Local Oestrogen for Pelvic Floor Disorders: A Systematic Review

M A Weber, M H Kleijn, M Langendam, J Limpens, M J Heineman, J P Roovers, M A Weber, M H Kleijn, M Langendam, J Limpens, M J Heineman, J P Roovers

Abstract

Objective: The decline in available oestrogen after menopause is a possible etiological factor in pelvic floor disorders like vaginal atrophy (VA), urinary incontinence (UI), overactive bladder (OAB) and pelvic organ prolapse (POP). This systematic review will examine the evidence for local oestrogen therapy in the treatment of these pelvic floor disorders.

Evidence acquisition: We performed a systematic search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the non-MEDLINE subset of PubMed from inception to May 2014. We searched for local oestrogens and VA (I), UI/OAB (II) and POP (III). Part I was combined with broad methodological filters for randomized controlled trials (RCTs) and secondary evidence. For part I and II two reviewers independently selected RCTs evaluating the effect of topical oestrogens on symptoms and signs of VA and UI/OAB. In part III all studies of topical oestrogen therapy in the treatment of POP were selected. Data extraction and the assessment of risk of bias using the Cochrane Risk of Bias Tool was undertaken independently by two reviewers.

Evidence synthesis: The included studies varied in ways of topical application, types of oestrogen, dosage and treatment durations. Objective and subjective outcomes were assessed by a variety of measures. Overall, subjective and urodynamic outcomes, vaginal maturation and vaginal pH changed in favor of vaginal oestrogens compared to placebo. No obvious differences between different application methods were revealed. Low doses already seemed to have a beneficial effect. Studies evaluating the effect of topical oestrogen in women with POP are scarce and mainly assessed symptoms and signs associated with VA instead of POP symptoms.

Conclusion: Topical oestrogen administration is effective for the treatment of VA and seems to decrease complaints of OAB and UI. The potential for local oestrogens in the prevention as well as treatment of POP needs further research.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow chart local oestrogens for…
Fig 1. Flow chart local oestrogens for vaginal atrophy.
Fig 2. Risk of bias graph: review…
Fig 2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies regarding local oestrogen treatment for vaginal atrophy.
Fig 3. Risk of bias summary: review…
Fig 3. Risk of bias summary: review authors’ judgements about each risk of bias item for each included study regarding local oestrogen treatment for vaginal atrophy
Fig 4. Flow chart local oestrogens for…
Fig 4. Flow chart local oestrogens for urinary incontinence and overactive bladder.
Fig 5. Risk of bias graph: review…
Fig 5. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies regarding local oestrogen treatment for urinary incontinence and/or overactive bladder.
Fig 6. Risk of bias summary: review…
Fig 6. Risk of bias summary: review authors’ judgements about each risk of bias item for each included study regarding local oestrogen treatment for urinary incontinence and/or overactive bladder.
Fig 7. Flowchart local oestrogens for pelvic…
Fig 7. Flowchart local oestrogens for pelvic organ prolapse.
Fig 8. Risk of bias graph: review…
Fig 8. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies regarding local oestrogen treatment for pelvic organ prolapse.
Fig 9. Risk of bias summary: review…
Fig 9. Risk of bias summary: review authors’ judgements about each risk of bias item for each included study regarding local oestrogen treatment for pelvic organ prolapse.

