Shufelt, Chrisandra

Abstract Disclosure: R. Castaneda: None. D. Bechenati: None. R.D. Rivera Gutierrez: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. P. Bennett: None. A. Acosta: Novo Nordisk, Gila Therapeutics, Amgen Inc, Regeneron Pharmaceuticals, Boehringer Ingelheim, Rhythm Pharmaceuticals, General Mills, Currax, Nestle, Phenomix Sciences, Busch Health, RareDiseases, National Institute of Health, Vivus Pharmaceuticals, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical. S. Faubion: Era Women’s Health Platform, PriMed, MedAll, AiCME, Medscape, Weight Watchers. C. Shufelt: Bayer Advisory Board. M.D. Hurtado: Novo Nordisk, National Institute of Health, Phenomix. Introduction: Tirzepatide, a dual GIP and GLP-1 receptor agonist, is an FDA-approved medication demonstrating the highest efficacy for weight loss among currently available treatments. However, the influence of sex and age on weight loss outcomes with tirzepatide remains unclear. Objective: To investigate the influence of sex and age on weight loss outcomes in patients treated with tirzepatide. Methods: This retrospective study evaluated weight loss outcomes associated with tirzepatide across sex and age groups. Patients with active malignancy, prior bariatric surgery, or concurrent anti-obesity medication were excluded. The primary endpoint was total body weight loss percentage (TBWL%) at 15 months by sex and age. The influence of age was analyzed as a categorical (≤45, 46-59, ≥60 years) and continuous variable. Secondary outcomes included TBWL% at 3, 6, 9, and 12 months by sex and age. Data were analyzed using independent t-tests, one-way ANOVA, and multivariate regression; results are reported as mean ± standard deviation. Results: The study included 1033 patients (57.1% female; mean age 56 ± 11 years; mean BMI, 37.7 ± 8 kg/m2). By age category, 18.8% (196) were ≤45 years (35.7% males, 64.3% females), 45.9% (473) were 46-59 years (42.7% males, 57.3% females), and 35.3% (364) were ≥60 years (54.7% males, 45.3% females). At all timepoints, TBWL was significantly greater in females compared to males at all timepoints. At 15 months females had a higher TBWL than males: 15.3% ± 10, n=340, vs. 10.2% ± 8, n=244, (p < 0.001). Among females, premenopausal women achieved a higher TBWL than postmenopausal women: 16.9% ± 10 vs 14.4% ± 9, p = 0.04. Analysis by age groups revealed a trend toward higher TBWL in younger patients that did not reach statistical significance (p = 0.152): ≤45 years (14.7% ± 10%), 46-59 years (12.9% ± 10%), and ≥60 years (12.7% ± 9%). After adjusting for baseline age, BMI, and diabetes status, sex remained a strong predictor for weight loss outcomes (PE= 4.5, 95% CI [2.96, 5.97], p < 0.001), following type 2 diabetes status (PE= 4.8, 95% CI [3.0, 6.7], p < 0.001). Conclusion: Sex but not age was a strong predictor of weight loss with tirzepatide. Female sex was associated with greater weight loss than male sex. These results emphasize the importance of considering sex-specific factors in weight loss strategies and warrant further investigation into the underlying biological mechanisms. Differential weight loss by menopause, underscores the role of sex hormones. Presentation: Monday, July 14, 2025

