Kapoor, Ekta

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.

Objectives: To investigate the association between hormone therapy use and severe outcomes due to COVID-19 in perimenopausal and postmenopausal women. Methods: Using the Rochester Epidemiology Project, we retrospectively searched for the records of women aged 40-65 years who had a documented case of COVID-19 between March 12 and September 29, 2020. We further identified those who were perimenopausal or postmenopausal. The rates of emergency department visits, hospitalizations, and deaths were compared by hormone therapy use. Logistic regression models were used to assess the odds of the combined outcome based on hormone therapy use. Results: Among the 689 patients included in this study, the median age was 56 years, and 77.5% were White. Compared with patients currently using hormone therapy, those with past/never use of hormone therapy were significantly older, had more risk factors for severe COVID-19, and had a higher incidence of diabetes. A total of 102 emergency department visits/hospitalizations/deaths occurred among both groups. Participants with current hormone therapy use had similar rates and risk of emergency department/hospitalization/death outcomes as those without hormone therapy, even after adjusting for age and severe COVID-19 risk factors. Conclusions: Severe COVID-19 outcomes were not significantly different between women with current versus past/never use of hormone therapy. Our study adds to the data suggesting no harm with hormone therapy use in women with severe symptoms of COVID-19.

Objective To study the reliability and validity of adverse childhood experiences (ACE) scores measured using a questionnaire versus abstraction of medical records, and to test whether the scores vary by history of bilateral oophorectomy, or by age and presence of anxiety or depressive symptoms at the time of questionnaire administration. Design The study involved a reliability component and a predictive validity component. Setting A population-based sample in Olmsted County, Minnesota, was derived from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Participants We included 198 women who underwent premenopausal bilateral oophorectomy for a non-malignant indication between 1988 and 2007 and 174 referent women of the same age randomly sampled from the general population (total of 372 women). At a later time (median of 22.7 years later), the women were contacted and invited to self-administer the ACE questionnaire during an inperson visit. Independent of the visit, their medical records were abstracted for ACE by a physician. Interventions Questionnaire and abstraction-based ACE scores. Main outcome measures Agreement between the two ACE scores (reliability; weighted kappa statistics) and comparison of incidence of multimorbidity in women with ACE scores ≥1 vs 0 (predictive validity; survival analyses). Data were analysed in March and April 2024. Results The 372 women in the study had a median age of 65 years at the time of ACE questionnaire self-administration (IQR, 62–69). Questionnaire-based ACE scores showed moderate agreement with abstracted ACE scores (weighted kappa 0.44 (95% CI 0.34 to 0.54)). The cut-off score of ACE ≥1 showed an overall fair agreement between the two scores (kappa 0.33 (95% CI 0.24 to 0.43)). A comparison of the cumulative incidence of multimorbidity in women with an ACE score ≥1 versus women with ACE score of 0 yielded a HR of 1.13 (95% CI 1.00 to 1.27) for abstracted ACE and 1.13 (95% CI 1.01 to 1.27) for questionnaire-based ACE. The best predictive validity was for ACE measured by both methods combined (either or) with a HR of 1.29 (95% CI 1.13 to 1.46). Conclusions and relevance Questionnaire-based ACE scores have moderate agreement with medical records abstracted ACE scores. However, both sets of ACE scores are predictive of the accumulation of multimorbidity at older age and should be considered complementary.

Objectives: To assess the long-term effects of 4 years of menopausal hormone therapy (mHT) on the brain’s white matter architecture in women who initiated mHT within 3 years of menopause onset. Methods: The Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, double-blind, randomized, placebo-controlled 4-year mHT trial with treatment arms of oral conjugated equine estrogens (oCEE), transdermal 17β-estradiol (tE2), and placebo in recently postmenopausal women. KEEPS Continuation was an observational follow-up of KEEPS participants. White matter integrity was evaluated in KEEPS Continuation participants 10 years after KEEPS completion using white matter hyperintensity volume, diffusion magnetic resonance imaging (dMRI) techniques, and cerebral infarcts. Linear regression models were fitted for each brain region to evaluate if there were differences in white matter between KEEPS treatment arms. Results: There was no evidence to suggest the long-term effects of 4 years of mHT on brain white matter in KEEPS Continuation participants [n=266, mean age 67 (58-73)]. No differences in dMRI metrics were found in each of the treatment arms (oCEE n=70; tE2 n=79) when compared to placebo (n=94), following a false discovery rate adjustment for multiple comparisons. There were no statistically significant differences in white matter hyperintensity volume or infarct occurrence when comparing each of the treatment arms to placebo. Conclusions: We found no evidence of the long-term effect of 4-year mHT on white matter integrity when compared to placebo, consistent with emerging evidence of the safety of short-term use of mHT in recently postmenopausal women.

