Original research publications

Young women with acute myocardial infarction (AMI) often present with distinct risk profiles compared with older women and men, but the role of reproductive factors remains poorly understood. This study examines associations of reproductive factors with AMI in young women. We conducted a case-control study of 1561 women aged 18-55 years with AMI from VIRGO and age-matched controls from NHANES. A wide range of reproductive factors were evaluated. Conditional logistic regression estimated odds ratios for AMI, sequentially adjusted for race/ethnicity, socioeconomic variables, and traditional risk factors. Stratified analyses were performed by menopausal status. Early menarche (<11 years; OR 2.07, 95% CI 1.56-2.73), menopause (OR 1.82, 95% CI 1.50-2.22), gestational diabetes (OR 1.65, 95% CI 1.23-2.19), birth control pills use for 1-5 years (OR 1.67, 95% CI 1.36-2.05), and ever use of female hormones (OR 1.99, 95% CI 1.62-2.46) were associated with higher odds of AMI, while first live birth at ≥30 years (OR 0.50, 95% CI 0.36-0.69), breastfeeding ≥1 month (OR 0.46, 95% CI 0.38-0.56), and current contraceptive use (OR 0.49, 95% CI 0.32-0.76) were associated with lower odds. After adjustment for traditional risk factors, birth control pills use for 1-5 years (OR 1.71, 95% CI 1.25-2.34) and female hormone use (OR 1.75, 95% CI 1.28-2.38) remained significantly associated. Associations varied by menopausal status. Reproductive factors are associated with early-onset AMI in young women. Recognition of reproductive history may inform prevention strategies in young women.

Menopause is associated with visceral obesity, low-grade chronic inflammation, and increased risk of dyslipidemia, insulin resistance, and type 2 diabetes. Although exercise (EXE) and GLP-1 receptor agonists, such as semaglutide (SEM), have demonstrated beneficial effects on metabolic regulation, their combined impact in menopause models has been less investigated. In this study, ovariectomized female Wistar rats were divided into four experimental groups: sedentary plus saline (SED + SAL), sedentary plus semaglutide (SED + SEM), exercise (EXE + SAL), and EXE + SEM. The aerobic exercise protocol consisted of treadmill running at moderate intensity for four weeks, during which the rats received either SEM or SAL weekly. At the end of the protocol, metabolic parameters were assessed in blood, liver, soleus and gastrocnemius muscles. Both SEM groups had lower body weight, weight gain, relative subcutaneous white adipose tissue (scWAT) mass, glucose, total proteins, and triglycerides in serum and liver, while LDL cholesterol, glycogen in liver and gastrocnemius, and AMPK and HSF1 expression in gastrocnemius increased. EXE decreased total and LDL cholesterol, liver triglycerides and HSF1 expression in both tissues, while glycogen in liver and gastrocnemius, liver HSF1 expression and relative mass were increased. The combination of SEM + EXE increased glycogen content in the gastrocnemius and AMPK expression in both gastrocnemius and liver. This combined treatment reduced HDL levels, hepatic triglycerides and scWAT relative weight. These results suggest that SEM and EXE exert complementary effects on glycemic and lipid metabolism, with partially distinct metabolic outcomes that may involve different underlying mechanisms.

Menopause is a universal physiological transition marked by the permanent cessation of ovarian estrogen secretion, with far-reaching consequences for cardiometabolic health. Among these consequences, lipid dysregulation stands as one of the most clinically significant, substantially elevating the risk of cardiovascular disease and metabolic syndrome in postmenopausal women. Estrogen deficiency disrupts hepatic lipid metabolism, alters lipoprotein particle composition, promotes visceral adiposity, and triggers a chronic low-grade inflammatory state, collectively establishing an atherogenic lipid profile. Although the broad association between menopause and dyslipidemia has long been recognized, the precise cellular and molecular mechanisms underlying this relationship remain incompletely characterized. This review synthesizes current evidence on the pathophysiological mechanisms linking estrogen deficiency to lipid dysregulation in menopause, encompassing alterations in LDL and HDL metabolism, triglyceride accumulation, changes in lipoprotein lipase (LPL) activity, hepatic lipid accumulation, and the roles of estrogen receptor signaling in adipose tissue and liver. Current and emerging therapeutic strategies are also discussed, including hormone replacement therapy (HRT), lifestyle modifications, lipid-lowering pharmacotherapy, and novel molecular targets. Advancing the mechanistic understanding of these processes is essential to developing precision therapeutic approaches that effectively address the heightened cardiometabolic risk in postmenopausal women.

Follicle-stimulating hormone (FSH) is traditionally regarded as a biochemical marker of menopause and declining ovarian function. However, emerging evidence suggests that its role may extend beyond reproductive physiology. During the menopause transition, FSH concentrations rise progressively, initially due to declining inhibin B and later to loss of ovarian estradiol and inhibin production. Evidence of FSH effects in bone, adipose tissue, the cardiovascular system and brain has raised the possibility of broader physiological actions. Higher FSH levels have been associated with bone loss and hip fracture risk, adverse cardiometabolic and vascular changes, and cognitive decline and Alzheimer's disease. Although these associations do not establish causality, they suggest that FSH may contribute to some consequences of reproductive aging rather than simply reflect ovarian failure. Experimental studies indicate that reducing FSH may benefit bone and adiposity, while preliminary clinical evidence regarding cognition remains inconclusive. Thus, FSH may represent not only a marker of menopause, but also a potential marker of risk and, ultimately, a therapeutic target.

