Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial.

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.

Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery.

OBJECTIVE: Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery. METHOD: Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed. RESULTS: Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed. CONCLUSIONS: The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.

Does preoperative locally applied estrogen treatment facilitate prolapse-associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse? A randomised controlled double-masked, placebo-controlled, multicentre study.

OBJECTIVE: To evaluate whether locally applied vaginal estrogen affects prolapse-associated complaints compared with placebo treatment in postmenopausal women prior to surgical prolapse repair. DESIGN: Randomised, double-masked, placebo-controlled, multicentre study. SETTING: Urogynaecology unit at the Medical University of Vienna and University Hospital of Tulln. POPULATION: Postmenopausal women with symptomatic pelvic organ prolapse and planned surgical prolapse repair. METHODS: Women were randomly assigned local estrogen cream or placebo cream 6 weeks preoperatively. MAIN OUTCOME MEASURES: The primary outcome was differences in subjective prolapse-associated complaints after 6 weeks of treatment prior to surgery, assessed with the comprehensive German pelvic floor questionnaire. Secondary outcomes included differences in other pelvic floor-associated complaints (bladder, bowel or sexual function). RESULTS: Out of 120 women randomised, 103 (86%) remained for the final analysis. After 6 weeks of treatment the prolapse domain score did not differ between the estrogen and the placebo groups (4.4 ± 0.19 versus 4.6 ± 0.19; mean difference, -0.21; 95% CI -0.74 to 0.33; P = 0.445). Multivariate analysis, including only women receiving the intervention, showed that none of the confounding factors modified the response to estradiol. CONCLUSIONS: These results demonstrate that preoperative locally applied estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse. TWEETABLE ABSTRACT: Preoperative local estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with pelvic organ prolapse.

Therapeutic Effects of 17ß-Estradiol on Pelvic Organ Prolapse by Inhibiting Mfn2 Expression: An In Vitro Study.

Objective: To assess the effects of 17ß-estradiol (E2) on proliferation, apoptosis, and protein expressions of fibroblasts at different concentrations and time intervals to reveal the mechanism of E2 in the treatment of pelvic organ prolapse (POP). Study Design: The uterosacral ligament fibroblasts were collected from seven POP patients for primary culture of fibroblasts. The culture media containing 0, 10-6, 10-7, 10-8, and 10-9 mol/L E2 were used for 24, 48, 72, and 96 h. Main Outcome Measures: The cells were collected for cell counting kit-8 (CCK-8), apoptosis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting assays. Results: Compared with the control group, in the values of fibroblasts cultured in 10-8 mol/L E2 for 72 h, the proliferation, mRNA and protein expression of Mitofusin-2 (Mfn2) separately increased (P < 0.05), decreased (P<0.001) and decreased (P<0.001). However, the expression level of procollagen 1A1/1A2/3A1 and cyclinD1 markedly increased (P<0.001, all), which was consistent with the results of protein level. What's more, the expression of estrogen receptor α(ERα), estrogen receptor ß(ERß) and G protein-coupled receptor 30(GPR30) were significantly increased in 10-8 mol/L E2 group. Conclusions: E2 can inhibit the progress of POP by inhibiting the expression level of Mfn2, as well as promoting expression of procollagens and proliferation of fibroblasts. This effect is time- and concentration-dependent. Only when the estrogen concentration reaches 10-8 mol/L, the therapeutic effect is the greatest after 72 h.

Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model.

Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury.

Microwave-assisted synthesis and characterization of novel chitosan-based biomaterials for pelvic organ prolapse treatment.

