Faubion, Stephanie S.

ABSTRACT Objective This study assessed the impact of sex and age on weight loss outcomes in patients receiving tirzepatide in real‐world clinical practice. Methods We conducted a retrospective cohort study of adults with overweight or obesity who initiated tirzepatide at Mayo Clinic between June 2022 and May 2024 and completed ≥ 12 months of continuous therapy. Primary outcome was total body weight loss percentage (TBWL%) at 15 months, stratified by sex and age groups (≤ 45, 46–59, ≥ 60 years). Results Among 1039 patients (57% women; mean age 56 ± 11 years), women achieved significantly greater TBWL% than men after 15 months of treatment (15.1% vs. 10.7%, p < 0.001). Patients aged ≤ 45 years had greater weight loss than those ≥ 60 years (15.1% vs. 12.3%, p = 0.024). In multivariable analyses, greater weight loss was independently associated with female sex, absence of type 2 diabetes, no prior obesity medication use, no concomitant weight gain‐promoting medications, and higher tirzepatide dosage. Age was not an independent predictor. Conclusions Sex, but not age, predicted weight loss with tirzepatide among individuals using the medication continuously for ≥ 12 months. These findings underscore the importance of incorporating sex‐specific considerations into personalized obesity treatment strategies.

Introduction To assess and compare the accuracy, readability, and overall performance of large language models (LLMs) in answering questions about functional hypothalamic amenorrhea (FHA) for patients and healthcare professionals. Methods A total of 11 patient-level and 15 clinician-level FHA-related questions were entered separately into four LLMs: ChatGPT 3.5 (free version), ChatGPT 4.0 (updated, paid subscription), Gemini, and OpenEvidence. OpenEvidence was used only for clinician-based questions. Responses were evaluated by three expert reviewers blinded to the LLM used who rated them as accurate and complete, accurate but incomplete, or inaccurate. A fourth reviewer resolved discordant scores. Readability for patient-level questions was assessed using the Flesch Reading Ease Score (FRES) and word count. Lower FRES scores indicate more difficult reading. Accuracy and completeness were compared using odds ratios (95% CI) with ChatGPT 3.5 as the reference model, and differences in readability were analyzed using Friedman’s test. Results LLM performance varied across question types. For patient-level questions, ChatGPT 4.0 achieved the highest accuracy (9 of 11; 82%), followed by ChatGPT 3.5 and Gemini (each 8 of 11; 73%), with no statistically significant differences. Among clinician-level questions, OpenEvidence demonstrated perfect accuracy (15 of 15; 100%), compared with 93% for and 80% for ChatGPT 4.0 and Gemini. Completeness followed similar patterns, with OpenEvidence providing the most complete clinician responses (93%) and ChatGPT 4.0 the most complete patient-level responses (89%). Readability differed significantly among models ( p = 0.012), with Gemini producing the most readable patient-level content (median FRES 43.5 [IQR 36.8–53.4]) compared with ChatGPT 3.5 (30.6 [16.8–48.4]) and ChatGPT 4.0 (28.8 [22.1–37.6]). Word counts did not differ significantly ( p = 0.39). Discussion LLMs demonstrated good overall performance in answering FHA-related questions but often provided incorrect or incomplete information. Fine tuning field-specific data, engineered prompts, and obtaining human-in-the-loop feedback may help improve the accuracy of these models.

This cohort study evaluates 20-year trends to quantify changes in menopause-related online searches compared with other health domains.

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.

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.

