The uterus is a hollow, fibromuscular organ involved in physiological processes such as menstruation and pregnancy. The content and organization of extracellular matrix constituents such as fibrillar collagen dictate passive (non-contractile) biomechanical tissue function; however, how extracellular matrix composition and biomechanical function change with age in the uterus remains unknown. This study utilizes Raman spectroscopy coupled with biaxial inflation testing to investigate changes in the murine uterus with age (2-3 months, 4-6 months, 10-12 months, and 20-24 months). Linear and toe moduli significantly decreased with reproductive aging (2 to 12 months); however, both moduli increased in the oldest age group (20-24 months). The optical concentration of the combined elastin and collagen spectrum was significantly higher in the oldest group (20-24 month), while the glycogen contribution was the highest in the 2-3 month murine uterus. The presented workflow couples biaxial inflation testing and Raman spectroscopy, representing a critical first step to correlating biomechanics and optical signatures in the aging uterus with the potential for clinical translation. Further, this study may provide critical compositional and structure-function information regarding age-related uterine disorders.

Estrogen replacement therapy and total joint arthroplasty (TJA) are prevalent in the geriatric population, with limited evidence for how estrogen replacement therapy influences postoperative outcomes. Estrogen replacement therapy is often held before arthroplasty due to the perceived risk for venous thromboembolism (VTE). Our primary aim was to investigate the relationship between estrogen replacement therapy and VTE risk, and secondarily to investigate major medical complications following TJA.

A retrospective review was performed with a large national database querying International Classification of Diseases, tenth revision procedure codes, identifying 893,759 primary total hip arthroplasty (THA) and 1,660,909 total knee arthroplasty (TKA) procedures from 2015-2020. Of THAs, a cohort of 3,425 (3.5%) were prescribed estrogen replacement therapy within 90 days before surgery and propensity matched to 6,850 control patients for age, tobacco use, obesity and diabetes diagnosis. Of TKAs, a cohort of 7,409 (3.5%) was prescribed estrogen replacement therapy and similarly propensity matched to 14,818 control patients. Propensity-matched data were qualified with adjusted odds ratios (OR) and 95% confidence intervals (CI) for deep venous thrombosis (DVT), pulmonary embolism (PE), and total medical complications.

After propensity matching, estrogen replacement therapy use in THA demonstrated decreased risk of DVT (OR 0.52, CI 0.29 to 0.91, P = 0.028) but no difference in PE (OR 0.67, CI 0.34 to 1.32, P = 0.31). The ERT cohort had lower medical complications (OR 0.47, CI 0.31 to 0.73, P < 0.001). Among TKAs, estrogen replacement therapy use was associated with decreased risk of DVT (OR 0.60, CI 0.44 to 0.82, P = 0.001), PE (OR 0.56, CI 0.37 to 0.83, P = 0.005), and medical complications (OR 0.53, CI 0.42 to 0.67, P < 0.001).

Estrogen replacement therapy use with TJA is associated with decreased risk of VTE and major medical postoperative complications. These findings should be considered when counseling patients regarding the management of estrogen replacement therapy when undergoing TJA.

Chemotherapy-induced amenorrhea and premature ovarian failure are important survivorship issues for young women undergoing treatment for breast cancer. However, factors predictive of ovarian function recovery are not well established, and there is a lack of evidence supporting an appropriate surrogate marker for ovarian function recovery in clinical practice. We therefore aimed to assess, in the real-world setting, the impact of various factors on menses recovery.

We retrospectively analyzed 408 pre-menopausal patients with early breast cancer who received chemotherapy from our department's database, 308 of whom were evaluable for menses recovery. The primary endpoint was the assessment of menses recovery. The factors evaluated were age at diagnosis, hormonal receptor status and adjuvant hormonal treatment, HER2 status, prophylactic use of GnRH analogs, anthracycline use, and a hormonal profile of FSH, LH, and E2. The impact of menses recovery on disease-free survival was also assessed.

Age was found to have a statistically significant impact on menstrual recovery (p < 0.0001), as did the prophylactic use of GnRH analogs (p < 0.0001). Patients that received adjuvant hormonal treatment had a statistically significant longer time to menstrual recovery than patients who did not (p < 0.0001), a difference which was more prominent in younger patients. Anthracycline use and HER2-positivity did not have an impact on ovarian function recovery. A hormonal profile of FSH, LH and β2-estradiol collected in the beginning of patient's follow-up was statistically significant for predicting menstrual recovery. The absence of menstrual recovery was statistically significant for improved disease-free survival (HR: 0.37, p = 0.0566).

Our study demonstrated parameters that can be used in clinical practice to guide patients counseling about ovarian function recovery in premenopausal women with early breast cancer.

Women exhibit unique vulnerabilities in health, especially regarding mental health and neurodegenerative diseases. Biological, hormonal, and metabolic differences contribute to sex-specific risks that remain underrepresented in clinical studies. Diseases such as major depressive disorder (MDD) and Alzheimer's disease (AD) are more prevalent in women and may be influenced by hormonal transitions, particularly during menopause. Chronic low-grade inflammation is emerging as a shared mechanism underlying both conditions, and this inflammatory state can be worsened by dietary habits. During menopause, mood and sleep disturbances can influence dietary behavior, leading to enhanced snacking and consumption of high-glycemic and comfort foods. Such foods, low in nutritional value, promote weight gain and elevated inflammatory markers. Their consumption combined (or not) with a preexisting Western diet pattern-already linked to inflammation-could reinforce systemic inflammation involving the gut-brain axis. Moreover, the symptoms "per se" could act on inflammation as well. Peripheral inflammation may cross the blood-brain barrier, sustaining mood disorders and promoting neurodegenerative changes. Finally, MDD and AD are both associated with conditions such as obesity and diabetes, which occur more frequently in women. The review highlights how menopause-related changes in mood, sleep, and diet may heighten susceptibility to mental and neurodegenerative diseases.

Women are increasingly choosing to delay childbirth, and those with low ovarian reserves indicative of primary ovarian insufficiency are at risk for sub- and infertility and also the early onset of menopause. Experimental strategies that promise to extend the duration of ovarian function in women are currently being developed. One strategy is to slow the rate of loss of existing primordial follicles (PFs), and a second is to increase, or 'boost', the number of autologous PFs in the human ovary. In both cases, the duration of ovarian function would be expected to be lengthened, and menopause would be delayed. This might be accompanied by an extended production of mature oocytes of sufficient quality to extend the fertile lifespan.

