Background: Peripheral artery disease (PAD) is a global health challenge. Advances in artificial intelligence (AI), such as large language models (LLMs) and chain-of-thought (CoT) reasoning, offer novel approaches for clinical recommendations. This study compared the readability and guideline adherence of responses from physicians and AI for a standardized PAD case. Methods: This cross-sectional study gathered responses from 30 specialized physicians (11 cardiologists, 19 vascular surgeons) across seven Latin American countries and 13 LLM systems (10 standard, three CoT). Both groups addressed diagnosis, treatment, risks, and prognosis; LLMs responded as vascular specialists. Responses were blindly evaluated with five validated Spanish readability indices and compared to the 2024 ACC/AHA multisocietal PAD guideline. Three experts scored guideline adherence; nonparametric tests were applied. Results: Guideline adherence did not differ significantly between physicians (median 5.8 [3.4–7.6]) and LLMs (7.3 [4.7–9.7], p = 0.169), though CoT-LLMs achieved the highest scores (9.7 [8.5–11.0]). LLMs more often recommended supervised exercise (84.6% vs 30.0%, p = 0.002) and revascularization for quality of life (69.2% vs 20.0%, p = 0.004), whereas physicians favored cilostazol (60.0% vs 30.8%, p = 0.104). LLM responses had lower Readability μ values (46.9 vs 51.4, p = 0.012). Inter-rater reliability was highest for CoT-LLMs (intraclass correlation coefficient [ICC] = 0.98) versus physicians (ICC = 0.76). Conclusion: LLM showed comparable guideline adherence to physicians although CoT models achieved the highest scores. The difference in physician and AI treatment preferences suggest the potential of AI as adjunct clinical tools and warrants further study.

Importance and Objective: Aging is a complex biological process uniquely shaped in women by hormonal transitions, particularly across the menopause transition. While chronological age alone fails to capture individual health variability, emerging molecular biomarkers offer tools to quantify biological aging and understand mechanisms underlying age-related decline. This review synthesizes the current landscape of aging biomarkers, including senescence-associated secretory phenotype factors, epigenetic clocks, clonal hematopoiesis of indeterminate potential, and telomere length, with a particular emphasis on their relevance to menopause. Methods: This narrative review synthesizes human studies, translational research, and foundational basic science identified through PubMed searches through June 2025, examining aging biomarkers in general populations, among women in the menopause transition, and in relation to vasomotor symptoms and hormone therapy. Discussion and Conclusion: Evidence demonstrates that changes in biological aging biomarkers are observed across multiple molecular systems during midlife, including the menopause transition, reflecting broader age-related biological remodeling. Postmenopausal status, particularly following early or surgical menopause, has been associated with biological aging phenotypes, including elevated senescence-associated secretory phenotype factors, epigenetic age acceleration, clonal hematopoiesis, and shorter leukocyte telomere length, likely reflecting a combination of chronological aging, hormonal changes, and individual biological vulnerability. While severe vasomotor symptoms have been linked to higher epigenetic age, hormone therapy may favorably influence certain senescence markers and biological age discrepancy. Despite these advances, significant limitations constrain clinical translation, as current biomarkers capture overlapping biological processes and lack validated thresholds to define biological aging, especially in women. Future research requires large, longitudinal studies across diverse populations to establish clinically meaningful thresholds and sex-specific calibration. Advancing precision health strategies for women requires a better understanding of how reproductive and hormonal factors modify biomarker trajectories to improve risk prediction and to facilitate the development of targeted interventions for age-related diseases.

Importance and Objective: Sexual health is a multidimensional aspect of women’s well-being. It is particularly vulnerable during midlife, when the physiological and psychosocial changes of the menopause transition intersect with the growing burden of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as highly effective pharmacologic treatments for obesity, yet their effects on female sexual function remain largely uncharacterized. This review aims to discuss the interplay among obesity, midlife, obesity treatments, and female sexual health, with a focused synthesis of available evidence on GLP-1–based therapies and sexual outcomes in women. Methods: This narrative review synthesizes preclinical studies, case reports, observational data, and clinical trials identified through PubMed searches from inception through March 2026, examining female sexual function in the context of obesity, the menopause transition, obesity treatments, and GLP-1 receptor agonist therapy. Discussion and Conclusion: Obesity impairs female sexual function through hormonal, vascular, and psychosocial mechanisms. Accordingly, lifestyle interventions and bariatric surgery have demonstrated meaningful improvements in sexual function. In contrast, GLP-1 receptor agonists, despite conferring substantial weight loss and favorable metabolic effects, may paradoxically suppress sexual desire and arousal through central neuroendocrine mechanisms, including the modulation of dopaminergic reward and serotonergic signaling. While emerging case reports and preclinical data support this concern, systematic clinical evidence remains limited, highlighting the need for prospective studies with longitudinal sexual function endpoints. In this context, clinicians should proactively assess sexual function before and during GLP-1 therapy using validated instruments and integrate sexual health into comprehensive obesity care for midlife women.

Purpose: To evaluate the association of long-term, continuous tirzepatide use with cardiometabolic risk parameters and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk in real-world practice. Methods: This multicenter retrospective observational study included 1028 adults with overweight or obesity who received weekly subcutaneous tirzepatide for at least 12 months within the Mayo Clinic Health System from June 2022 through May 2024. Atherosclerotic cardiovascular disease risk analyses included 275 individuals with complete baseline and 12-month follow-up data. Outcomes were changes in cardiometabolic parameters, estimated 10-year ASCVD risk, and ASCVD risk category. Results: At 12 months, median total body weight loss (TBWL) was 12.6%. Fasting glucose, HbA1c, triglycerides, and alanine aminotransferase decreased by 19.5%, 16.0%, 8.5%, and 10.6%, respectively, whereas HDL-cholesterol increased by 11.3% (all P < .001). Mean 10-year ASCVD risk did not change significantly overall (mean relative change, −3.7%; P = .18), but changes differed by TBWL category (analysis of variance, P < .001). Atherosclerotic cardiovascular disease risk decreased among individuals achieving 10% to 20% TBWL (−9.6%; P = .009) and >20% TBWL (−14.2%; P = .005), but not among those achieving <10% TBWL (+7.7%; P = .22). Low-risk prevalence increased from 38.3% to 46.4% (P < .001), with 11.7% transitioning from higher-risk categories to low risk. Main findings: Continuous tirzepatide use for at least 12 months was associated with clinically meaningful improvements in cardiometabolic parameters. Reductions in estimated 10-year ASCVD risk were observed among individuals achieving at least 10% TBWL, supporting greater weight loss as an important marker of cardiovascular risk improvement.

In this issue, the American College of Physicians publishes clinical guidelines for the pharmacologic treatment of menopausal vasomotor symptoms. The editorial discusses the recommendations and the...