Objective: To explore potential differences in physical activity and sedentary behavior volumes and patterns among postmenopausal women with and without premenopausal bilateral oophorectomy (PBO). Methods: Women with a history of PBO (n = 50) and age-matched postmenopausal referent women (n = 50) were recruited. Participants wore accelerometers on both ankles for 7 days. Volume metrics of sedentary behavior and physical activity, such as step counts, active time, and sedentary time, as well as the sedentary behavior and habitual physical activity distribution, and accumulation patterns, were quantified from the accelerometer data and compared between groups. Results: Metrics indicating volume of sedentary behavior and physical activity were not statistically different between groups. PBO was significantly associated with higher variability in stepping bout time ( P = 0.022), indicating a potentially more complex walking pattern. In addition, PBO was significantly associated with lower variability in sedentary break time ( P = 0.012), and lower activity time Gini index ( Z = −2.428, P = 0.015). This suggests that women with PBO may have broken up their sedentary time with shorter and less variable activity bouts, and because they had relatively shorter average daily active time, they might be at a higher risk of subsequent adverse health outcomes such as low bone mineral density. Conclusions: Although there were no differences in overall activity volume, some differences in activity patterns emerged between women with PBO and referent women. The study highlights the need for longitudinal research to understand how physical activity and sedentary behavior patterns evolve in postmenopausal women with a history of PBO.

Abstract Introduction Female sexual dysfunctions (FSDs) are prevalent yet underrecognized concerns among menopausal women, particularly those aged 65 and older. Age- and menopause-related sexual health issues often go unaddressed due to societal stigma and misconceptions, leading many women to attribute their symptoms to a normal part of aging. This perception limits diagnosis and treatment of conditions like hypoactive sexual desire disorder and genitourinary syndrome of menopause. Objective This study aims to compare sexual function and distress between women aged 50-64 and those aged 65 and older, with a focus on addressing critical knowledge gaps in sexual function among older women. Methods This cross-sectional study included women aged 50 and above who visited Mayo Clinic Women’s Health Clinics in Rochester, MN; Scottsdale, AZ; and Jacksonville, FL between, May 1, 2015, and August 31, 2022. Participants completed the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS-R), along with assessments of chief sexual health complaints, mood (PHQ-9), and anxiety (GAD-7) included in the Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS). Results Among 4900 women included in the analysis, the median number of sexual health complaints was 2.0 in midlife (50-64 yrs) and 1.0 in older (65+ yrs) age groups (p = 0.004). Chief complaints of loss of sexual desire (47.6% vs. 33.4%; p &lt; 0.001) and reduced genital sensation (16.9% vs. 13.0%; p = 0.024) were more common in the midlife age group. No significant differences were found in rates of complaints of vaginal dryness (51.2% vs. 52.5%; p = 0.57), painful intercourse (32.6% vs 30.7%; p = 0.38), or of difficulties with arousal or orgasm (24.0% vs 20.8%; p = 0.09). Midlife age women were also more likely to report pelvic pain (6.7% vs. 4.5%; p = 0.050), while older women reported more genital pain (8.1% vs. 5.8%; p = 0.038). FSFI scores indicated age-related differences in desire (2.4 vs. 3.0; p &lt; 0.001), lubrication (3.9 vs. 3.6; p &lt; 0.001), and pain (4.8 vs. 4.0; p &lt; 0.001), aligning with the chief complaints, while arousal (3.6, p = 0.890), orgasm (4.0, p = 0.926), and satisfaction (4.4, p = 0.346) scores were similar between groups. Total FSFI scores showed no significant difference between the age groups (total = 22.2 vs 21.2, p = 0.109). Median FSDS-R scores indicated higher distress in the midlife group (15.0 vs. 13.0; p = 0.015), while overall FSD prevalence (FSFI ≤26.55 and FSDS ≥11) was similar between groups (56.2% vs 51.8%; p = 0.056). Conclusions Midlife and older women were equally likely to experience FSD in women presenting to women’s health clinics, but older women reported less distress. These results are strikingly similar to previous research indicating that while older women have FSD, there is less distress associated with it. Raising awareness and promoting open dialogue can help older women recognize that their sexual health concerns are both valid and treatable, ultimately improving quality of life. Disclosure No.

Abstract The impact of early-life traumatic experiences on late-life morbidity remains partly unknown. We tested the hypothesis that adverse childhood experiences (ACE) and specifically abuse (physical, verbal or emotional, or sexual) experienced during childhood or early adulthood are associated with a higher rate of accumulation of multi-morbidity in women. Here we show strong evidence in support of the hypothesis. We studied 1,026 women aged 21–45 years randomly selected from the general population in Olmsted County, Minnesota and used the Rochester Epidemiology Project medical records-linkage system to measure the rate of development of 18 chronic conditions. The women had a median age of 41 years at inclusion in the study and were followed historically for a median of 21 years. Women with an ACE score ≥ 2 had higher incidence of 10 of the 18 chronic conditions considered separately and an accelerated accumulation of multi-morbidity measured as a score compared to women with ACE score 0. In addition, women exposed specifically to abuse in childhood or early adulthood had accelerated accumulation of multi-morbidity. We excluded the possible confounding effect of socioeconomic status and explored a series of possible mediation events or characteristics. We discuss several possible biological and social or behavioral mechanisms underlying these associations.

