Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy

INTRODUCTION: The vaginal microbiome of postmenopausal women has been shown to have increased rates of anaerobic, mixed flora communities, and decreased predominance of Lactobacillus associated with genitourinary symptoms of menopause. OBJECTIVE: The objective of this study was to assess the quantitative change in relative abundance of Lactobacillus among the community composition of bacteria and inflammatory biomarkers and pelvic floor symptoms in the vagina pre- and post-vaginal conjugated estrogen cream therapy. METHODS: Twenty postmenopausal participants ≥55 years old with clinically diagnosed vulvovaginal atrophy were in the intervention arm; five participants served as a placebo-controlled cohort to demonstrate microbiome stability across the 8-week time period. The primary aim compared the quantitative change in relative predominance of lactobacilli over the 8-week intervention period. Secondary aims included characterization of vaginal maturation index (VMI), vaginal pH, and prevalent cytokine biomarkers over 8 weeks. Wilcoxon signed-rank tests were used for comparisons of dependent paired samples and Mann-Whitney U tests for independent group comparisons. Chi-squared tests or complementary exact tests for categorical measures. Level of significance was assessed at 0.05. All statistical analyses were performed using SAS 9.4 (SAS Institute, Inc., Cary, NC). RESULTS: There were no differences in clinico-demographic variables between cases and controls (Table 1). Median age (interquartile range) of the intervention arm was 65.5 (57, 71), majority white (70%), BMI 27.3 (23.8, 30.9). There was a significant increase in the median IQR relative proportion of Lactobacillus (baseline: 0.070 0.020–0.140; 8 weeks: 0.120 0.060–0.960, p=0.0398) (Table 2, Figure 1). Significant changes were noted in beta diversity in both unweighted (p=0.03) and weighted-UniFrac (p=0.04) and in alpha diversity, observed species (p=0.01), Shannon index (p=0.01) and Simpson index (p=0.01). Significant decreases were observed in the genera of Shigella (p=0.0049), Finegoldia (p=0.0049), and Anearococcus (p=0.0039). There was a significant improvement in median IQR VMI (baseline: 37.5 10, 50; 8 weeks: 60 50, 60, p=0.001) and vaginal pH (baseline: 7.25 6.5, 7.5; 8 weeks: 5 4.5, 5.5, p=0.0004) in the intervention group. Changes in proinflammatory mediators were variable with significant decreases in IL-8 (p=0.034), MCP-1 (p=0.002). A significant median (IQR) decrease in the Pelvic Floor Impact Questionnaire (Short Form 7) scoring was also observed (p=0.008). CONCLUSIONS: The findings from this study indicate that postmenopausal women with vaginal atrophy have a significant increase in relative predominance of Lactobacillus with concomitant reductions in overall microbial diversity with use of vaginal conjugated-estrogen cream. Subjects also experienced improvements in subjective and objective measures with significant decreases in vaginal pH and increased vaginal maturation index. Changes in pro-inflammatory cytokines were variable with significant decreases in IL-8, MCP-1.Table 1Table 2Figure 1