Combined Tolterodine and Vaginal Estradiol Cream for Overactive Bladder Symptoms After Randomized Single-Therapy Treatment

Abstract

Objectives To compare 12 week outcomes of single-therapy tolterodine (Detrol LA ®) extended release to intravaginal estrogen (Estrace ®) for overactive bladder (OAB) symptoms and characterize 24 and 52 week outcomes in women undergoing combined therapy. Methods A single-site randomized, open-label trial in women with urinary frequency, urgency, nocturia, and/or urgency urinary incontinence symptoms was performed. Fifty-eight participants were randomized to oral tolterodine extended release daily or intravaginal estradiol cream nightly for six weeks then twice per week. The primary outcome was change in OAB-questionnaire (OAB-q) symptom bother score at 12 weeks. Secondary outcomes included the health-related quality of life (HRQL) of the OAB-q and a 3-day bladder diary. At 12 weeks, subjects were offered addition of the alternative therapy with follow-up at 24 and 52 weeks. Results There was no difference in symptom bother score improvement between the tolterodine and intravaginal estradiol groups baseline to 12 weeks (20.6±21.7, −15.8±23.3, respectively, p=0.45). There was a significant within group decrease in symptom bother score from baseline to 12 weeks (tolterodine, p < 0.0001, and intravaginal estradiol, p = 0.002). Secondary outcome improvement within groups was noted in the HRQL total, UI episodes and median voiding frequency (all p≤0.03) in the tolterodine group and in the HRQL total score (p=0.03) in the intravaginal estradiol group; with no differences between groups. Combined therapy outcomes at 24 and 52 weeks compared to single therapy at 12 weeks revealed significant improvement in symptom bother score in the intravaginal estradiol +tolterodine group at 24 and 52 weeks (20.0±23.9, p=0.008; −16.7±23.3, p=0.02, respectively) Conclusions Significant within group improvement in OAB-q symptom bother was noted in both the intravaginal estradiol and tolterodine groups for OAB symptoms, with no difference between groups. Greater improvement from 12 week single therapy to 24 and 52 weeks of combined therapy was noted in the group originally assigned to intravaginal estradiol. The role of combined medical therapy for OAB symptoms needs further investigation.

Combination therapy in overactive bladder‐untapped research opportunities: A systematic review of the literature

“…We find it interesting that despite many combination therapy studies being less than robust in terms of design or number of patients studied, there is a significant body of research assessing the utility of off‐label treatments in combination with approved OAB therapies. Several of these studies focus on nonapproved neuromodulation techniques that have yet to undergo proper clinical trials (even as monotherapies) while in other studies, the use of off‐label medications such as desmopressin, pregabalin, vaginal estrogen, and Weng‐li‐Tong (an herbal medicine) were investigated . Interestingly, several of these combinations were able to elicit a clinical benefit with improvements in OAB symptoms compared to monotherapy, however, as these treatments are not standard of care, it is not clear if they will garner widespread use.…”

“…Several of these studies focus on nonapproved neuromodulation techniques that have yet to undergo proper clinical trials (even as monotherapies) while in other studies, the use of off-label medications such as desmopressin, pregabalin, vaginal estrogen, and Weng-li-Tong (an herbal medicine) were investigated. 42,43,49,50,64,65 Interestingly, several of these combinations were able to elicit a clinical benefit with improvements in OAB symptoms compared to monotherapy, however, as these treatments are not standard of care, it is not clear if they will garner widespread use. In addition, given a lack of data examining approved OAB therapies in combination, it is likely prudent that future efforts should be focused on combining guideline treatments first.…”

“…In addition to the 32 studies included in our systematic review, we encountered another 13 that investigate nonapproved OAB therapies in combination with an approved OAB therapy. [38][39][40][41][42][43][44][45][46][47][48][49][50] Overall, these studies were generally underpowered due to small sample sizes and demonstrate variable OAB improvements (Table 4).…”

Mouse urothelial genes associated with voiding behavior changes after ovariectomy and bladder lipopolysaccharide exposure

“…Therefore, mechanisms underlying the host response, manifested as increased voiding frequency symptoms, in response to urinary bacteria whether from FUM or uropathogens, deserve investigative efforts. Estrogen has been shown to be effective in treating both OAB and recurrent UTI . Thus estrogen (or lack of it during menopause) plays a role in modulating the host response of voiding behavior.…”

“…Estrogen has been shown to be effective in treating both OAB and recurrent UTI. 5,6 Thus estrogen (or lack of it during menopause) plays a role in modulating the host response of voiding behavior.…”