Abstract Disclosure: R.D. Rivera Gutierrez: None. D. Bechenati: None. R. Castaneda: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. T.M. Taaffe: None. P.K. Bennett: None. A.J. Acosta: Novo Nordisk, Gila Therapeutics, Rhythm Pharmaceuticals, Amgen Inc, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Currax, Nestle, Phenomix Sciences, Busch Health, RareDiseases, National Institute of Health, Vivus Pharmaceuticals, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical. S. Faubion: Era Women’s Health Platform, PriMed, AiCME, MedAll, Medscape, Weight Watchers. C. Shufelt: Bayer Advisory Board. M.D. Hurtado: Novo Nordisk, National Institute of Health, Phenomix Sciences. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular (CV) benefits. Tirzepatide (TZP), a dual GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist approved for weight management and glycemic control, currently lacks evidence on CV outcomes. This study evaluates TZP’s impact on cardiometabolic parameters and atherosclerotic cardiovascular disease (ASCVD) risk scores. Methods: We conducted a multicenter retrospective study of adults prescribed TZP from June 1, 2022, to November 1, 2024. Inclusion criteria included 12 months of TZP use and age >18 years. Exclusion criteria were pregnancy, active malignancy, concurrent FDA-approved antiobesity medications, and prior bariatric surgery. Endpoints included changes in blood pressure, lipid profiles, liver enzymes, glucose control parameters, medication use (statins, aspirin, antihypertensives), and ASCVD risk scores from baseline to 12 months, stratified by sex. Data were obtained from electronic medical records. We present data as mean differences [95% CI]. We used T-tests and multivariate regression analyses for analyses. Results: Among 831 participants (59.4% female; 91.2% White; mean age: 58 ± 12 years), 12-month weight loss was -12% [-13, -11], p<0.001. We observed significant improvement in systolic blood pressure (SBP) (-4 [-5, -3] mmHg, p<0.001), triglycerides (TG) (-38 [-52, -23] mg/dL, p<0.001), total cholesterol (TC) (-7 [-10, -4] mg/dL, p<0.001), LDL cholesterol (LDL) (-6 [-9, -4] mg/dL, p<0.001), fasting glucose (FG) (-39 [-48, -29] mg/dL, p<0.001), ALT (-10 [-15, -5] U/L, p<0.001), HbA1c (-1.3% [-1.5, -1.2], p<0.001), and HDL cholesterol (HDL) (+4 [+3, +5] mg/dL, p<0.001). The Lifetime and 10-year ASCVD scores did not significantly change after 12 months (p>0.05), underscoring TZP’s potential in mitigating the aging-associated increase in CV risk. Considering sex, females had greater weight loss (-13% [-14, -12] vs. -10% [-11, -9], p<0.001), and greater improvements in TC (-5% [-8, -2] vs -3% [-6, 0.1], p<0.001) and LDL (-10% [-14, -6] vs -4% [-8, 1], p<0.001). Males had a greater reduction in DBP (-2% [-4, -1] vs (-1% [-6, 3], p=0.006). Both males and females demonstrated similar improvements in FG and HbA1c. Conclusion: TZP significantly improved CV and metabolic parameters after 12 months, with greater benefits observed in females. These improvements effectively mitigated the age-related rise in ASCVD risk scores. Larger, prospective studies are warranted to confirm these findings and further investigate TZP’s long-term CV effects. Presentation: Monday, July 14, 2025

Objective: To evaluate whether effects of oral hormone therapy (HT) on risks of venous and arterial vascular events differ by baseline statin or aspirin use. Methods: We performed time-to-event analysis using data from the Women’s Health Initiative menopausal HT randomized trials to assess risk of thrombotic events. Women were randomized to oral conjugated equine estrogens (CEEs) alone or placebo among women with prior hysterectomy (n = 10,739), and CEE with medroxyprogesterone acetate (MPA) or placebo among women with an intact uterus (n = 16,608), stratified by baseline personal use of statins and aspirin. We evaluated risk of prespecified, adjudicated thrombotic events, including coronary heart disease, stroke, venous thromboembolism, and/or composite major adverse cardiovascular events, at 2 and 5 years. Results: Baseline statin use (n = 827 in CEE-alone trial; n = 1,115 in CEE+MPA trial) or aspirin use (n = 2,212; n = 3,431) was limited. At 5-year follow-up, coronary heart disease risk for CEE-alone versus placebo was hazard ratio (HR) = 0.81 (95% CI: 0.44-1.49) in statin users, similar to nonusers, HR = 1.07 (95% CI: 0.82-1.40). For CEE+MPA, there was also no difference by statin use, HR = 1.02 (95% CI: 0.55-1.89) and HR = 1.47 (95% CI: 1.13-1.90), respectively. Neither statin nor aspirin exposure significantly modified effects of HT on any arterial or venous thrombotic outcome at 2 or 5 years. Conclusions: In this secondary randomized clinical trial analysis, neither statins nor aspirin significantly modified effects of oral HT on key arterial or venous thrombotic outcomes at 2 or 5 years. Results, however, may be underpowered given low baseline exposure prevalence for both statins and aspirin.

