Faubion, Stephanie S.

Abstract Objective To compare weight loss response and changes in cardiometabolic risk markers in postmenopausal women using semaglutide with and without menopause hormone therapy (HT) use. Methods Retrospective cohort study of postmenopausal women treated with semaglutide for overweight or obesity for ≥3 months. Endpoints: total body weight loss percentage (TBWL%) at 3, 6, 9, and 12 months after semaglutide initiation; and percentage of women achieving ≥5% and ≥10% TBWL and changes in cardiometabolic risk markers (glucose, blood pressure, and lipids) at 12 months. Results There were 16 women on HT and 90 on no-HT; mean age 56 ± 8 vs 59 ± 8 yr, P = 0.2 and mean BMI 36 ± 5 vs 39 ± 8 kg/m2, P = 0.1; respectively. Among women on no-HT, White race, dyslipidemia, and depression were more prevalent. Women on HT had a higher TBWL% at 3, 6, 9, and 12 months: 7 ± 3% vs 5 ± 4%, P = 0.01; 13 ± 6% vs 9 ± 5%, P = 0.01; 15 ± 6% vs 10 ± 6%, P = 0.02; and 16 ± 6% vs 12 ± 8%, P = 0.04; respectively. After adjusting for potential confounders, this association remained significant across time. At 12 months, a greater percentage of women on HT achieved ≥5% and ≥10% TBWL. Both groups experienced an improvement in cardiometabolic risk markers. Conclusion In postmenopausal women with overweight or obesity treated with semaglutide, HT use was associated with an improved weight loss response. This association was maintained when adjusted for confounders. Larger studies should be conducted to confirm these results.

Abstract Introduction Obesity is a global health crisis that has been growing over the past few decades. The economic burden associated with obesity is substantial as it is associated with multiple disabling chronic diseases, such as cardiovascular disease, certain cancers, osteoarthritis, chronic pain, and mental illness. Obesity is known to be a risk factor for sexual dysfunction in men, but this association is less well understood in women. Aims To provide a narrative review of the available literature on the relationship between overweight/obesity and female sexual dysfunction, elaborate on the possible mechanisms explaining this association, and discuss the effects of weight loss on sexual function in those with obesity. Methods A search of the medical literature was carried out in PubMed and Medline, focusing on original research and systematic reviews of original research on obesity and sexual function in women. Results The relationship between obesity and female sexual function is not consistent across studies. While women with obesity are more likely to have worse sexual function and avoid sexual activity, many studies have failed to identify these associations. Lifestyle changes resulting in weight loss lead to better sexual function, and bariatric surgery has been shown to improve sexual function in the first couple of years following the procedure; yet, the long-term effects of weight loss and bariatric surgery are still uncertain. Conclusions The evidence on the relationship between obesity and female sexual function is mixed. Nevertheless, weight loss has been shown to improve sexual function in women with obesity. The impact of weight loss medications and the long-term effect of bariatric surgery on female sexual function require further study.

