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Int Urogynecol J (2015) 26:3–13

DOI 10.1007/s00192-014-2554-z


Vaginal estrogen use in postmenopausal women with pelvic
floor disorders: systematic review and practice guidelines
David D. Rahn & Renée M. Ward & Tatiana V. Sanses & Cassandra Carberry & Mamta M. Mamik &
Kate V. Meriwether & Cedric K. Olivera & Husam Abed & Ethan M. Balk & Miles Murphy &
for the Society of Gynecologic Surgeons Systematic Review Group

Received: 9 September 2014 / Accepted: 18 October 2014 / Published online: 13 November 2014
# The International Urogynecological Association 2014

Abstract efficacy outcomes, and adverse events, and they were indi-
Introduction and hypothesis Risk of pelvic floor disorders vidually and collectively assessed for methodological quality
increases after menopause and may be linked to estrogen and strength of evidence.
deficiency. We aimed to systematically and critically assess Results Evidence was generally of poor to moderate quality.
the literature on vaginal estrogen in the management of pelvic Vaginal estrogen application before pelvic organ prolapse
floor disorders in postmenopausal women and provide surgery improved the vaginal maturation index and increased
evidence-based clinical practice guidelines. vaginal epithelial thickness. Postoperative vaginal estrogen
Methods MEDLINE and Cochrane databases were searched use after a midurethral sling resulted in decreased urinary
from inception to July 2014 for randomized controlled trials of frequency and urgency. Vaginal estrogen and immediate-
commercially available vaginal estrogen products compared release oxybutynin were similar in improvement of urinary
with placebo, no treatment, or any medication for overactive urgency, frequency, and urgency urinary incontinence in
bladder or urinary incontinence. We double-screened 1,805 women with overactive bladder, but oxybutynin had higher
abstracts and identified 12 eligible papers. Studies were ex- rates of side effects and discontinuation. Conversely, the ad-
tracted for participant information, intervention, comparator, dition of vaginal estrogen to immediate or extended-release

This review and guidelines were presented at the 40th Annual Scientific
Meeting of the Society of Gynecologic Surgeons in Scottsdale, AZ, USA,
on 24 March 2014
Electronic supplementary material The online version of this article
(doi:10.1007/s00192-014-2554-z) contains supplementary material,
which is available to authorized users
D. D. Rahn (*) K. V. Meriwether
Department of Obstetrics and Gynecology, University of Texas University of New Mexico Health Sciences Center, Albuquerque,
Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, NM, USA
TX 75390-9032, USA
H. Abed
R. M. Ward Henry Ford Health System, Detroit, MI, USA
Vanderbilt University Medical Center, Nashville, TN, USA

T. V. Sanses
University of Maryland School of Medicine, Baltimore, MD, USA E. M. Balk
Center for Evidence Based Medicine, Brown University School of
C. Carberry Public Health, Providence, RI, USA
Women and Infants Hospital/Alpert Medical School of Brown
University, Providence, RI, USA
M. Murphy
M. M. Mamik : C. K. Olivera Institute for Female Pelvic Medicine and Reconstructive Surgery,
Icahn School of Medicine at Mount Sinai, New York, NY, USA North Wales, PA, USA