In this work, we consider how slowing physiological ovarian aging might improve the health and well-being of patients, and summarize the current state-of-the-art of approaches being developed. We then use mathematical modeling to determine how interventions are likely to influence the duration of ovarian function quantitatively. Finally, we consider efficacy benchmarks that should be achieved so that individuals will benefit, and propose criteria that could be used to monitor ongoing efficacy in different patients as these strategies are being validated.

Current methods to estimate the size of the ovarian reserve and its relationship to the timing of the menopausal transition and menopause were compiled, and publications establishing methods designed to slow loss of the ovarian reserve or to deliver additional ovarian PFs to patients were identified.

We review our current understanding of the consequences of reproductive aging in women, and compare different approaches that may extend ovarian function in women at risk for POI. We also provide modeling of primordial reserve decay in the presence of therapies that slow PF loss or boost PF numbers. An interactive online tool is provided that estimates how different interventions would impact the duration of ovarian function across the natural population. Modeling output shows that treatments that slow PF loss would need to be applied as early as possible and for many years to achieve significant delay of menopause. In contrast, treatments that add additional PFs should occur as late as possible relative to the onset of menopause. Combined approaches slowing ovarian reserve loss while also boosting numbers of (new) PFs would likely offer some additional benefits in delaying menopause.

Extending ovarian function, and perhaps the fertile lifespan, is on the horizon for at least some patients. Modeling ovarian aging with and without such interventions complements and helps guide the clinical approaches that will achieve this goal.

Not applicable.

Women experiencing more severe menopausal symptoms exhibit poorer quality of life, and those with early menopause have a higher risk of developing chronic diseases. However, the extent to which neighborhood disadvantage contributes to menopause onset and symptom severity remains understudied.

To examine the association of Social Vulnerability Index (SVI) with age of natural menopause onset and menopausal symptom severity.

This cohort study used data from a prospective cohort of women participating in Project Viva who were initially enrolled in eastern Massachusetts and followed up from pregnancy to midlife between April 1999 and August 2021. Participant inclusion required geocoded residential addresses at enrollment (1999-2002), 8-year follow-up (2006-2010), and 13-year follow-up (2012-2016); age at natural menopause; and menopausal symptoms. Data were analyzed between March 1 and June 30, 2024.

SVI grouped into 5 categories: very low (<20th percentile), low (20th to <40th percentile), moderate (40th to <60th percentile), high (60th to <80th percentile), or very high (≥80th percentile) vulnerability.

Age at natural menopause and self-reported menopausal symptoms based on the presence and severity of 11 symptoms over the past year. These symptoms were assessed using the Menopause Rating Scale (total score range: 0-44, with higher scores indicating greater severity).

Of the 691 women included in the study (mean [SD] enrollment age, 33.7 [3.8] years; 41 with Asian [6.0%], 79 with Black [11.5%], 39 with Hispanic [5.7%], 507 with White [73.6%], and 23 with other [3.3%] race and ethnicity), 87 (12.6%) resided in neighborhoods with very high SVI at enrollment, 38 of 635 (6.0%) at 8-year follow-up, and 41 of 660 (6.2%) at 13-year follow-up. The Kaplan-Meier estimate for median age of natural menopause was earlier in women residing in neighborhoods with very high vs very low SVI at enrollment (52.0 [95% CI, 51.0-53.0] years vs 53.0 [95% CI, 53.0-54.0] years), 8-year follow-up (51.0 [95% CI, 50.0-53.0] years vs 53.0 [95% CI, 53.0-54.0] years), and 13-year follow-up (51.0 [95% CI, 50.0-53.0] years vs 53.0 [95% CI, 53.0-54.0] years). After adjusting for covariates, residence in neighborhoods with very high (but not low, moderate, or high) vs very low SVI at enrollment (adjusted hazard ratio [AHR], 1.36; 95% CI, 0.90-2.06), 8-year follow-up (AHR, 2.23 (95% CI, 1.29-3.85), and 13-year follow-up (AHR, 2.18 (95% CI, 1.30-3.66) was associated with higher risk of earlier natural menopause. SVI was not associated with menopausal symptoms.

In this cohort study, women who resided in neighborhoods with very high vulnerability within 10 years of the perimenopause period exhibited higher risk of earlier natural menopause. Future research is warranted to explore whether initiatives to improve neighborhood conditions could mitigate the association of neighborhood disadvantage with earlier menopause onset.

Although studies have explored the development of postoperative anemia after metabolic bariatric surgery, little is known about the effect of metabolic bariatric surgery on anemia recovery in patients with pre-existing anemia. Therefore, the objective of this study was to determine the prevalence of anemia recovery six months after metabolic bariatric surgery and predictors associated with recovery.

This was a retrospective cohort study of 1,664 patients with pre-existing anemia aged 18-80 years who received a primary metabolic bariatric procedure between January 2010 and June 2020. The primary outcome of interest was the percentage of patients who recovered from anemia as defined by the World Health Organization thresholds at six-months post-metabolic bariatric surgery.

Of the 1,664 patients identified with preoperative anemia, 952 (57.2%) recovered six-months post-metabolic bariatric surgery. Female sex (OR 1.93, 95% CI 1.42-2.61, p < 0.001), age between 45-54 years vs. under 35 years (OR 1.48, 95% CI 1.08-2.05, p < 0.05), and receiving sleeve gastrectomy vs. Roux-en-Y gastric bypass (OR 1.41, 95% CI 1.06-.86, p < 0.05) were associated with significantly higher odds of recovery. A preoperative hemoglobin of 11-20 g/L below normal as compared to 0-10 g/L below normal (OR 0.52, 95% CI 0.40-0.69, p < 0.001) was associated with significantly lower odds of recovering from anemia.

More than half of patients with preoperative anemia undergoing metabolic bariatric surgery recover from anemia after their procedure. Age, sex, preoperative hemoglobin, and surgery type all influence recovery. The total body weight lost after six-months post-surgery conferred no significant effect.

Studies have shown that women are asking for more knowledge and guidance about menopause. The professional competence of midwives encompasses menopause as a potential area of expertise. Midwives have good knowledge of women's health and are used to providing health advice.

The aim was to examine midwives' experiences of working with menopause counselling.

Data were collected by using semi-structured individual interviews with 14 midwives who had experience in conducting menopause counselling. The data analysis was carried out using Malterud systematic text condensation.