References

    1. Iosif CS, Batra S, Ek A, Astedt B (1981) Estrogen receptors in the human female lower uninary tract. AmJObstetGynecol 141: 817–820.
    1. Chung dJ, Bai SW (2006) Roles of sex steroid receptors and cell cycle regulation in pathogenesis of pelvic organ prolapse. CurrOpinObstetGynecol 18: 551–554.
    1. Rud T, Andersson KE, Asmussen M, Hunting A, Ulmsten U (1980) Factors maintaining the intraurethral pressure in women. Invest Urol 17: 343–347.
    1. Matsubara S, Okada H, Shirakawa T, Gotoh A, Kuno T, et al. (2002) Estrogen levels influence beta-3-adrenoceptor-mediated relaxation of the female rat detrusor muscle. Urology 59: 621–625.
    1. Shenfeld OZ, McCammon KA, Blackmore PF, Ratz PH (1999) Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder. Urol Res 27: 386–392.
    1. Kenton K, Mueller ER (2006) The global burden of female pelvic floor disorders. BJUInt 98 Suppl 1: 1–5.
    1. Nygaard I, Barber MD, Burgio KL, Kenton K, Meikle S, et al. (2008) Prevalence of symptomatic pelvic floor disorders in US women. JAMA 300: 1311–1316. 10.1001/jama.300.11.1311
    1. Weber MA, Limpens J, Roovers JP (2014) Assessment of vaginal atrophy: a review. IntUrogynecolJ.
    1. Suckling J, Lethaby A, Kennedy R (2006) Local oestrogen for vaginal atrophy in postmenopausal women. [Review] [57 refs][Update of Cochrane Database Syst Rev. 2003;(4):CD001500; ]. Cochrane Database SystRev: CD001500.
    1. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A (2012) Oestrogen therapy for urinary incontinence in post-menopausal women. CochraneDatabaseSystRev 10: CD001405.
    1. Hendrix SL, Cochrane BB, Nygaard IE, Handa VL, Barnabei VM, et al. (2005) Effects of estrogen with and without progestin on urinary incontinence. JAMA 293: 935–948.
    1. Ewies AA, Alfhaily F (2010) Topical vaginal estrogen therapy in managing postmenopausal urinary symptoms: a reality or a gimmick? Climacteric 13: 405–418. 10.3109/13697137.2010.500748
    1. Cardozo L, Lose G, McClish D, Versi E (2004) A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder. Acta ObstetGynecolScand 83: 892–897.
    1. Benness CJ, Wise BG, Cutner A, Cardozo LD (1992) Does low dose vaginal estradiol improve frequency and urgency in postmenopausal women? (Abstract). Proceedings of the American Urogynecology Society, 13thannual meeting, Sept2730, 1992, Cambridge, Massachussetts 3: 281.
    1. Robinson D, Cardozo L, Milsom I, Pons ME, Kirby M, et al. (2013) Oestrogens and overactive bladder. NeurourolUrodyn.
    1. Kerkhof MH, Hendriks L, Brolmann HA (2009) Changes in connective tissue in patients with pelvic organ prolapse—a review of the current literature. Int Urogynecol J Pelvic Floor Dysfunct 20: 461–474. 10.1007/s00192-008-0737-1
    1. Moalli PA, Shand SH, Zyczynski HM, Gordy SC, Meyn LA (2005) Remodeling of vaginal connective tissue in patients with prolapse. Obstet Gynecol 106: 953–963.
    1. Reay Jones NH, Healy JC, King LJ, Saini S, Shousha S, et al. (2003) Pelvic connective tissue resilience decreases with vaginal delivery, menopause and uterine prolapse. BrJSurg 90: 466–472.
    1. Ismail SI, Bain C, Hagen S (2010) Oestrogens for treatment or prevention of pelvic organ prolapse in postmenopausal women. CochraneDatabaseSystRev: CD007063.
    1. US Department of Health and Human Services.Food and Drug Administration. (2003) Center for Drug Evaluation and Research (CDER). Guidance for Industry. Estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms—recommendations for clinical evaluation.
    1. US Department of Health an Human Services. (2006) Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Guidance for Industry. Patient-reported outcome measures: use in medical product development to support labeling claims.
    1. Raghunandan C, Agrawal S, Dubey P, Choudhury M, Jain A (2010) A comparative study of the effects of local estrogen with or without local testosterone on vulvovaginal and sexual dysfunction in postmenopausal women. J Sex Med 7: 1284–1290. 10.1111/j.1743-6109.2009.01667.x
    1. Simunic V, Banovic I, Ciglar S, Jeren L, Pavicic BD, et al. (2003) Local estrogen treatment in patients with urogenital symptoms. Int J Gynaecol Obstet 82: 187–197.
    1. Greendale GA, Zibecchi L, Petersen L, Ouslander JG, Kahn B, et al. (1999) Development and validation of a physical examination scale to assess vaginal atrophy and inflammation. Climacteric 2: 197–204.
    1. Bachmann G (1994) Vulvo-vaginal complaints: Lobo R, editor.
    1. Castelo-Branco C, Cancelo MJ, Villero J, Nohales F, Julia MD (2005) Management of post-menopausal vaginal atrophy and atrophic vaginitis. [Review] [32 refs]. Maturitas 52 Suppl 1: S46–S52.
    1. Manonai J, Theppisai U, Suthutvoravut S, Udomsubpayakul U, Chittacharoen A (2001) The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: a comparative study. J Obstet Gynaecol Res 27: 255–260.