with the balance of these benefits and harms Introduction used to generate evidence-based clinical practice guidelines. Similarly. tablets. Nine percent of menopausal women receiving a were also permitted as comparators. 12]. have minimal effectiveness in the management of pel- ment in stress urinary incontinence with use of vaginal vic floor disorders or that its utility might be underap- estrogen. Menopause . and was limited to English-language comparative stud- of POP after surgery is common [5]. recurrence nence.. perioperative use of vag. preciated. overactive bladder (OAB). and we did not medications have only a modest treatment effect with contact study authors. With increasing age. 2]. overactive bladder. We searched MEDLINE and dicate that the menopause is a major risk factor for the devel. clear reluctance of patients to continue vaginal estro. The Society of Gynecologic Surgeons (SGS) Keywords Incontinence . urgency urinary incontinence. Systematic Group Review (SRG) aimed to systemati- Pelvic organ prolapse .4 Int Urogynecol J (2015) 26:3–13 tolterodine did not improve urinary symptoms more therapy) suggests either that vaginal estrogen might than tolterodine alone. able vaginal estrogen creams. or incontinence in postmenopausal women. including an aging population. common side effects and high discontinuation rates [7]. USA. Participants of interest were postmenopausal women for Systemic estrogen replacement does not treat [8]. of vaginal estrogen replacement on urinary inconti. pelvic floor disorders increase in frequency. urogynecological complaints. no intervention. including pelvic Materials and methods organ prolapse (POP). and whom vaginal estrogen was considered preoperatively before may aggravate stress [9] and urgency [10] urinary planned repair of POP or after pelvic reconstructive surgery. 4]. Although it The overall search focused on two populations: women with a is difficult to separate the effects of declining estrogen levels general genitourinary syndrome of menopause (i. nocturia. urinary inconti- Despite innovations in surgical technique. Forty-one products not FDA-approved but commonly used outside the percent of women have long-term safety concerns. of patients who have surgery need a repeat operation Reference lists of selected articles and review papers were within 10 years [6]. suppositories. but the impact presenting with urogynecological complaints such as OAB. and those interest were patient-reported subjective changes in urinary who do fill prescriptions for estrogen creams typically symptoms including urinary frequency. pelvic floor disorders in coming decades [1. Overactive bladder . and oral agents (not oral 30 % are particularly apprehensive about breast cancer estrogens) used for urinary incontinence and OAB treatment [11]. and rings inal estrogen replacement in postmenopausal women intended for local (not systemic) absorption/therapy were may have an impact upon postoperative outcomes. Relevant to studies of perioperative use of vaginal estrogen gens (or physician disinclination to recommend were measures of objective tissue atrophy and inflammation: . including estriol Patients are wary of estrogen treatment. pelvic organ prolapse. forecast a marked comparing vaginal estrogen application with other interven- increase in demand for health care and therapies for these tions following standard systematic review methodology [13]. who are covered in a separate review organs and their surrounding muscular and connective tissue [14]. ment of pelvic floor disorders in postmenopausal wom- en. a need exists for a compre- Conclusion Vaginal estrogen application may play a useful hensive. in menopause from aging in general. First-line medications for the treat. In either case. This urgency. All commercially avail- nence is not clear. and a smaller population presenting specifically with support are estrogen-responsive. urgency.e. and UTI frequency. and the symptoms and inception through 15 July 2014. Cochrane Central Register of Controlled Trials from their opment of pelvic floor disorders. Aging is a well-known factor affecting pelvic floor and lower urinary tract anatomy and function. reconstructive surgery. stress uri- nary incontinence (SUI). anticholinergic to identify unpublished articles or abstracts. allowed as interventions and comparators. and sexual dysfunction. or SUI. discontinue therapy after just 3 months [11. pelvic menopause [3. Placebo. and up to 17 % ies in humans (see Appendix A for complete search details). epidemiological studies in. The search included numer- severity of these disorders increase significantly after the ous terms for estrogen products. screened for additional eligible references. Vaginal estrogen cally and critically assess the efficacy and safety of vaginal estrogens in the management of pelvic floor disorders. systematic review of the efficacy and safety of role as an adjunct in the management of common pelvic floor vaginal estrogens and their alternatives in the manage- disorders in postmenopausal women. We did not attempt ment of OAB are also disappointing. it is clear that the pelvic vulvovaginal atrophy). A number of We performed a search to identify randomized controlled trials factors. One study reported an improve. and stress urinary incontinence. The main outcomes of vaginal estrogen prescription never fill it.

