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Background Menopause-related symptoms are common but undertreated. Digital tools that support symptom assessment and patient education may improve engagement. Objective To assess whether a previsit digital menopause symptom assessment and education tool increased treatment initiation and patient engagement compared to an educational pamphlet. Design Women aged 45–55 years with upcoming primary care appointments were invited to participate. Those with a total Menopause Rating Scale (MRS) score ≥5 indicating bothersome menopause symptoms were included. Participants were randomized to a digital menopause symptom assessment tool or a digital educational pamphlet and completed a post-visit survey (NCT06919887). Participants Of the 14,726 women invited to participate between May 12, 2025, and December 5, 2025, there were 653 (4.4%) enrolled that met eligibility criteria. Interventions Randomized to an mHealth app called emmii or a standard digital menopause educational pamphlet. Main measures Menopause treatment initiation within 30 days of the clinical visit was assessed by electronic health data. Baseline and post-visit surveys were collected assessing patient experience, engagement, and perceived usefulness. Rates of menopause hormone therapy (HT) prescribing were compared with a reference population of nonparticipants aged 45–55 who had a primary care appointment at Mayo Clinic during the same period and received no study education materials. Key results Of 653 participants enrolled and randomized, 383 completed both the baseline and post-surveys (171 intervention and 212 control). HT initiation among study participants was significantly higher than in the reference population of women (9.3% vs. 4.4%, p < 0.001). There was no difference in HT initiation between the intervention (9.1%) and control groups (9.6%) ( p = 0.83). Initiation rates were 3.8% and 4.5%, respectively ( p = 0.64) for nonhormone therapies. Conclusions Among women with bothersome menopause symptoms, those who underwent previsit symptom screening and received educational materials had higher rates of HT initiation than women who did not participate in the study. These findings suggest that structured menopause education may improve recognition and management of menopause symptoms in routine clinical practice.

Background Premature and early menopause involve ovarian hormone deprivation, which may contribute to later-life vulnerability to cognitive decline and neurodegenerative diseases. Multimodal neuroimaging biomarkers provide a means of detecting structural, microstructural, functional, and molecular brain changes before clinical symptoms emerge. Methods Following PRISMA guidelines, we conducted a systematic search of PubMed. Study quality was assessed using the Newcastle–Ottawa Scale. Results Neuroimaging modalities included in vivo structural magnetic resonance imaging (MRI) ( n = 16), functional MRI ( n = 2), diffusion tensor imaging ( n = 4), and positron emission tomography ( n = 3). Women with premature or early menopause showed regionally specific structural and microstructural brain abnormalities, including lower gray-matter volume or cortical thickness in medial temporal, frontal, and basal forebrain regions; white-matter microstructural abnormalities in the anterior corona radiata, corpus callosum, and fronto-occipital tracts; and reduced posterior hippocampal activation during memory encoding. In one study, earlier age at menopause was associated with higher amyloid- β (Aβ) burden in women who underwent premenopausal bilateral oophorectomy (PBO), and elevated tau deposition was reported predominantly among women with higher Aβ levels. Conclusion Converging multimodal neuroimaging evidence suggests that premature and early menopause may be associated with Alzheimer’s disease-relevant brain changes. However, findings remain heterogeneous, and longitudinal studies are needed to clarify the temporal relationships between ovarian hormone deprivation and neurodegeneration, and to determine the clinical implication of these findings.

Objectives: Sexual minority women (SMW) have worse mental and physical health outcomes compared with heterosexual women. Limited research has explored menopause in SMW. This study compared menopause symptoms in cisgender SMW and heterosexual women. Methods: This cross-sectional analysis examined questionnaires from women 40-65 years, seen at women’s health clinics in Arizona, Florida, and Minnesota between December 2016 and February 2023. Menopause symptoms were evaluated using the Menopause Rating Scale (MRS). An MRS score ≥ 12 indicates moderate or greater symptoms. Multivariable logistic regression was used to compare scores between cisgender SMW and heterosexual women, adjusting for factors that may impact menopause symptoms. Results: Data from 2,273 women were included, with 69 SMW. The mean age was 53.2 (SD: 6.1), body mass index 25.7 kg/m 2 , and a majority were White (91.9%). The median MRS score among all participants was 15 (interquartile range=10, 20); 67.3% reported MRS scores ≥ 12. The likelihood of being on hormone therapy or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors was comparable between groups. In both univariate (OR: 0.85, 95% CI: 0.52-1.40) and multivariable (OR: 0.83, 95% CI: 0.47-1.48) analyses, no significant associations between sexual orientation and MRS ≥ 12 were found. Conclusions: Menopause symptoms and likelihood of treatment were similar for cisgender SMW and heterosexual women presenting to tertiary care centers. Limited diversity in the cohort and the small number of SMW reduce the generalizability of the results. The lack of adverse social determinants of health may have contributed to the findings, but additional research in larger cohorts is needed.