Pelvic organ disorders affect up to one in four women in the United States. The prevalence of pelvic organ prolapse (POP) is increasing with each year, particularly in the setting of prolonged life expectancy and an aging population. Current treatment approaches, including polypropylene monofilaments are associated with numerous painful and worrisome side-effects. Therefore, scientists are looking for new solutions. A promising alternative to the current treatment is tissue engineering, which can be utilized to re-create support to the vagina and pelvic organs. Tissue engineering requires the use of three-dimensional scaffolds, derived from biocompatible materials. Chitosan is a natural polymer, obtained from shellfish exoskeletons. It is known for its biodegradability, lack of cytotoxicity and non-pyrogenicity. Due to the presence of free hydroxyl and amino groups, it may undergo various modifications. In this paper, we describe a new type of chitosan-based biomaterials, which can be used as a new alternative scaffold that may provide support to prolapse organs. The chitosan scaffold was obtained under microwave radiation using multifunctional amino and organic acids. We discuss the scaffold's characteristics, with an emphasis on its chemical structure and morphology. Fourier transform infrared spectroscopy (FT-IR) analysis confirmed cross-linking processes with preservation of free amino groups. Moreover, mechanical durability, the stability and swelling ability of the scaffolds in a simulated body fluid were investigated. All of the prepared scaffolds demonstrated very good antioxidant activity and biodegradability. Importantly, the biocompatibility of chitosan scaffolds was examined on human vaginal VK2/E6E7 cell line. No evidence of toxicity was documented, and the cells maintained their presence on the studied materials. These results allude to the lack of toxicity of the scaffolds, and indicate that chitosan-based scaffold should be further investigated in in vivo studies as they may be a promising alternative treatment to pelvic organ prolapse.

Local oestrogen therapy modulates extracellular matrix and immune response in the vaginal tissue of post-menopausal women with severe pelvic organ prolapse.

This study investigates the effect of local oestrogen therapy (LET) on the expression of proteins participating in collagen/elastin biogenesis and immune markers in vaginal tissues of post-menopausal women with severe pelvic organ prolapse (POP). Vaginal biopsies were collected from the anterior vaginal wall of informed and consented 52 post-menopausal women with severe POP undergoing total hysterectomy. Twenty-nine of the 52 women were treated with LET (in the form of vaginal oestrogen cream or tablet), while the remaining 23 untreated patients served as the controls. This study was approved by Sinai Health System REB. Vaginal tissue specimens were analysed for gene and protein expression using real-time RT-PCR and Luminex assays, protein localization and immune cell infiltration were assessed by immunohistochemistry. Forty-four cytokines were detected. We found that LET application: (a) significantly increased (P < 0.05) gene and protein expression levels of extracellular matrix (ECM) structural proteins, collagen and elastin, as well as the expression of ECM maturation enzyme BMP1; (b) decreased protein expression level of ECM degradation enzymes MMP1, MMP2 and MMP3 accompanied by an increase in their tissue inhibitors, TIMP1 and TIMP4; (c) significantly increased (P < 0.05) the gene and protein expression levels of 14 vaginal cytokines involved in leucocyte infiltration, which was confirmed by immunohistochemistry. Our results indicate that LET plays an important role in the activation of immune system within the local vaginal environment, limiting the undesirable ECM degradation, which supports the strengthening of vaginal ECM in post-menopausal women, therefore resisting menopause/age-related changes and inducing urogenital tract tissue regeneration.

The mysteries of menopause and urogynecologic health: clinical and scientific gaps.

OBJECTIVES: A significant body of knowledge implicates menopausal estrogen levels in the pathogenesis of the common pelvic floor disorders (PFDs). These health conditions substantially decrease quality of life, increase depression, social isolation, caregiver burden, and economic costs to the individuals and society. METHODS: This review summarizes the epidemiology of the individual PFDs with particular attention to the understanding of the relationship between each PFD and menopausal estrogen levels, and the gaps in science and clinical care that affect menopausal women. In addition, we review the epidemiology of recurrent urinary tract infection (rUTI)-a condition experienced frequently and disproportionately by menopausal women and hypothesized to be potentiated by menopausal estrogen levels. RESULTS: The abundance of estrogen receptors in the urogenital tract explains why the natural reduction of endogenous estrogen, the hallmark of menopause, can cause or potentiate PFDs and rUTIs. A substantial body of epidemiological literature suggests an association between menopause, and PFDs and rUTIs; however, the ability to separate this association from age and other comorbid conditions makes it difficult to draw definitive conclusions on the role of menopause alone in the development and/or progression of PFDs. Similarly, the causative link between the decline in endogenous estrogen levels and the pathogenesis of PFDs and rUTIs has not been well-established. CONCLUSIONS: Innovative human studies, focused on the independent effects of menopausal estrogen levels, uncoupled from tissue and cellular senescence, are needed.