The or after (3 studies) [24–26] pelvic reconstructive surgery or as following data were collected: study characteristics (year. histological thickness harm. all with experience in the of a second review [14]. The quality of lance. March 2014 and posted on the SGS website. Studies were graded as being of good (A). 2 and 3) and assessed customized forms in the Systematic Review Data Repository the utility of vaginal estrogen given before (4 studies) [20–23] (SRDR) and can be accessed at http://srdr. Perioperative estrogen the AHRQ [18]. physi- of the vaginal epithelium and muscularis. after which sociated with strong urge to void. moderate. Assessment. length of follow-up. fair trials had study durations that varied from 12 weeks of preop- (B). Abstract screening was interventions. a treatment for OAB or SUI (5 studies) [27–31] and are the design. Individual reviewers The search identified 1. [dose. tion was up to 12 weeks. preoperative use of vaginal estrogen before prolapse repair. This strength of recom.. and full texts (when necessary) were Results double-screened for eligibility by nine reviewers.brown. The wording and its implications for patients. including public comment at the 40th SGS Annual Scientific Meeting in maximum bladder capacity. study search and systematic review is shown in Fig. outcomes of interest. Study arm predefined criteria from a three-category system modified from sample sizes ranged from 12 to 129. the likelihood erative medication use up to 3 years of postoperative surveil- of biases. and other factors participants (Table 1) [20–23]. Vaginal estrogen use in the OAB and SUI subpopula- individual outcomes was separately graded within each study.ahrq. serum estradiol Discussion. i. outcome descriptions and results. “we recom. we generated an “evidence profile” by grading Among women with POP planning surgical repair. Development and Evaluation such as epithelial and subepithelial thickness serving as sur- (GRADE) system [19]. 96 full-text articles were evaluated in detail. and policy makers are detailed further in the granulation tissue.805 citations. After title and abstract recused themselves from the evaluation. directness of evidence. and the presence of cians. and the overall quality of maturation index at the time of surgery (high-quality evidence (high [A] to very low [D]). and poor in 1 study. Use of vaginal estrogen improved the vaginal mend” or 2=weak. For each grouping. and urodynamic measures were extracted. low. healing. ventions were provided for 2 to 12 weeks preoperatively with ing the balance between benefits and harms of the compared patient surveillance continuing from the time of surgery [20. data extraction. beneficial. 1. medication details good in 4 studies. vaginal maturation index. Overall quality of evidence was poor. Adverse events and discontinuation rates and reasons were also collected. frequency. comparators or study design.cebm. postoperative use after Preoperative vaginal estrogen before prolapse repair pelvic reconstructive surgery. volume as. lack of blinding. consistency of various methods with placebo (or no treatment) with 111 total results across studies. overall quality of evidence in accordance with the Grades for largely because of the sparseness of evidence and outcomes Recommendation. but this did not translate to in- that adherence to the recommendation will do more good than creased vaginal subepithelial/muscularis thickness (low . length of follow-up). 3 studies the quality of evidence for each outcome across studies. and very low. No vaginal estrogen was given such as imprecision or sparseness of evidence to determine an following surgery. The inter- Guideline statements were then developed by incorporat. Endometrial biopsy results. “we suggest”). 44 (47 articles) reported women presenting [15]. and poor clarity of results reporting. abstracts. fair in 7 studies. and maximum urethral closure pressure. duration]. and use for OAB and SUI. and the completeness of reporting. 22. or poor (C) quality based on scientific merit. evidence) [20. subject of this review. maximum flow rate. comments were solicited for 4 weeks. The and screening. number enrolled/analyzed. 23] until 4 weeks [20] to 3 years [21] postoperatively. Data were extracted into urogynecological population (Tables 1. with discrep- ancies adjudicated by a third reviewer. 22] and increased vaginal epithelial thickness mendation indicates the extent to which one can be confident (low quality) [ maining studies. and long-term integrity of surgical repair. Thirty- quality grading of any study they in which they were involved seven of these were rejected primarily because of ineligible or for which they had co-authorship. 17]. detrusor overactivity. 23]. The review and guidelines were presented for levels. This system categorizes based on four rogate outcomes for tissue quality. interventions and the overall quality of evidence across all 22.Int Urogynecol J (2015) 26:3–13 5 vaginal pH. Each guideline received a “grade” in two It is uncertain whether preoperative vaginal estrogen was parts: the strength of recommendation (1=strong. intervention (type of estrogen. unclear or inappropriate randomization We assessed the methodological quality of each study using technique. Overall study quality was deemed to be patient age. Data extraction was then completed in duplicate by the with genitourinary syndrome of menopause and are the topic same nine independent reviewers.e. Studies were grouped by sub-population. A flow diagram of the postvoid residual. postoperative wound quality ratings: high. Among the re- conducted using Abstrackr (http://abstrackr. The remaining 12 studies involved a systematic review process [16. and Downgrades in quality were commonly due to small sample comparator). size. This (in 4 papers) compared preoperative vaginal estrogen by process considered the methodological quality.

