Menopause causes more than hot flashes, mood swing and changes in libido; it also impacts diseases caused by shifting changes in the vaginal microbiome. Bridget Briggs, MD, sheds light on the vaginal microbiome, its influences on a woman’s health throughout various life stages, as well as how HRT helps mediate changes — and associated diseases — in the vaginal microbiome during menopause.

by Dr. Bridget Briggs, PCCA HRT Symposium Keynote Speaker

The vaginal microbiome (VM) is a complex ecological system that includes commensal, symbiotic and pathogenic organisms that inhabit the vaginal surfaces and its cavity. These organisms include bacteria, viruses and fungi.

The composition of organisms within the VM changes throughout the various stages of a woman’s life:

• Childhood: Corynebacterium spp., Escherichia coli (E. coli), and Mycoplasma spp. form the vaginal microbiome.
• Puberty: At puberty, the vaginal microbial niche shifts toward other predominant colonies, including Lactobacillus spp., Atopobium and Streptococcus spp.
• Reproductive Ages: During reproductive age, the vaginal microbiome houses a range of bacterial communities, including lactobacilli (L. crispatus, L. gasseri, L. jensenii and L. iners) along with anaerobic bacteria.
• Menopause: Further changes in the composition of the VM include Gardnerella vaginalis, Ureaplasma urealyticum, Candida albicans and Prevotella spp., with a progressive decrease in species of lactobacillus.

VM and Lactobacillus

The composition of the vaginal microbiome can vary widely between individuals. It influences a woman’s reproductive health, immune responses and overall wellbeing. Imbalance in the microbiome is linked to bacterial vaginosis (BV), thrush (a common yeast infection), urinary tract infections (UTIs) and influences fertility.

Lactobacillus species dominate in a healthy vagina and are associated with cervicovaginal health. Disruption of the microbial status quo — notably during menopause — is associated with disease. Hormone replacement therapy (HRT), however, has shown to improve the vaginal microbiome:

• Vaginal estradiol (E2) tablets resulted in substantial changes in the VM and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline.
• Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH.
• Estradiol use may offer additional genitourinary health benefits to postmenopausal women.
• A small randomized clinical trial of a vaginal probiotic in postmenopausal women found short-term decreases in proinflammatory gene pathways with increased vaginal lactobacilli.
• A 2020 study conducted on 228 premenopausal women suggested that daily administration of a vaginal dose of Lactobacillus crispatus, after treatment with vaginal metronidazole, can reduce recurrence of bacterial vaginosis after 12 weeks.¹

Menopause, VM and Urinary Health

Decrease in lactobacillus results in an elevated vaginal pH and higher microbial diversity. Decreased levels may also cause vaginal epithelium atrophy (thinning of the vaginal epithelium), dyspareunia (painful intercourse), dysuria (pain when urinating) and other genitourinary symptoms of menopause (GSM), due in part from the changes in the local microenvironment.

• GSM affects approximately 50% of postmenopausal women. A 2013 cross-sectional study (n = 87) showed that women with signs of mild or moderate vulvovaginal atrophy (VVA) had greater odds of having highly diverse microbiota depleted of lactobacilli than microbiota dominated by L. crispatus when compared to women with no VVA.
• Use of HRT in menopause indicates the reversion of lactic acid bacteria (LAB) microbial diversity to premenopausal levels; use of HRT has also shown not to increase the prevalence of bacterial vaginosis in postmenopausal women.
• Postmenopausal women have been found to display significantly lower levels of free glycogen than premenopausal women.²

Benefits of Estriol

A study on the effect of ultra-low dose estriol vaginal tablets (0.03 mg) and Lactobacillus acidophilus compared to placebo was investigated in 87 postmenopausal women. The instillation of lactobacilli and ultra-low dose estriol was found to significantly improve the vulvovaginal symptoms in these women.

A second study was conducted on 60 postmenopausal women, who were randomly assigned to receive oral isoflavone alone, isoflavone plus probiotic or hormonal replacement therapy (1 mg estradiol and 0.5 mg norethisterone acetate). After 16 weeks, the hormonal therapy group showed an increased number of lactobacilli in the vagina, similar to that seen in premenopausal state, and a decrease in vaginal pH. Conversely, no change in pH value was found in the isoflavone group and isoflavone plus probiotic group.¹

Impact of Progesterone on the VM

• DMPA injection reduced total bacterial load and abundance of Gardnerella vaginalis.
• Localized progesterone contraceptive also reduced lactobacillus abundance.
• Progesterone inhibits vaginal epithelium proliferation. Lack of epithelial-derived glycogen in a progesterone-enriched environment may reduce lactobacillus and other bacterial abundance.
• Due to increased levels of endogenous estrogen and progesterone during pregnancy, the contributions of exogenous progesterone may be obscured in pregnant women.¹

Additional Influences

The intestinal microbiota have a role in shaping the vaginal microbiota. Both are formed throughout the stages of development and are influenced by lifestyle, use of antibiotics and hormones; both produce metabolites that help guide the immune system to be tolerogenic (producing immunological tolerance) or pro-inflammatory. The use of antibiotics can have long lasting negative impacts on a person’s microbiome and promote chronic disease development. Various forms of oral, vaginal or fecal transplanted probiotics can help to influence disease states.

References

1. Auriemma, R.S., Scairati, R., del Vecchio, G., et al. (2021). The Vaginal Microbiome: A Long Urogenital Colonization Throughout Woman Life. Front. Cell. Infect. Microbiol. 11. Sec. Microbiome in Health and Disease. Accessed July 2021 at https://www.frontiersin.org/articles/10.3389/fcimb.2021.686167/full
2. Meštrović, T., Matijašić, M., Perić, M., et al. (2020). The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside. Diagnostics (Basel, Switzerland), 11(1), 7. Accessed December 2020 at https://pubmed.ncbi.nlm.nih.gov/33375202/

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.