Shufelt, Chrisandra

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 < 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 < 0.001), lubrication (3.9 vs. 3.6; p < 0.001), and pain (4.8 vs. 4.0; p < 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.

Importance and Objective: Menopause is the natural cessation of ovarian function, typically occurring at a mean age of 52 years in the United States. Vasomotor symptoms (VMS; hot flashes and night sweats) affect over 75% of midlife women and typically last 7 to 9 years, with only 54% seeking medical attention. Although hormone therapy is the most effective treatment for VMS, <4% of women currently use it, primarily due to safety concerns. There is evidence that cognitive behavioral therapy (CBT) is an effective management strategy for VMS. Virtual reality (VR) has shown promise in delivering an immersive form of CBT for various medical conditions, including acute and chronic pain, sleep, and mood disorders, potentially overcoming barriers such as access and cost while improving quality of life. This narrative review aims to summarize the existing literature on VR for managing menopause symptoms. Methods: A comprehensive literature review was conducted through PubMed and Medline databases. The search focused on keyword combinations related to VR, artificial intelligence, and menopause symptoms. Discussion and Conclusion: The search yielded one study specifically targeting symptoms related to menopause. A pilot study (n = 42) evaluating an immersive VR and artificial intelligence intervention based on CBT and mindfulness techniques for managing hot flashes in women with breast or ovarian cancer demonstrated a significant reduction in frequency of hot flashes ( P < 0.01) and improvements in sleep quality, mood, anxiety, stress, and overall quality of life. However, these women experienced hot flashes that might have been associated with their cancer diagnosis or treatment rather than relating specifically to menopause, potentially limiting the generalizability of the findings to women with menopause symptoms. Although VR has shown effectiveness in delivering CBT for other conditions, there remains a significant gap in research on its specific use for menopause-related symptoms.

Abstract Objective Metabolic dysfunction–associated steatotic liver disease (MASLD) and vasomotor symptoms (VMS) are associated with increased cardiovascular disease risk. Although visceral adiposity has been linked to MASLD and VMS independently, this study aimed to evaluate associations between the two in midlife women. Methods A cross-sectional study of women aged 45-60 years receiving primary care at one of four sites was conducted from March 1 through June 30, 2021. MASLD diagnosis was obtained utilizing the International Classification of Diseases , Ninth Revision and Tenth Revision codes. VMS burden was evaluated with the Menopause Rating Scale and categorized as severe/very severe versus none/mild/moderate. Logistic regression models were used to assess the association between VMS and diagnosed MASLD both univariately and after individually adjusting for several risk factors. Results A total of 4,599 women were included in the final analysis, 304 (7%) of whom had an MASLD diagnosis. On univariate analysis, women with an MASLD diagnosis were more likely to have severe/very severe VMS (odds ratio [OR], 1.50; 95% CI, 1.08-2.08; P = 0.015). However, the association between MASLD diagnosis and severe/very severe VMS was no longer statistically significant after individually adjusting for body mass index (adjusted OR, 1.36; 95% CI, 0.97-1.92) and hypertension (adjusted OR, 1.38; 95% CI, 0.99-1.93). Conclusions The relationship between MASLD and VMS appears to be best explained by other variables including BMI and hypertension. Although they do not appear to be directly linked, given the prevalence of bothersome VMS in midlife women, addressing VMS may enable greater adherence to lifestyle modifications as part of MASLD management.

Abstract Objectives Patients with hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD. Methods In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. Results From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities. Conclusion Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.

Abstract Background Adverse pregnancy outcomes (APO) are associated with increased maternal risk of cardiovascular disease (CVD) and mortality. Ischemia with no obstructive coronary artery disease (INOCA) is predominant in women, however the association of APO history with INOCA is poorly understood. Purpose To compare clinical characteristics, symptoms, cardiac structure and function and coronary microvascular dysfunction in women suspected to have INOCA with or without a history of APO. Methods Women’s Ischemia Syndrome Evaluation (WISE) CVD (NCT00832702) and WISE pre-HFpEF (NCT02582021) prospective cohorts of women with suspected INOCA were merged and utilized to determine among women with at least 1 prior pregnancy whether a history of APO was associated with ischemic symptoms, and to characterize CMRI measured left ventricle (LV) structure and function, myocardial deformation (systolic and diastolic strain) and coronary microvascular dysfunction on invasive coronary functional testing (CFT). Self-reported APO was defined as hypertensive disorder of pregnancy (HDP), gestational diabetes, preterm birth (&lt;37-week gestation), low birth weight (&lt;5lbs). Results In a cohort of 469 women with suspected INOCA, (mean average age 55 [SD 10.2] years) and at least 1 prior pregnancy, 138 (29%) had history of at least 1 APO. Among women with history of APO, 78 reported HDP, 50 gestational diabetes, 27 pre-term birth, 8 low birth weight. Women with a history of APO were younger, had higher rates of hypertension and diabetes, higher BMI and lower SAQ and DASI scores compared to those with no history of APO (Table). LV ejection fraction (EF) was lower and early diastolic strain rate/LVEDP was higher in women with APO history compared to those without APO history. Conclusion(s) In cohort of women with INOCA, history of APO was highly prevalent. Despite younger age, women with history of APO had higher rates of CVD risk factors, worse ischemic symptoms and functional capacity, lower EF, and higher filling pressures. Our findings suggest a potential for APO history to better identify women with worse prognosis that warrants further investigation and aggressive management.