    1. Bachmann G, Bouchard C, Hoppe D, Ranganath R, Altomare C, et al. (2009) Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally. Menopause 16: 719–727. 10.1097/gme.0b013e3181a48c4e
    1. McEndree B (1955) Clinical application of the vaginal maturation index. [Review] [31 refs]. Nurse Pract 24: 48–42.
    1. van der Laak JA, Schijf CP, Kerstens HM, Heijnen-Wijnen TH, de Wilde PC, et al. (1999) Development and validation of a computerized cytomorphometric method to assess the maturation of vaginal epithelial cells. Cytometry 35: 196–202.
    1. Schaffer J, Fantl JA (1996) Urogenital effects of the menopause. [Review] [69 refs]. Baillieres ClinObstetGynaecol 10: 401–417.
    1. Capobianco G, Donolo E, Borghero G, Dessole F, Cherchi PL, et al. (2012) Effects of intravaginal estriol and pelvic floor rehabilitation on urogenital aging in postmenopausal women. Arch Gynecol Obstet 285: 397–403. 10.1007/s00404-011-1955-1
    1. Dessole S, Rubattu G, Ambrosini G, Gallo O, Capobianco G, et al. (2004) Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women. Menopause 11: 49–56.
    1. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JO, et al. (1996) The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. AmJObstetGynecol 175: 10–17.
    1. Higgins JPT, Green S, editors (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane collaboration. Available from .
    1. Ayton RA, Darling GM, Murkies AL, Farrell EA, Weisberg E, et al. (1996) A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. BrJ Obstet Gynaecol 103: 351–358.
    1. Casper F, Petri E (1999) Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study. Vaginal Ring Study Group. Int UrogynecolJ Pelvic Floor Dysfunct 10: 171–176.
    1. Foidart JM, Vervliet J, Buytaert P (1991) Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Maturitas 13: 99–107.
    1. Jaisamrarn U, Triratanachat S, Chaikittisilpa S, Grob P, Prasauskas V, et al. (2013) Ultra-low-dose estriol and lactobacilli in the local treatment of postmenopausal vaginal atrophy. Climacteric 16: 347–355. 10.3109/13697137.2013.769097
    1. Lima SM, Yamada SS, Reis BF, Postigo S, Galvao da Silva MA, et al. (2013) Effective treatment of vaginal atrophy with isoflavone vaginal gel. Maturitas.
    1. Nachtigall LE (1995) Clinical trial of the estradiol vaginal ring in the U.S. Maturitas 22 Suppl: S43–S47.
    1. Nash HA, Alvarez-Sanchez F, Mishell DR Jr, Fraser IS, Maruo T, et al. (1999) Estradiol-delivering vaginal rings for hormone replacement therapy. Am J Obstet Gynecol 181: 1400–1406.
    1. Speroff L (2003) Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. Obstet Gynecol 102: 823–834.
    1. Bygdeman M, Swahn ML (1996) Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas 23: 259–263.
    1. Cano A, Estevez J, Usandizaga R, Gallo JL, Guinot M, et al. (2012) The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study. Menopause 19: 1130–1139.
    1. Dugal R, Hesla K, Sordal T, Aase KH, Lilleeidet O, et al. (2000) Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy. Acta Obstet Gynecol Scand 79: 293–297.
    1. Eriksen PS, Rasmussen H (1992) Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. EurJ Obstet Gynecol ReprodBiol 44: 137–144.
    1. Griesser H, Skonietzki S, Fischer T, Fielder K, Suesskind M (2012) Low dose estriol pessaries for the treatment of vaginal atrophy: a double-blind placebo-controlled trial investigating the efficacy of pessaries containing 0.2mg and 0.03mg estriol. Maturitas 71: 360–368. 10.1016/j.maturitas.2011.12.022
    1. Henriksson L, Stjernquist M, Boquist L, Alander U, Selinus I (1994) A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy. Am J Obstet Gynecol 171: 624–632.
    1. Melis GB, Paoletti AM, Murgia C, Piras B, Pilia I, et al. (1997) Vaginal estriol and benzidamine in the treatment of urogenital disorders during the postmenopause. <ORIGINAL> ESTRIOLO VAGINALE E BENZIDAMINA NEL TRATTAMENTO DEI DISTURBI UROGINECOLOGICI DEL CLIMATERIO. Giornale Italiano di Ostetricia e Ginecologia 19: 303–312.
    1. Nachtigall LE (1994) Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril 61: 178–180.
    1. Simon J, Nachtigall L, Gut R, Lang E, Archer DF, et al. (2008) Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet.[Erratum appears in Obstet Gynecol. 2008 Dec;112(6):1392]. Obstet Gynecol 112: 1053–1060. 10.1097/AOG.0b013e31818aa7c3
    1. Weisberg E, Ayton R, Darling G, Farrell E, Murkies A, et al. (2005) Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric 8: 83–92.
    1. Bruno RV (2012) Treatment of urogenital atrophy with the local administration of oestrogens: A randomized, controlled study in climateric and postmenopausal women. Revista Brasileira de Medicina 69: 230–235.
    1. Barentsen R, van de Weijer PH, Schram JH (1997) Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. EurJ Obstet Gynecol ReprodBiol 71: 73–80.
