Menopause and estrogen associations with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV

Abstract

Objectives: Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV. Design: Longitudinal and cross-sectional studies nested in the Women’s Interagency HIV Study. Methods: Intestinal fatty acid binding protein (IFAB), lipopolysaccharide binding protein (LBP), and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (∼6 measures per woman over ∼13 years). A separate cross-sectional analysis was conducted among 72 post-menopausal women with HIV with these biomarkers and serum estrogens. Results: Women in the longitudinal analysis were a median age of 43 years at baseline. In piece-wise linear mixed-effects models with cut-points 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]=38 [12, 64] ng/mL/year, p=0.004), followed by a decrease post-transition (-46 [-75, -18], p=0.001), with the piece-wise model providing a better fit than a linear model (p=0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses among women with HIV, free estradiol was inversely correlated with sCD14 levels (r=-0.26, p=0.03). LBP and IFAB levels did not appear related to the menopausal transition and estrogen levels. Conclusion: Women with HIV may experience heightened innate immune activation during menopause, possibly related to depletion of estrogens.