Abstract Disclosure: S. Fansa: None. W. Ghusn: None. E. Tama: None. B. Nicolalde: None. D. Anazco: None. S. D'Andre: None. S. Faubion: None. C. Shufelt: None. A. Acosta: None. M.D. Hurtado: None. Background: Aromatase inhibitors (AIs) block estrogen synthesis and are used as adjuvant treatment for breast cancer. AIs are associated with weight gain that can lead to increased cardiometabolic risk, thereby affecting health and survivorship quality in these patients. The role of anti-obesity medications (AOMs) in patients using AIs has not been studied. We sought to investigate weight loss outcomes to AOMs in patients taking AIs for breast cancer treatment. Methods: This is a matched case-control retrospective cohort study of breast cancer survivors on AI using FDA-approved AOMs (AI/AOM group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOMs (AOM group). We matched patients by age and body mass index (BMI). Exclusion criteria: AOM initiation prior to AI therapy, ≤3 months of AOM use, history of bariatric surgery, active malignancy, or pregnancy. Primary endpoint: total body weight loss % (TBWL%) at 12 months. Secondary endpoints: TBWL% at 3 and 6 months and % of patients achieving categorical TBWL ≥5%, ≥10% and ≥15% at 12 months. We used Pearson χ2 and unpaired t-test to compare baseline characteristics and outcomes between groups, and univariate analyses to estimate the contribution of variables to TBWL% in the AI/AOM group. We present results as mean ± standard deviation. Results: We included 99 patients: 63 in the AI/AOM group (63.5±10 years, BMI 34.4±7.0 kg/m2) and 36 in the AOM group (60.4±8.7 years, BMI 36.3±6.9 kg/m2). Liraglutide, semaglutide and phentermine were the only AOMs used. There was no difference in the frequency of use of these three AOMs among both groups (p= 0.1). AI/AOM group had a lower TBWL% compared to the AOM group during follow-up: 3.7± 4.3% vs. 5.6 ± 4.1% (p= 0.03) at 3 months, 3.9± 4.3% vs. 9.5± 4.7% (p< 0.0001) at 6 months, and 5.2± 5.3% vs. 10.5± 6.8% (p< 0.0001) at 12 months. Although the AI/AOM group was more likely to use lower doses of AOMs (p= 0.0004), TBWL% differences persisted among groups at 12 months after adjusting for AOM dosing (p< 0.0001). There was no difference in nutritional and behavioral modification sessions among groups (p=0.06 and p=0.9, respectively). At 12 months, the percentage of patients achieving ≥5%, ≥10%, and ≥15% TBWL was greater in the AOM group compared to the AI/AOM group: ≥5% TBWL, 85.7% vs. 50.0% (p< 0.0001); ≥10%, 57.1 vs. 20.0% (p< 0.0001); and ≥15%, 28.6 vs. 5.0% (p< 0.0001); respectively. We found no predictors of TBWL% at 12 months in the AI/AOM group. Conclusion: Weight loss outcomes in breast cancer survivors on AIs taking AOMs are poorer compared to patients without breast cancer history and not taking AIs. Studies are needed to assess the mechanisms behind the different weight loss response to AOMs in women taking AIs, which we hypothesize may relate to AIs’ anti-estrogenic effect on lean and fat mass. Presentation: Friday, June 16, 2023

Abstract Objective Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause. Methods This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders. Results A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, −3.2 to 0.6; P = 0.18). Conclusions Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.

AbstractBackgroundInfertility has been linked with an increased risk of sexual dysfunction in reproductive-aged women, with longer periods of infertility associated with a greater risk.AimThe study’s aim was to examine whether a history of infertility treatment in women is linked to sexual dysfunction during midlife.MethodsThe cross-sectional study was conducted among sexually active women, between the ages of 45 and 65 years, who sought consultation at the women’s health clinics at a US tertiary care center. History of infertility treatment was assessed with a single question that asked participants if they were treated for infertility in the past. The association between a history of infertility treatment and sexual dysfunction—which was diagnosed by a combination of Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale–Revised score ≥11—was assessed in a multivariable logistic regression model that adjusted for multiple confounders.OutcomesThe primary outcome was sexual dysfunction in midlife women.ResultsThe analysis included 5912 women, with a mean age of 54.1 years. Nearly 16% of women reported receiving treatment for infertility. More than half the women (55%) had sexual dysfunction: 56.3% of those with previous fertility treatments and 54.4% of those without any fertility treatment (P = .3). Receiving treatment for infertility in the younger years did not significantly increase the odds of sexual dysfunction in midlife in univariate (odds ratio, 1.08; 95% CI, 0.94-1.24; P = .3) and multivariable analyses (odds ratio, 1.11; 95% CI, 0.96-1.29; P = .17).Clinical ImplicationsWhile infertility is known to be predictive of sexual dysfunction in women during their reproductive years, there was no association between a history of infertility treatment and sexual dysfunction in midlife women in the current study.Strengths and LimitationsThe study used validated questionnaires accounting for sexual complaints and distress and adjusted for multiple confounding factors. Limitations include the selection bias introduced by the study of women presenting for evaluation of sexual dysfunction, which may have been a result of factors stronger than the influence of infertility. Other limitations include the study’s cross-sectional nature with suboptimal racial and ethnic representation.ConclusionAlthough infertility is commonly associated with female sexual dysfunction in women of reproductive age, the association was not present in midlife women in the current study.

