover) displayed variable results, often failing to achieve clinically meaningful improvements in vasomotor symptoms. Other supplements like vitamin E and evening primrose oil lacked robust evidence for efficacy.

Key implications

This review supports the use of mind-body interventions, especially hypnosis, as effective and safe CAM options for managing vasomotor and psychological menopausal symptoms. Other CAM therapies show potential but require further rigorous trials with standardized protocols to establish efficacy and safety. Healthcare providers should actively discuss CAM use with patients to provide integrative care and reduce risks from unregulated treatments. Incorporating microbiome-focused research may enhance understanding of CAM mechanisms and guide personalized therapeutic strategies for menopause.

What was reviewed?

This comprehensive review systematically examines the multifaceted health disorders associated with menopause, focusing on microbiome alterations and their implications across various body sites, including the vaginal, gut, urethral, oral, and duodenal microbiomes. It explores the interplay between declining estrogen levels during menopause and disruptions in microbial communities, the consequent impact on disease risks, ranging from reproductive disorders, metabolic syndrome, cardiovascular diseases, bone health, mental health, and other systemic conditions, and discusses current and emerging interventions including dietary modifications, hormone therapy, probiotics, plant extracts, and traditional therapies.

Who was reviewed?

The review synthesizes findings from a wide range of human observational and interventional studies involving peri- and postmenopausal women, alongside relevant animal models and mechanistic research. It includes clinical and molecular studies examining microbiome compositional changes, microbial metabolic functions, immune modulation, and symptom relief strategies. It also incorporates data on socioeconomic and lifestyle factors influencing menopausal health outcomes.

Most important findings

Menopause triggers a decline in estrogen that profoundly alters microbial communities, particularly the depletion of Lactobacillus in the vaginal and urethral microbiomes, increasing susceptibility to infections and genitourinary syndrome of menopause (GSM). Gut microbiota diversity decreases with shifts in Firmicutes/Bacteroidetes ratios, leading to reduced production of beneficial metabolites like short-chain fatty acids, impairing intestinal barrier integrity and immune regulation. Duodenal microbiome alterations, such as increased Proteobacteria and decreased Bacteroidetes, associate with elevated cardiovascular risk, influenced further by hormone therapy. Oral microbiota imbalances increase periodontal disease risk, while microbial dysbiosis broadly correlates with metabolic disorders like obesity and type 2 diabetes, osteoporosis, and mental health disturbances. Interventions including dietary fiber, soy isoflavones, probiotic supplementation, menopausal hormone therapy (MHT), and plant extracts (black cohosh, red clover, soybean) show promise in modulating these microbiomes, improving symptoms, and reducing disease risks.

Key implications

This review highlights the critical role of microbiome dysbiosis in menopause-associated health disorders and supports integrative intervention strategies that target microbial balance alongside hormonal and lifestyle factors. It advocates for personalized medicine approaches combining diet, probiotics, hormone therapy, and traditional treatments to optimize menopausal health. Future research should prioritize mechanistic studies, synergistic interventions, and psychosocial factors to enhance disease prevention, diagnosis, and management in menopausal women.

What was studied?

This exploratory study investigated the impact of a low-fat, plant-based dietary intervention including daily cooked soybeans on the frequency and severity of postmenopausal hot flashes, with a particular focus on the role of the gut microbiome. The study aimed to identify microbial changes associated with symptom improvements, especially changes in bacteria known to influence estrogen metabolism and inflammation.

Who was studied?

The study enrolled 84 postmenopausal women aged 40–65 years experiencing at least two moderate-to-severe hot flashes per day. Participants were randomly assigned either to follow the dietary intervention or to continue their usual diets for 12 weeks. Gut microbiome analyses using deep shotgun metagenomic sequencing were conducted on stool samples from a subset of 11 women from the intervention group, collected before and after the dietary period.

Most important findings

The dietary intervention resulted in a dramatic 95% reduction in total hot flashes and a 96% decrease in moderate-to-severe hot flashes. Significant decreases were observed in both daytime and nighttime hot flashes. Although overall microbial diversity (alpha and beta diversity) did not change significantly, specific taxa exhibited changes in relative abundance. Notably, decreases in Porphyromonas and Prevotella corporis correlated with reductions in severe daytime hot flashes, and decreases in Clostridium asparagiforme correlated with reductions in total severe and severe nighttime hot flashes. These bacteria are linked to inflammatory pathways and estrogen metabolism. Increases in genera such as Erysipelatoclostridium, Fusicatenibacter, and Holdemanella, known for anti-inflammatory effects and fiber fermentation, were also observed. The plant-based diet rich in fiber and soy isoflavones likely modulated the microbiome to reduce systemic inflammation and improve estrogen receptor-mediated signaling, contributing to symptom relief. However, after correction for multiple testing, these associations were not statistically significant, highlighting the exploratory nature of the findings.