Abstract INTRODUCTION Associations of short‐term use of menopausal hormone therapy (mHT) with Alzheimer's disease (AD) and structural magnetic resonance imaging (MRI) biomarkers were investigated 10 years after an mHT trial. METHODS Recently menopausal women with good cardiovascular health were randomized to oral conjugated equine estrogens (oCEE) or transdermal 17β‐estradiol (tE2) and micronized progesterone, or placebo for 4 years. Amyloid beta (Aβ) on positron emission tomography, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI were assessed 10 years after completion of the mHT trial ( n = 266). RESULTS Aβ and structural MRI biomarkers were not different in the oCEE and tE2 groups compared to placebo. Apolipoprotein E ε4 status did not modify the findings. DISCUSSION There was no evidence of adverse effects or benefits associated with 4 years of use of oral or transdermal mHT on Aβ and structural MRI biomarkers in relatively healthy women, 10 years after mHT. Findings support the long‐term safety of short‐term use of mHT on brain health. CLINICAL TRIALS REGISTRATION NCT00154180 Kronos Early Estrogen Prevention Study (KEEPS) Highlights There were no menopausal hormone therapy–related adverse effects or benefits on amyloid beta and magnetic resonance imaging biomarkers in the long term. Apolipoprotein E ε4 carrier status did not modify these findings. Findings align with neutral cognitive and cerebrovascular outcomes in this cohort.

ABSTRACT Purpose Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath‐held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free‐breathing cardiac MRE. Methods A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k ‐space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post‐processing specialized for cardiac imaging. Results Feasibility of free‐breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant‐specific images, 17‐segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin‐systole), 5.74 ± 0.94, 5.42 ± 0.87 (end‐systole), 3.84 ± 0.71 (begin‐diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end‐diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one‐way, repeated‐measures ANOVA ( p < 0.001) and Friedman's test ( p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject‐specific. Comparison of free‐breathing stiffness measurements against reference breath‐held measurements yielded similar systolic stiffness estimates. Conclusions This study establishes the feasibility of free‐breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject‐specific.

Objective: Generative artificial intelligence is rapidly evolving and is now being explored in health care to support patient and clinician education. This study evaluated the accuracy, completeness, and readability of four large language models (LLMs): ChatGPT 3.5, Gemini, ChatGPT 4.0, and OpenEvidence in answering questions about menopause and hormone therapy. Methods: A total of 35 questions (20 patient-level, 15 clinician-level) were entered into each LLM. OpenEvidence was only used for clinician-level questions. Four blinded expert reviewers rated responses as accurate and complete, accurate but incomplete, or inaccurate. Readability of patient-level responses was assessed using the Flesch Reading Ease Score (FRES) and word count. Analysis used ANOVA for readability, odds ratios for accuracy comparisons. Results: For patient-level questions, ChatGPT 3.5 achieved the highest accuracy (70%), followed by ChatGPT 4.0 (60%) and Gemini (30%); Gemini had significantly lower odds of accuracy compared with ChatGPT 3.5 (OR=0.18, 95% CI=0.05-0.71; P =0.014). FRES scores differed significantly ( P <0.001): Gemini scored 38.9±7.3 (“difficult”), ChatGPT 3.5 scored 31.0±11.2, and ChatGPT 4.0 scored 26.5±8.6 (both “very difficult”). For clinician-level questions, ChatGPT 4.0 achieved the highest accuracy (67%), followed by ChatGPT 3.5 and OpenEvidence (60% each) and Gemini (47%); no significant differences were observed among models (all P >0.05). Conclusion: LLMs demonstrated limited accuracy and frequent incorrect or incomplete responses to menopause-related queries, highlighting the need to improve model performance to ensure accurate and reliable information for both patients and clinicians.

The goal in selecting these recent articles was to help identify literature that may change the clinical practice of women’s health for practitioners in the primary care setting. Articles were identified by reviewing the high-impact medical and women’s health journals, national guidelines, ACP JournalWise, and NEJM Journal Watch. In this Clinical Update, we selected recent publications relevant to the cardiovascular health of women.

