Winham, Stacey

Objectives: Sexual minority women (SMW) have worse mental and physical health outcomes compared with heterosexual women. Limited research has explored menopause in SMW. This study compared menopause symptoms in cisgender SMW and heterosexual women. Methods: This cross-sectional analysis examined questionnaires from women 40-65 years, seen at women’s health clinics in Arizona, Florida, and Minnesota between December 2016 and February 2023. Menopause symptoms were evaluated using the Menopause Rating Scale (MRS). An MRS score ≥ 12 indicates moderate or greater symptoms. Multivariable logistic regression was used to compare scores between cisgender SMW and heterosexual women, adjusting for factors that may impact menopause symptoms. Results: Data from 2,273 women were included, with 69 SMW. The mean age was 53.2 (SD: 6.1), body mass index 25.7 kg/m 2 , and a majority were White (91.9%). The median MRS score among all participants was 15 (interquartile range=10, 20); 67.3% reported MRS scores ≥ 12. The likelihood of being on hormone therapy or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors was comparable between groups. In both univariate (OR: 0.85, 95% CI: 0.52-1.40) and multivariable (OR: 0.83, 95% CI: 0.47-1.48) analyses, no significant associations between sexual orientation and MRS ≥ 12 were found. Conclusions: Menopause symptoms and likelihood of treatment were similar for cisgender SMW and heterosexual women presenting to tertiary care centers. Limited diversity in the cohort and the small number of SMW reduce the generalizability of the results. The lack of adverse social determinants of health may have contributed to the findings, but additional research in larger cohorts is needed.

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 Background Sexual minority women (SMW) have worse mental and physical health outcomes compared to heterosexual women, but literature on sexual function in SMW compared to heterosexual women is lacking. Aim To evaluate sexual function and sexual distress in women across sexual orientations. Method Questionnaire data were analyzed for women aged 18 and older who presented to women’s health clinics at Mayo Clinic in Minnesota, Arizona, and Florida from 2016 to 2023. Female Sexual Function Index (FSFI) and Female Sexual Distress Scale–Revised (FSDS-R) scores assessed sexual dysfunction (FSFI ≤ 26.55 and FSDS-R ≥ 11). Multivariable logistic models adjusted for confounding factors. Outcomes Our main outcome was female sexual dysfunction as defined by a composite of FSFI ≤ 26.55 and FSDS-R ≥ 11 to include both sexual function and sexual distress. Results Of 6241 sexually active women, 3% were SMW and 97% were heterosexual women. The majority were White (93%), with average age 51.6 years old. There was no significant difference in sexual dysfunction rates between heterosexual and SMW by combined endpoint on univariate or multivariable analysis. SMW had higher total FSDS scores (17 vs 15, P = 0.037), indicating more sexual distress. Clinical Implications Sexual health concerns may differ between SMW and heterosexual women emphasizing the need for inclusive, culturally competent care. Strengths & Limitations This study assessed the association of sexual orientation and sexual dysfunction by incorporating sexual functioning problems and sexual distress. Limitations include a small number of SMW and a predominantly White, married, employed, and educated study sample, limiting the generalizability of the findings. Conclusion Rates of sexual dysfunction were similar between mostly White SMW and heterosexual women presenting to tertiary care centers. SMW reported more sexual distress than heterosexual women. Evaluating these variables in larger, more diverse cohorts is a critical next step.

Abstract Background Alcohol consumption behaviors and alcohol use disorder risk and presentation differ by sex, and these complex traits are associated with blood concentrations of the steroid sex hormones, testosterone and estradiol, and their regulatory binding proteins, sex hormone binding globulin (SHBG) and albumin. Genetic variation is associated with alcohol consumption and alcohol use disorder, as well as levels of steroid sex hormones and their binding proteins. Methods To assess the contribution of genetic factors to previously described phenotypic associations between alcohol-use traits and sex-hormone levels, we estimated genetic correlations (rg) using summary statistics from prior published, large sample size genome-wide association studies (GWAS) of alcohol consumption, alcohol dependence, testosterone, estradiol, SHBG, and albumin. Results For alcohol consumption, we observed positive genetic correlation (i.e. genetic effects in the same direction) with total testosterone in males (rg = 0.084, p = 0.007) and trends toward positive genetic correlation with bioavailable testosterone (rg = 0.060, p = 0.084) and SHBG in males (rg = 0.056, p = 0.086) and with albumin in a sex-combined cohort (rg = 0.082, p = 0.015); however in females, we observed positive genetic correlation with SHBG (rg = 0.089, p = 0.004) and a trend toward negative genetic correlation (i.e. genetic effects in opposite directions) with bioavailable testosterone (rg = -0.064, p = 0.032). For alcohol dependence, we observed a trend toward negative genetic correlation with total testosterone in females (rg = -0.106, p = 0.024) and positive genetic correlation with BMI-adjusted SHBG in males (rg = 0.119, p = 0.017). Several of these genetic correlations differed between females and males and were not in the same direction as the corresponding phenotypic associations. Conclusions Findings suggest that shared genetic effects may contribute to positive associations of alcohol consumption with albumin in both sexes, as well as positive associations between alcohol consumption and bioavailable testosterone and between alcohol dependence and SHBG in males. However, relative contributions of heritable and environmental factors to associations between alcohol-use traits and sex-hormone levels may differ by sex, with genetic factors contributing more in males and environmental factors contributing more in females.

Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P &lt; 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6). In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Our study suggests a limited role of gene–environment interactions in breast cancer risk.