Faubion, Stephanie S

Objectives: Psychological health changes are known to occur during perimenopause, but the extent to which these differ from premenopause remains unclear. This study aimed to assess psychological symptoms during perimenopause compared with premenopause and evaluate differences by country. Methods: Flo app users aged 35 years or above not taking hormonal contraception or hormone therapy were included. The psychological domain of the Menopause Rating Scale (range 0-16) and symptoms within this domain of depressive mood, irritability, anxiety, and exhaustion (range 0-4 each) were evaluated. Participants in perimenopause were compared with those in premenopause (self-reported not in perimenopause or postmenopause). Results: A total of 7,975 women were included, with 2,353 in perimenopause (mean age 45 years [SD±4.5]) and 5,622 in premenopause (39 y [SD±4.0]). Psychological Menopause Rating Scale scores in the perimenopause group were significantly higher (7.3 [SD±3.56]) than in the premenopause group (4.8 [SD±3.56]; P <0.001). The individual symptoms of depressive mood, irritability, anxiety, and exhaustion were also higher in the perimenopause group ( P <0.001, for all respectively), with the largest difference being exhaustion. These findings remained after adjusting for known confounders, including an existing diagnosis of anxiety or depression. Geographic analysis included 20 countries across 6 continents, with significant differences identified between countries for the overall psychological symptom domain score and all individual symptoms. Conclusion: Significantly greater psychological symptom burden was identified in the perimenopause group compared with the premenopause group, with the greatest difference noted for the individual symptom of exhaustion. Differences in symptom burden were also identified by country.

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.

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.