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.

Objective: To compare the prevalence of female sexual dysfunction (FSD) and distress between sexually active midlife women (50-64 y) and older women (65+ y) presenting for care at women’s health clinics at a tertiary care center. Methods: This cross-sectional study included women aged 50 and above who received care at Mayo Clinic women’s health clinics in Rochester, MN; Scottsdale, AZ; and Jacksonville, FL, between May 1, 2015, and August 31, 2022. Sexual function and distress were compared between midlife and older women using the Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and self-reported sexual health concerns. Results: Among 3,465 sexually active women, older women were less likely to report loss of sexual desire (33.4% vs. 47.6%; P <0.001) and reduced genital sensation (13.0% vs. 16.9%; P =0.024) compared with midlife women. There were no significant differences for vaginal dryness, painful intercourse, or arousal/orgasm difficulties. FSFI scores were higher in older women for desire (3.0 vs. 2.4; P <0.001) and lubrication (3.9 vs. 3.6; P <0.001). While total FSFI scores were similar between older and midlife women (21.2 vs. 22.2; P =0.11), sexually related distress was lower in older women compared with midlife women (13.0 vs. 15.0; P =0.015). The prevalence of FSD (defined as FSFI score ≤26.55 and FSDS-R score ≥11) was similar between groups (51.8% vs. 56.2%; P =0.056). Conclusions: Older women experienced FSD at similar rates as midlife women but reported less sexual distress, potentially reflecting lower expectations regarding sexual function. Addressing sexual health concerns in older women may enhance quality of life.

Abstract Objective Perimenopause is an under-recognized transition poorly measured by existing tools, which often overlook symptoms characteristic of this phase. To address this, we developed and validated the Perimenopause Symptom Scale (Peri-SS): a concise, phase-specific, psychometrically robust instrument for digital self-assessment and research use among U.S. women aged 35-59 who self-reported in perimenopause. Methods We conducted a longitudinal validation study with 1,255 U.S. women aged 35-59 (633 identified as perimenopausal) recruited via Prolific. Participants completed the Peri-SS, Menopause Rating Scale (MRS), and EuroQol 5-Dimension, 5-Level (EQ-5D-5L) at baseline and 7-14 days later. Following COSMIN guidelines, we assessed structural validity, internal consistency, test-retest reliability, criterion and construct validity, and responsiveness to change. Results The Peri-SS demonstrated strong psychometric performance. Confirmatory factor analysis confirmed a four-domain structure (vasomotor, psychological, sexual, physical), with excellent model fit (CFI = 0.932, RMSEA = 0.069). Internal consistency was excellent (α = 0.90 overall; domain range 0.73-0.86), and test-retest reliability was high (ICC = 0.82). Criterion validity was strong, with Peri-SS scores highly correlated with MRS (r = 0.88). Construct validity was supported through moderate correlations with EQ-5D-5L utilities (ρ = -0.50) and effective discrimination between groups by age, menopausal status, and hormone therapy use. The scale was also responsive to symptom changes over time (η² = 0.277). Conclusions The Peri-SS is a reliable, valid, responsive tool for assessing perimenopausal symptom burden. Its concise format and strong psychometric performance make it well-suited for research, clinical care, and digital health applications. Two sentence summary The Perimenopause Symptom Scale (Peri-SS) is a novel 16-item instrument developed to measure symptom burden during perimenopause across four domains. In a validation study among U.S. women aged 35-59 years, the Peri-SS demonstrated strong reliability, validity, and responsiveness, supporting its use in research, clinical care, and digital health settings.