To examine the effect of DT56a (Femarelle®), a non-hormonal oral treatment for the management of menopause, on symptoms of vulvovaginal atrophy (VVA)/genitourinary syndrome of menopause (GSM) in postmenopausal women. Twelve ( n = 12) postmenopausal women with severe VVA (100% parabasal cells on cervical cytology) and at least one severe VVA symptom were recruited for a 12-week open-label pilot study. At baseline and week 12, participants underwent physical examination, Pap smear, vaginal ultrasound, vaginal cultures, vaginal pH assessment, and vaginal maturation index evaluation. Subjects also completed questionnaires assessing atrophy symptoms and quality of life using the Utian Quality of Life (UQoL) scale. Follow-up at 24 months was available for several participants. After 12 weeks of treatment, all patients showed a significant reduction in vaginal pH. In addition, 11 of the 12 women demonstrated significant improvement in the vaginal maturation index and UQoL questionnaire scores. DT56a significantly improved subjective and objective parameters of VVA/GSM, including vaginal pH, vaginal maturation index, and quality of life. These findings support its potential role as a non-hormonal systemic treatment option for women with VVA/GSM.

Sex differences in major cardiometabolic diseases (CMD), such as type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, have been increasingly recognized across the life course. During the reproductive stage, women generally have a more favorable cardiometabolic risk profile than men, but their risk of experiencing CMD significantly increases after menopause. Emerging evidence suggests that sexually dimorphic gut microbiota and gut microbiota-related metabolites (GMRMs) may contribute to such sex disparities. However, existing findings are heterogeneous and underlying mechanisms remain incompletely understood. In this review, we synthesize the evidence examining sex differences in gut microbial diversity, overall composition, taxa abundances, and levels of GMRMs across key life stages, including pre-puberty, adolescence, and different phases of adulthood (with emphasis on pre- and post-menopausal periods). We summarize potential biological mechanisms underlying sexual dimorphism in the gut microbiome and GMRMs, emphasizing the central role of sex steroids, along with contributions from immune function and other host and environmental factors. We further integrate evidence linking sexually dimorphic microbial taxa (e.g., Akkermansia muciniphila , Eubacterium , Ruminococcus , and other Firmicutes taxa) and GMRMs (e.g., microbiota-derived short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide) to key cardiometabolic pathways involving inflammation, glucose and lipid metabolism, and vascular function. Finally, we identify critical knowledge gaps and emphasize the need for future large longitudinal studies that would integrate repeated measurements of the gut microbiome, untargeted metabolomics, and sex steroid hormones across the life course. Such approaches are essential to clarify biological pathways and inform sex-specific microbiome-based interventions for CMD prevention and management.

Identify estradiol serum levels associated with vasomotor symptom relief and assess their effects on osteoporosis and cardiovascular prevention using an estradiol hydro-alcoholic gel formulation. Estradiol serum concentrations from two pivotal efficacy and safety trials with transdermal (TdL) estradiol gel were compared to those reported in the KEEPS and ELITE trials regarding skeletal and cardiovascular disease prevention. A total of 567 patients were included in the intent-to-treat efficacy population. In the first study ( n = 216), the daily 2.5 g dose of TdL E2 gel reduced the moderate to severe hot flash frequency from a baseline of 10.5 to 2.0 ± 4.2 (-82%). In the second study ( n = 351), a daily 2.5 g dose of TdL E2 gel reduced moderate-to-severe hot flushes from 11.8 to 2.3 ± 3.8, similar to the TdL E2 patch, which decreased them from 10.9 to 1.3 ± 3.2. The serum concentrations of E2 from patients receiving the TdL E2 gel once daily were within the normal range of young premenopausal women in the mid-follicular phase, with a proportional dose‒response effect. These results on vasomotor symptoms are consistent with the optimal cardiovascular and skeletal benefits observed in KEEPS (TdL estradiol) and ELITE (oral estradiol), corresponding to serum levels of approximately 60 pg/mL.

Aging and menopause negatively affect women's sexual quality of life, and midlife women often report sleep difficulties. The aim of the present study was to investigate the relationship between sleep quality and sexual quality of life in postmenopausal women. A total of 303 postmenopausal women attending the Gynecology and Menopause Clinics of a university-affiliated training hospital completed the sexual quality of life questionnaire-female (SQoL-F) and the Pittsburgh sleep quality index (PSQI). SQOL-F and PSQI scores were compared by time since menopause, educational level, and age in decades. Correlations between SQoL-F and PSQI domain scores were analyzed. One hundred thirteen women (37.3%) had good sexual quality of life (SQoL-F > 84). SQoL-F and PSQI domain scores did not differ by time since menopause. Sexual and relationship satisfaction were higher among women aged 40-49 years, while other SQoL-F domains showed similar scores across age groups. PSQI domains were also comparable between age categories. Demographic characteristics did not differ between women with good versus poor sleep quality. Correlations between SQoL-F and PSQI domains were negligible to low, including total scores. The correlations reported are unadjusted. The Spearman rho values between the four domains of SQoL-F and seven domains of PSQI ranged between -0.181 and 0.033 (95% CI: -0.281 to 0.129), -0.144 and 0.026 (95% CI: -0.256 to 0.173), -0.159 and 0.043 (95% CI: -0.270 to 0.170), -0.087 and 0.009 (95% CI: -0.207 to 0.140), respectively. Younger and better-educated postmenopausal women showed a better overall sexual quality of life. No meaningful association was found between sleep parameters and sexual outcomes.

