Shufelt, Chrisandra L

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.

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.

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.