Abstract Objective To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations. Methods Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT. The associations between KEEPS baseline blood pressure (BP) with KEEPS continuation WMH volume were examined adjusting for covariates in model 1 (age, total intracranial volume, study site, mHT type) and model 2 (additionally conventional CVD risk factors). Interaction terms (BP × mHT type) were added into the linear regression models. Results The mean ± SD ages of participants were 53 (±2) years at KEEPS baseline and 67 (±2) years at KEEPS continuation. Elevated BP at KEEPS baseline was associated with greater WMH volume measured 14 years later (model 1: SBP: β = 0.01 [95% CI, 0.001‐0.01] and DBP: β = 0.01 [95% CI, 0.003‐0.03]) and after additionally adjusting for CVD risk factors (model 2). We did not find any evidence that mHT versus placebo modified these associations. Topographically, higher BP was associated with greater periventricular WMH in the frontal and parietal lobes. Conclusion Our findings suggest the importance of maintaining normal BP in recently postmenopausal women with low CVD risk, irrespective of short-term mHT usage, to potentially reduce the risk of WMH later in life.

Abstract INTRODUCTION Premenopausal bilateral oophorectomy (PBO) before the age of 46 years is associated with an increased risk of dementia. We investigated the long‐term effects of PBO performed before age 50 years on amyloid beta (Aβ), tau, and neurodegeneration imaging biomarkers of Alzheimer's disease (AD). METHODS Mayo Clinic Cohort Study of Oophorectomy and Aging‐2 participants were divided into early PBO (< 46 years; n = 61), and late PBO (46–49 years; n = 51) groups and were compared to referent women who did not undergo PBO ( n = 119). RESULTS Early PBO was associated with thinner entorhinal cortex ( p = 0.014), higher tau load at higher levels of Aβ load ( Pp = 0.005), higher Aβ load ( p = 0.026), and smaller temporal lobe cortical thickness ( p = 0.022), only at older ages compared to the referent group. DISCUSSION PBO before the age of 46 years is associated with entorhinal cortex thinning, elevated tau at higher Aβ levels, along with an AD‐like pattern of atrophy at older ages. CLINICAL TRIALS REGISTRATION NCT03821857 sex‐specific effects of endocrine disruption on aging and AD. Highlights Premenopausal bilateral oophorectomy (PBO) before the ages of 46 (early PBO) years and ages 46 to 49 (late PBO) years was studied. Early PBO was associated with reduced entorhinal cortex thickness later in life. Early PBO was associated with greater amyloid beta (Aβ) load at older ages. Early PBO was associated with greater Alzheimer's disease pattern of atrophy at older ages. Early PBO was associated with higher tau load at higher Aβ levels.

Abstract Objectives The aims of the study were to identify conditions diagnosed in at least 10% of midlife women living in the US upper midwest and to assess prevalence by age, race, ethnicity, and sociodemographic status. Methods The Rochester Epidemiology Project was used to conduct a cross-sectional prevalence study of 86,946 women between 40 and 59 years residing in a 27-county region of the United States on January 1, 2020. Diagnostic billing codes were extracted and grouped into broader condition categories using the Clinical Classification System Refined. The prevalence of 424 conditions was calculated by age, race, ethnicity, and area deprivation index quartiles. Logistic regression was used to examine associations between participant characteristics and conditions that affected 10% or more of the study population. Results Twenty-eight conditions affected ≥10% of women, and eight conditions increased by ≥45% between the ages of 40 and 59 (disorders of lipid metabolism, hypertension, sleep/wake disorders, thyroid disorders, esophageal disorders, osteoarthritis, tendon and synovial disorders, and menopausal disorders; all test for trend P < 0.01). Black women had a significantly higher prevalence of hypertension and esophageal disorders at all ages (adjusted P values <0.05). Women living in more deprived areas had a significantly higher prevalence of hyperlipidemia, hypertension, sleep/wake disorders, and esophageal disorders (adjusted P values <0.05). Women living in less deprived areas had a significantly higher prevalence of thyroid disorders at age 40 to 44 and menopausal disorders at ages 50 to 59 (adjusted P values <0.05). Conclusions These data suggest that additional attention should focus on Black women and women with a lower socioeconomic status to ensure that common midlife conditions are diagnosed and treated.