Written by Dr. Jen Gunter (The Vagenda)
While vaginal estrogen is often thought of as a treatment for vaginal dryness (and it is) and also for treating painful sexual activity in menopause (also true), there is another benefit that is often forgotten: reducing the risk of urinary tract infections (UTIs). As many women struggle with recurrent UTIs, I think it’s worth discussing the role of estrogen because not everyone is seeing a provider who is up to date on these benefits. Sadly, sometimes, that includes a few OB/GYNs and urologists. Another reason to discuss vaginal estrogen is that while it can be helpful, it’s not 100% preventative, so it’s good for people to know the limitations of a specific therapy so they are not disappointed and stop using it, thinking it’s not helpful. And finally, the more you know, the better!
Recurrent UTIs: Scope of the Issue
For women, the lifetime risk of having a bladder infection is 50%. Recurrent UTIs are defined as two or more infections in 6 months or three or more in 12 months, and the risk of having at least one episode of recurrent infections ranges from 10-18%, depending on the study. What women in menopause need to know is that age is a significant risk factor, and the risk of UTIs, including recurrent infections, increases over age sixty.
Menopause is believed to be a risk factor for recurrent UTIs for several reasons. Some of the main ones are the fact that low levels of estrogen impact the microbiomes in the vagina and the bladder, blood flow to the bladder and urethra decreases, and the cells in the urethra can become more fragile, which may make it easier for bacteria to attach. But there are likely many other factors.
Other non-menopause-related risk factors for recurrent UTIs are genetics (having a mother with recurrent UTIs increases the risk), a new sexual partner in the past year, incontinence, and age.
Vaginal Estrogen and Recurrent UTIs
Before we go further, it’s important to know that studies often use different endpoints. Two of the most common are the number of recurrent infections over a given time frame and the time to first infection. This can sometimes make it challenging to compare results between studies.
The first randomized clinical trial looking at vaginal estrogen for the prevention of UTIs was published in 1993 and enrolled 93 women and compared vaginal estriol
cream with a placebo. The results were impressive–if the data from eight months (the length of the study) were extrapolated to one year, there were 5.9 infections/year with the placebo cream and 0.5 for estriol. That’s significant.
Other clinical trials have shown beneficial results with vaginal estrogen:
From 1999: 108 women were randomized to the estradiol vaginal ring or placebo, and by six months, 51% who had used the vaginal ring had a recurrent infection vs. 80% who used the placebo.
From 2022: 35 women were randomized to either vaginal estradiol cream, the vaginal estradiol ring, or placebo. Unfortunately, the study struggled with enrollment, and nine women dropped out. If these women were considered to have failed the treatment, then 61% of those who used vaginal estrogen and 94% who used the placebo had a recurrent infection within six months. If those who dropped out are removed, then 53% using estrogen had a recurrent infection within six months vs 90% for placebo.
(An an aside, and an angry one, these three studies seem to represent the total of the clinical trials comparing vaginal estrogen with placebo for prevention of recurrent UTIs for women in menopause. I may have missed one, but even if I have, four studies really wouldn’t be any better for something that is such a significant issue for so many)
There is another clinical trial from 2003, but it doesn’t have a placebo arm. Women were randomized to using a vaginal estriol suppository vs. oral nitrofurantoin daily (an antibiotic), and those who used vaginal estrogen had an average of 2 infections in the year of the study versus 0.8 for the nitrofurantoin. As there was no placebo arm, we don’t know if the estriol might have performed better than placebo. The investigators raised some concerns that perhaps there wasn’t the full effect of the vaginal estriol, meaning maybe the dose or the delivery system was suboptimal.
A relatively recent (2022) retrospective study examined the records of over 5600 primarily postmenopausal women with an average of 3.9 urinary tract infections a year. After receiving a prescription for vaginal estrogen, the average number of urinary tract infections dropped to 1.8 a year. In the year after receiving a prescription for vaginal estrogen, 31% had no bladder urinary tract infections. Factors that increased the risk of having a UTI despite receiving a prescription for estrogen were age ≥ 75 years, a greater number of UTIs entering the study, urinary incontinence, and diabetes. The investigators looked at how many prescriptions were filled in the year as a marker for adherence to the therapy, and they paradoxically found that patients with a high medication adherence did not have as much benefit as those who filled fewer prescriptions. While overall, receiving a prescription for vaginal estrogen reduced the risk of bladder infections for all women, why those women who filled the most prescriptions had more infections isn’t known. We can’t jump to any conclusions here as there could be issues with using medication refills as a proxy or another explanation that the study design can’t account for. But, of course, it may be possible that there is an optimal frequency or dose of vaginal estrogen.
Oral Estrogen
Oral estrogen in traditional menopause hormone (MHT) has not proven to be effective in reducing UTIs, so if someone is having recurrent infections, adding vaginal therapy would be recommended. Most assume this lack of benefit would be the same with transdermal estrogen.
Is there a “Best” Vaginal Estrogen for Preventing UTIs?
The best vaginal estrogen is the one that you are going to use. Some people hate the cream, and others love it. Some love the idea of a ring that is changed every 12 weeks, and others hate it. Some want to use the vaginal tablets as they have the lowest dose. It’s all good. I have a good summary of the different products here. Neither vaginal DHEA (Intrarosa) nor oral ospemifene (Osphena) have been studied for recurrent UTIs, so I would not recommend either of them if preventing UTIs were the primary goal of therapy.