Estrogen fluctuations during menopause are linked to increased psychiatric symptoms like depression and anxiety. Depression rates in menopausal women are 2-3 times higher than in premenopausal women, primarily due to rapid estrogen changes. Estrogen affects emotional stability by regulating neurotransmitters, adjusting HPA axis sensitivity, and influencing neuroinflammatory and epigenetic pathways. Menopausal hormone therapy (MHT) is a key treatment, stabilizing neurotransmitter systems and HPA axis activity, but requires personalized and evidence-based approaches. This paper aims to systematically summarize the association between estrogen fluctuations and menopausal psychiatric symptoms, elucidate the underlying physiological and molecular mechanisms driving these symptoms, and evaluate the therapeutic potential of MHT, so as to provide a robust theoretical basis for clinical decision-making in menopausal mental health management. We performed a thorough review of peer-reviewed studies from medical and psychiatric databases, examining the connections between menopausal estrogen changes, neurotransmitter regulation, HPA axis function, neuroinflammation, epigenetic changes, and the effectiveness and safety of MHT for managing psychiatric symptoms. We prioritized high-quality clinical trials, epidemiological studies, and mechanistic research to ensure reliable evidence. The review highlights that sudden estrogen changes during menopause disrupt serotonin and norepinephrine signaling, alter HPA axis activity, and trigger neuroinflammation and epigenetic changes, increasing the risk of depression and anxiety. Menopausal hormone therapy (MHT) can alleviate these symptoms by restoring neurotransmitter balance and normalizing HPA axis function. However, its effectiveness depends on factors like treatment timing, hormone type, and individual patient characteristics, including medical history and symptom severity. Estrogen fluctuation is a significant modifiable risk factor for psychiatric symptoms during menopause, affecting neurotransmitter, endocrine, inflammatory, and epigenetic pathways. Menopausal hormone therapy (MHT) is effective for symptom management when personalized and administered within recommended timeframes. This underscores the importance of assessing estrogen levels and psychiatric symptoms in menopausal women to optimize MHT and enhance mental health outcomes.

To conduct a comprehensive assessment of physical, functional, emotional, cognitive, nutritional, metabolic, and sexual health in mid-aged women. This cross-sectional study was conducted at the Universidad Espíritu Santo Clinic (UEES Clinic), Ecuador, as part of a multidisciplinary integrated health initiative. Women aged 40-60 years were recruited through social media outreach by the UEES Research Center and Clinic between 1 October 2024 and 1 October 2025. Interested participants scheduled a clinical evaluation by telephone. Assessments included laboratory tests (complete blood count, FSH, estradiol, HDL-C, triglycerides, glucose, and thyroid hormones [T3, T4]); validated surveys: Menopause Rating Scale (MRS) for climacteric symptoms and quality of life; Center for Epidemiologic Studies Depression Scale, 10-item version (CESD-10) for depressive mood; short Everyday Memory Questionnaire-Revised (EMQ-R) for cognition; and FSFI-6 for sexual function. Participants also underwent anthropometric measurements, body composition analysis, muscle strength testing, and dietary assessment. This methods paper describes a multidisciplinary approach for the comprehensive health evaluation of mid-aged women. It enables early identification of factors affecting quality of life and provides a replicable framework relevant to both local and broader Latin American contexts, serving as a model for similar initiatives across the region.

Genitourinary syndrome of menopause (GSM) is characterized by vulvovaginal dryness, irritation, dyspareunia, and elevated vaginal pH due to estrogen deficiency-related changes of the lower genital tract. Non-hormonal therapies, including hyaluronic acid (HA)-based vaginal gels, are increasingly used to improve local tissue hydration and symptoms. To assess short-term clinical outcomes and local tolerability associated with a hyaluronic acid-based vaginal gel (Gynexelle Hyalo-Duo) in women with GSM. This retrospective, single-center observational study included 60 women aged 18-65 years (30 reproductive-age and 30 postmenopausal) managed at Studio Medico Capasso, Naples, Italy. The gel was applied daily for 7 days, followed by three applications per week for 3 weeks. Outcomes included the Vaginal Health Index (VHI), Vulvar Health Index (VuHI), Subjective Evaluation of Specific Symptoms (SESS), and vaginal pH, assessed at baseline (T₀), after 1 week (T₁), and after 4 weeks of treatment (T₂). At T₂, mean VHI increased from 12.7 ± 3.3 to 19.3 ± 4.0 ( p < 0.001), VuHI decreased from 5.3 ± 3.8 to 2.5 ± 3.5 ( p < 0.001), and SESS improved from 11.8 ± 3.3 to 2.4 ± 3.9 ( p < 0.001). Vaginal pH decreased from 6.1 ± 1.0 to 4.7 ± 0.8 ( p < 0.001). Improvements were observed in both reproductive-age and postmenopausal women. No adverse events were documented. Short-term use of a hyaluronic acid-based vaginal gel was associated with improvements in vulvovaginal symptoms and vaginal health parameters, with good local tolerability, in a real-world observational setting.

