The Role of Local Hormone Replacement in Overactive Bladder
Purpose of Review
Overactive bladder (OAB) is a common and distressing condition which is known to increase with age and to have a significant effect on quality of life (QoL). Whilst OAB is a symptomatic diagnosis, many patients will require basic investigations prior to initiating the appropriate management. This paper will explore the prevalence and pathophysiology of OAB as well as diagnosis and management of the condition.
There is increasing evidence that local oestrogen therapy may be beneficial in the management of postmenopausal women with OAB, either when used alone or as combination therapy with an antimuscarinic drug. This paper will review the postulated mechanisms of action as well as exploring the available evidence base supporting efficacy.
There is now a substantial evidence base to support the use of local vaginal oestrogen therapy in postmenopausal women with OAB either in isolation or alternatively as an adjunctive therapy when used with antimuscarinic medication. Available evidence supports an improvement in lower urinary tract symptoms as well as a significant improvement in health-related quality of life (HRQoL).
KeywordsOestrogen Vaginal oestrogen Overactive bladder OAB Detrusor overactivity Antimuscarinics
Compliance with Ethical Standards
Conflict of Interest
Dudley Robinson has received fees for Consultancy work and Speaking from Astellas, Allergan, Ixaltis, Contura and Ferring. He has performed Research with Astellas, Ixaltis and Allergan. Linda Cardozo has received fees for Consultancy work and Speaking from Atlantic Therapeutics, Boston and Allergan.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, et al. An International Urogynaecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010;21:5–26. Standardisation of lower urinary tract terminology document. PubMedCrossRefPubMedCentralGoogle Scholar
- 2.Stewart WF, Corey R, Herzog AR, et al. Prevalence of overactive bladder in women: results from the NOBLE program. Int Urogynaecol. J. 2001;12(3):S66.Google Scholar
- 7.Braverman AS, Ruggieri MR. The M2 receptor contributes to contraction of the denervated rat urinary bladder. Am J Physiol. 1998;275:1654.Google Scholar
- 10.Nixon A, Colman S, Sabounjian L, et al. A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials. JUrol. 2005;174:604–7.Google Scholar
- 17••.NICE Guideline (NG123). The Management of Urinary Incontinence in Women. Department of Health. www.nice.org.uk. 2019. Recent update of the National UK guidelines.
- 18••.Dumoulin C, Adewuyi T, Booth J, Bradley C, Burgio K, Hagen S, Hunter K, Imamura M, Morin M, Morkved K, Thakar R, Wallace S, Williams K. Adult Conservative Management. In: Incontinence, 6th Edition. Abrams P, Cardozo L, Wagg A, Wein A, editors. IUCD ICS 1443-1628. 2017. Sixth report of the International Consultation on Incontinence. Google Scholar
- 19••.Prasad Rai B, Cody JD, Alhasso AA, Stewart L. Anticholinergic drugs versus non drug active therapies for overactive bladder syndrome in adults. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.CD003193.pub4Cochrane review examining the efficacy of antimuscarinic therapy in overactive bladder.
- 20••.Andersson KE, Cardozo L, Cruz F, Lee KS, Sahai A, Wein AJ. Pharmacological treatment of urinary incontinence. In Incontinence, 6th Edition. Abrams P, Cardozo L, Wagg A, editors. Wein IUCD ICS 805 - 958. 2017. Sixth report of the International Consultation on Incontinence. Google Scholar
- 27•.Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics ad incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175:401–7. A prospective study looking at the association of anticholinergic drug usage and the long term risk of cognitive decline.PubMedPubMedCentralCrossRefGoogle Scholar
- 28••.www.ageingbraincare.org/uploads/products/ACB_Scale_-_legal_size.pdf. An Anticholinergic Burden scale which is useful in clinical practice.