secretory.. Regarding safety. Use in OAB (n=3) or SUI (n=2) population: n=5 (5) quality) [22. MUS midurethral sling.710 Full-text articles Full-text articles reviewed and excluded from assessed systematic review: n=37 n=96 • Study design (e.g.6 Int Urogynecol J (2015) 26:3–13 Fig.. gave vaginal estradiol tablets (25 μg) and creased the frequency of bacteriuria in the first postoperative estriol ovules respectively. non-comparative or systematic review): n=11 • Wrong population (e. with decreased prevalence or severity of urinary frequen- (9 %) receiving 3 weeks of daily preoperative 25 μg vaginal cy and urgency (moderate quality) [24. Postoperative use after MUS (n=2) or POP repair (n=1): n=3 (3) 3. Using vaginal estrogen preoperatively de. Data were insufficient to a vaginal estradiol ring (Estring®) or placebo ring for 12 weeks compare subjective measures of other urinary complaints. 23]. laboratory or eligible for non-clinical outcomes only): n=6 systematic review • Duplicate Publication: n=2 n= 56 (59) Trials (articles) in postmenopausal GSM population n= 44 (47) (secondary review) Trials (articles) in population with pelvic floor disorders n= 11 (12) 1. Karp et al. Five studies with 441 total participants evaluated vaginal all quality of evidence was poor (Table 2) [24–26]. Preoperative use before POP repair: n=3 (4) 2. nocturia. or the integrity of prolapse repair or There were net benefits to estrogen application after sur- wound healing. There were no significant adverse events attributable to the vaginal estrogen treatment. and citations screened as GSM genitourinary syndrome of described in “Materials and menopause. low plasia without atypia on curettage at the time of surgery [20]. 1 Flow diagram of study Literature search performed search and systematic review. Liapis estrogen against other agents in postmenopausal women .e. 6–8 weeks preoperatively had any notable endometrial pa. or postoperative UTI was uncertain. 26] and less common estradiol tablets (Vagifem®) had simple endometrial hyper. serum estradiol levels. or hy. The impact of local estrogen upon prolapse gens cream (Premarin® 0.e. and Zullo et al. and none assessed for impact on the endometrium or with preoperative vaginal estrogen application [20. systemic estrogens only): n=13 Trials (articles) • Inappropriate outcomes (i. No studies were powered to determine the effect of postoper- perplastic endometrium) [23]. placement of a midurethral sling [24.805 OAB overactive bladder. low quality) [25]. 2 out of 22 participants gery. granulation tissue (compared with placebo vaginal ring.625 mg/g cream) twice-weekly for recurrence. Postoperative vaginal estrogen use after pelvic reconstructive surgery Vaginal estrogen use in postmenopausal women with OAB or SUI Three studies evaluated the use of vaginal estrogen after pelvic reconstructive surgery with 297 combined participants..g. quality) [25] and other objective signs of atrophy (very low to while none of the 12 women receiving 1 g conjugated estro. SUI stress urinary incontinence Titles. evaluated atic cystitis (very low quality) [21]. proliferative. thology at hysterectomy (i. Serum estradiol levels did not ative vaginal estrogen on surgical complications such as mesh increase above postmenopausal norms (moderate quality) erosion. 23]. urodynamic measures. N=1. but no difference was seen for symptom. 26].. abstracts or both reviewed and excluded: n=1. following transvaginal repair of POP [25]. over. POP pelvic organ methods” prolapse. mixing in premenopausal women): n=5 • Ineligible intervention or comparator (e. et al. vulvovaginal atrophy. or no treatment for 6 months after month (low quality). urgency urinary incontinence.g..

estrogens (20) significant difference between intervention and comparator.625 mg/g) (12) at surgery 1 g. [20] tablet 25 μg. Same frequency postoperatively [21]a Daily 3 weeks. proliferative. USA B Conjugated Placebo cream. 3 weeks I I I NS NS NSb et al. (19) then surgery (21) Vaccaro USA A Conjugated No treatment 2–12 weeks I NS NS NS et al. NS. 3 years NS et al. Serum Endometrial Int Urogynecol J (2015) 26:3–13 within 4weeks beyond immediate estradiol pathology Vaginal Epithelial Subepithelial Investigator postoperatively postoperative maturation thickness thickness scales of period indices atrophy Felding Denmark B Vaginal estradiol Placebo tablet. or hyperplastic endometrium 7 . Same frequency preoperatively. Nightly 2 weeks. UTI frequency.625 mg/g) at surgery 1 g nightly (22) Rahn et al. [20] b Two cases of simple hyperplasia without atypia in estrogen-treated participants c All patients underwent hysterectomy with 0 cases of secretory. (23) observation then surgery 4 weeks (22) postoperatively Mikkelsen Denmark C Vaginal estradiol Placebo tablet. cream frequency then observation (0. [22] cream then observation (0. tablet 25 μg.Table 1 Preoperative vaginal estrogen use before pelvic organ prolapse repair surgery Reference Country Study Intervention Comparator Study duration Summary of findings quality (n) (n) Objective atrophy measures UTI frequency. then 2x/week (12) I outcome more favorable in intervention. UTI urinary tract infection a This is the 3-year extension of Felding et al. 6–8 weeks I NS NS NSc [23] estrogens Same preoperatively. Daily 3 weeks.