Postmenopausal osteoporosis (PMO) is a prevalent metabolic bone disorder characterized by accelerated bone loss, reduced bone mineral density, and increased fragility fracture risk. Although estrogen deficiency is considered a central driver of PMO, increasing evidence indicates that bone loss after menopause results from broader endocrine remodeling involving multiple hormones. Estrogen decline and the accompanying rise in follicle‑stimulating hormone (FSH) are characteristic of the menopausal transition. Alterations in the parathyroid hormone (PTH)‑vitamin D axis, oxytocin (OT) and calcitonin (CT) may also influence skeletal homeostasis, although their patterns and causal contributions are less consistently established in postmenopausal women. These pathways are discussed as interacting components of an endocrine framework with differing levels of supporting evidence. These coordinated hormonal alterations disrupt bone remodeling through several mechanisms, including impaired bone mechanical homeostasis, dysregulated osteoimmune interactions, altered calcium metabolism, and gut microbiota‑bone axis imbalance. Collectively, these changes promote osteoclast activation, suppress osteoblast function, and accelerate skeletal deterioration. Current therapeutic approaches, such as hormone replacement therapy, bisphosphonates, selective estrogen receptor modulators, and PTH analogs, have improved the management of PMO but remain limited by safety concerns or restricted long‑term efficacy. Emerging approaches, including FSH blockade, selected phytoestrogen‑related interventions, modified CT delivery, and OT‑related pathways have different levels of supporting evidence; most specific experimental strategies require human efficacy and safety validation before clinical application. An improved understanding of hormonal interactions and endocrine network remodeling may facilitate the development of more precise and individualized strategies for the prevention and treatment of PMO.

Female sexual dysfunction is a prevalent yet under-recognized condition encompassing disorders of sexual desire, arousal, orgasm, and genitopelvic pain. The International Society for the Study of Women's Sexual Health advocates a biopsychosocial, patient-centered framework integrating routine sexual health assessment, comprehensive evaluation, and individualized treatment. Common conditions include hypoactive sexual desire disorder, arousal and lubrication disorders associated with genitourinary syndrome of menopause, female orgasmic disorder, and genitopelvic pain/penetration disorder. Management combines behavioral, psychological, hormonal, pharmacologic, and physical therapy interventions. Improved clinician education, multidisciplinary collaboration, and proactive sexual health discussions are essential to enhance diagnosis, treatment, and quality-of-life outcomes.

Menopause in breast cancer survivors and high-risk women is abrupt, severe, and treatment-induced. Hormone therapy remains the most effective treatment of vasomotor symptoms and genitourinary syndrome of menopause (GSM), but it is frequently avoided because of concerns about cancer risk. Randomized trial data support avoidance of systemic hormone therapy in breast cancer survivors, although risk varies by patient population and formulation. Nonhormonal therapies are effective options for vasomotor symptoms, and low-dose vaginal estrogen is safe for most patients with GSM. Management requires balancing oncologic risk with symptom burden, taking into account tumor biology, baseline risk, and patient preferences.

Biomechanical parameters play a crucial role in glaucoma development, the world-leading cause of irreversible blindness. Although age is known to affect the tissues' biomechanical properties, early-onset menopause has recently been associated with the risk of developing glaucoma, and the effects of aging relative to early-onset menopause on eyes' biomechanical parameters remain underexplored. This work's goals were to study the effects of aging and early-onset menopause on intraocular pressure (IOP), aqueous humor outflow facility, and ocular compliance. Female Brown Norway rats underwent Sham or surgical menopause (ovariectomy; OVX) at 3-4 months of age and were split into young (5-6 months) or middle-aged groups (9-10 months). We monitored IOP until the established aging time points and performed ex vivo biomechanical measurements via the iPerfusion system. IOP was higher for the middle-aged Sham and OVX animals by 25% and 35%, respectively (p < 0.001), when compared to their respective initial IOPs. Furthermore, middle-aged OVX animals had an 11% higher IOP compared to Sham animals (p = 0.005), and a 20% lower outflow facility (p = 0.031). Ocular compliance decreased with age in the Sham (24.9%, p = 0.011) and OVX (24.5%, p = 0.005) cohorts and by 24.1% independent of cohort (p = 0.0001). Elucidating the effects of age and early-onset menopause on biomechanical parameters that contribute to glaucoma pathology is necessary to move the field forward and help preserve the eyesight of millions of patients.

Genitourinary syndrome of menopause (GSM) is a prevalent yet underrecognized condition in postmenopausal women, characterized by progressive vulvovaginal and lower urinary tract symptoms from estrogen deficiency. Vaginal estrogen therapy is the first-line pharmacologic treatment for GSM. However, as new evidence emerges, understanding of its efficacy, safety, and use in special populations continues to evolve. This review summarizes current evidence on vaginal estrogen formulations, clinical effectiveness, safety, and therapeutic applications. Recent randomized controlled trials confirm that low-dose vaginal estrogen significantly improves GSM symptoms - including vaginal dryness, dyspareunia, and irritation - while restoring epithelial integrity and normalizing pH. Evidence also supports its role in reducing recurrent urinary tract infections by restoring lactobacilli-dominant flora, reinforced by a 2025 multisociety clinical guideline recommending topical, but not systemic, estrogen for this indication. Comparative studies show similar efficacy across creams, tablets, inserts, and rings, differing primarily in convenience and absorption rather than effectiveness. Large cohort studies indicate no increased risk of cardiovascular disease, venous thromboembolism, or malignancy. Use in breast cancer survivors remains controversial, but emerging data suggest minimal systemic absorption and no clear increase in recurrence risk, supporting shared decision-making. In addition, long-term outcomes show that adjunctive vaginal estrogen does not improve anatomic surgical success after native tissue apical prolapse repair. Nonhormonal therapies and agents like ospemifene or prasterone offer alternative options, though they demonstrate lower or more variable efficacy than vaginal estrogen. Vaginal estrogen therapy is the most effective, evidence-based treatment for GSM and helps prevent recurrent urinary tract infections in postmenopausal women. Its favorable safety profile and multiple formulations enable individualized care. Recent evidence clarifies that while overall safety is reassuring, caution is necessary for breast cancer survivors using aromatase inhibitors. Additionally, longer-term perioperative trial data temper expectations regarding surgical-recurrence benefits, while confirming its value for local tissue optimization. Ongoing research should focus on long-term safety in high-risk groups and the effectiveness of emerging non-estrogen alternatives.