Effect of puerarin on collagen metabolism of fibroblasts in pelvic tissue of women with pelvic organ prolapse.

The aim of the present study was to investigate the protective effect of puerarin on pelvic organ prolapse (POP) and the underlying mechanisms that regulate the metabolism of human parametrial ligament fibroblasts (HPLFs). HPLFs obtained from the pelvic tissue of patients with (n=10) or without (n=8) POP during hysterectomy were isolated by enzymatic digestion and subsequently identified by immunocytochemistry in a previous study of the authors. Following this, cultured HPLFs were treated with 0.01, 0.10 or 1.00 mmol/l puerarin, followed by detection of proliferation rate by Cell Counting kit­8 assay. Following incubation with puerarin for 48 h, mRNA and protein expression levels of tissue inhibitor of metalloproteinase­1 (TIMP­1), matrix metalloproteinase (MMP)­2 and ­9, and collagen (COL)I and III in HPLFs were quantified by reverse transcription­quantitative polymerase chain reaction, and western blot and gelatin zymography analyses, respectively. MMP­2 and ­9 expression levels were increased, whereas expression levels of TIMP­1, and COL I and III were decreased, in patients with POP compared with healthy controls. Following puerarin treatment, the expression levels of TIMP­1, and COL I and III were enhanced, whereas MMP­2 and ­9 were inhibited. In conclusion, the present study demonstrated evidence increased degradation of the extracellular matrix in pelvic tissues of patients with POP compared with controls, and the protective effect of puerarin against POP via its anti­degradation effect on collagen. These results provide evidence for puerarin as a novel approach for the treatment of POP.

Bacterial uropathogens and antibiotic susceptibility of positive urine cultures in women with pelvic organ prolapse and urinary incontinence.

AIMS: The aims of the study are to describe the speciation and resistance patterns of positive urinary cultures in women with pelvic floor disorders (PFDs) and those undergoing pelvic reconstructive surgery. METHODS: Urine cultures with a colony count of >10(5) CFU and <3 isolated uropathogens at a tertiary care Urogynecology practice over a 5-year period for patients with anterior wall dominant pelvic organ prolapse (POP) or urinary incontinence (UI) were identified. Speciation and culture sensitivity data were described for each group and compared to a control group who did not currently have a PFD and who had not undergone pelvic surgery within a year of their positive culture. Additionally, early post-operative UTIs (≤6 weeks) and late post-operative UTIs (>6 weeks but ≤1 year) were compared. RESULTS: 1,306 positive urine cultures over the 5-year period with 51 different species of uropathogens were identified. The percentage of Escherichia coli identified was not significantly different between groups: POP 57.1%, Stress UI 58.4%, Urge UI 54.3%, non-operative controls 54.3%. Cultures obtained from patients on prophylactic antibiotics were significantly less likely to have E. coli (adjusted OR 0.45, 95% CI 0.22, 0.89, P < 0.0216). Non-E. coli cultures were more common in the early post-operative period compared to the late post-operative cultures (69% vs. 41%, adjusted OR 0.33, 95% CI 0.22, 0.48, P < 0.0001). CONCLUSIONS: Patients with PFDs who develop UTIs have rates of non-E. coli over 40% of the time. Treatment based on culture and antibiotic sensitivity data should be considered.

Local Oestrogen for Pelvic Floor Disorders: A Systematic Review.

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.

Role of perioperative low dose vaginal oestrogens in improving the outcomes of pelvic organ prolapse surgery.