The data analysis yielded four themes: The midwife can fulfil a need for care; Menopause counselling, a midwifery task; Factors that facilitate; Promote equal menopause care. The midwives felt they were addressing a healthcare need that had previously been unmet. They thought midwives were well suited to perform this task, had good knowledge of women's health and were used to working from a holistic and salutogenic perspective. The midwives perceived certain conditions as essential, structured menopausal counselling, support in the organisation, education at advanced level and established cross-professional collaborations. They also thought an investment in menopause care is needed to promote equal care.

This work indicates that midwives with their skills and working methods are well suited to conduct menopausal counselling and thereby could satisfy a healthcare need. Resources needed are investments in menopausal counselling visits by midwives.

Changes in thermoregulation, notably the emergence of hot flashes, occur during the menopause transition in association with reproductive hormonal changes. Hot flashes constitute the most characteristic symptom of menopause (prevalence of 50-80%), and have a substantial negative effect on quality of life. Here, we review the endocrine changes associated with menopause and the thermoregulatory system and its sensitivity to female sex hormones. We then review current knowledge on the underlying neural mechanisms of hot flashes and how the reproductive and thermoregulatory systems interact in females. We consider the kisspeptin-neurokinin B-dynorphin (KNDy) neuron complex, which becomes hyperactive when estradiol levels decrease. KNDy neurons project from the arcuate nucleus to thermoregulatory areas within the hypothalamic preoptic area, where heat loss mechanisms are triggered, including cutaneous vasodilation and sweating - characteristics of the hot flash. We describe the physiology and measurement of hot flashes and discuss the mixed research findings about thresholds for sweating in symptomatic individuals. We consider the unique situation of hot flashes that arise during sleep, and discuss the relationships between the environment, exercise, and body mass index with hot flashes. We also discuss the unique situation of surgical menopause (with oophorectomy) and cancer therapy, conditions that are associated with frequent, severe, hot flashes. We then provide an overview of treatments of hot flashes, including hormone therapy and targeted neurokinin B-antagonists, recently developed to target the neural mechanism of hot flashes. Finally, we highlight gaps in knowledge about menopausal thermoregulation and hot flashes and suggest future directions for research.

The aim was to assess the differences in the burden and risk factors of female cancers among women aged 20-94 years across regions and countries, in order to provide a reference for formulating tailored interventions. The study analyzed the incidence, deaths, and disability-adjusted life years (DALYs) using data from the Global Burden of Disease 2021 study. Age-period-cohort model evaluated the effects of the age, period, and cohort on the burden, and negative binomial regression explored the association of the socio-demographic index (SDI) with the burden. From 1990 to 2021, regional and national incidence, deaths, and DALYs of female cancers varied markedly. Overall, SDI was significantly positively associated with the incidence of female cancers, except for cervical cancer (with a negative relationship). High body-mass index as the leading risk factor of uterine cancer contributed to the higher burden, such as in the USA and higher SDI regions. Diet high in red meat, unsafe sex, and high body-mass index were the leading risk factors for breast cancer, cervical cancer, and uterine cancer, respectively; however, other socioeconomic and cultural factors should be considered, such as in the rural areas of China and lower SDI regions. A slightly increasing trend in the burden of breast cancer in the recent birth cohorts indicated the effect of generational experiences. The disease burden of female cancers has increased and varies with SDI levels and regions. The findings provide new insights into the development of targeted preventive measures for the specific region from the perspective of social and cultural context.

Iron deficiency (ID) is a top five leading cause of disability-adjusted life-years in women of reproductive age around the world. Despite its enormous health burden, no screening guidelines exist for the detection and treatment of ID in women of reproductive age. We sought to determine the cost-effectiveness of screening versus no screening for ID in women of reproductive age in the United States. A lifetime simulation of women of reproductive age was conducted using a Markov cohort model under three strategies: (1) no screening, (2) screening at a ferritin threshold of 15 μg/L, and (3) screening at a ferritin threshold of 25 μg/L, from the US health system perspective, and at a willingness-to-pay threshold of $100 000/quality-adjusted life year (QALY). Epidemiologically informed ID prevalence estimates sourced from the National Health and Nutrition Examination Survey were employed for model parameterization. The primary outcome was the incremental cost-effectiveness ratio (ICER, in $/QALY). Base-case results for the three strategies accrued $209 700, $210 200, and $210 200 discounted lifetime costs and 23.6, 24.0, and 24.4 discounted lifetime QALYs, respectively. Screening at a ferritin threshold of 25 μg/L was the cost-effective intervention with an ICER of $680/QALY (95% credible interval $350-$750/QALY). In dual base-case analyses examining intravenous rather than oral iron repletion for treatment, screening at a ferritin threshold of 25 μg/L remained the cost-effective intervention with an ICER of $2300/QALY (95% CI $1800-$3800/QALY). In probabilistic sensitivity analyses, screening at a ferritin threshold of 25 μg/L was the cost-effective intervention in 100% of 10 000 second order Monte Carlo iterations.

Recent years have seen an influx in interest on the role of death anxiety in human behavior. Terror Management Theory prevails as the leading theoretical and empirical paradigm utilized in the literature; however emerging research has revealed serious shortcomings with the paradigm. In this paper we examine the concept of death anxiety from a socio-evolutionary perspective. We outline how the attachment system evolved to prevent death during an extended period of juvenile vulnerability and is further co-opted into adulthood to maintain survival. Through a broader understanding of contemporary evolutionary thinking, including attachment theory, we propose that the hitherto inconsistent and amorphous definition of death anxiety be more usefully re-conceptualized as a fear of premature death. We explore how this re-conceptualization can be used to help explicate phenomena that existing paradigms have until now struggled to explain.

AMH inhibits hormone production in luteinized granulosa cells (GCs) and stalls ovarian follicle development in vitro and in vivo. We sought to confirm AMH's mechanism of action through SMAD activation and investigate AMH inhibition of follicle development and function, in vitro and in vivo.

A primary culture of GCs isolated from follicular fluid was used, and cells were treated with recombinant AMH (rAMH) or placebo for 24 h. For the mouse model, 18-weeks old C57BL female mice were either euthanized at the beginning or treated with rAMH or normal saline for 3 weeks. Primordial (PDF), primary follicle (PRF), secondary (SEF), and tertiary follicles (TEF) were calculated. Real-time RT-PCR and ELISA were performed to quantify GC gene expression and protein translation of human SMAD 1, 5, and 8, FSH-R and mouse FSH-R, inhibin B, caspase 3, Ki67, BMP15, GDF9, and the epigenetic regulators miRNAa and b.