PAX1/JAM3 methylation are promising biomarkers for high-grade cervical intraepithelial neoplasia (CIN) detection, but menopausal status may affect diagnostic accuracy. This retrospective study compared their clinical performance between premenopausal and postmenopausal women undergoing colposcopy. 705 women undergoing colposcopy for abnormal screening results and/or clinical symptoms were stratified by menopausal status, including 192 postmenopausal and 513 premenopausal women. Subjects were further classified into ≤CIN1 and CIN2+ groups according to histopathology. Diagnostic and triage utility of PAX1/JAM3 methylation for identifying CIN2+ lesions were compared between premenopausal and postmenopausal women. PAX1/JAM3 methylation demonstrated superior diagnostic performance for CIN2+ detection in postmenopausal women compared with premenopausal women, either alone or in combination. Sensitivities of PAX1 m and JAM3 m in postmenopausal women (90.00%, 95% CI: 76.34-97.21%; 82.50%, 95% CI: 67.22-92.66%) were higher than those in premenopausal women (61.98%, 95% CI: 52.71-70.65%; 60.33%, 95% CI: 51.04-69.11%) (all p < 0.05). The combination improved sensitivity to 72.73% in premenopausal women and maintained 92.50% in postmenopausal women. Besides, PAX1/JAM3 methylation outperformed cytology and HPV16/18 testing in both groups ( p < 0.001). In HPV16/18-positive or cytology triage, methylation increased positive predictive values (PPVs) for CIN2+/CIN3+ and reduced colposcopy referrals . However, CIN2+ missed rates in premenopausal women (27.54% for HPV16/18-positive triage and 23.85% for cytology triage) were higher than those in postmenopausal counterparts. The diagnostic performance of PAX1/JAM3 methylation for high-grade cervical lesions differs distinctly between premenopausal and postmenopausal women undergoing colposcopy. Menopausal status should be considered when applying methylation biomarkers, particularly as a valuable auxiliary tool to improve diagnostic accuracy in elderly women.

Menopause, modeled by ovariectomy (OVX) in rodents, causes cognitive decline and emotional disturbances due to estrogen withdrawal. While probiotics and aerobic exercise independently show beneficial effects, their combined contribution remains poorly characterized. This study investigated whether concurrent administration of Lactobacillus plantarum and aerobic exercise alleviates cognitive and behavioral deficits in OVX rats. Fifty female Wistar rats (9-12 weeks old) were randomly allocated into five groups (n = 10/group): Sham, OVX+PBS, OVX+Exercise (Exe), OVX+L. plantarum, and OVX+ Exe+ L. plantarum. Following a 16-day postoperative recovery, L. plantarum (1.5 × 10 8 CFU/mL) was administered via oral gavage (1 mL/day, 5 days/week), and treadmill training was performed for five weeks. Neurobehavioral outcomes were assessed via three-chamber social interaction, elevated plus-maze, forced swim test, Barnes maze test, novel object recognition, and marble-burying tests. Molecular changes were evaluated using ELISA for pro-inflammatory cytokines and RT-qPCR for Bdnf and Ntrk2 expression. Data were analyzed by one- or two-way ANOVA followed by Tukey's post hoc test (P < 0.05). OVX rats exhibited significant cognitive impairment, social withdrawal, and increased obsessive-compulsive-like behavior (p < 0.05). While either intervention alone produced moderate effects, their combined application (OVX+Exe+ L. plantarum) yielded the greatest improvement, significantly attenuating anxiety and restoring social and cognitive performance to levels comparable to the Sham group (P > 0.05). Furthermore, the combined intervention significantly downregulated pro-inflammatory cytokines and upregulated hippocampal Bdnf and Ntrk2 expression. Combined L. plantarum and aerobic exercise effectively counteract the neurobehavioral and molecular sequelae of hormonal deficiency in post-menopausal models, suggesting that integrating psychobiotics with physical activity is a potent non-pharmacological strategy for managing menopause-related cognitive and behavioral challenges.

There is growing recognition that anger and irritability may increase in the menopause transition (MT). Although sensitivity to ovarian hormone fluctuations may contribute to heightened psychological vulnerability, the potential effects on anger and irritability remain understudied. The aim of the present study was therefore to investigate whether within-person changes of ovarian hormones predict anger and irritability while accounting for inter-individual variability. Two samples encompassing n = 100 individuals with clinically significant depressive symptoms and n = 101 individuals from a general MT sample provided weekly measures of anger and irritability, subjective sleep quality, subjective hot flashes, and urinary metabolites of estradiol (estrone-3 glucuronide or E1G) and progesterone (pregnanediol glucuronide or PdG) for 15 and 12 weeks, respectively. Multilevel regression models were used to investigate within-person effects, as well as their inter-individual variability. Anger and irritability were highly prevalent, with 76.7% and 55.1% of depressed and general samples, respectively, reporting having moderate to extreme anger and irritability at least once during the study period. Among depressed individuals, higher-than-usual PdG levels (β=0.05, p = 0.02) and hot flashes (β=0.03, p = 0.008), as well as poorer-than-usual sleep quality (β=-0.14, p = 0.002) were significantly associated with higher anger and irritability. None of these predictors were significant in the general sample (all p > 0.05). Random effects revealed considerable individual variability in both E1G and PdG effects on anger and irritability. These results suggest that increased hot flashes and poor sleep may predict greater anger and irritability, particularly in those reporting clinically significant depressive symptoms. Ovarian hormones may also contribute to anger and irritability during the MT, but with substantial individual variability in the strength and direction of the effect. Among depressed individuals, higher-than-usual PdG levels (β=0.05, p = 0.02) and hot flashes (β=0.03, p = 0.008), as well as poorer-than-usual sleep quality (β=-0.14, p = 0.002) were significantly associated with higher anger and irritability. None of these predictors were significant in the general sample (all p > 0.05). Random effects revealed considerable individual variability in both E1G and PdG effects on anger and irritability.