- 32.Hicks A, McCafferty G, Riedel E, Aiyar N, Pullen M, Evans C, et al. GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. J Pharmacol Exp Ther. 2007;323:202–9.PubMedCrossRefPubMedCentralGoogle Scholar
- 33.Khullar V, Amarenco G, Angulo JC, Cambronero J, Hoye K, Milsom I, et al. Efficacy and tolerability of mirabegron, a beta 3 adrenoreceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase III trial. Eur Urol. 2013;63:283–95.PubMedCrossRefPubMedCentralGoogle Scholar
- 34.Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, et al. Randomised double-blind, active-controlled phase III study to assess 12 month safety and efficacy of mirabegron, a beta 3 adrenoreceptor agonist, in overactive bladder. Eur Urol. 2013;63:296–305.PubMedCrossRefPubMedCentralGoogle Scholar
- 35.Drake MJ, Chapple C, Esen AA, Athanasiou S, Cambronero J, Mitcheson D, et al. Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4-week solifenacin monotherapy: a randomised double blind muticentre phase 3B study (BESIDE). Eur Urol. 2016;70:136–45.PubMedPubMedCentralCrossRefGoogle Scholar
- 44.Samsicoe G, Jansson I, Mellstrom D, Svanberg A. Urinary incontinence in 75 year old women. Effects of oestriol. Acta. Obstet. Gynaecol. Scand. 1985;93:57.Google Scholar
- 46.Benness C, Wise BG, Cutner A, Cardozo LD. Does low dose vaginal oestradiol improve frequency and urgency in postmenopausal women. Int. Urogynaecol. J. 1992;3(2):281.Google Scholar
- 48.Cardozo L, Lose G, McClish D, Versi E. Estrogen treatment for symptoms of an overactive bladder, results of a meta analysis. Int J Urogynaecol. 2001;12(3):V.Google Scholar
- 49•.Tseng LH, Wang AC, Chang YL, Soong YK, Lloyd LK, Ko YJ. Randomized comparison of tolterodine with vaginal estrogen cream versus tolterodine alone for the treatment of postmenopausal women with overactive bladder syndrome. Neurourol Urodyn. 2009;28(1):47–51. A small but important study examining the synergistic usage of vaginal oestrogen therapy and antimuscarinic medication in the management of OAB. PubMedCrossRefPubMedCentralGoogle Scholar
- 50•.Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell DR. Radomised trial of oestradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause. 2011;18:962–6. A small but important study examining the synergistic usage of vaginal oestrogen therapy and antimuscarinic medication in the management of OAB. PubMedCrossRefPubMedCentralGoogle Scholar
- 51.Jiang F, Zhu L, Xu T, Gong MY, Huang YL, Li HF, et al. Menopause. 2016;23:451–7. A small but important study examining the synergistic usage of vaginal oestrogen therapy and antimuscarinic medication in the management of OAB. Google Scholar
- 52•.Chughtai B, Forde JC, Buck J, Asfaw T, Lee R, Te AE, et al. The concomitant use of fesoterodine and topical vaginal oestrogen in the management of overactive bladder and sexual dysfunction in post menopausal women. Post Reprod Health. 2016;22:34–40 A small but important study examining the synergistic usage of vaginal oestrogen therapy and antimuscarinic medication in the management of OAB.PubMedCrossRefPubMedCentralGoogle Scholar
- 53•.Serati M, Salvatore S, Uccella S, Cardozo L, Bolis P. Is there a synergistic effect of topical oestrogens when administered with antimuscarinics in the treatment of symptomatic detrusor overactivity? Eur Urol. 2009;55(3):713–9. A small but important study examining the synergistic usage of vaginal oestrogen therapy and antimuscarinic medication in the management of detrusor overactivity. PubMedCrossRefPubMedCentralGoogle Scholar
- 54••.Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in postmenopausal women. Cochrane Database Syst Rev. 2012:CD001405. A Cochrane review of the use of topical and systemic oestrogen therapy in postmenopausal women with urinary incontinence. Google Scholar
- 55••.Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for pelvic floor disorders: a systematic review. PLoS One. 2015;10(9):e0136265. A systematic review of local oestrogen therapy in the management of pelvic floor dysfunction. PubMedPubMedCentralCrossRefGoogle Scholar