In vitro, rAMH-treated GC showed activation of the SMAD 1, 5 and downregulation of SMAD 8, with greater magnitude at increasing rAMH doses (p < 0.04) and consequential control of downstream regulators. In vivo, the rAMH-treated mice showed increased SEFs and decreased PRFs while PDFs, TEFs, were unchanged compared with baseline. Compared with Placebo, the rAMH group showed increased PDFs, while PRFs, and TEFs were significantly decreased, and SEFs were unchanged.

AMH caused SMAD activation in a dose-dependent manner, with downstream downregulation of cell function and replication, also through activation of miRNAs. These mechanisms were confirmed by the in vivo findings with ultimate downregulation of follicular development and preservation of the ovarian follicle number. Counteracting follicular depletion, AMH could be used to protect the ovarian follicle reservoir.

We aimed to determine the incidence of and explore risk factors for pelvic insufficiency fractures (PIFs) among patients that received curative-intent pelvic intensity-modulated radiation therapy (IMRT) for gynecologic (GYN), gastrointestinal (GI), and genitourinary (GU) cancers.

We audited records of adult patients with GYN, GI, and GU cancers who received neoadjuvant, definitive, or adjuvant pelvic IMRT from 2011 to 2015 with a treatment volume that included the primary tumor or post-operative bed and at least one pelvic lymph node region, and a prescription dose of at least 40 Gy (if conventionally fractionated at 1.8-2 Gy per fraction) or a prescription dose of 25 Gy in 5 fractions for patients with rectal cancer treated with hypo-fractionated neoadjuvant short course IMRT. All baseline and follow-up pelvic imaging reports were reviewed to identify PIF diagnoses. Demographic and relevant clinical, treatment, and dosimetric factors were analyzed to explore risk factors for PIFs.

Among 658 audited patients, 46 (7%) developed 86 PIFs. The incidence for GYN, GI, and GU patients was 8% (13/159), 11% (30/276), and 1% (3/223), respectively, with anal and endometrial subsites having the highest incidence at 14% each. IMRT was delivered as neoadjuvant therapy for 16/46 (35%), definitive therapy for 22/46 (48%), and adjuvant therapy for 8/46 (17%). The median time to PIF diagnosis was 14 months (range 3-53 months), and 26/46 (57%) were symptomatic at diagnosis. The most common PIF location was the sacrum (67/86 [78%]). Multivariable logistic regression analysis found female gender (odds ratio [OR] 2.74, 95% CI 1.36-5.80; p = 0.006), osteoporosis (OR 6.91, 95% CI 2.43-18.8; p = 0.0002), and a dose fractionation of 25 Gy in 5 fractions (compared to schedules of > 25 to < 50 Gy (OR 5.34, 95% CI 1.87-15.6; p = 0.0019) or ≥ 50 Gy (OR 9.53, 95% CI 1.82-50.1; p = 0.0077)) to be significant PIF risk factors.

In our cohort, PIFs were a common complication for patients with GYN and GI cancers, but not GU cancers, in the IMRT era. Most PIFs occurred within 2 years of treatment, and most occurred in the sacrum. Female patients and patients with osteoporosis appeared to be at higher risk. Prospective studies using validated PIF diagnostic criteria should further examine the relationships between PIFs and dosimetric variables, including hypo-fractionated regimens such as 25 Gy in 5 fractions.

To explore the association between smoking, genetic susceptibility and early menopause (EM) and clarify the potential mechanisms underlying this relationship.

An observational and Transcriptome-wide association analysis (TWAS) study.

UK Biobank and public summary statistics.

139 869 women with full baseline and menopause data, and no gynaecological surgery history.

Adjusted modified Poisson regression models were developed to determine the smoking and genetic risk effects on EM. TWAS was used to identify gene expression between smoking and EM, with Mendelian randomisation (MR) to infer causality. Enrichment analysis explored regulatory networks of transcription factors, microRNAs and potential therapeutic targets. Small molecule drugs were predicted using drug-gene interaction analysis.

EM prevalence and common gene expression patterns.

Women with over 30 pack-years of smoking had about 1.5 times higher EM risk, with RRs of 1.39 (95%CI, 1.23-1.56), 1.45 (1.33-1.59) and 1.45 (1.36-1.55) in the low, intermediate and high genetic risk groups. TWAS identified hub genes such as IMMP2L, BMPR2 and HMGN1. MR confirmed daily cigarette consumption as a causal factor in early menopause. Several potential therapeutic targets (e.g., SP600125, INCB18424 and ruxolitinib) were identified.

Smoking reduction significantly lowered the risk of EM. Hub genes and therapeutic targets identified provided new avenues for mitigating harmful effects of smoking.

Menopause marks a critically important biological event that ends a woman's fertility. It is a result of ovarian aging and depletion of ovarian reserve. Although many aspects of these processes are now well understood, the overall dynamic picture remains unclear. Here, we present a novel theoretical framework to analyze human ovarian aging dynamics and menopause timing. Our method is based on stochastic analysis of underlying processes stimulated by observing follicles sequentially transitioning between different stages during ovulation. This allows us to obtain a fully quantitative description of ovarian aging and menopause timing consistent with available experimental observations. Our model accurately predicts the average age of menopause across geographically diverse human populations. Theoretical analysis suggests a universal relation between the initial follicle reserve, the depletion rates, and the threshold that triggers menopause. In addition, it is found that the distributions of menopause times are quite narrow, and it is proposed that this might be a result of a precise regulation due to the synchronization of transitions between different stages of follicles. Our theoretical approach not only quantitatively explains the dynamics of human ovarian aging and menopause timing but also provides important insights into individual variability in ovarian aging. It can be used as a powerful tool for predicting menopause timing and investigating complex processes of reproductive aging.

The objective of this study was to identify a female-specific prognostic biomarker for peripheral artery disease (PAD) and develop a prediction model for 2-year major adverse limb events (MALE). Patients with/without PAD were recruited (n=461). Plasma concentrations of 68 circulating proteins were measured and patients were followed for 2 years. The primary outcome was MALE (composite of vascular intervention, major amputation, or acute/chronic limb threatening ischemia). We trained a random forest model using: 1) clinical characteristics, 2) female-specific PAD biomarker, and 3) clinical characteristics and female-specific PAD biomarker. Galectin-9 was the only protein to be significantly elevated in females compared to males in the discovery/validation analyses. The random forest model achieved the following AUROC's: 0.72 (clinical features), 0.83 (Galectin-9), and 0.86 (clinical features + Galectin-9). We identified Galectin-9 as a female-specific PAD biomarker and developed an accurate prognostic model for 2-year MALE using a combination of clinical features and plasma Galectin-9 levels.