[25]a USA B Vaginal estradiol ring. [25]a I outcome more favorable in intervention. [26] NS NS NS NS NS NS NS Karp et al. [24]Greece B Vaginal estradiol No treatment (91) 6 months after TVT-O I tablet 25 μg. NS no significant difference between intervention and comparator. 8 Table 2 Postoperative vaginal estrogen use after pelvic reconstructive surgery Reference Country Study quality Intervention (n) Comparator (n) Study duration Summary of findings Objective atrophy measures Urinary complaints Vaginal Vaginal Granulation Investigator Urinary urgency maturation pH tissue scales of atrophy indices Liapis et al. then 2x/week (92) Zullo et al. TVT-O trans-obturator tape mid-urethral sling. No treatment (28) 6 months after TVT I Daily 1 month. Placebo ring. [24]I NS NS NS NS NS NS NS Zullo et al. then 2 mg/week (28) Karp et al. [26] Italy A Estriol ovule 1 mg. 12 weeks after I I I I Placed once (22) Placed once vaginal POP repair (21) or no treatmenta (22) Reference Summary of findings Urinary complaints Urodynamic study measures UTI frequency Urinary frequency Nocturia Urgency urinary Max urethral Maximum flow Maximum bladder Postvoid residual Proportion with incontinence closure pressure rate capacity detrusor overactivity Liapis et al. POP pelvic organ prolapse a A third study arm with no treatment was performed (results not shown here) Int Urogynecol J (2015) 26:3–13 . Daily 2 weeks. TVT tension-free vaginal tape mid-urethral sling.

[31] I NS Stress urinary incontinence sub-population Beisland et al. PPA phenylpropanolamine a A third study arm with combined estriol+PPA was performed – results not shown here b ISD parameters not strictly defined by authors c 9 A third study arm with promestriene 10 mg cream daily was also performed (results not shown here) .Table 3 Vaginal estrogen use in postmenopausal women with overactive bladder and stress urinary incontinence Reference Country Study quality Intervention (n) Comparator (n) Study duration (weeks) Summary of findings Objective atrophy measures Urinary complaints Vaginal maturation Vaginal Investigator Urinary urgency indices pH scales of atrophy Overactive bladder sub-population Int Urogynecol J (2015) 26:3–13 Nelken et al. [30] Italy A Tolterodine ER 4 mg po daily Tolterodine ER 4 mg 12 NS +daily estriol cream (102) po daily (129) Tseng et al. SUI stress urinary incontinence. [28]c I SUI without ISD I outcome more favorable in Intervention. [28]c Brazil B Conjugated estrogens cream Estriol 1 mg cream 12 SUI without ISD (0. ISD intrinsic sphincteric deficiency. ER estradiol. [31] Taiwan A Tolterodine 2 mg po bid+ Tolterodine 2 mg po 12 NS conjugated estrogens cream bid (40) (0. [29] USA B Vaginal estradiol ring. [29] NS NS I I I C Serati et al. NS no significant difference between Intervention and Comparator.625 mg/g) 1 g 2x/week (40) Stress urinary incontinence sub-population Beisland et al. [27]a C NS SUI with ISDb Kobata et al. Oxybutynin 5 mg po 12 I I NS Placed once (28) bid (31) Serati et al. C outcome more favorable in Comparator. improvement or cure Dry mouth Constipation Blurry vision Vaginal discharge Overactive bladder sub-population Nelken et al.625 mg/g) 1 g daily (17) daily (16) or promestriene 10 mg cream dailyc (18) Reference Summary of findings Urinary complaints Maximum urethral Adverse events closure pressure Frequency/nocturia Urgency urinary incontinence SUI. [27]a Norway B Estriol 1 mg suppositories PPA 50 mg po bid (20) or 4 I SUI with ISDb daily (20) combined treatmenta (20) Kobata et al. [30] NS NS Tseng et al.