ObjectivesTo explore pregnancy-related concerns among women with systemic lupus erythematosus (SLE) and impact of the disease on desired family size.MethodCross-sectional, single-center study, including women with SLE diagnosed before menopause. Data were collected via questionnaires and medical records. Participants were classified into three groups: (i) those who never conceived (Group 1); (ii) those who had conceived before SLE diagnosis (Group 2), and (iii) those who had conceived at least once after disease diagnosis (Group 3). Continuous variables were analyzed using Kruskal-Wallis with Mann-Whitney U post-hoc tests; categorical variables using Chi-square or Fisher's exact tests.Results152 patients were included and 75% had received information from their treating physician on reproductive health. Most common pregnancy-related concerns were the need to receive medication during pregnancy (56.6%), followed by concerns about pregnancy complications (53.9%). Women in Group 1 were younger and mainly attributed not having children to personal choice and not to SLE (56.4%). In contrast, women in Groups 2 and 3 frequently reported having fewer children than desired (35.3% and 44.6%, respectively), mostly due to SLE-related concerns (83.3% and 86.2%, respectively). In Group 3, deviation from desired family size was smaller among women who conceived in more recent periods (2015-2024, 32%), although attribution of deviations to SLE remained high.ConclusionsSLE affects women's reproductive decisions, underscoring the importance of tailored counseling.

IntroductionAdvancements in transplant care have led to an increasing number of women with solid organ transplantation (SOT) living through peri- and postmenopause. Menopause can significantly impact quality of life, and the added burden of SOT may exacerbate symptoms. Few studies have evaluated the menopausal experience in this population, and existing data rarely use validated questionnaires.Research QuestionThis study aimed to characterize menopausal symptoms and menopausal hormone therapy (MHT) use in peri- and postmenopausal SOT recipients using validated measures.DesignA cross-sectional survey study of female patients ≥18 years who underwent SOT between 2018 and 2023 was conducted at a tertiary transplant center. A reproductive and sexual health questionnaire incorporating validated instruments, including the Menopause Rating Scale (MRS), was administered.ResultsAmong peri- and postmenopausal SOT recipients ( n = 192), 8.9% reported use of MHT. The median MRS total score was 8.0, consistent with mild-to-moderate symptom severity overall. Symptom severity differed by menopausal status for vasomotor symptoms ( P =.03), sleep disturbances ( P = .04), depressive mood ( P = .04), and anxiety ( P <.001), with perimenopausal participants generally reporting more symptoms in these domains than postmenopausal participants. Despite these differences, overall symptom severity remained mild to moderate in both groups.ConclusionMenopausal symptoms among female SOT recipients are common but generally mild to moderate, with low utilization of MHT. The lack of increased vasomotor burden compared to prior literature may reflect under-recognition or misattribution of symptoms to transplant-related factors. Incorporating menopause-specific screening into transplant care may improve symptom recognition, quality of life, and long-term health outcomes.

Natural menopause, a biological transition in women, is often underrepresented in medical education, leading to knowledge gaps among health care professionals. This Staying Current article aims to provide physiology educators with an updated, comprehensive overview of menopause, including its physiological basis, symptomatic manifestations, and systemic effects and the current controversies and benefits surrounding menopausal hormone therapy (MHT). This article details the hormonal regulation of reproductive aging, the STRAW and STRAW + 10 criteria for characterization of menopausal staging, and the pathophysiology of common menopausal symptoms such as vasomotor disturbances, genitourinary syndrome, mood and sleep disturbances. It critically examines the history, risks, and benefits of MHT, referencing pivotal studies like the Women's Health Initiative, and outlines nonhormonal management strategies. Addressing educational gaps in menopause physiology is essential for improving women's health outcomes. This article equips physiology educators with current evidence and recommendations to enhance curricula and patient-centered care. NEW & NOTEWORTHY Natural menopause remains underrepresented in medical curricula, leaving clinicians with gaps in reproductive-aging knowledge. This Staying Current article gives physiology educators an updated, evidence-based overview-covering hormonal regulation, STRAW/STRAW + 10 staging criteria, and the pathophysiology of vasomotor, genitourinary, mood, and sleep symptoms. It critically revisits menopausal hormone therapy, including lessons from the Women's Health Initiative, alongside nonhormonal alternatives, equipping instructors to strengthen curricula and advance patient-centered women's health care.