To identify changes in morphological and mechanical properties in the volar ligament complex (VLC), dorsoradial ligaments (DRL), and posterior oblique ligaments (POL) in healthy and osteoarthritic female trapeziometacarpal (TMC) joints.

Twenty-four fresh-frozen female cadaveric TMCs were separated into (1) younger healthy/early-stage osteoarthritic, (2) elder healthy/early-stage osteoarthritic, and (3) advanced-stage osteoarthritic groups based on age and Eaton-Littler grading. Stress relaxation and load-to-failure testing were performed to characterize mechanical tensile properties. Light imaging and scanning electron microscopy (SEM)/energy dispersive spectroscopy (EDS) were performed to further assess enthesis structural integrity.

The VLC in advanced-stage osteoarthritic TMCs had attenuated mechanical properties in stress relaxation experiments compared to the elder healthy/early-stage osteoarthritic specimens: Young's modulus at 20% strain (P = 0.044), instantaneous (P = 0.023), relaxed (P = 0.017) moduli. VLCs in advanced-stage osteoarthritic TMCs also had significantly lower properties in the load-to-failure experiments compared to the younger healthy/early-stage osteoarthritic specimens: stiffness (P = 0.048), ultimate load (P = 0.017), toughness (P = 0.003). Light and SEM/EDS imaging revealed partial detachment and loss of enthesis mineral gradient at VLC metacarpal insertion in advanced-stage osteoarthritic specimens. There were no mechanical or structural changes in the DRL and POL between experiment groups.

VLC morphological and mechanical properties deteriorate across progressively severe osteoarthritis classifications while the DRL and POL remain unchanged. The attenuated mechanical properties of VLCs in advanced-stage osteoarthritic TMCs can be explained by ligament degradation as evidenced by partial detachment and loss of mineral gradient at the metacarpal insertion.

Breast cancer is the most common malignancy among women globally, with incidence rates continuing to rise. A comprehensive understanding of its risk factors and the underlying biological mechanisms that drive tumor initiation is essential for developing effective prevention strategies. This review examines key non-modifiable risk factors, such as genetic predisposition, demographic characteristics, family history, mammographic density, and reproductive milestones, as well as modifiable risk factors like exogenous hormone exposure, obesity, diet, and physical inactivity. Importantly, reproductive history plays a dual role, providing long-term protection while temporarily increasing breast cancer risk shortly after pregnancy. Current chemoprevention strategies primarily depend on selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, which have demonstrated efficacy in reducing the incidence of estrogen receptor-positive breast cancer but remain underutilized due to adverse effects. Emerging approaches such as aromatase inhibitors, RANKL inhibitors, progesterone antagonists, PI3K inhibitors, and immunoprevention strategies show promise for expanding preventive options. Understanding the interactions between risk factors, hormonal influences, and tumorigenesis is critical for optimizing breast cancer prevention and advancing safer, more targeted chemopreventive interventions.

The contribution of MTHFR and TP53 genetic variants to breast carcinoma (BC) susceptibility has been examined, but their findings have been inconclusive. This work is designed to explore the potential roles of the MTHFR (rs1801131, rs1801133) and TP53 (rs1042522) variants with increased risk of BC using genetic and bioinformatic approaches.

This work included a total of 242 female participants [142 BCE patients and 100 healthy controls]. We genotyped the allelic discrimination analysis for these genetic variants using the T-ARMS-PCR technique. Logistic regression, haplotype analysis, genetic association models, and multivariate clustering were executed.

The rs1801131*C allele revealed a significant association with elevated risk of breast carcinoma compared to healthy controls under allelic (OR = 2.02, p-value < 0.001) and recessive (OR = 3.26, p-value < 0.001) models. Moreover, the rs1801133*T allele was correlated to cancer susceptibility under allelic (OR = 1.81, p-value = 0.002) and dominant (OR = 3.33, p-value < 0.001) models, while the rs1042522*G allele was associated with increased risk of BC under allelic (OR = 2.98, p-value < 0.001) and recessive (OR = 3.21, p-value < 0.001) models. BC women carrying the rs1801131*C/C genotype were associated with histological grade III, while those with the rs1801133*T/T and rs1042522*G/G genotypes were correlated with a moderate/poor NPI score (p-value < 0.05).

The rs1801131*C, rs1801133*T, and rs1042522*G alleles are associated with an increased risk of BC. The rs1801133*T and rs1042522*G alleles correlated with moderate/poor NPI score. These findings pave the way for the diagnostic functions of these genetic variants as potential prognostic biomarkers.

Menopause is a major biological transition that may influence women's late-life brain health. Earlier estrogen depletion-via earlier menopause-has been associated with increased risk for Alzheimer's disease (AD). Synaptic dysfunction also incites and exacerbates AD progression. We investigated whether age at menopause and synaptic health together influence AD neuropathology and cognitive trajectories using clinical and autopsy data from 268 female decedents in the Rush Memory and Aging Project. We observed significant interactions between age at menopause and synaptic integrity on cognitive decline and tau tangles, such that earlier menopause strengthened the associations of reduced synaptic integrity with faster cognitive decline and elevated tau. Exploratory analyses showed that these relationships were attenuated in women who took menopausal hormone therapy. These findings suggest that midlife endocrine processes or their sequalae may influence synaptic vulnerability to AD. Interventions addressing both hormonal factors and synaptic health could enhance resilience to dementia in women.

Energy intake may differ across the menstrual cycle, with some studies identifying greater energy intake in the luteal phase (LP) compared with the follicular phase (FP) and others finding no clear differences. To date, no study has systematically synthesized the available data to draw more definite conclusions while considering any methodological inconsistencies between studies.

The aim was to conduct a systematic review/meta-analysis in an effort to determine if there are differences in energy intake between the FP and LP.

A systematic search strategy was developed and the search was conducted in 5 databases for studies that investigated any changes in energy intake across menstrual phases.

Using Covidence, studies were identified and included if they contained individuals between the ages of 18 and 45 years, maintained an average body mass index (BMI) of 18.5-25 kg/m2, had no history of disordered eating, and included energy intake and menstrual cycle measurements in the FP and LP.

Effect sizes were calculated for each study and a random-effects model was used to pool the results of each study.