Abstract Disclosure: E.M. Lewiecki: Amgen Inc, Kyowa Kirin, Ultragenyx, Angitia, Radius Health, Inc, Ascendis. E. Kapoor: Fresenius Kabi USA Inc., Astellas Pharma, Estetra SRL, WellFound Inc., Exeltis. S. Hurtado: None. V.M. Navarro: Bayer, Inc. M. Torres: Bayer, Inc. J. Beau: Bayer, Inc. I. Gkioni: Syneos Health LLC (providing service to Bayer), AstraZeneca. K. Genga: Bayer, Inc.. Background: The neuropeptide substance-P and its receptor neurokinin-1 (SP-NK1R pathway) play a role in bone metabolism and remodelling. Pre-clinical evidence also points to a role of this pathway in energy homeostasis. NK-1R antagonists have been proposed as potential therapies in obesity and musculoskeletal disorders like osteoporosis. Elinzanetant (EZN) is a dual neurokinin-1 and -3 receptor antagonist in late-stage development for vasomotor symptoms (hot flashes) associated with menopause. This post hoc analysis evaluates potential benefits of EZN on the skeleton, body weight, and body composition in postmenopausal women. Methods: Data were gathered from exploratory endpoints of the 52-week (wk), placebo (PL)-controlled, OASIS-3 Phase 3 EZN efficacy and safety trial. Mean percentage (%) change in total bone mass (kg) (measured indirectly by bioelectrical impedance analysis at baseline (BL), wks 4, 8, 12, 18, 24, 36, 52); mean % change in bone mineral density (BMD, measured directly by dual-energy X-ray absorptiometry at BL, wks 24 and 52) in femoral neck, total hip, and lumbar spine; and mean % change in key bone turnover markers osteocalcin (OC) and procollagen 1N-terminal propeptide (P1NP) at BL, wks 4, 8, 12, 18, 24, 36, 52 were evaluated. Weight, body mass index (BMI: weight/height2), waist circumference (WC), fat mass index (FMI; fat mass/height2), lean mass index (LMI; lean mass/height2) and body water were measured to monitor body composition at BL and wks 4, 8, 12, 18, 24, 36, 52. A sub-analysis was performed based on FMI at baseline (FMI ≤9 normal fat mass; &gt;9 excess fat mass). Descriptive statistics were used to evaluate all parameters and trends. Results: From BL to wk 52, increasing trends in bone mass were observed with EZN (mean [SD]: 2.81 [1.02] to 2.95 [1.96]) but not PL (mean [SD]: 2.87 [1.09] to 2.87 [1.13]). In parallel, lower BMD reductions were seen in EZN vs PL at all skeletal sites [EZN vs PL, mean % change from BL: femoral neck (0.00% vs -1.22%), total hip (-0.70% vs -1.37%), and lumbar spine (-0.57% vs -1.22%), with considerable variability in both groups (SD range 3.01 - 4.70)]. Lower levels of circulating OC and P1NP were consistently observed over 52 wks of EZN treatment, suggesting a lower rate of bone resorption with EZN vs PL. Trending reductions in weight, BMI, and WC, along with increases in LMI and body water were observed with EZN vs PL. Trends of higher LMI in patients with excess fat, or lower FMI in patients with normal fat at BL were observed with EZN, suggestive of a positive body re-composition with EZN. Conclusions: These data expand on EZN safety profile and further point to novel potential benefits for the skeleton and body composition of postmenopausal women. Further research is warranted to provide conclusive evidence of the benefits of EZN specifically in post-menopausal women with obesity/overweight status or osteoporosis. Sponsorship: Bayer U.S., Whippany, NJ, USA Presentation: Monday, July 14, 2025

Objective: To evaluate the documentation of menopause-related International Classification of Diseases-10 (ICD-10) codes in the electronic health record (EHR) among midlife women with moderate or greater menopause symptoms receiving primary care. Methods: This cross-sectional study from the Hormones and Experiences of Aging (HERA) cohort included women aged 45-60 years receiving primary care at one of 4 Mayo Clinic sites who completed a one-time survey between March 1, 2021 and June 30, 2021. The survey captured demographic data, menopause symptoms using the Menopause Rating Scale (MRS), health care utilization, and treatment. Women with an MRS score ≥12 were included. The primary outcome was documentation of a menopause-related ICD-10 code in the EHR in the 12 months before survey completion. Results: Of 5,254 women with completed surveys, 2,414 (49%) had an MRS score ≥12 and were included. Among these, 1,519 (63%) reported seeking care for their menopause symptoms in the past 12 months, but only 345 (23%) had a menopause-related ICD-10 code. Women with an ICD-10 code had higher MRS scores (18 [IQR: 14-22] vs 17 [IQR: 14-20]; P = 0.002) and were more likely to use systemic hormone therapy (HT; 26% vs 9%; P < 0.001), and vaginal HT (20% vs 6%; P < 0.001). Conclusions: Menopause-related ICD-10 diagnosis codes were under-documented in women with significant menopause symptom burden. Those with a code were more likely to report menopause treatment. These findings highlight a critical gap between symptom burden and diagnosis coding in the EHR, underscoring the need to improve identification and management of menopause symptoms.