The relationship between sleep characteristics in caregivers and care recipients with Alzheimer's disease (AD) and caregiver burden, especially regarding sex-related differences, still needs to be clarified. The aims of the present study were to examine associations between caregiver and patient sleep characteristics and caregiver burden, including sex-differences and menopausal status among female caregivers. The SexDemCare study is a multicenter Italian study conducted within the SINdem Study Group "Sex and Gender Differences in Dementia." Caregivers and their non-institutionalized care recipients with clinically diagnosed AD across different stages of disease severity were enrolled. The Caregiver Burden Inventory was administered. Sleep characteristics of both caregivers and care-recipients were assessed using the Pittsburgh Sleep Quality Index. 238 caregivers (65.9% women; mean age 59.6 ± 12.4 years) and 238 care-recipients (153 women; mean age 77.5 ± 7.9 years) were enrolled. Caregiver burden was associated with snoring, daytime hypersomnolence, longer sleep latency, and use of sleep medication. In sex-stratified analysis, caregiver burden was associated with several sleep characteristics only among female caregivers. Female caregivers may be especially vulnerable to the negative consequences of poor sleep on caregiving burden.

BackgroundNurse researchers from six participating countries (Great Britain, Australia, New Zealand, USA, Finland and Denmark) collaborated on an international menopause study on nurses.PurposeTo demonstrate an iterative two stage thematic analysis within a qualitative paradigm as it applied to an international menopause study.MethodsUsing an exploratory approach, the Framework Method and Braun and Clarke's thematic analysis were applied to data from 48 participants.ResultsThe Framework method provided an organising structure capturing large amounts of narrative data into a structured matrix. Following detailing of the larger data set into abstracted categories, Braun & Clarke's thematic analysis method enabled researchers to abstract themes into specific narratives reflective of participants voices.ConclusionThe iterative thematic analysis approach enabled nurse researchers to effectively collaborate across different countries, different time-zones and different cultures to synthesise a large body of qualitative data in a systematic, structured approach. This research demonstrates an iterative systematic methodological approach that can be used by nurse researchers analysing data manually where other programmes are not available.

To describe treatment patterns for perimenopause and menopause symptoms, including hormone therapy (HT), nonhormonal medications, and supplements and to examine peer, social, and structural correlates of HT use in a nationally representative sample of U.S. women. In February 2025, a cross-sectional online survey was conducted through YouGov ( n = 1,500 women). Eligible participants were women who reported being told by a healthcare professional (HCP) they were in perimenopause or menopause, or who were within the midlife age range associated with these stages (45-54 years). Participants reported symptom burden, treatment use, peer influences, and perceived barriers to care. Multivariable logistic regression was used to identify demographic and sociocultural predictors of HT use. Approximately half of the respondents reported vasomotor symptoms, yet only 7.2% reported current HT use. Marked disparities by education and income were observed: women with a 4-year college degree or higher had more than twofold higher odds of HT use, and those with household incomes >$100,000 had twice the odds compared with those earning <$20,000 ( p < 0.001). Peer influence was independently associated with treatment choice: women whose peers used HT had 3.4-fold higher odds of HT use, whereas peer use of mind-body approaches was associated with 63% lower likelihood of HT use. In a nationally representative sample of U.S. women with substantial symptom burden, reported HT use was low. Treatment decisions were strongly shaped by sociodemographic disparities and peer influence, suggesting opportunities for targeted risk communication and equitable access to evidence-based menopause care.

Chronic kidney disease (CKD) poses a growing global health burden, and reproductive history may influence CKD risk via hormonal pathways. We conducted a population-based cross-sectional analysis using ten cycles of the National Health and Nutrition Examination Survey (NHANES, 1999-March 2020), including 12,912 postmenopausal women with complete reproductive and kidney data. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2 (CKD Epidemiology Collaboration 2021) or urinary albumin-to-creatinine ratio ≥30 mg/g. Survey-weighted logistic regression and restricted cubic spline models were used to examine associations between reproductive factors and CKD, adjusting for demographic and clinical confounders. After adjustment, higher parity was associated with increased CKD odds: three to four live births (OR = 1.17, 95% CI 1.01-1.34) and five or more live births (OR = 1.22, 95% CI 1.03-1.46) compared with one to two live births. Younger age at first live birth also increased risk (≤20 years: OR = 1.36, 95% CI 1.06-1.75; 21-24 years: OR = 1.35, 95% CI 1.07-1.72). In contrast, hormone replacement therapy (OR = 0.75, 95% CI 0.66-0.84) and oral contraceptive (OR = 0.79, 95% CI 0.69-0.91) use were inversely associated with CKD. Other reproductive factors, including age at menarche, menopause, reproductive span, hysterectomy, bilateral oophorectomy, and type of menopause, showed no significant associations. Restricted cubic spline analyses indicated nonlinear relationships for most continuous reproductive exposures, except age at menarche, which was approximately linear. These findings suggest reproductive history may influence kidney health in postmenopausal women and warrant further studies to clarify underlying mechanisms.

Women face unique challenges in bone development and loss due to the role of estrogen, which leads to lower peak bone mass and a higher fracture risk, especially after menopause. Resistance and weight training are effective strategies to maintain bone health, yet societal biases often deter women from engaging in these activities. This article aims to challenge these misconceptions and advocate for the integration of strength training into women's fitness routines to promote overall well-being. Misconceptions surrounding excessive muscle gain, loss of femininity, and perceived barriers discourage many women from participating in strength training. Studies show that women who do not engage in strength training perceive higher barriers compared to those who do, highlighting the influence of societal discrimination against exercise trends among women. Cultural opinions, societal norms, and biological limitations shape these perceptions, often confining women's success within traditional notions of femininity. While the health benefits of resistance training are clear, the complexities of these biases require further investigation to foster a culture where women can freely participate in resistance and weight training without stigma or limitations. Resistance and weight training and the associated prejudice against women's engagement in these activities is an underdefined topic, and future research in this field will allow us to create a community where both resistance trainers and non-resistance trainers can understand and appreciate individualized health goals.KEY MESSAGESAcknowledging prejudice toward women in resistance and weight training is essential for addressing the elements that limit women's full participation in strength training activity.Prejudice surrounding women's resistance and weight training participation is not an isolated bias but a multifaceted societal problem rooted in longstanding gender norms, cultural expectations, among others.

