Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy

Abstract

Objective: The vaginal microbiota helps protect the female genital tract from disease. We sought to describe the composition of the vaginal microbiota in premenopausal, perimenopausal, and postmenopausal women and to explore the association between the microbiota and vulvovaginal atrophy (VVA).

Methods: Eighty-seven women (aged 35-60 y) were classified as premenopausal (n = 30), perimenopausal (n = 29), or postmenopausal (n = 28) according to Stages of Reproductive Aging Workshop guidelines. Midvaginal bacterial community composition was characterized by 16S ribosomal RNA gene analysis.

Results: Bacterial communities clustered into six community state types (CSTs), of which four were dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, or Lactobacillus jensenii, and two (CST IV-A and CST IV-B) had low relative abundance of Lactobacillus. CST IV-A was characterized by Streptococcus and Prevotella, whereas CST IV-B was characterized by Atopobium. There were significant associations between menopause stage and CST (P = 0.004) and between VVA and CST (P = 0.002). Perimenopausal women were more likely to be classified as CST IV-A or L. gasseri CST, whereas postmenopausal women were often classified as CST IV-A. CSTs dominated by L. crispatus and L. iners were more prevalent in premenopausal women. Nineteen participants had signs of mild or moderate VVA. Compared with women with no VVA, the vaginal microbiota of women with mild or moderate atrophy had 25-fold greater odds of being classified as CST IV-A versus L. crispatus CST (adjusted odds ratio, 25.89; 95% credible interval, 2.98-406.79).

Conclusions: A distinct bacterial community state (CST IV-A) with a low relative abundance of Lactobacillus is associated with VVA. Future studies recruiting a larger number of women are needed to replicate the findings. This study provides an impetus for future longitudinal studies designed to manage, modulate, and restore vaginal microbiota homeostasis, which would provide stronger evidence for a causal relationship with VVA and ultimately improve the treatment and prevention of atrophic vaginitis in menopause.

Figure 1. Heatmap of relative percent abundance of bacterial taxa found in the vaginal bacterial communities of 87 women in pre-, peri- and post-menopause

Vaginal microbiota clustered into six community state types; CST-I, II, III and V were dominated by Lactobacillus crispatus, L. gasseri, L. iners, or L. jensenii, respectively. Two CSTs lacked significant numbers of lactobacilli (CST-IV-A and IV-B). This heatmap lists the top 25 most abundant bacteria; however data is available on more than 200 bacteria found in the female genital tract of these participants. CSTs are defined using Jensen-Shannon divergence between all pairs of community states and Ward linkage hierarchical clustering as described by Gajer et al.. Menopause stage is indicated at the top of the heatmap.

Figure 2

Odds ratio for community state type (CST) by menopausal stage adjusted for sexual activity in prior 6 months, race/ethnicity, marital status, and lifetime number of sexual partners