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How effective is vaginal estrogen for the prevention of recurrent urinary tract infections associated with the genitourinary syndrome of menopause (GSM)?

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Conclusion: Urology guidelines recommend low-dose vaginal estrogen as an option for reducing the risk of recurrent UTIs associated with GSM however a number needed-to-treat cannot be confidently estimated. When considering a vaginal estrogen product for this indication, prioritize the selection of products and doses with endometrial safety data.

The BC Provincial Academic Detailing (PAD) service’s topic Medications for menopause-associated vasomotor and genitourinary symptoms delivers evidence and practical drug information for the most commonly prescribed estrogen and progestogen products (oral, transdermal, vaginal).¹ Visit www.bcpad.ca to book a session with an academic detailing pharmacist in your area.

GSM and vaginal estrogens

GSM can include the following symptoms: a) vaginal dryness, burning, irritation; b) urinary urgency, frequency, dysuria, recurrent urinary tract infections; c) dyspareunia or bleeding during intercourse. From randomized clinical trials we can estimate the effect of three vaginal estrogen products (Premarin cream, Vagifem tablets, Imvexxy softgel inserts) on dyspareunia and vaginal dryness.¹ Learn more on BC PAD’s handout where this evidence is described.¹

Guidelines and evidence for the prevention of recurrent UTIs

2025 American Urological Association GSM guidelines include this recommendation: “In patients with GSM and recurrent urinary tract infections, clinicians should recommend local low-dose vaginal estrogen to reduce the risk for future urinary tract infections.”² Informing this recommendation are two principal trials which enrolled postmenopausal participants (mean ages 64 and 68) with a history of at least three symptomatic UTIs in the previous year, but these small trials have methodologic limitations (Table).^3,4,5 The recommendation is rated as “moderate certainty” meaning that “the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.”² A 2021 meta-analysis includes these trials and shows large and unexplained differences in the magnitude of the effect on recurrent UTIs, reporting a 75% reduction in RAZ versus a 36% reduction in ERIKSEN.⁵ This makes it challenging to confidently estimate the number of patients needed-to-treat to prevent one person from experiencing a recurrent UTI.

Trial		Trial size	Intervention	Methodologic limitations
RAZ 19933		93	Estriol vaginal cream (not available in Canada)	Single center, incomplete outcome data
ERIKSEN 19994		108	Estradiol vaginal ring (available in Canada)	Open label, incomplete outcome data

Trials to date have been too small to address whether vaginal estrogen reduces the risk of urosepsis or death.

Endometrial safety of vaginal estrogens¹

The US Food and Drug Administration required that drug companies submit 52-week endometrial safety data which could support their use without the need for a concomitant progestogen. Products with this endometrial safety data include:

• Vagifem (estradiol) vaginal tablets: 10 mcg once daily for 2 weeks then twice a week (Note: Imvexxy softgel inserts also provide 10 mcg of estradiol and a lower 4 mcg dose with endometrial safety data due in 2026)
• Premarin (conjugated estrogens) vaginal cream: 0.3 mg (measured as 0.5 gram with the supplied applicator) twice a week or cyclically (21 days on, 7 days off)
• Estring (estradiol) vaginal ring: 2 mg delivered over 90 days

Patients should be counselled to report any unexpected vaginal bleeding. Estragyn (estrone) vaginal cream was approved by Health Canada without efficacy or safety data. For information on the use of vaginal estrogen products in people with a history of breast cancer, please refer to BC PAD’s handout.

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¹BC PAD Service Medications for Menopause-Associated Vasomotor and Genitourinary Symptoms (May 2025); ²KAUFFMAN J Urol 2025 (PMID:40298120; ³RAZ NEJM 1993 (PMID:8350884); ⁴ERIKSEN Am J Obestet Gynecol 1999 (PMID:10329858); ⁵CHEN Int Urogynecol J 2021 (PMID:32564121)