Fifteen datasets were included consisting of 330 female participants with a mean age of 26 ± 4 years and mean BMI of 22.4 ± 2.3 kg/m2. Overall, there was a statistically significant difference (standardized mean difference = 0.69; P = .039) with increased energy intake in the LP compared with the FP (crude 168 kcal⋅d-1 average difference between phases).

Energy intake was found to be greater in the LP compared with the FP, providing insight into the effect of the menstrual cycle on energy intake. However, there were repeated methodological inconsistencies and future work should strive to utilize best practices for both energy intake measurement and menstrual phase specification.

Introduction: We investigated associations of menopausal age category with body mass index (BMI), waist circumference, waist-hip ratio, and waist-height ratio. We also explored the moderating effect of anthropometric measures on associations of menopausal age category with prespecified sex hormones: estradiol, dehydroepiandrosterone (DHEA), sex hormone-binding globulin, bioavailable testosterone, and total testosterone-estradiol (T/E) ratio. Methods: In this cross-sectional study, we included 2,436 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis who had menopausal age, anthropometric, and sex hormone data at baseline. Menopausal age was categorized as <45 years (early menopause), 45-49 years, 50-54 years (referent), and ≥55 years (late menopause). Linear models were used for analysis. Results: The mean (standard deviation) age was 64.7 (9.2) years. After multivariable adjustment, women who experienced late menopause had higher waist circumference (2.28 cm), waist-hip ratio (0.013 units), and waist-height ratio (0.014 units) but not BMI than those in the referent category. The interaction terms between menopausal age category and anthropometric measures were not significant for prespecified sex hormones (all Pinteraction >0.05). When compared with the referent category, T/E ratio was 21% (4.72 - 39.8%) higher among women with late menopause while DHEA levels were 9% (1 - 16%) higher among women who experienced menopause between 45 and 49 years in multivariable adjusted models. Conclusion: Women with late menopause had higher abdominal adiposity but not generalized adiposity when compared with those who experienced menopause between 50 and 54 years of age. Androgenicity was higher among women who experienced menopause between 45 and 49 years of age and those with late menopause, based on DHEA and T/E ratios, respectively.

Diabetes mellitus is a chronic disease and a public health challenge worldwide, associated with numerous complications, including genitourinary infections and sexual dysfunction in women, particularly in menopause. The vaginal microbiome, which comprises beneficial and pathogenic bacteria, their genomes, and the surrounding environment, plays a crucial role in maintaining genitourinary health. Chronic hyperglycemia disrupts immune functions, exacerbates oxidative stress, and alters the vaginal microbiome, increasing the risk of genitourinary infections. Recent advances in microbial analysis, including 16S rRNA sequencing, have provided insights into the complex composition of the vaginal microbiome and its dysbiosis in diabetes mellitus. Some glucose-lowering drugs, such as sodium-glucose cotransporter 2 inhibitors, may increase the risk of genitourinary infections. Additionally, psychological distress, hormonal imbalances, and diabetes-related genitourinary symptoms contribute to sexual dysfunction in diabetic women. Healthcare for diabetic women requires a multidisciplinary approach, including not only glycemic control but also vaginal and sexual health assessment. A holistic approach is essential to advance personalized strategies, including medications and psychological support.

Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD).

This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy.

A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed to hormone replacement therapy showed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality.

This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes.

Several recent reports have indicated positive health benefits of consuming (-)-epicatechin-rich cocoa products. Postmenopausal women are predisposed to reduced metabolism due to decreased levels and activity of the sex hormones estrogen, progesterone, and estradiol. The purpose of this study was to investigate the influence of dark chocolate consumption on resting and exercise metabolism in postmenopausal women. Using a randomized, double-blind design, 26 postmenopausal participants were assigned to a 30-day supplementation with 20-g per day of 72% dark chocolate (DC) or calorically matched white chocolate (WC). Before supplementation, participants underwent two control trials for assessments (PRE1, PRE2) of resting energy expenditure (REE) and exercise energy expenditure (EEE). Following the PRE2 assessment, participants were randomized and supplemented for 30 days, after which they repeated the assessments for REE and EEE. PRE1 and PRE2 REE and EEE were not significantly different within or between groups (REE: PRE1 DC 1215± 170, WC 1127 ± 174, p=0.662; PRE2 DC 1211 ± 174, WC 1145 ± 165 kcal/d, p=0.720; EEE: PRE1 DC 3.67 ± 0.72, WC 3.40 ± 0.81, p=0.665; PRE2 DC 3.41 ± 0.88, WC 3.39 ± 0.73kcal/min, p=0.373). Post-supplementation REE was significantly increased by 3.2% in the DC group (Pre-Post change: DC 38.6 ± 49, WC -15 ± 31.2 kcal per day, p =0.039, Cohen's d= 0.724 [95% CI: 0.078, 1.513]). These results indicate that DC supplementation in postmenopausal women was associated with a significant 3.2% increase in REE with no significant influence on EEE.

Menopause is a timely opportunity to screen for cardiovascular disease (CVD) and intervene with healthier lifestyles. We investigated the association between premature/early menopause and the likelihood of CVD and whether a healthy lifestyle is associated with a lower likelihood of CVD in menopausal woman.

The Sax Institute's 45 and Up Study prospectively recruited participants aged ≥45 years (n=267 357) between 2005 and 2009 (New South Wales, Australia). Our study included women without prior CVD and reporting menopausal age at baseline. Primary outcome was new-onset CVD (self-reported heart disease/stroke) based on survey data at Wave 2 (2012-2015) and/or Wave 3 (2018-2020). Logistic regression models assessed the associations of premature (age <40 years) and early (age 40-44 years) menopause with CVD, compared with menopause between 50 and 52 years, adjusting for sociodemographic and clinical variables. Healthy lifestyle adherence was assessed using a score of five factors: smoking, physical activity, sitting, sleep and diet.

We included 46 238 women (mean age 62.1±8.2 years), with 5416 (11.7%) cases of CVD over 15-year follow-up. After adjustment, the odds of CVD was higher in women with premature menopause (OR 1.36, 95% CIs 1.17 to 1.59; p<0.0001) and early menopause (OR 1.15, 95% CI 1.03 to 1.28; p=0.013) compared with menopause between 50 and 52 years. Among all women, high (score 9-10) versus low (score 0-5) healthy lifestyle adherence led to 23% lower odds of CVD (OR 0.77, 95% CI 0.68 to 0.86; p<0.0001), and in women with premature menopause, led to 52% lower odds of CVD (OR 0.48, 95% CI 0.30 to 0.77, p=0.0022). Lifestyle effect did not significantly differ between menopause categories (interaction, p=0.71).