Abstract Disclosure: N. Safwan: None. E.R. Uddenberg: None. M.D. Hurtado: None. M. Saadedine: None. S.S. Faubion: None. O. Obrutu: None. S.L. Berga: None. M.D. Pisarska: None. C. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea due to suppression of GnRH associated hypercortisolemia resulting in chronic hypoestrogenemia. FHA occurs as a result of varying combinations of psychosocial stress, excessive exercise, and/or disordered eating. FHA is associated with decreased bone mineralization; however, it is unknown how bone health compares to older, menopausal women who also experience bone loss. We compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women and evaluated if previous oral contraceptive (OC) use among FHA women has an impact on bone mineral density (BMD). Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. All participants were not on hormone therapy. FHA was defined as amenorrhea &gt;3 consecutive months, estradiol &lt;50 pg/ml, FSH &lt;10 mIU/L, and LH &lt;10 mIU/L, excluding other etiologies including PCOS, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menses confirmed with day 22-24 progesterone &gt;3 ng/ml. Recently menopausal women had natural menopause &lt;3 years of final menstrual period, and FSH &gt;30 mIU/L. DXA bone health parameters were measured using Lunar iDXA (GE) including BMD from the lumbar spine (L1-L4) and hip. Statistical analysis included nonparametric testing with pairwise Wilcoxon rank sum and Kruskal Wallis, reported as median [interquartile ranges]. Results: By design, the mean age of FHA was 28 ± 6 yr, 29 ± 3 yr for controls, and 54 ± 2 yr for recently menopausal women (p&lt;0.0001). There were no differences in weight or BMI among the groups (p=0.27, p=0.30, respectively). BMD L1-L4 differed among the three groups with 1.10 g/cm2 [1.00, 1.24] for FHA, 1.18 [1.15, 1.29] for eumenorrheic controls, and 1.02 [0.96, 1.08] for menopausal women (p=0.002). Pairwise analysis revealed a significant difference in BMD L1-L4 between FHA and controls (p=0.04) and menopausal women and controls (p=0.009, age-adjusted). However, there was no difference in BMD L1-L4 between FHA and menopausal women (p=0.08, age-adjusted). In FHA women with previous OC use, BMD L1-L4 was not different from eumenorrheic controls (p=0.20), while BMD L1-L4 differed from that of recently menopausal women (p=0.004). These differences were not observed at the hip. Conclusion: Compared to eumenorrheic controls, lumbar spine BMD in young women with FHA (mean age 28 yr) was similar to recently menopausal women (mean age 54 yr) emphasizing the profound bone impact of FHA. Previous OC use seems to mitigate FHA bone mineralization changes. Future studies should investigate if bone health differs among women with FHA based on underlying cause and if previous OC use plays a role in maintaining bone health. Presentation: 6/3/2024