    1. Gupta P, Ozel B, Stanczyk FZ, Felix JC, Mishell DR Jr (2008) The effect of transdermal and vaginal estrogen therapy on markers of postmenopausal estrogen status. Menopause 15: 94–97.
    1. Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS (2000) 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause 7: 156–161.
    1. Bachmann G, Lobo RA, Gut R, Nachtigall L, Notelovitz M (2008) Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Obstet Gynecol 111: 67–76. 10.1097/01.AOG.0000296714.12226.0f
    1. Capobianco G, Wenger JM, Meloni GB, Dessole M, Cherchi PL, et al. (2014) Triple therapy with Lactobacilli acidophili, estriol plus pelvic floor rehabilitation for symptoms of urogenital aging in postmenopausal women. Arch Gynecol Obstet 289: 601–608. 10.1007/s00404-013-3030-6
    1. Cardozo LD, Wise BG, Benness CJ (2001) Vaginal oestradiol for the treatment of lower urinary tract symptoms in postmenopausal women—a double-blind placebo-controlled study. J Obstet Gynaecol 21: 383–385.
    1. Enzelsberger H, Kurz C, Schatten C, Huber J (1991) Effects of intravaginal application of oestriol tablets in women with urge incontinence. <ORIGINAL> ZUR WIRKSAMKEIT EINER INTRAVAGINALEN OSTRIOLTABLETTENAPPLIKATION BEI FRAUEN MIT URGE-INKONTINENZ. Geburtshilfe Frauenheilkd 51: 834–838.
    1. Sacco F, Rigon G, Carbone A, Sacchini D (1990) Transvaginal estrogen therapy of stress incontinence. Minerva Ginecol 42: 539–544.
    1. Holtedahl K, Verelst M, Schiefloe A (1998) A population based, randomized, controlled trial of conservative treatment for urinary incontinence in women. Acta Obstet Gynecol Scand 77: 671–677.
    1. Henalla SM, Millar DR, Wallace KJ (1990) Surgical versus conservative management for post-menopausal genuine stress incontinence of urine. NeurourolUrodyn 9: 436–437.
    1. Henalla SM, Hutchins CJ, Castleden CM (1989) Non-operative methods in the treatment of female genuine stress incontinence or urine. JObstetGynaecol 9: 222–225.
    1. Beisland HO, Fossberg E, Moer A, Sander S (1984) Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation. Urol Int 39: 211–216.
    1. Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell DR Jr (2011) Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause 18: 962–966. 10.1097/gme.0b013e3182104977
    1. Serati M, Salvatore S, Uccella S, Cardozo L, Bolis P (2009) Is there a synergistic effect of topical oestrogens when administered with antimuscarinics in the treatment of symptomatic detrusor overactivity? EurUrol 55: 713–719.
    1. Tseng LH, Wang AC, Chang YL, Soong YK, Lloyd LK, et al. (2009) Randomized comparison of tolterodine with vaginal estrogen cream versus tolterodine alone for the treatment of postmenopausal women with overactive bladder syndrome. NeurourolUrodyn 28: 47–51.
    1. Lose G, Englev E (2000) Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. BJOG 107: 1029–1034.
    1. Enzelsberger H, Schatten C, Kurz C, Zorzi P (1990) [Treatment of female urge incontinence by local estrogen therapy]. [German]. GynakolRundsch 30 Suppl 1: 235–236.
    1. Long CY, Liu CM, Hsu SC, Chen YH, Wu CH, et al. (2006) A randomized comparative study of the effects of oral and topical estrogen therapy on the lower urinary tract of hysterectomized postmenopausal women. Fertil Steril 85: 155–160.
    1. Felding C, Mikkelsen AL, Clausen HV, Loft A, Larsen LG (1992) Preoperative treatment with oestradiol in women scheduled for vaginal operation for genital prolapse. A randomised, double-blind trial. Maturitas 15: 241–249.
    1. Nikas I, Koundouri MRA, Gavriil I, Kilbasanis I (2012) Management of cystocele with associated urine incontinence in menopausal women. Maturitas Conference: 9th European Congress on Menopause and Andropause Athens Greece. Conference Start: 20120328 Conference End: 20120331. Conference Publication:: S74.
    1. Vaccaro CM, Crisp CC, Estanol MV, Fellner AN, Mutema GK, et al. (2011) Administration of vaginal estrogen in women with vaginal atrophy prior to prolapse surgery: An assessment of quality of life outcomes and medication adherence. International Urogynecology Journal and Pelvic Floor Dysfunction Conference: 36th Annual Meeting of the International Urogynecological Association, IUGA 2011 Lisbon Portugal. Conference Start: 20110628 Conference End: 20110702. Conference Publication:: S1839-S1840.
    1. Rees M, Perez-Lopez FR, Ceasu I, Depypere H, Erel T, et al. (2012) EMAS clinical guide: low-dose vaginal estrogens for postmenopausal vaginal atrophy. Maturitas 73: 171–174. 10.1016/j.maturitas.2012.06.009
    1. Smith P (1993) Estrogens and the urogenital tract. Studies on steroid hormone receptors and a clinical study on a new estradiol-releasing vaginal ring. Acta ObstetGynecolScandSuppl 157: 1–26.

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