Abstract Importance and Objective Gastroesophageal reflux disease (GERD) is a chronic condition associated with several risk factors, but little is known about the association between hormone therapy (HT) and GERD in postmenopausal women. Evidence Review We investigated the association between ever or current menopausal HT use and GERD using a systematic review and meta-analysis. Studies published between 2008 and August 31, 2022, were pooled using a DerSimonian and Laird random-effects model, and outcomes were reported as adjusted odds ratios (aOR) with a corresponding 95% CI. Findings The pooled analysis of five studies found a significant direct association between estrogen use and GERD (aOR, 1.41; 95% CI, 1.16-1.66; I 2 = 97.6%), and progestogen use and GERD (two studies: aOR, 1.39; 95% CI, 1.15-1.64; I 2 = 0.0%). The use of combined HT was also associated with GERD (1.16; 95% CI, 1.00-1.33; I 2 = 87.9%). Overall, HT use was associated with 29% higher odds for GERD (aOR, 1.29; 95% CI, 1.17-1.42; I 2 = 94.8%). The large number of pooled participants, differences in study design, geography, patient characteristics, and outcome assessment resulted in significant high heterogeneity. Conclusions and Relevance There is a significant association between ever or current HT use and GERD. However, the results should be interpreted with caution, given the small number of included studies and high heterogeneity. This warrants careful evaluation of GERD risk factors when prescribing HT to reduce the risk of potential GERD complications.

Abstract Background One in 3 children has had at least 1 adverse childhood experience (ACE), and ACEs have been associated with multiple medical and psychiatric morbidities in women later in life, including greater menopause symptom burden. Aim To evaluate the association between ACEs and female sexual dysfunction (FSD) in midlife women. Methods A cross-sectional analysis from DREAMS—the Data Registry on Experiences of Aging, Menopause, and Sexuality—was conducted with questionnaires completed by women aged 40 to 65 years who presented to a women’s health clinic at Mayo Clinic in Rochester, Minnesota, from May 2015 to December 2016. History of ACEs was obtained with the validated ACE questionnaire. FSD was assessed by the Female Sexual Function Index and the Female Sexual Distress Scale–Revised. Outcomes The association between ACEs and FSD (defined as Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale–Revised score ≥11) was evaluated via a multivariable logistic regression model, adjusting for age, menopause status, hormone therapy use, anxiety, depression, relationship satisfaction, hot flash severity, and history of abuse in the past year. Results Women (N = 1572) had a mean age of 53.2 years. Overall 59% reported having at least 1 ACE. When compared with no ACEs, a history of ≥4 ACEs significantly increased the odds of not being sexually active (odds ratio, 1.83; 95% CI, 1.30-2.57; P < .001). Among sexually active women, the proportion of women with FSD increased sequentially as the number of ACEs increased. In the univariate analysis, a history of ≥4 ACEs significantly increased the odds of FSD as compared with no ACEs (odds ratio, 2.12; 95% CI, 1.50-2.99; P < .001). The association remained statistically significant in the multivariable analysis after adjusting for confounders (odds ratio, 1.75; 95% CI, 1.15-2.68; P = .009). Clinical Implications The findings highlight an opportunity for clinicians to screen for ACEs in women with sexual dysfunction and offer appropriate treatment and counseling as indicated. Strengths and Limitations Strengths of the study include the large cohort, the use of validated tools for assessment of ACEs and FSD, and the adjustment for multiple potential confounding factors. Limitations include the cross-sectional study design, recall bias in reporting ACEs and recent abuse, and the low representation of racially and ethnically diverse women in the cohort. Conclusion The study demonstrates an increased risk of sexual inactivity and sexual dysfunction in midlife women who experienced childhood adversity. The sexual dysfunction in women with ACEs seems to be independent of other factors that potentially affect female sexual function in midlife.