but one of the studies did demonstrate significantly fewer voids per day and greater voided volumes in the tolterodine plus estrogen arm [31]. were insufficient to assess impact on the endometrium or serum estradiol levels. combining quality of the supporting evidence (A high to D very low) with the size of the net medical benefit.625 mg/g) or estriol 1 mg cream. or urgency urinary incontinence (low quality evi- ring. but many would not. nocturia. although the oral anticholinergic demonstrated a higher rate of side effects (constipation. blurry vision) and discontinuation compared with vaginal estrogen [29]. data Presuming no contraindication to vaginal estrogen. Greater cure or improvement in leakage was observed in combined estrogen plus PPA therapy compared with either estrogen or PPA alone (very low quality evidence).. See Discussion Grade presenting with OAB or SUI (Table 3) [27–31]. by mouth twice daily) similarly improved urinary urgency. both the vaginal estradiol ring and twice a day) or application of vaginal estrogen (agent studied: vaginal estradiol ring). there is still much room for debate and need for additional evidence. considering immediate-release oral anticholinergic presenting with symptoms of SUI (without intrinsic Using this comprehensive systematic review of randomized frequency. data were insufficient to comment on the potential harms of PPA or we suggest we suggest we suggest estrogen therapy [27]. or urgency urinary incontinence (moderate quality evidence) [30. improve- ment in leakage was observed for both therapies (very low Table 4 Clinical practice guidelines for vaginal estrogen use in postmenopausal women with urogynecological complaints quality evidence) [28]. Most of these recommendations are sphincteric deficiency) 2C. urgency urinary incontinence (very low- “Grade” provides a level of strength (1 “strong” or 2 “weak”) to the guideline.. Physicians must still judge each patient indepen- dently and arrive at a management decision consistent with the individual’s preferences. Beisland et al. quality evidence). in postmenopausal women. Outcomes were evaluated fol- lowing 4 [27] to 12 weeks [28–31] of therapy. and estriol ovules) to prevent or treat urinary urgency and frequency dence). the SGS-SRG has de- veloped evidence-based clinical practice guidelines describing the utility of vaginal estrogen in the management of postmen- opausal women presenting with various urogynecological complaints (Table 4). and anticholinergic agents. either immediate-release oral anticholinergics (agent studied: oxybutynin 5 mg po application of vaginal estrogen (agents studied: conjugated estrogens and estriol frequency. a . and urgency urinary incontinence) controlled trials comparing vaginal estrogen with placebo. SUI stress urinary incontinence presenting with symptoms of OAB (urinary urgency. Overall 2D 2C 2C quality of evidence was poor. no longer FDA approved) to combined estriol plus PPA. From a policymaking standpoint. examined postmeno- pausal women with SUI with intrinsic sphincteric deficiency (not specifically defined) and compared vaginal estriol 1 mg suppositories with an alpha agonist (phenylpropanolamine creams) (PPA). For postmenopausal women with SUI without intrinsic sphincteric deficiency treated daily with 1 g of conjugated estrogen cream (0. The addition of local estrogen (various methods) to oral anticholinergics had a greater occurrence of side effects tolterodine (immediate or extended-release forms) did not offer an advantage over tolterodine alone in urinary urgency. dry mouth. 31]. undergoing pelvic reconstructive surgery with a midurethral slinga Discussion OAB overactive bladder. an immediate-release oral anticholinergic (oxybutynin 5 mg postoperative application of vaginal estrogen (agents studied: vaginal estradiol tablet. or UTI frequency (very low-quality evidence) in this population In all these studies from this patient subpopulation. no treatment. meaning low quality of evidence supporting a suggestion that the majority of patients would want to follow.10 Int Urogynecol J (2015) 26:3–13 Postoperative use of vaginal estrogens did not demonstrate an improvement over no treatment in addressing symptoms of nocturia (moderate-quality evidence). For women with OAB.

