Topical interventions on the vaginal microbiota in postmenopausal women


Vaginal estradiol tablets produced significant changes in vaginal microbiota and metabolome with a lowering pH, especially in women with highly divers bacterial communities at baseline, according to a secondary analysis in JAMA Network Open.

Despite lowering vaginal pH, a low-pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome.

The authors noted that postmenopausal women with genitourinary symptoms of menopause are frequently prescribed vaginal estradiol or moisturizer for symptom improvement, but the result of these treatments on the local microenvironment is poorly understood.

The original randomized controlled trial was conducted by the Menopause Strategies - Finding Lasting Answers for Symptoms and Health (MsFLASH) research network, which included 203 postmenopausal women with a mean age of 61 years. Enrollment occurred from April 2016 to February 2017.

The secondary analysis examined the data from 144 MsFLASH participants. After 12 weeks of treatment, the microbiota was dominated with lactobacillus and bifidobacterium communities in 80% of women in the estradiol group, compared to 36% of women in the moisturizer group, and 26% in the placebo group (P < 0.001).

The composition of vaginal fluid metabolites also varied after 12 weeks among women in the estradiol group, with significant changes in 53% of the 171 metabolites measured (P < 0.001), including an increase in lactate.

The 12-week pH among women in the estradiol group was lower than placebo with a median interquartile range (IQR) pH of 5 vs 6 (P = 0.005).The moisturizer and placebo groups had the same median IQR pH of 6. Still, there was a decrease in median IQR pH, from 7 to 6, from baseline to 12 weeks in both the moisturizer and placebo groups (P < 0.001).

Women with high-diversity bacterial communities at baseline showed a greater change in pH as opposed to women with low-diversity communities: median IQR pH change of -1 vs -0.3 (P = 0.007).

“What is of interest is that vaginal estrogen contributed to an additional reduction in pH even among women with a low-diversity community, suggesting that estradiol facilitates an increase in metabolic activity of lactic acid–producers, such as lactobacilli and bifidobacterial,” wrote the authors.

The study demonstrates that a decrease in vaginal pH alone is insufficient to change the vaginal microbiota. While the changes with estrogen were somewhat anticipated by the authors, the observation that low-pH vaginal products fail to change the vaginal microbiota is contrary to some expectations and suggests that “low pH” products may not be as helpful as their marketing claims.

A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women, according to the authors. Such a microenvironment is also typically associated with low inflammation.

On the other hand, changes—or lack thereof—in the vaginal microenvironment might have implications beyond symptoms, such as risk for cervical cancer, genital infections and other outcomes.

Besides being a subset analysis of a limited number of trial participants, it is unknown if observed changes are durable beyond 12 weeks of therapy, or whether longer-term treatment could lead to additional or different shifts in microbes or metabolites.

Future areas of investigation should focus on understanding potential benefits of a lactobacillus-dominant microbiota in postmenopausal women, according to the authors.


  1. Srinivasan S, Hua X, Wu MC, et al. Impact of topical interventions on the vaginal microbiota and metabolome in postmenopausal women: a secondary analysis of a randomized clinical trial. JAMA Netw Open. Published online March 30, 2022. doi:10.1001/jamanetworkopen.2022.5032
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