The decline in estrogen following menopause is a major driver of metabolic and immune dysfunction in aging females. While hormone replacement therapy improves many of these outcomes, its clinical use remains limited due to concerns regarding estrogen-sensitive malignancies. Tissue-selective estrogen complexes (TSECs), which combine estrogens with selective estrogen receptor modulators (SERMs) such as tamoxifen (TAM), represent a promising strategy to preserve the metabolic and immunological benefits of estrogen while reducing oncogenic risk. However, the systemic effects of TAM under conditions of estrogen deficiency remain incompletely defined. In this study, we investigated the metabolic and immunomodulatory actions of low-dose TAM, alone or in combination with 17β-estradiol (E2), in adult ovariectomized (OVX) female mice. OVX resulted in increased adiposity, hepatic steatosis, glucose intolerance, insulin resistance, immunoglobulin G3 (IgG3) concentration, and systemic inflammation, along with decreased immunoglobulin G1 (IgG1) concentration. E2, TAM, and E2 + TAM each attenuated OVX-induced adipose expansion, adipocyte hypertrophy, and proinflammatory cytokine production. TAM improved insulin sensitivity but did not fully restore glucose tolerance. Transcriptomic analysis of visceral adipose tissue-resident B cells revealed that E2 and E2 + TAM modulate overlapping yet distinct immune-regulatory networks, including suppression of pro-inflammatory signaling, regulation of immune checkpoints, and genes linked to adipose homeostasis. Low-dose TAM emerges as a modulator of estrogen receptor signaling that attenuates multiple features of OVX-induced metabolic and inflammatory dysfunction, though its limited effect on glycemic control highlights the need for tissue-specific evaluation of SERM-based interventions. These findings provide mechanistic insight into endocrine-immune-metabolic interactions and inform strategies to reduce aging-related disease risk in postmenopausal women.

Premature coronary artery disease (PCAD) in women, defined as onset ≤65 years, accounts for 20-30% of CAD cases. The clinical implications, pathogenic processes, and sex-specific risk factors of female PCAD are summarized in this review. Women have unique patterns in the traditional metabolic risk factors of smoking, diabetes, obesity, and hypertension. Elevated triglyceride-rich lipoproteins and lipoprotein(a) are highly associated with early atherosclerosis. Premature menopause, autoimmune diseases like systemic lupus erythematosus, and pregnancy difficulties like preeclampsia and gestational diabetes are among the special factors that affect women and worsen inflammation and endothelial dysfunction. PCAD progression is also influenced by inflammatory pathways (e.g. NLRP3 inflammasome activation) and genetic predispositions (e.g. 9p21 locus polymorphisms, familial hypercholesterolemia). Diagnostic delays occur because women frequently appear clinically atypically (e.g. fatigue, nausea) and show non-obstructive lesions or spontaneous coronary artery dissection (SCAD). Sex-tailored approaches are needed for management, such as aggressive lipid control, metabolic risk reduction, and psychosocial support. Female PCAD is a complex condition influenced by a combination of traditional metabolic risk factors, sex-specific factors, and genetic predispositions. Sex-specific biomarkers and multi-omics techniques should be given top priority in future studies in order to improve early detection and tailored treatment. Female PCAD patients exhibit distinct metabolic and sex-specific risk factor profiles, necessitating tailored management strategies.Genetic predispositions and sex-specific factors, including premature menopause and autoimmune diseases, significantly contribute to the risk and progression of PCAD in women.Early detection and sex-tailored interventions, incorporating advanced biomarkers and multi-omics techniques, are crucial for improving outcomes in female PCAD.

Menopause is a normal part of aging and in the general population is associated with chronic conditions that impact health, mortality, and well-being. Menopause is experienced differently by autistic individuals, although no studies have investigated this topic in a large sample. The purpose of this study was to investigate rates of, and factors associated with symptomatic menopause among autistic individuals and to identify the prevalence of co-occurring conditions in symptomatic individuals. We included autistic females aged 35-70 years enrolled for 10 + months in 2014-2016 Medicare and/or Medicaid (n = 26,904), excluding those with gender dysphoria. Those with symptomatic menopause were compared to a non-symptomatic reference group on demographic, enrollment characteristics, and co-occurring conditions through logistic regression. Approximately 4% of publicly-insured autistic females aged 46-70 years had symptomatic menopause in their medical records. Intellectual disability was associated with a lower likelihood of symptomatic menopause, and being Medicare-enrolled or dual-enrolled was associated with higher likelihood of having symptomatic menopause recorded. In adjusted models, rates of ADHD, anxiety and depressive disorders, headache/migraine, altered sensory experiences, altered sexual function, and sleep disturbance were significantly higher in the symptomatic menopause sample compared to the reference group. More work to better support autistic women in discussing menopausal symptoms and co-occurring conditions with primary care providers is needed, particularly among those for whom self-report of symptoms are more challenging to ascertain. Factors associated with specific types of health care coverage warrant greater investigation to support better identification.