Key implications

This study provides preliminary evidence linking dietary modulation of the gut microbiome to reductions in menopausal vasomotor symptoms. The findings suggest that plant-based diets with soy may beneficially alter gut bacteria involved in inflammation and estrogen metabolism, offering a potential non-hormonal therapeutic avenue for hot flash management. Larger, controlled studies are necessary to confirm these microbiome-symptom relationships and to explore personalized dietary strategies targeting gut microbiota for menopausal symptom relief.

What was studied?

This review explored the role of ketogenic diets (KDs) as a non-pharmacological therapy for major endocrine diseases of the female reproductive system, focusing on conditions such as polycystic ovary syndrome (PCOS), infertility, menopause-related metabolic disorders, and hormone-related cancers, including breast cancer and endometrial cancer. It examined how KDs impact body weight, insulin resistance, chronic inflammation, hormone levels, and cancer progression through metabolic modulation, including effects on mitochondrial function and reactive oxygen species (ROS).

Who was studied?

The review synthesized evidence from a broad range of studies involving women of reproductive age, women with obesity, PCOS, and menopausal women, as well as patients diagnosed with hormone-sensitive cancers. It included clinical trials, observational studies, and mechanistic research focusing on diet-induced metabolic changes and endocrine outcomes.

Most important findings

Ketogenic diets promote rapid weight loss and improve metabolic profiles by reducing fat mass, especially visceral adipose tissue, a key driver of inflammation and insulin resistance. KDs lower circulating insulin and glucose levels, which modulate the insulin-mediated synthesis of androgens in PCOS, improving hormonal imbalances and ovulatory function. Furthermore, KDs increase sex hormone binding globulin (SHBG) levels, reducing free testosterone and mitigating hyperandrogenism, a hallmark of PCOS.

In menopausal women, KDs counteract weight gain and visceral fat accumulation associated with estrogen decline, thereby lowering cardiovascular and metabolic risks. The diet’s anti-inflammatory effects are mediated partly through ketone bodies like beta-hydroxybutyrate inhibiting NLRP3 inflammasome activation, which reduces proinflammatory cytokine production. In hormone-related cancers, KDs reduce glucose availability for tumor cells, suppress inflammatory tumor microenvironments, and promote tumor cell apoptosis. The diet’s modulation of ROS and enhancement of mitochondrial function may contribute to these anticancer effects. Importantly, very low-calorie ketogenic diets (VLCKD) show promise in both weight management and cancer adjunctive therapy, enhancing quality of life and physical function in affected women.

Key implications

This review highlights ketogenic diets as a multifaceted therapeutic approach for managing endocrine disorders in women, from fertility challenges in PCOS to metabolic and oncologic complications postmenopause. By addressing obesity-related inflammation and insulin resistance, KDs offer a metabolic reset that can restore hormonal balance and reduce disease burden. Their anti-inflammatory and anticancer properties also position KDs as valuable adjuncts to conventional therapies. However, personalized protocols and careful nutritional monitoring are crucial for safety and efficacy. Clinicians should consider KDs as part of integrated care for women with complex endocrine and metabolic conditions, tailoring interventions to individual needs and stages of reproductive life.

What was studied?

This study conducted a dietary intervention to evaluate the effects of daily consumption of (poly)phenol-rich foods on cardiometabolic risk biomarkers in postmenopausal women. Over two months, participants supplemented their diets with specific foods rich in (poly)phenols, 85% cocoa dark chocolate, green tea, and a fruit juice blend (pomegranate, orange, and berries), to assess impacts on oxidative stress, inflammation, lipid profiles, blood pressure, and endothelial function.

Who was studied?

The study recruited 25 postmenopausal women aged 45 to 65 years from Murcia, Spain, with at least 12 months of amenorrhea, overweight or obesity, and at least one cardiometabolic risk marker such as high body fat or waist-to-hip ratio. Participants followed their usual Mediterranean-based diet during the trial and were free from endocrine, hepatic, or other severe pathologies. Smoking and restrictive diet users were excluded to avoid confounders.

Most important findings

The intervention provided a daily total of 1226 µmol (poly)phenols, mainly flavan-3-ols, hydrolyzable tannins, flavanones, anthocyanins, and phenolic acids, with dark chocolate contributing the most antioxidant capacity. After two months, participants showed slight but consistent improvements in multiple cardiometabolic parameters, including reduced systolic and diastolic blood pressure, decreased triglycerides and very-low-density lipoprotein cholesterol, and improvements in insulin resistance indices (HOMA-IR). Oxidative stress biomarker thiobarbituric acid-reacting substances (TBARs) significantly decreased, indicating a lowered oxidative burden. Additionally, improvements were observed in endothelial function biomarkers (sICAM-1, sVCAM-1) and anti-inflammatory adiponectin, though these changes were modest and subject to high inter-individual variability. The gut microbiome’s role is implicated as a key factor influencing (poly)phenol metabolism, affecting the bioavailability and subsequent health benefits of these compounds.

