Exploring the post-menopausal vaginal ecosystem

From the Fredricks Lab, Vaccine and Infectious Disease Division

            The onset of menopause in women causes many changes, including variations in the vaginal microbiota. Nearly half of postmenopausal women complain of genitourinary syndrome of menopause. This syndrome presents with signs and symptoms affecting the vagina (dryness, pain with intercourse and itching/ irritation) and urinary bladder (frequency, and incontinence). Little is known about the cause of the symptoms except that they are linked to decreased serum estrogen. In most cases symptoms improve with estrogen therapy. In a study published in Menopause: The journal of the North American menopause society Dr. Fredricks (Vaccine and Infectious Disease Division) and colleagues aimed to identify associations between improved symptoms and vaginal microbiota, vaginal glycogen, and serum estrogen. Prior studies have suggested that certain bacterial species could be associated with reduced symptoms. It was also recently suggested that vaginal colonization with Lactobacillus bacteria may lessen symptoms and that when this bacterium was decreased symptoms worsened. Armed with this information, the group hypothesized that symptom improvement would be associated with increased detection and or dominance of Lactobacillus species.

            In order to test this hypothesis, the researchers utilized a cohort of 30 women from an 8-week, double blind, randomized trail where oral estradiol, venlafaxine (an anti-depressant), or placebo was given to alleviate menopause side effects. The women’s most bothersome symptom was used as an indicator of changes in the genitourinary syndrome of menopause. Of the 30 women sampled, 21 (70%) reported improvement in symptoms and of that a larger proportion of the treatment group (88% and 78%) showed improvement compared to placebo (54%).  Comparatively, only 9 (30%) of the untreated women reported improvement. Aside from symptom reporting, vaginal microbiota was sampled from each participant. Upon entry into the study, baseline measures of microbiota were taken and then again at 8 weeks after therapy. This information was used to look for correlations between levels of Lactobacillus and outcomes. Of the 21 women who reported symptom improvement 12 out of the 30 women (57%) had a Lactobacillus-dominate microbiota compared with only 2 (22%) of those that did not improve (see figure). After 8 weeks, 11 (52%) had Lactobacillus-dominate microbiota, with one women losing dominance. Of the group that did not improve, 3 (33%) had increased Lactobacillus bacteria communities with 2 new women gaining dominance. Looking at overall species diversity, women who had higher diversity scores tended to have symptoms that did not improve, however this difference was not statistically significant. In regards to vaginal-free glycogen, there was an increase over the 8-week time period in women with improved symptoms with a trend of decreasing amounts in women who did not improve. This same trend was also seen in serum unconjugated and total estradiol levels with higher levels in the treated groups.

Top graph represents treatment group for each person (individual bars) with people to the left of the dotted line showing symptom improvement and ones to the left with no improvement. The bottom graph shows Lactobacillus-status after 8 weeks. Image provided by Dr. Fredrticks

            In conclusion Dr. Fredricks stated, “The bottom line is that the results were counter to our expectation. We believed that use of oral estrogen would lead to an increase in deposition of glycogen in the vaginal wall, which would then be used by lactobacilli for growth, and we would see a shift towards more vaginal colonization with lactobacilli.  Since high concentrations of lactobacilli and resulting lower pH are associated with health, we thought this would correlate with reduced symptoms.  Although we did see a significant increase in glycogen, we did not see a shift towards more lactobacilli in the vagina, either with the use of oral estrogen, or with oral venlafaxine. The fact that Lactobacillus crispatus at baseline was associated with improvement in symptoms may suggest that this organism is a marker for a healthier vaginal mucosa, and we don’t think it is a driver since the concentrations of this bacterium did not change in those who improved versus not.”

This work is supported by National Institutes of Health.

Mitchell CM, Srinivasan S, Plantinga A, Wu MC, Reed SD, Guthrie KA, LaCroix AZ, Fiedler T, Munch M, Liu C, Hoffman NG, Blair IA, Newton K, Freeman EW, Joffe H, Cohen L, Fredricks DN. 2017. Associations between improvement in genitourinary symptoms of menopause and changes in the vaginal ecosystem. Menopause.