Abstract Context Endothelial dysfunction and altered psychological measures have been identified in women with functional hypothalamic amenorrhea (FHA). Estradiol (E2) replacement, a known vasodilator, may potentially reverse vascular dysfunction and improve psychological health. Objective To evaluate 12 weeks of physiologic E2 replacement on vascular, hormonal, and psychological outcomes in women with FHA. Methods A randomized, double-blind, placebo-controlled trial was conducted in 29 women with FHA with 0.1 mg/day transdermal E2 (n = 14) or placebo patch (n = 15) twice weekly for 12 weeks. FHA was defined as amenorrhea ≥3 consecutive months, E2 &lt; 50 pg/mL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) &lt;10 mIU/L, LH:FSH &lt;1, excluding other etiologies. Endothelial dysfunction (reactive hyperemic index ≤ 1.67) was assessed, as were hormonal and psychological measures. Results Women with FHA had a mean age of 26.2 ± 6.3 years, body mass index of 21.5 ± 3.3 kg/m2, with 63% being non-Hispanic White. Baseline characteristics did not differ between groups. After 12 weeks, E2 levels were significantly higher in the E2 group (112.0 vs 36.5 pg/mL, P = .0002). However, there were no significant differences in vascular, hormonal, or psychological outcomes between E2 and placebo groups at week 12. Cortisol levels showed a near-significant decrease in the E2 group compared to an increase with placebo (−.4 vs 3.1 µg/dL, P = .05). Conclusion In women with FHA, 12 weeks of transdermal E2 increased serum E2 levels but did not improve vascular or psychological health measures. Further studies with larger sample sizes and longer follow-up are needed to explore the long-term effects of E2 therapy on cardiovascular and mental health outcomes in this population.

1530 Background: Regular breast cancer screening reduces mortality. The American College of Radiology (ACR) recommends annual screening mammography for asymptomatic, average risk 1) transgender and gender diverse (TGD) men (individuals assigned female sex at birth but identify as men) age 40+ and with residual breast tissue and 2) TGD women (individuals assigned male sex at birth but identify as women) age 40+ and on gender-affirming hormone therapy for 5+ years. This nationwide study investigated screening mammography in TGD individuals. Methods: Four cohorts were identified with complex algorithms of medical and pharmacy data in the OptumLabs Data Warehouse, a longitudinal, administrative insurance claims database that includes patients with commercial insurance and Medicare Advantage: 1) TGD men, 2) TGD women, 3) individuals with gender dysphoria not meeting other TGD criteria (NMOT), and 4) cisgender women -- all of whom met ACR screening criteria. The primary endpoint was the percentage of individuals with high adherence, defined as completing >75% of recommended screenings; comparisons were made across the cohorts (Chi-square test). Multivariable logistic regression was used to compare adherence between TGD men and cisgender women with adjustment for demographics and with 1:4 matching (on race/ethnicity, age group, year of healthcare plan enrollment, and duration of follow-up). Results: 10,478 TGD individuals (3,778 TGD men; 1,294 TGD women; and 5,406 with gender dysphoria NMOT) and 6,218,369 cisgender women were identified. For TGD men, TGD women, individuals with gender dysphoria NMOT, and cisgender women, high adherence was observed in 41.1% (95% confidence interval (CI): 39.5, 42.6%); 7.4% (95% CI: 6.0, 8.8%); 11.9% (95% CI: 11.0, 12.7%); and 38.3% (95% CI: 38.3, 38.4%), respectively, p < 0.0001. No screening ever in these same populations was observed in 23.6% (95% CI: 22.2, 24.9%); 81.3% (95% CI: 79.2, 83.4%), 72.8% (95% CI: 71.6, 74%), and 35.9% (95% CI: 35.8, 35.9%), respectively, p < 0.0001. When TGD men were matched and compared to 15,112 cisgender women, a differential association was observed between gender and high adherence by age group (p < 0.0001); compared to cisgender women, the likelihood of high adherence in TGD men ages 40-49 (n = 2,472), 50-59 (n = 852), 60-69 (n = 320), and 70+ (n = 134) were as follows: odds ratios (OR‘s): 1.38 (95% CI: 1.28, 1.50), p < 0.0001; 1.57 (95% CI: 1.35, 1.81), p < 0.0001; 0.812 (95% CI: 0.619, 1.065), p = 0.1316; and 1.277 (95% CI 0.835, 1.951), p = 0.2595, respectively. Conclusions: This study found that TGD men manifest relatively high adherence to screening mammography, whereas TGD women and individuals with gender dysphoria NMOT manifest low adherence. Future research should focus on improving breast cancer screening in these underserved populations.