Women with premature/early menopause are at higher likelihood for CVD. Lifestyle modification is associated with consistent reduction of the likelihood of CVD in women and should be encouraged across the life course.

Iron deficiency anemia is a significant global health concern, diagnosed by measuring hemoglobin concentrations in combination with plasma ferritin concentration. This study investigated the variability in ferritin reference intervals among laboratories in the Netherlands and examined how this affects the identification of iron-related disorders.

Ferritin reference intervals from 52 Dutch ISO15189-certified medical laboratories were collected. Ferritin, hemoglobin and mean corpuscular volume data of non-anemic apparently healthy primary care patients, measured by four laboratory platforms (Beckman, Abbott, Siemens, and Roche), were collected (n=397,548). Median ferritin levels were determined per platform, stratified by sex and age. The proportion of ferritin measurements outside of the reference interval was calculated using the reference intervals from the 52 laboratories (using a total of n=1,093,442 ferritin measurements). Lastly, ferritin data from 3,699 patients as captured in general practitioner (GP) data from the PHARMO Data Network were used to assess the variation of abnormal ferritin measurements per GP.

Median plasma ferritin concentrations were approximately four times higher in men and twice as high in postmenopausal women compared to premenopausal women. Moreover, there are substantial differences in the median plasma ferritin concentration between the four platforms. However, even among laboratories using the same platform, ferritin reference intervals differ widely. This leads to significant differences in the percentages of measurements classified as abnormal, with the percentage of ferritin measurements below the reference limit in premenopausal women ranging from 11 to 53 %, in postmenopausal women from 3 to 37 %, and in men from 2 to 19 %. The percentage of ferritin measurements above the reference limit in premenopausal women ranged from 0.2 to 11 %, in postmenopausal women from 3 to 36 % and in men from 7 to 32 %.

The lack of harmonization in ferritin measurement and the disagreement in plasma ferritin reference intervals significantly impact the interpretation of the iron status of patients and thereby the number of iron disorder diagnoses made. Standardization or harmonization of the ferritin assays and establishing uniform reference intervals and medical decision limits are essential to reduce the substantial variability in clinical interpretations of ferritin results.

To determine the association between unilateral oophorectomy (UO) and age at natural menopause.

Secondary analysis of survey data from Alberta's Tomorrow Project (2000-2022).

Prospective cohort study in Alberta, Canada.

23 630 women; 548 experienced UO and 23 082 did not experience UO.

Flexible parametric survival analysis was used to analyse age at natural menopause, and logistic regression was used to analyse early menopause and premature ovarian insufficiency by UO status, controlling for birth year, parity, age at menarche, past infertility, hormonal contraceptive use and smoking.

Age at natural menopause occurred by a final menstrual period without medical cause and sub-classified as early menopause (< 45 years) and premature ovarian insufficiency (< 40 years).

Compared to no UO, any UO was associated with elevated risk of earlier age at natural menopause, which was strongest in early midlife (adjusted HR at age 40 1.71, 95% CI 1.31-2.19) and diminished over time. Compared to age 55 years at UO, risks of earlier age at natural menopause were largest and uniform in magnitude when UO occurred between approximately ages 20-40 years (adjusted HR for UO at age 30 2.32, 1.46-3.54) and then diminished as age at UO approached the average age at natural menopause. Any UO was associated with higher odds of early menopause (adjusted OR 1.90, 1.30-2.79) and premature ovarian insufficiency (adjusted OR 3.75, 1.72-8.16).

Unilateral oophorectomy is associated with earlier age at natural menopause, particularly when performed before 40 years of age.

Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics approaches identified chronological age-related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and were influenced by genetic variation, sex, and body mass index. Integrating multi-omics data and metabolite quantitative trait loci (mQTL) in humans and 525 diversity outbred mice functionally linked metabolism of arginine during RBC storage to increased vesiculation-a hallmark of RBC aging-and lower post-transfusion hemoglobin increments. Thus, arginine metabolism is a biomarker of RBC and organismal aging, suggesting potential new targets for addressing sequelae of aging.

Meningiomas are central nervous system tumors whose incidence increases with age. Benign meningioma pathogenesis involves germline or somatic mutation of target genes, such as NF2, leading to clonal expansion. We used an established cancer epidemiology model to investigate the number of rate-limiting steps sufficient for benign meningioma development.

Incidence data was obtained from the Surveillance, Epidemiology and End Results Program (SEER) for nonmalignant meningioma from 2004 to 2020. Age-adjusted incidence rates per 100,000 person-years were divided into 5-year bands. This was repeated for vestibular schwannomas as a negative control. The Armitage-Doll methodology was applied. Mathematical solutions correcting for volatile tumor microenvironments were applied to fit higher-order models using polynomial regression when appropriate. A 75:25 training:test split was utilized for validation.

222,509 cases of benign meningiomas were identified. We noted strong linear relationships between log-transformed incidence and age across the cohort and multiple subpopulations: male, white, black, Hispanic, Asian/Pacific Islander, and American Indian subpopulations all demonstrated R2 = 0.99. Slopes were between 3.1 and 3.4, suggesting a four-step process for benign meningioma development. Female patients exhibited nonlinear deviations, but the corrected model demonstrated R2 = 0.99 with a four-hit pathway. This model performed robustly on test data with R2 = 0.99. Vestibular schwannomas demonstrated a slope of 2.1 with R2 = 0.99, suggesting a separate three-step process.

Four mutations are uniquely required for the development of benign meningiomas. Correcting for volatile tumor microenvironments reliably accounted for nonlinear deviations in behavior. Further studies are warranted to elucidate genomic findings suggestive of key mutations in this pathway.

Inflammation is a marker of immune activation. Inflammation may have an effect on both ovarian function and luteal function, both essential to pregnancy. High inflammation may also signal dysregulated processes within the ovary, which could be in part measured through Anti-Müllerian hormone, follicle-stimulating hormone, and inhibin B levels.

To determine the relationship between inflammation, measured by C-reactive protein, and three biomarkers of ovarian function during the early follicular phase: Anti-Müllerian hormone, follicle-stimulating hormone, and inhibin B.