Abstract Disclosure: M.D. Hurtado: None. E. Tama: None. D. Hodge: None. A. Weston: None. S. Fahad: None. K. Ruddy: None. J. Olson: None. F. Coach: None. R. Carter: None. S. D'Andre: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. Background: Breast cancer (BC) is the most common cancer in women. Weight gain after treatment for early-stage BC is associated with a higher risk of recurrence. Excess adiposity is also a major risk factor for cardiovascular disease, the leading cause of non-BC related death in BC survivors. This study aimed to describe weight trends in a large cohort of BC survivors and to identify predictors of weight gain after BC diagnosis. Methods: This was a retrospective study of BC survivors from the prospectively consented Mayo Clinic Breast Cancer Registry, which has enrolled &gt;10,000 patients seen at least once at Mayo Clinic Rochester for a BC diagnosed within the prior year. We extracted data on weights at baseline, and years 1, 4, and 6 after BC diagnosis to generate longitudinal weight trajectory curves on the change from baseline. Weights were either reported by patients in the registry questionnaires or extracted from the electronic health records. We identified BC survivors with weight gain &gt;10% from baseline weight at years 1, 4, and 6. We then conducted univariable logistic regression analyses to identify predictors of &gt;10% weight gain. Variables considered included: demographics, anthropometrics, BC clinical and pathologic characteristics, BRCA 1 and 2 genetic mutation status, and treatment (surgery, neoadjuvant or adjuvant chemotherapy, and/or radiotherapy). Results: We included 4744 BC survivors, mostly white (95%) and non-Hispanic (91%), with a mean age and weight at BC diagnosis of 58 ± 13 years and 76 ± 18 kg. Most patients had clinical stage I (43%) and ER+ and PR+ BC (83% and 76%, respectively). Most patients underwent breast preserving surgery (62%), half received radiation (54%), one third (36%) received systemic chemotherapy, and two thirds (61%) received endocrine therapy. At one year after BC diagnosis the average weight change was negligible compared to baseline (mean difference -0.2 ± 8 kg), but there were small but significant average increases by years 4 and 6 (0.5 ± 9 kg, p=0.002; and 0.8 ± 10 kg, p&lt;0.001; respectively). At years 1, 4, and 6, the percentage of BC survivors gaining &gt;10% of their baseline weight was 10%, 15%, and 18%, respectively. Baseline characteristics associated with &gt;10% weight gain at 6 years included lower baseline weight (p&lt;0.001), younger age at BC diagnosis (p&lt;0.001), more advanced clinical and pathologic BC stage (p=0.008), ER+ and PR+ tumor biology (p=0.02 for both), BRCA2 mutation (p&lt;0.001), mastectomy (compared to breast preserving surgeries, p=0.008), the use of systemic chemotherapy treatment (p&lt;0.001), and the use of endocrine therapy (p=0.03). Conclusion: While most BC survivors do not experience weight gain after survivorship, 1 out 5 may experience excessive weight gain of more than 10%. Baseline anthropometric and BC-related variables are associated with excessive weight gain and could be used as predictors of weight gain in this population. Presentation: 6/3/2024

Abstract Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a common form of secondary amenorrhea that results in hypoestrogenemia and hypercortisolemia. The underlying cause of FHA is due to a mismatch between energetic intake and expenditure that often manifests as disordered eating, excessive exercise, and psychosocial stress. Previous research identified that 1 in 3 women with FHA had endothelial dysfunction, a preclinical marker for cardiovascular disease. We sought to evaluate the nutrition content in young women with FHA compared to eumenorrheic controls and further assess the relationship to endothelial dysfunction. Methods: We enrolled 30 women with FHA and 29 eumenorrheic controls, not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol &lt;50 pg/mL, FSH&lt;10 mIU/L, and LH&lt;10 mIU/L, and exclusion of polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Eumenorrheic controls had monthly menses with ovulation (progesterone ≥4 ng/mL). Vascular function was measured using EndoPAT 2000 (Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI). An RHI ≤1.67 indicates endothelial dysfunction. Nutritional intake was collected using a 3-day food diary and analyzed using ESHA Research Food Processor® Nutrition Analysis. Percent (%) recommendation values for nutrition content comparison were calculated based on height, weight, and age. Statistical analysis included Analysis of Variance and Kruskal Wallis test with nonparametric variables reported as median [IQR]. Results: The mean age and BMI of FHA and controls were 26.4 ± 6.2 yrs and 30.3 ± 3.7 yrs (p=0.008), and 21.6 ± 6.2 and 21.8 ± 2.0 kg/m2 (p=0.16), respectively. The median months of FHA amenorrhea was 12 months [5.0, 34.0]. After adjusting for age, there was no difference in caloric intakes in women with FHA compared to controls (1783.9 [1465, 2011] kcal vs. 1731.9 [1578, 1982] kcal, p=0.73); however FHA has higher intake of grams of protein (84.2 [74, 112] g vs. 74 [59, 92] g, p=0.0036), and higher grams of dietary fiber (30.1 [22, 43] g vs. 17.3 [15, 23] g, p=0.0037), respectively. In women with FHA, endothelial dysfunction was associated with a higher % recommended calories (p=0.0098), calories from fat (p=0.02), grams of saturated fat (p=0.03), and grams of carbohydrates (p=0.049). Conclusions: Our results demonstrate that women with FHA consumed similar daily calories, although more grams of protein and dietary fiber than controls. In women with FHA, higher calories, calories from fat, grams of saturated fat and carbohydrates were associated with endothelial dysfunction. Future studies should aim to identify other factors related to endothelial dysfunction among women with FHA and whether some FHA phenotypes are associated with more endothelial dysfunction than others. Presentation: 6/1/2024