There is a well-documented link between post-menopausal reductions in estrogen and the prevalence of recurring urinary tract infections (rUTIs), and ongoing studies point to a number of mechanisms at work.

Vaginal and Bladder Microbiomes Closely Linked
Recent studies indicate that changes in the vaginal microbiome are linked to changes in the bladder and urinary tract—and not just in terms of the proliferation of common UTI-causing pathogens. A study from 2018 suggests that “microbial sharing between the vaginal and bladder microbiota is not limited to known and emerging uropathogens, such as E. coli and S. anginosus, but also includes health-associated commensal bacteria, such as L. iners and L. crispatus. Now, we propose that some bacteria that can reside in both the bladder and vagina could provide protection against urinary infection.”1

It follows that managing a healthy vaginal microbiome may be key to preventing rUTIs. Just what vaginal and urinary bacteria are considered “part of a healthy microbiome” differs greatly,2 but it is widely assumed that the Lactobacillus bacteria are the most beneficial, in part because they produce lactic acid,3 making it hard for uropathogens like E.coli to grow.4

Estrogen and the Microbiome
So what is the role of estrogen, and why are post-menopausal women more at risk for UTIs? It is thought that estrogen increases the stores of glycogen on the surface of the vaginal epithelial cells (vaginal lining), and glycogen acts as a food source for Lactobacilli. So the reduced estrogen reduces the food source for the Lactobacilli, thereby reducing their protective acid byproducts.5

While the pre-menopausal vaginal microbiome is dominated by Lactobacilli, the post-menopausal microbiome is far more diverse.

Probiotic Lactobacillus alone can’t create this environment without a stimulation in the production of glycogen to feed the healthy colony, but studies have shown that patients on hormone (oral estrogen with progesterone) replacement therapies (HRT) have greater Lactobacillus-dominant microbiomes than same-age patients without HRT.6

While oral estrogen therapy can relieve many symptoms of menopause (including the reduction of rUTIs), it is not without risks. Known adverse effects include an increased risk of breast, ovarian and endometrial cancer7, venous thrombosis8 and gallbladder disease9. Transdermal formulations of menopausal hormone therapy are associated with a lower risk of gallbladder disease than oral preparations,10 but the other risks seem to remain the same. Because of this, estrogen is contraindicated in women with any history of cancer, cardiovascular disease, or liver dysfunction.11

Applying estrogen directly to the vagina can alleviate atrophic vaginitis (itching, burning, dryness) and can increase Lactobacilli dominance (and therefore reduce rUTIs).12 And it appears to be safe—at least in the short term. Vaginal estrogen has been shown to reduce cancer, cardiovascular and liver impacts because less estrogen is circulated in the bloodstream. However, topical (low-dose) applications are not without some risk: Estrogen levels in the bloodstream tend to vary with estrogen creams because it’s difficult to measure out a precise low dose.13 This can make it challenging to comply with the National Institutes of Health’s (NIH) caution that women use the lowest possible dose of vaginal estrogen to control their symptoms. The NIH also advises women to revisit their use of vaginal estrogen with their physician every 3-6 months.14

Resistance of a Different Kind
Regardless of prevailing evidence supporting estrogen creams—and the mounting concerns about antibiotic resistance with the use of antibiotics to treat UTIs15,16—women are still hesitant to accept prescription (vaginal estrogen creams) prevention. A February 2019 survey study confirms: “Physicians reported that patients had concerns over the safety (of vaginal estrogen therapy) as a reason for not starting therapy, and also discontinuing treatment, which was consistent with other published studies. In the Women’s EMPOWER survey, 43% of women did not use hormonal products (such as vaginal ET) because of concern over risk of side effects, and 30% of women had concern over hormone safety in women with cancer or history of familial cancer. In this same survey, women also stopped taking prescribed VVA (vulvar and vaginal atrophy) products because they became concerned about the risks (31%) and side effects (17%).”17

Looking to Alternatives
The urinary and vaginal microbiome holds the key to helping prevent UTIs. The Theraworx Protect U-Pak contains safe, topical, non-systemic hygiene products for at-home use, designed to reduce macro and micro debris from the skin, while simultaneously supporting the vaginal microbiome. As a non-antiseptic, non-drug product, the U-Pak can help you achieve your patient genitourinary health goals without the risk of antiseptic resistance. Contact us for more information.

