Estrogen, the vaginal microbiome and the role probiotics in vaginal health across the lifespan

If you are someone who suffers with or who is interested learning more about urinary tract infections (UTIs), vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) read on!  Below is a science snapshot including research from the clinic, contributed from our Jamieson Wellness Education team Naturopath, Dr. Jordan Robertson.  Put on your glasses and think like a scientist for this one.  It will leave you with a new spotlight on daily probiotic supplementation beyond digestive health along with some good ideas for lifestyle thought starters and education. 

The female urogenital microbiome is a delicate relationship between hormone levels and bacteria that when disrupted, creates a vulnerability that can lead to microbial imbalance, infection and discomfort in people.

At puberty, the surging of estrogen changes both vaginal cells and tissue as well as colonization of the vaginal tract with bacteria while the declining levels of estrogen at menopause by contrast create a window of vulnerability for vaginal and urinary infections. Estrogen has multiple actions in the vaginal canal, including maturation of vaginal tissue, thickening of the vaginal epithelium and maintenance of the protective mucous layer of the vagina. In addition this particular area supports Lactobacillus species growth and maintenance1. This environment creates the optimal site for lactobacilli strains to thrive and dominate. Through the cycling years, this interplay between estrogen, glycogen and bacteria creates a desirable vaginal environment and decreases the risk of urinary tract infections (UTIs), vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) 2.

A healthy vaginal microbiome inhibits the growth of unwanted or pathogenic strains through multiple actions. A Lactobacilli dominated environment maintains vaginal pH in an acidic state, prevents the accumulation and creation of biofilms of strains such as E coli and Gardnerella and prevents adhesion of unwanted bacteria in the urinary tract 1.

Disruptions to the vaginal microbiome can occur from:

  1. Medications (notably antimicrobials)
  2. Hormone changes (though the regular menstrual cycle,
  3. Pregnancy,
  4. Perimenopause and menopause
  5. Declines in host immunity,
  6. Dietary changes
  7. Stress

This disruption of the microbiome does not necessarily lead to an elimination of the healthy strains, but a disruption in bacterial counts that allows for other strains to colonize.

Hormone replacement therapy2 and estrogen containing contraceptives (COC, patch or estrogen-containing ring) maintain or improve the vaginal microbiome and reduce infections such as UTIs, BV and VCC3. Although vaginal dryness and painful intercourse are common side effects reported from people who use contraceptives, the actual microbiome is maintained when women use estrogen containing contraceptives, different from the vulvovaginal atrophy experienced at menopause which includes a change in vaginal tissue health and a change in vaginal microbiome4. Non-estrogen contraceptives such as progestin-only contraception or the copper-IUD have been shown to have negative impacts on the vaginal microbiome and may increase infections such as BV3,5.

Probiotics have the potential to influence the vaginal microbiome and reduce the colonization of species that cause infection and symptoms in people. The advancements of probiotics for urogenital health have moved away from simply repleading lost colonies towards the therapeutic use of specific strains that have action against pathogens6.

The number of studies on probiotics have increased exponentially over the last 15 years and have focused on both the prevention of urogenital infections and the treatment of infections either as a sole intervention or combined with antimicrobials. Administering probiotics orally, with species such as Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus plantarum, Lactobacillus rhamnosus and Bifidobacterium species improve vaginal colonization, indicating that oral use of probiotics does influence the type and quantity of bacteria maintained vaginally 7. The study of vaginal probiotics is limited mostly based on the classification of vaginal delivery being considered a drug-route of administration in many jurisdictions and the costs and approvals required for such a trial to be conducted. The few vaginal probiotic studies also demonstrate a re-colonization of the vaginal canal with the healthy flora.

A recent Cochrane review concluded when oral or vagina probiotics were added to standard care for VCC that people experienced a greater mycological cure rate and lower 1-month relapse rates compared with standard care alone 8,9. Reviews on the use of probiotics in combination with metronidazole for BV have been mixed, likely owing to the diversity of strains tested in individual RCTs 10. Specific strains such as L. rhamnosus and L reuteri have been shown to reduce bacterial counts and improve eradication when combined with regular care 11. The role of probiotics in BV may be best for reducing relapse and reinfection rates, which are high 12. The use of probiotics to prevent UTI has mostly been conducted in children 13. Studies in post-menopausal people show a reduction in recurrence rates (from 6.8 to 3.3 infections per 12 months) and lower antibiotic resistance but probiotics have thus far not been proven to be as effective as prophylactic antibiotic therapy in people with recurrent UTIs 14.

With the commonalty of genitourinary symptoms in people combined with a fluctuating microbiome based on hormone levels, the interest in probiotics for female genitourinary health and wellness is a natural evolution. The addition of probiotic strains to people at various points of their hormonal life and medical care has the potential to improve vaginal and urinary colonies and reduce the risk of infection and discomfort. Although studies on specific strains are needed for the development of standards of care, commercially available oral probiotics have been shown to colonize the vaginal tract of people and improve health outcomes.

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  1. Amabebe, E. & Anumba, D. O. C. The Vaginal Microenvironment: The Physiologic Role of Lactobacilli. Front. Med. 5, (2018).
  2. Muhleisen, A. L. & Herbst-Kralovetz, M. M. Menopause and the vaginal microbiome. Maturitas 91, 42–50 (2016).
  3. Song, S. D. et al. Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise. mSphere 5, (2020).
  4. Vodstrcil, L. A. et al. Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis. PloS One 8, e73055 (2013).
  5. Achilles, S. L. et al. Impact of contraceptive initiation on vaginal microbiota. Am. J. Obstet. Gynecol. 218, 622.e1-622.e10 (2018).
  6. Reid, G. Has knowledge of the vaginal microbiome altered approaches to health and disease? F1000Research 7, (2018).
  7. Mezzasalma, V. et al. Orally administered multispecies probiotic formulations to prevent uro-genital infections: a randomized placebo-controlled pilot study. Arch. Gynecol. Obstet. 295, 163–172 (2017).
  8. Barrientos-Durán, A., Fuentes-López, A., de Salazar, A., Plaza-Díaz, J. & García, F. Reviewing the Composition of Vaginal Microbiota: Inclusion of Nutrition and Probiotic Factors in the Maintenance of Eubiosis. Nutrients 12, (2020).
  9. Xie, H. Y. et al. Probiotics for vulvovaginal candidiasis in non‐pregnant women. Cochrane Database Syst. Rev. 2017, (2017).
  10. Tan, H., Fu, Y., Yang, C. & Ma, J. Effects of metronidazole combined probiotics over metronidazole alone for the treatment of bacterial vaginosis: a meta-analysis of randomized clinical trials. Arch. Gynecol. Obstet. 295, 1331–1339 (2017).
  11. Anukam, K. et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial. Microbes Infect. 8, 1450–1454 (2006).
  12. Kim, J.-M. & Park, Y. J. Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections: Review Article. J. Menopausal Med. 23, 139–145 (2017).
  13. Sihra, N., Goodman, A., Zakri, R., Sahai, A. & Malde, S. Nonantibiotic prevention and management of recurrent urinary tract infection. Nat. Rev. Urol. 15, 750–776 (2018).
  14. Beerepoot, M. A. J. et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch. Intern. Med. 172, 704–712 (2012).