Key implications

This study supports the potential of dietary (poly)phenol-rich foods to ameliorate cardiometabolic risk factors during menopause by reducing oxidative stress and improving vascular and inflammatory markers. Given the variability in response linked to gut microbiome activity, personalized nutrition approaches that consider microbiome composition may optimize therapeutic effects. These findings highlight the importance of non-pharmacological, diet-based interventions as adjuncts or alternatives to hormone replacement therapy for managing menopause-associated cardiometabolic risk.

What was studied?

This review assessed the impact of intermittent fasting (IF) on weight management and overall health in postmenopausal women. It focused on how different IF protocols, such as time-restricted feeding, alternate-day fasting, and the 5:2 method, affect metabolic health, weight control, insulin sensitivity, hormonal balance, and inflammation in women post-menopause. The review aimed to evaluate the potential benefits of IF in managing menopause-associated conditions, particularly metabolic syndrome, cardiovascular risk, and obesity, which are prevalent in postmenopausal women.

Who was studied?

The review consolidated findings from various studies involving postmenopausal women, typically aged between 45 and 65 years, who are at a heightened risk of developing metabolic conditions due to hormonal changes that occur during and after menopause. These women often experience significant weight gain, insulin resistance, and an increased risk of cardiovascular disease, making them a key demographic for evaluating non-pharmacological interventions like intermittent fasting. The studies included clinical trials and observational studies that explored the effects of IF protocols on metabolic health, specifically in postmenopausal women.

Most important findings

The review demonstrated that intermittent fasting (IF) could provide significant metabolic benefits for postmenopausal women, particularly in managing weight gain and improving insulin sensitivity. Studies indicated that IF could help reduce visceral fat and overall body weight, with improvements in metabolic biomarkers such as glucose levels, insulin sensitivity, and lipid profiles. Additionally, IF was found to influence hormonal levels, potentially reducing insulin and cortisol spikes, which are crucial for managing menopause-related metabolic disturbances. The positive impact of IF extended to cardiovascular health, where improvements in blood pressure and lipid profiles were observed. Furthermore, preliminary evidence suggested that IF could enhance cognitive function by improving brain-derived neurotrophic factor (BDNF), supporting neuronal health. Although promising, the review also highlighted the need for further research into the long-term effects of IF on bone health and its interaction with hormone replacement therapy (HRT), as these aspects were not comprehensively studied.

Key implications

The findings of this review suggest that intermittent fasting may be a beneficial non-pharmacological intervention for managing menopause-related metabolic and cardiovascular risks in women. IF provides a promising strategy to address obesity, insulin resistance, and other metabolic disorders without relying on medication. Its ability to improve hormonal balance, reduce inflammation, and potentially enhance cognitive function makes it a valuable tool for postmenopausal women. However, the review also emphasizes the need for individualized approaches to IF, as its effectiveness may vary based on the woman’s health status and adherence levels. Further research is required to explore its long-term impact, particularly regarding bone health, and to determine how it interacts with other therapeutic options such as HRT.

What was studied?

This systematic review assessed the impact of intermittent fasting (IF) on the human gut microbiota, focusing on different types of IF, such as time-restricted feeding (TRF), alternate-day fasting (ADF), and the 5:2 diet. The review aimed to explore how these fasting interventions affect microbiota richness, alpha and beta diversity, and composition.

Who was studied?

The review included studies on healthy adults as well as those with conditions like obesity or metabolic syndrome. Participants from various ethnic groups, including Chinese and Pakistani populations, were examined to evaluate how IF affects their gut microbiota during fasting periods like Ramadan and structured diets like TRF and ADF.

Most important findings

The review found that IF interventions significantly influenced gut microbiota composition and diversity. Specifically, time-restricted eating (TRF) led to increases in microbial richness and diversity in healthy males and those observing Ramadan. Some studies showed a significant rise in specific bacterial species like Akkermansia muciniphila and Lachnospiraceae. However, the results varied significantly across studies, and the effects on alpha diversity were inconsistent. Beta diversity changes indicated distinct microbiome communities between fasting and non-fasting groups. Interestingly, studies on ADF and the 5:2 diet showed limited data, with only minor changes in microbiota composition observed.

Key implications

This review underscores the need for more targeted research to clarify the health benefits of IF-induced changes in gut microbiota. Given that the effects on microbiota diversity are still under investigation, IF could potentially offer benefits for gut health, particularly in managing metabolic disorders and inflammation. However, the substantial heterogeneity in study designs and populations means that healthcare professionals should be cautious about recommending IF without further evidence on its specific microbiome benefits. Future studies should standardize measures of microbiota diversity and control for confounding dietary variables to offer clearer insights into IF's role in gut health.