Anticholinergics and B3 agonists are the mainstay of medical treatment for overactive bladder (OAB).Research has also demonstrated efficacy of vaginal oestrogen for OAB. This systematic review aims to evaluate the use of combined therapy (vaginal oestrogen + OAB medication) versus monotherapy (OAB medication alone) in the treatment of OAB symptoms. We hypothesised combination therapy would offer a significant benefit in OAB outcomes when compared to monotherapy.

The project was registered with Prospero. A literature search was conducted using Embase, Medline and CINAHL. Articles were screened by two reviewers in accordance with PRISMA. Statistical analyses were performed using Review Manager. Newcastle-Ottawa Scale was used for quality assessment.There was  6 studies that were included in the review. They were published from 2008-2018. 5 of the studies were randomized and 1 was not. The number of participatnt varied from 23-229. The length of follow up varied from 12 weeks to 12 months. 3 of the studies used tolterodine, 2 of the studies used fesoterodine and one study used solifenacin. Of note, none of the studies used mirabegron although we did include it in our literature search.   All of the studies used vaginal estrogen but the dosage and frequency varied between the studies

Results: Initial search yielded 17 results. After screening, 6 articles were included in qualitative synthesis and 5 in quantitative synthesis. 5 studies were randomised controlled trials and 1 was non-randomised. All articles were of good quality (7 points Newcastle- Ottawa scale). Total number of participants was 557. 3 studies reported combination therapy is associated with significantly greater improvements in OAB symptoms, Health- related quality of life (HRQL) and sexual function. 3 studies reported no significant difference in OAB symptoms between monotherapy and combination therapy. When data were pooled: there was no significant difference between combination therapy and monotherapy for OAB symptoms (SMD-0.26[-0.56,0.05]p=0.07,I2=54%) and health related quality of life (SMD-0.15[-0.41,0.10]p=0.24,I2=0%). There was a significantly greater reduction in urinary frequency in the combination group compared with monotherapy (SMD-0.36[-0.63,-0.08]p=0.01,I2=0%).

Most studies report benefit of adding vaginal estrogen to anticholinergic medication for overactive bladder symptoms, improvement in health related quality of life questionaire and sexual function. Our meta-analysis showed only significance in the number of micturition.

Data comparing combination therapy and monotherapy for overactive bladder are conflicting. Meta-analysis demonstrated benefit in the reduction in frequency but failed to demonstrate significance in other OAB symptoms and HRQL. Further research is required to determine the benefit of vaginal oestrogen in this context.

1.National Institute for Health and Care Excellence (NICE). Urinary incontinence and pelvic organ prolapse in women: management. NICE guideline 2019. https://www.nice.org.uk/guidance/ng123 [ accessed 10/9/23]
2. Cardozo L, Lose G, McClish D, Versi E. A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder. Acta Obstet Gynecol Scand. 2004 Oct;83(10):892-7. doi: 10.1111/j.0001-6349.2004.00581.x.