Secondary cross-sectional analysis of data and serum obtained in Time to Conceive, a prospective cohort study sample of 843 women attempting pregnancy in central North Carolina from 2008 to 2016. Participants were aged 30 and 44 years, had no history of infertility, endometriosis, or polycystic ovarian syndrome, and were not currently breastfeeding. Serum samples were obtained on days 2, 3, or 4 of the menstrual cycle. C-reactive protein (natural-log transformed), Anti-Müllerian hormone (natural-log transformed), follicle-stimulating hormone (natural-log transformed), and inhibin B (untransformed) were measured in serum. Diminished ovarian reserve was examined dichotomously and defined as an Anti-Müllerian hormone level below 0.7 ng/mL.

The analysis included 703 participants with C-reactive protein measured. In an adjusted linear regression model, a 20% increase in C-reactive protein was associated with a 0.57 pg/mL decrease in inhibin B (95% CI: -0.84 to -0.29 pg/mL) and a 0.535% decrease in follicle-stimulating hormone (95% CI: -1.01 to -0.06). Although there was not a significant relationship between Anti-Müllerian hormone and C-reactive protein, a 20% increase in C-reactive protein was associated with a 0.87% increase in Anti-Müllerian hormone (95% CI: -0.27 to 2.01). C-reactive protein was not associated with the odds of diminished ovarian reserve in an adjusted logistic regression model (OR: 0.97, 95% CI: 0.77-1.20).

Inflammation, as measured by C-reactive protein, is associated with early follicular phase follicle-stimulating hormone and inhibin B, although this is not true of AMH. Inflammation may exert an effect on ovarian function.

Female individuals who are post-menopausal present with higher incidence of knee osteoarthritis (KOA) than male counterparts; however, the mechanisms underlying this disparity are unknown. The most commonly used preclinical models lack human-relevant menopausal phenotypes, which may contribute to our incomplete understanding of sex-specific differences in KOA pathogenesis. Here we chemically induced menopause in middle-aged (14-16 months) C57/BL6N female mice. When we mapped the trajectory of KOA over time, we found that menopause aggravated cartilage degeneration relative to non-menopause controls. Network medicine analyses revealed that loss of 17β-estradiol and progesterone with menopause enhanced susceptibility to senescence and extracellular matrix disassembly. In vivo, restoration of 17β-estradiol and progesterone in menopausal mice protected against cartilage degeneration compared to untreated menopausal controls. Accordingly, post-menopausal human chondrocytes displayed decreased markers of senescence and increased markers of chondrogenicity when cultured with 17β-estradiol and progesterone. These findings implicate menopause-associated senescence and extracellular matrix disassembly in the sex-specific pathogenesis of KOA.

Depression has been associated with adverse diet-related outcomes and women are particularly vulnerable to depression around the menopause transition. Therefore, we hypothesized that depression and postmenopausal status would be associated with lower diet quality, and that depression would be associated with lower diet quality in both pre- and post-menopausal women, but that the association would be stronger in postmenopausal women. Data from 5,634 nonpregnant women age > 20 years from the National Health and Nutrition Examination Survey from 2007-2018 were analyzed. Diet quality was determined using the Healthy Eating Index 2020 (HEI-2020). Multivariable linear regression was used to examine the association between depression and diet quality, menopause and diet quality, and depression and diet quality by menopause status, adjusting for covariates. Mean age was 49.6 ± 0.4; 12% of women were classified as depressed and 46% as postmenopausal. In multivariable-adjusted models, depression was associated with lower HEI-2020 total (β = -3.33, P < .001) and adequacy scores (β = -2.41, P < .0001) but not moderation scores. Postmenopausal women had higher HEI-2020 total (β = 2.48, P < .0001), moderation (Β = 1.19, P < .0001), and adequacy (β = 0.81, P < .01) scores than premenopausal women. In a nationally representative sample of U.S. women, depression was associated with lower diet quality across all women and in both pre- and post-menopause. Further research is needed to better understand the relationship between depression and diet quality throughout the menopause transition, when hormonal changes could make women more vulnerable to depression.

Research shows a decline in physical activity (PA) in women during the menopause transition (MT). Therefore, the purpose of this study was to explore experiences of the MT in Irish women and how it impacts motivators, facilitators, and barriers to PA engagement.

Twelve Irish women (age: 49 ± 4 years) who were in the MT participated in individual, online, semi-structured interviews. During each interview participants were asked about their experience of the MT and its influence on PA engagement to identify motivators, facilitators and barriers. All interviews were digitally recorded and transcribed verbatim, resulting in ≈ 72,610 words for descriptive and thematic analysis.

The MT had a notable influence on PA engagement in Irish women. The main motivators to engage in PA throughout the MT included managing menopause symptoms, optimising future health, the opportunity for social engagement and rewards, as well as relatable role models. Many women discussed that menopause fraternities focused on community and collective experience, adapting and modifying PA, and medical supports were key factors that facilitated engagement in PA throughout this life stage. There were a multitude of barriers that women in midlife faced before they could engage in PA, such as perceived reduced capability, symptoms associated with the MT, the busyness of life and competing demands, as well as a lack of supportive environments.

The motivators, facilitators, and barriers to PA engagement throughout the MT are unique. These factors are important considerations for stakeholders when facilitating women to either continue or (re)introduce PA during this life stage.

To develop and externally validate a 10-year risk prediction model of natural onset of menopause using ready-to-use predictors.

Population-based prospective cohort study.

Community-dwelling, premenopausal women aged 28 years and older enrolled in the Swiss (CoLaus) and Dutch (PREVEND) study.

Incidence of self-reported natural menopause.

Based on existing literature, 11 predictors were tested in this study. The CoLaus cohort was used to develop the model by applying the backward-elimination approach and Bayesian Model Averaging. Internal validation was performed by bootstrapping. External validation was performed using data from the PREVEND cohort and recalibrating the baseline survival estimate. C-statistics, calibration slopes, and expected/observed probabilities were calculated as measures of model internal and/or external performances.

The final analysis included 750 and 1032 premenopausal women from the CoLaus and the PREVEND cohorts, respectively. Among them, 445 (59%) from CoLaus and 387 (38%) from PREVEND experienced menopause over a median follow-up of 10.7 and 9 years, respectively. The final model included age, alcohol consumption, smoking status, education level, and systolic blood pressure. Upon external calibration in the PREVEND cohort, the model exhibited good discrimination, with a C-statistic of 0.888 and an expected/observed probability of 0.82.

We present the first internally and externally validated prediction model of natural menopause onset using readily available predictors. Validation of our model to other populations is needed.