Pelvic organ prolapse (POP) is the most common gynaecological disorder requiring surgical treatment in postmenopausal women. Surgical treatment of POP might include anterior or posterior vaginal repair, vaginal hysterectomy, vault fixation procedures like sacrocolpopexy and sacrospinous fixation. Complications of POP surgery include excessive bleeding, visceral injuries, postoperative wound infection, urinary tract infection (UTI), sexual dysfunction secondary to vaginal scarring and recurrence. Postmenopausal vaginal atrophy may increase the risk of visceral injuries due to thinning of vaginal wall and also increases the risk of surgical site wound infections due to alteration of vaginal flora and urinary tract infections (UTI). Use of vaginal low dose oestrogens to treat atrophy of the vagina may improve the subjective cure rates and minimise surgical site wound infections by altering the vaginal flora to premenopausal levels. To date there has not been any data on the outcomes of POP surgery when low dose vaginal oestrogens are used perioperatively. Hence we want to study the effectiveness of vaginal low dose oestrogen on the outcome of POP surgery in postmenopausal women.

The management of lower urogenital changes in the menopause.

Currently, 25% of women seek the advice of a medical professional for symptoms related to the menopause. However, with an increasingly ageing and medically aware population, it is likely this proportion will grow. The main symptoms related to the menopause are systemic vasomotor and localized urogenital symptoms. Numerous forms of estrogen have been used to alleviate these symptoms. Further problems that increase during the menopause include incontinence, pelvic organ prolapse and recurrent urinary tract infections. This article reviews the process by which estrogen affects the tissues of the urogenital tract, what symptoms occur during this period and what modalities of treatments are available.

Histologic and cytologic effects of vaginal estrogen in women with pelvic organ prolapse: a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the histologic and cytologic effects of preoperative vaginal estrogen in women with atrophic vaginitis and pelvic organ prolapse. METHODS: Forty-two women with atrophic vaginitis and stage greater than or equal to 2 prolapse were enrolled in this assessor-blinded randomized controlled trial comparing daily vaginal estrogen cream use for 2 to 12 weeks preoperatively versus no intervention. Data were analyzed using t test and analysis of variance. RESULTS: Of these 42 women, 22 received treatment and 20 were controls. After a mean 7 (3) weeks of use, the vaginal maturity index increased 15.5% in the treatment group and declined 1.5% in the control group (P < 0.001). The vaginal epithelial thickness was 339 (96) µm in the treatment group compared to 302 (119) µm (P = 0.275) in the controls. CONCLUSIONS: Preoperative vaginal estrogen application for 2 to 12 weeks restores vaginal cytology to premenopausal levels, but does not increase vaginal epithelial thickness in women with prolapse.

The epidemiology and management of gynatresia in Lagos, southwest Nigeria.

OBJECTIVE: To document data from patients presenting with gynatresia at 2 tertiary health centers in Lagos, southwest Nigeria. METHODS: In a prospective, descriptive study, clinical history and physical examination data were collected for women who presented with gynatresia between January 2004 and January 2011. Ultrasonography results and abnormality at surgery were also documented. Where possible, the severity of stenosis and surgical outcome were assessed by published scales. RESULTS: Forty-seven patients were included in the study. Eight patients (17.0%) presented with congenital gynatresia, the commonest cause of which was Mayer-Rokitansky-Küster-Hauser syndrome (4 patients, 50%). Thirty-nine patients (83.0%) presented with acquired gynatresia, the main cause of which was herbal pessaries (30 patients, 76.9%). Herbal pessaries were used to treat fibroids (23 patients, 76.7%), uterovaginal prolapse (3, 10.0%), and infertility (2, 6.7%); and to procure abortion (2, 6.7%). The ages of the patients who used herbal pessary ranged from 18 to 50 years (mean 36.10 ± 1.24 years). Other causes of acquired gynatresia were birth injuries (6 patients, 15.4%), and female genital mutilation (2, 5.1%). CONCLUSION: Acquired gynatresia was more common in Lagos than congenital gynatresia. The causes of acquired gynatresia are preventable and could be eliminated by health education.

Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse.