References:

  1. Thomas-White K, Forster SC, Kumar N, et al. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nat Commun. 2018;9:1557. https://doi.org/10.1038/s41467-018-03968-5. Accessed February 19, 2020.
  2. Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108(1):4680-4687. https://doi.org/10.1073/pnas.1002611107. Accessed February 19, 2020.
  3. Tachedjian G, O’Hanlon DE, Ravel J. The implausible “in vivo” role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota. Microbiome. 2018;6(1):29. https://doi.org/10.1186/s40168-018-0418-3. Accessed February 19, 2020.
  4. O’Hanlon DE, Moench TR, Cone RA. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis. 2011;11:200. https://doi.org/10.1186/1471-2334-11-200. Accessed February 19, 2020.
  5. Live UTI Free website. UTI and menopause: estrogen may improve recurrent UTI. https://liveutifree.com/uti-and-menopause/#RUTIestrogenlink. Accessed February 19, 2020.
  6. Christine H and Gregor R. Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy. Can J Microbiol. 2005;51(9):777-781. https://doi.org/10.1139/w05-070. Accessed February 19, 2020.
  7. Beral V, Peto R, Pirie K, Reeves G, et al. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019; VOL 394, ISSUE 10204, P1159-1168. https://doi.org/10.1016/S0140-6736(19)31709-X.
  8. ACOG website. Postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Postmenopausal-Estrogen-Therapy. Accessed February 19, 2020.
  9. Cirillo DJ, Wallace RB, Rodabough RJ, et al. Effect of Estrogen Therapy on Gallbladder Disease. JAMA. 2005;293(3):330–339. https://doi.org/10.1001/jama.293.3.330
  10. NEJM Journal Watch website. The two faces of estrogen therapy: transdermal vs. oral. https://www.jwatch.org/na41669/2016/07/06/two-faces-estrogen-therapy-transdermal-vs-oral. Accessed February 19, 2020.
  11. RxList website. Menest. https://www.rxlist.com/menest-drug.htm. Accessed February 19, 2020.
  12. Shen J, Song N, Williams C. et al. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 2016;6:24380. https://doi.org/10.1038/srep24380. Accessed February 19, 2020.
  13. Harvard Health Publishing website. By the way, doctor: Is vaginal estrogen safe? https://www.health.harvard.edu/womens-health/by_the_way_doctor_is_vaginal_estrogen_safe. Accessed February 19, 2020.
  14. MedlinePlus website. Estrogen vaginal. https://medlineplus.gov/druginfo/meds/a606005.html. Accessed February 21, 2020.
  15. Fisher H, Oluboyede Y, Chadwick T, et al. Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label trial. Lancet Infect Dis. 2018;18(9):957-968. https://doi.org/10.1016/S1473-3099(18)30279-2. Accessed February 19, 2020.
  16. Lancet T. Balancing treatment with resistance in UTIs. Lancet. 2018;391(10134):1966. doi:10.1016/s0140-6736(18)31077-8. https://doi.org/10.1016/S0140-6736(18)31077-8. Accessed February 19, 2020.
  17. WISDOM survey. Kingsberg, Sheryl A. PhD; Larkin, Lisa MD; Krychman, Michael MD; Parish, Sharon J. MD; Bernick, Brian MD; Mirkin, Sebastian MD. Attitudes and behaviors of physicians toward vulvar and vaginal atrophy (VVA) treatment in women including those with breast cancer history. Menopause: February 2019 – Volume 26 – Issue 2 – p 124-131. https://doi.org/10.1097/GME.0000000000001194. Accessed February 19, 2020.