Topical estriol gel prevents UTI, improves vaginal health in postmenopausal women

Ultra-low-dose 0.005 % estriol vaginal gel helps reduce the incidence of recurrent urinary tract infections (UTIs) and improve vaginal pH in postmenopausal women with genitourinary syndrome of menopause (GSM), as reported in a study.

In a cohort of 108 postmenopausal women, the incidence rate of UTIs by the end of the 24-week treatment was 26 percent lower among women who received the vaginal estriol gel than among those who received an identical vaginal gel without estriol (control) (32.34 vs. 43.76 per 100 person-years; incidence rate radio [IRR], 0.7390, 95 percent confidence interval [CI], 0.6459–0.8455; p<0.001). [Maturitas 2024;190:108128]

“All women using the ultra-low-dose 0.005 % estriol vaginal gel reported a decrease in the number of UTI episodes. Specifically, 86.8 percent reported no UTI, while the remaining 13.2 percent reported experiencing only one UTI episode. Therefore, all patients in the active arm improved, [with] the frequency of UTI episodes [decreasing] to less than two episodes during the 24 weeks of treatment,” the investigators noted.

Favourable changes in vaginal pH in the estriol group were observed at all time points relative to baseline, with a reduction of 7.28 percent at 3 weeks (p<0.001), 7.73 percent at 12 weeks (p<0.01), 6.64 percent at 18 weeks (p<0.05), and 8.42 percent at 24 weeks (p<0.05). In contrast, no significant changes were seen in the control arm.

“Although no significant differences were found between pH and the presence of UTIs, previous studies have linked the improvement in vaginal pH produced by estriol could potentially result in a lower susceptibility and less frequent urogenital infections, which are very prevalent in this group of women,” according to the investigators. [Menopause 2012;19:1130-1139]

As for safety, adverse events (AEs) were documented in 71 women (61.7 percent) overall, including AEs related to the study drug in 10 women (17.5 percent) in the estriol arm and 16 (27.6 percent) in the control arm (p<0.05). AEs led to treatment discontinuation in two estriol-treated women (vaginal irritation and fungal infection) and six of those who received the control treatment. Most AEs recorded in the estriol group were mild and related to the symptoms of the disease.

“Only one patient in the control arm reported vaginal bleeding of moderate intensity, which led to the permanent interruption of study treatment. No bleeding episodes were found in the active arm,” the investigators said.

Minimal estrogenic exposure

Of the 141 postmenopausal women enrolled in the study, 115 (estriol arm n=57, control arm n=58) carried out the baseline visit, underwent randomization, and received at least one dose of the study drug. All 115 women were included in the safety analysis, while 108 were included in the efficacy analysis (estriol arm n=53, control arm n=55). The mean age of the cohort was 65 years, with a mean weight of 64.58 kg and a mean height of 160.56 cm. Most women (89 percent) underwent natural menopause, and all of them reported vaginal dryness as a symptom of vaginal atrophy. More than half (67 percent) had a minimum of two UTIs in the 6 months preceding the enrolment in the study.

“Our results provide clinical evidence on the efficacy and safety of an ultra-low-dose 0.005 % estriol vaginal gel in preventing recurrent UTIs in postmenopausal women with GSM,” the investigators said.

They pointed out that the ultra-low-dose 0.005 % estriol vaginal gel formulation is in line with the recommendation to use the lowest effective hormone dose treatments and offers a tenfold reduction in estrogen use relative to other GSM treatments. [Menopause 2010;17:242-255; Menopause 2012;19:1130-1139]

“The data from this study suggest that this risk minimization in estrogen exposure does not compromise the effectiveness of the intervention in reducing UTIs in women with symptoms of GSM, obtaining efficacy results in line with hormones of greater potency and exposure,” according to the investigators. [JAMA 2023;329:405-420]

Antibiotic alternative

The findings have important clinical implications, given that more than half of women who will have a UTI in their lifetime will experience recurrent UTIs and be exposed to antibiotics, according to the investigators. This could potentially leading to antimicrobial resistance, which can make treatment considerably more difficult, they said. Additionally, the use of antibiotics modifies the microbiota with a negative consequential impact on long-term health. [BJU Int 2022;130:11-22; Urol Clin North Am 2022;49:283-297; Am J Med 2022;135:236-244]

The investigators highlighted the potential of ultra-low-dose estriol vaginal gel as a low-risk preventive measure that could be used as an alternative to antibiotic prophylaxis, particularly among women prone to recurrent UTI episodes.

“In our study, high compliance, excellent acceptability, safety and tolerability shown in the estriol arm after 24 weeks of intervention indicate the benefits of an ultra-low-dose estriol vaginal gel, while minimizing systemic and local side effects due to its minimal hormonal exposure. This results in an exceptional balance between benefits and risks,” they said. [Gynecol Endocrinol 2020;36:535-539]