The precise role of estrogen in the pathogenesis of pelvic organ prolapse (POP) is still unclear, while the results concerning the effect of selective estrogen receptor modulators on pelvic organ prolapse are contradictory. Our aim was to test whether alteration in the expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women is related to genital prolapse status. The mRNA levels of ERα and ERß in 60 biopsy specimens were measured. Significantly higher expression of ERα and higher ERα/ERß ratio were demonstrated in post-menopausal women compared to pre-menopausal women. Higher expression of ERα and higher ERα/ERß ratio were detected in all studied groups with POP, thus it did not reach significance in the post-menopausal group. Pre-menopausal and post-menopausal women presenting pelvic organ prolapse had no difference in the ERα expression. Our preliminary study may indicate that pelvic organ prolapse is associated with higher expression of ERα/ERß in the pelvic floor of both pre- and post-menopausal women; thus not reaching statistical significance in the post-menopausal women was probably due to the group's size. We believe that the inevitable changes in the estrogen receptor expression over women's different lifetimes may affect the risk of genital prolapse progression, and might contribute to the further search for appropriate selective estrogen receptor modulators as a treatment for women with pelvic organ prolapse.

Oestrogens for treatment or prevention of pelvic organ prolapse in postmenopausal women.

BACKGROUND: Pelvic organ prolapse is common and can be detected in up to 50% of parous women although many are asymptomatic. Oestrogen preparations are used to improve vaginal thinning (atrophy). It is possible that oestrogens, alone or in conjunction with other interventions, might prevent or assist in the management of pelvic organ prolapse, for example by improving the strength of weakened supporting structures. OBJECTIVES: To determine the effects of oestrogens or drugs with oestrogenic effects alone, or in conjunction with other treatments, both for prevention and treatment of pelvic organ prolapse. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register of trials (searched 6 May 2010), MEDLINE (January 1950 to April 2010) as well as reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included the use of any oestrogens or drugs with oestrogenic (or anti-oestrogenic) actions for pelvic organ prolapse. DATA COLLECTION AND ANALYSIS: Trials were assessed and data extracted independently by two review authors. MAIN RESULTS: Three trials and one meta-analysis of adverse effects of a further three trials were identified. One trial did not provide useable data. Two trials included 148 women with prolapse, one included 58 postmenopausal women and the meta-analysis reported a mixed population (women with and without prolapse) of postmenopausal women (N=6984). The meta analysis and one other small trial investigated the effect of selective oestrogen receptor modulators (SERMs) for treatment or prevention of osteoporosis but also collected data of the effects on prolapse. Interventions included oestradiol, conjugated equine oestrogen and two (SERMs), raloxifene and tamoxifen. Only one small trial addressed the primary outcome (prolapse symptoms).One small treatment trial of oestradiol for three weeks before prolapse surgery found a reduced incidence of cystitis in the first four weeks after surgery but this unexpected finding needs to be confirmed in a larger trial.A meta-analysis of adverse effects of a SERM, raloxifene (used for treatment or prevention of osteoporosis in postmenopausal women) found a statistically significant reduction in the need for prolapse surgery at three year follow up (OR 0.50, 95% CI 0.31 to 0.81), but this was statistically significant only in women older than 60 years (OR 0.68, 95% CI 0.22 to 2.08) and the total number of women having prolapse surgery was small. A further small trial comparing conjugated equine oestrogen, raloxifene, tamoxifen and placebo in postmenopausal women having pelvic floor muscle training was too small to detect effects on prolapse outcomes. AUTHORS' CONCLUSIONS: There was limited evidence from randomised controlled trials regarding the use of oestrogens for the prevention and management of pelvic organ prolapse. The use of local oestrogen in conjunction with pelvic floor muscle training before surgery may reduce the incidence of post-operative cystitis within four weeks after surgery. Oral raloxifene may reduce the need for pelvic organ prolapse surgery in women older than 60 years although this cannot be taken as an indication for practice.There is a need for rigorous randomised controlled trials with long term follow up to assess oestrogen preparations for prevention and management of pelvic organ prolapse, particularly as an adjunctive treatment for women using pessaries and also before and after prolapse surgery.