One pro-tip: if you are starting estrogen for recurrent UTIs, record the number of culture-proven urinary tract infections in the previous three or six months before starting therapy so you can look back after you start to see the effect.
“I Am Using Vaginal Estrogen and Still Getting a Lot of UTIs”
We clearly have knowledge gaps, and vaginal estrogen is not 100% effective. There are probably a variety of reasons that women continue to get UTIs despite vaginal estrogen, for example, genetics, biofilms, diabetes, the virulence of the organisms, and age-related changes that estrogen isn’t going to treat, to name a few.
If someone is getting recurrent infections while using vaginal estrogen, if they are using the vaginal tablets or ring, I suggest switching to estradiol cream or Premarin cream, as the study that had the best outcome used a vaginal estrogen cream. In addition, the creams deliver a higher dose than the ring or tablets, and some can be targeted to the opening of the urethra. To be clear, switching to an estrogen cream is a hypothesis, and while it seems biologically sound, it isn’t based on super strong data.
Also, it’s essential to consider other therapies for recurrent UTIs, and if people are interested, I can address some of them in additional posts. I am planning on writing about D-Mannose at some point.
Should Everyone Use Vaginal Estrogen To Prevent UTIs, Even Those Who Have Never Had a UTI?
We don't have any data to tell us that women without a history of recurrent bladder infections should start vaginal estrogen to prevent bladder infections in menopause. Obviously, if someone is using vaginal estrogen for other reasons, it’s a moot point. I recommend vaginal estrogen for someone who previously had recurrent UTIs, whose mother had recurrent UTIs, or who has other risk factors. But for someone who isn’t using vaginal estrogen because they don’t need it or who is using systemic MHT and having the sex they want without any difficulties, we don’t have good studies to guide us. I review these pros and cons with my patients:
The pros of recommending vaginal estrogen to everyone is that we might prevent people from getting the increase in bladder infections that seems to happen around age 60. Preventing people from the hassle and pain is important, but also the potential serious complication of a bloodstream infection. In addition, fewer infections mean fewer antibiotic prescriptions, reducing antibiotic resistance risk. Vaginal estrogen is also about as safe as a medication can be (although people with breast cancer who are taking aromatase inhibitors do need to have a more in-depth discussion, read more about that here).
The cons of recommending vaginal estrogen to everyone are we don’t know who will benefit, so we might be treating more people than necessary. Some people dislike using a vaginal product, either due to the hassle, the mess, or the expense (or all three), and so this therapy may be a bigger burden for some. In addition, some people just don’t want a prescription they may not need. I also have some patients who are vehemently opposed to using hormones of any kind, and it’s important to respect that and meet people where they are.
Summary
Vaginal estrogen is effective at reducing the risk of recurrent urinary tract infections, but the evidence is considered moderate quality. Based on the data, it seems vaginal estrogen may reduce recurrent infections by about 50%, or possibly more.
We don’t have data comparing the cream with the ring or the vaginal tablet, so the best estrogen is the one someone will use.
It’s not possible to say if vaginal estrogen is inferior to daily antibiotics based on a tiny study, and vaginal estrogen can absolutely be used in addition to antibiotics.
There are several advantages of vaginal estrogen over antibiotics:
Vaginal estrogen doesn’t negatively affect the gastrointestinal microbiome
Vaginal estrogen doesn’t cause gastrointestinal side effects like nausea or diarrhea
Vaginal estrogen doesn’t increase the risk of resistant bacteria\
If someone is still struggling with infections and is using the vaginal tablets or ring, I suggest switching to the cream.
As always, the information here is not direct medical advice. If you have questions, leave them below. I try to reply to the easier ones directly in the comments (obviously, again, not individual medical advice). For those questions that are more complex, I tuck them away to try to incorporate them in future posts.
References
Risto Ikähelmo, Anja Siitonen, Tarja Heiskanen, Ulla Kärkkäinen, Pauli Kuosmanen, Pertti Lipponen, P. Helena Mäkelä, Recurrence of Urinary Tract Infection in a Primary Care Setting: Analysis of a I-Year Follow-up of 179 Women, Clinical Infectious Diseases, Volume 22, Issue 1, January 1996, Pages 91–99, https://doi.org/10.1093/clinids/22.1.91
Vazquez-Montes MDLA, Fanshawe TR, Stoesser N, Walker AS, Butler C, Hayward G. Epidemiology and microbiology of recurrent UTI in women in the community in Oxfordshire, UK. JAC Antimicrob Resist. 2024 Jan 10;6(1):dlad156. doi: 10.1093/jacamr/dlad156. PMID: 38204597; PMCID: PMC10781434.
Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102. PMID: 8350884.
Ferrante KL, Wasenda EJ, Jung CE, Adams-Piper ER, Lukacz ES. Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial. Female Pelvic Med Reconstr Surg. 2021 Feb 1;27(2):112-117. doi: 10.1097/SPV.0000000000000749. PMID: 31232721.
Perrotta C, Aznar M, Mejia R, et al. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 2008;(2): CD005131.
Chen YY, Su TH, Lau HH. Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials. Int Urogynecol J. 2021 Jan;32(1):17-25. doi: 10.1007/s00192-020-04397-z. Epub 2020 Jun 20. PMID: 32564121.
Erikson B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausat women. Am J obstet Gynecol 1999; 180: 1072-1079.
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