Background: Functional hypothalamic amenorrhea (FHA) is a common form of secondary amenorrhea caused partly by undernutrition relative to demand. Objective: To compare the dietary nutritional intake between women with FHA and eumenorrheic controls and evaluate micronutrient profiles. Methods: This cross-sectional study included 30 women with FHA and 29 eumenorrheic controls not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol of <50 pg/mL, and FSH and LH of <10 mIU/L, excluding other etiologies. A 3-day food diary was collected for dietary analysis, excluding dietary supplements using ESHA Research Food Processor. Results: The mean age of women with FHA and controls was 26.4 years ± 6.2 versus 30.3 years ± 3.7 ( p = 0.002), with no differences in BMI ( p = 0.16) or the waist-to-hip ratio ( p = 0.71). Women with FHA and controls consumed comparable median calorie intake (1784 kcal [1465, 2011] vs. 1732 kcal [1578, 1982], p = 0.62), with no differences in self-reported exercise patterns. Women with FHA consumed more dietary protein (84.2g [74, 112] vs. 74 g [59, 92], p = 0.001) and dietary fiber (30.1 g [22, 43] vs. 17.3 g [15, 23], p = 0.02) versus controls, respectively. When expressed as a percentage of estimated average requirements (% estimated average requirement), women with FHA had higher intakes of vitamin A (105% [45, 219] vs. 43% [21, 86], p = 0.005), vitamin C (201% [139, 351] vs. 107% [75, 190], p = 0.004), and iron (169% [146, 220] vs. 120% [99, 192], p = 0.027) compared with controls. Conclusions: Women with FHA had similar caloric intake to eumenorrheic controls but consumed more dietary protein, fiber, vitamin A, vitamin C, and iron. Future studies should examine the nutritional profiles of women with FHA in relation to long-term health consequences such as bone and vascular health.

Objective: Perimenopause is the time leading up to a woman’s last menstrual cycle and includes the 12 months afterward. Studies that systematically compare perimenopause symptoms across diverse cultural and geographic settings are lacking. This study, utilizing data from Flo, an international mobile health application, aimed to assess global knowledge and symptom experiences related to perimenopause. Methods: This cross-sectional survey was conducted via the Flo application, offered to users aged 18 years and above. The primary endpoints were knowledge of perimenopause symptoms from all survey participants, and self-reported perimenopause symptoms for survey participants aged 35 years and above. Secondary analyses compared knowledge scores and symptoms across geographic regions. Results: A total of 17,494 women from 158 countries were included. Commonly recognized perimenopause symptoms included hot flashes (71%), sleep problems (68%), and weight gain (65%). Of the participants, 12,681 were aged 35 years or above, with the most common self-reported symptoms being fatigue (83%), physical and mental exhaustion (83%), irritability (80%), depressive mood (77%), sleep problems (76%), digestive issues (76%), and anxiety (75%). This pattern of symptoms was similar among those who self-reported being in perimenopause, though higher than in those not in perimenopause. International variation in perimenopause symptom knowledge and symptoms experienced was noted ( P <0.001). Conclusions: This survey highlights a discordance between perimenopause knowledge and actual symptoms experienced across diverse global populations. While hot flashes were the most widely recognized symptom, respondents aged 35 years or above most commonly reported experiencing fatigue, physical and mental exhaustion, and irritability.

Abstract Objective Perimenopause is an under-recognized life stage that may be accompanied by complex and fluctuating symptoms. We aimed to quantify the prevalence of perimenopause uncertainty and explore the underlying drivers. Methods We conducted a mixed-methods study based on a cross-sectional survey of U.S. women aged 35 years and above (N=7,640). Closed-ended responses were analyzed to estimate the prevalence of perimenopause uncertainty with subgroup differences investigated by age and symptom severity. Content analysis of free-text responses (n=409) was conducted to identify the main uncertainty drivers. Results Overall, 34% of participants reported being unsure of their reproductive stage. Uncertainty peaked among those aged 40-44 (42%) and was highest among those with severe symptom burden (37%). The content analysis revealed three main uncertainty drivers. Symptom confusion and attribution was the most common (56%), reflecting difficulties interpreting bodily changes and distinguishing perimenopause from other causes. Knowledge gaps and information seeking accounted for 28% of responses, highlighting limited health literacy, assumptions about age, and active searches for evidence. Barriers to confirmation and care (16%) described dismissive healthcare encounters and reluctance to acknowledge perimenopause. Younger women (35-39 years) were more likely to cite knowledge gaps, while healthcare barriers peaked in the 40-44 age group. Conclusion Perimenopause uncertainty is a prevalent and clinically meaningful challenge. This uncertainty is conceptually distinct from illness-focused models: it is a universal transition with ambiguity and often lack of validation. Better symptom recognition and targeted communication is a crucial first step toward improving women’s awareness and support during perimenopause.