Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis

Abstract

Atrophic vaginitis (AV) is common in postmenopausal women, but its causes are not well understood. The symptoms, which include vaginal itching, burning, dryness, irritation, and dyspareunia, can usually be alleviated by low doses of estrogen given orally or locally. Regrettably, the composition of vaginal bacterial communities in women with AV have not been fully characterized and little is known as to how these communities change over time in response to hormonal therapy. In the present intervention study we determined the response of vaginal bacterial communities in postmenopausal women with AV to low-dose estrogen therapy. The changes in community composition in response to hormonal therapy were rapid and typified by significant increases in the relative abundance of Lactobacillus spp. that were mirrored by a decreased relative abundance of Gardnerella. These changes were paralleled by a significant four-fold increase in serum estradiol levels and decreased vaginal pH, as well as nearly a two-fold increase in the Vaginal Maturation Index (VMI). The results suggest that after menopause a vaginal microbiota dominated by species of Lactobacillus may have a beneficial role in the maintenance of health and these findings that could lead to new strategies to protect postmenopausal women from AV.

Figure 1. Hierarchical clustering of vaginal microbial communities in healthy postmenopausal women and a heat map showing the log₁₀-transformed proportions of bacterial genera in each community.

The visit time of each sample is indicated by the color-coded bar immediately below the dendrogram. Analysis of similarities in community composition and structure resulted in three clusters as indicated in the color bar above the heatmap.

Figure 2

Interpolated bar plots of phylotype relative abundances in four selected subjects in the H group over 4 weeks (panels A–D). Color key for each phylotype represented in the interpolated bar plots are on the right side.

Figure 3. Canonical variable analysis of vaginal bacterial communities in healthy women at 0, 2, and 4 weeks (H-0, H-2, and H-4) compared to each other and the vaginal communities of women with AV at 0, 2, and 4 weeks (AV-0, AV-2, and AV-4).

Asterisks indicate communities that were significantly different (P < 0.05) than those of AV-0 (AV patients at time zero).

Figure 4. Relationships among vaginal bacterial communities visualized by principal component analysis (PCA).

Each point corresponds to a single subject at a single time point and was colored according to group membership and time of sampling. The percentages given in the axis labels wee the proportion of variation explained by that principal component. (A) Comparison of vaginal bacterial communities of healthy post-menopausal women at week 0 (green dots) to those of women with atrophic vaginitis at week 0 (red dots). (B) Comparison of vaginal bacterial communities of women with atrophic vaginitis at week 0 (red dot) to those in the AV group after 4 weeks of estrogen therapy (blue dots).

Figure 5. Interpolated bar plots of phylotype relative abundance observed in four subjects selected from the AV group.

Color codes for each phylotype represented in the interpolated bar plots are displayed on the right side of the figure. See Supplementary Fig. S2 interpolated bar plots for all subjects.