the tinence (RR 1. however. in fact. 95 % time of complete scar maturation [23]. In conclusion. ranging from 448 to 1. studies of incontinence.. safety data were extremely limited in all lation tissue compared with those using a placebo vaginal ring of these trials.. thus. Preoperative use before POP role for vaginal estrogen as a treatment or adjunct in the repair may decrease the likelihood of early postoperative UTI treatment of OAB and SUI. and of safety with evaluation of the endometrium—if still with tion. There are. While application of support from Karp et al. this Cochrane review included many currently that provides this combination of pre. Mikkelsen et al. and reoperation dyspareunia). Foremost. if vaginal estrogen does. where participants receiving the vaginal estrogen for a short duration is presumed to have postoperative vaginal estradiol ring demonstrated less granu. non-hormonal moisturizers. [34]. while vaginal estrogen therapy may need to be continued postoperatively until the (creams or pessaries) improved incontinence (RR 0. The foreign body placebo ring likely contributed to this estrogen studies including data on serum estradiol concentra- inflammatory reaction. Our review collected the few studies of post. 24–26] or of vaginal estrogen before POP repair. 23]. In those crease in vaginal epithelial thickness observed in those partic. with vaginal estradiol or placebo tablets before POP repair. It is unknown whether other anti.11. We also concluded that vaginal estrogen appears to have a uterus—in addition to sensitive measurements for changes utility in the treatment of both conditions and may even in serum estradiol [35]. of OAB or SUI and receiving vaginal estrogen as an interven. we are limited by the quality of the studies reduce the need for POP surgery in women older than 60 years included. However. this review underscores that there remains a ders in postmenopausal women. guideline development. nence has also been reviewed by Cody et al.620 to objectively track prolapse recurrence for a meaningful participants depending on the power and the possible efficacy postoperative duration. vaginal estrogen application need more consistent assessment menopausal women presenting specifically with a complaint of discontinuation rates and the reasons for discontinuation.04–1.18). the in. who described the of vaginal estrogen [33]. Finally. designed to determine The strengths of this review are its robust methodology and the effects of estrogen (or drugs with estrogenic effects) on the the transparent means of evidence-based clinical practice prevention or management of POP concluded that the evi. the oral selective estrogen receptor modula- state transition model to simulate the probability of 2-year tor approved for the treatment of moderate to severe outcomes of mesh erosion. There is no study CI 0. we cannot utilized in transvaginal repairs and sacral colpopexies. an oral agent with no vaginal placebo [27. provide similar improvements to short-acting oxybutynin in OAB [29].74. adding estrogen to tolterodine did not significantly reduce urgency. Clinical practice guidelines are primarily based on [32]. visceral injury. Weidner trials of vaginal estrogens for the management of POP. While our review adds two additional studies to those poor to moderate overall quality of evidence. came to the important conclusion that the route of therapy has Further. However. Patient blinding identified by the Cochrane review [22. with or without vaginal estrogen. Of note. and could provide a better substrate for suture or mesh . or sufficiently large to address this question. 3-year postoperative outcomes after preoperative treatment Estrogen’s utility in the management of urinary inconti.Int Urogynecol J (2015) 26:3–13 11 A Cochrane review by Ismail et al. 23] may provide therapy only lasted up to 12 weeks. Given the estrogens included may translate to a reduction in erosion of mesh materials and the available comparators in the literature. several limita- dence was extremely limited. comment on the relative efficacy or safety of compounded though none of the studies identified in this review were vaginal estrogen products. the evidence was to intervention was not possible for many of these studies that still too sparse to support a guideline for the preoperative use allowed either no treatment as the comparator [22. studies of vaginal estrogen for the treatment of OAB or SUI. 29–31]. or urgency urinary Conclusion incontinence beyond those improvements seen with tolterodine alone [30. No and colleagues suggest that the required sample size for such a study providing vaginal estrogen preoperatively has attempted trial might be prohibitively large..86). with only two of the preoperative vaginal [25]. al. Nonetheless.and postoper- participants receiving estrogen for reasons other than urinary ative vaginal estrogen. nocturia. after vaginal mesh prolapse surgery or minimally invasive This review reveals areas for improvement in subsequent sacral colpopexy. few consequences. but no included studies of both systemic and vaginal estrogen and standardized or validated metric of prolapse symptoms [21]. ipants complying with vaginal estrogen [20.e. this systematic review of randomized trials cholinergic drugs or newer beta agonist medications will also confirms that vaginal estrogen can play an important role as be superior to vaginal estrogens alone in the management of an adjunct in the management of common pelvic floor disor- OAB. one cannot comment a benefit for wound healing. Using a Markov ospemifene (i. They did include a questionnaire of patient satisfaction. but that oral raloxifene may tions. as noted above. This hypothesis gains some on the long-term efficacy or safety. improve the substrate very different effects: oral systemic estrogen worsened incon. An improvement in wound healing tions and endometrial pathology. for suture (or mesh) placement at the time of surgery. 31]. 95 % CI 1.64–0.

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