Vaginal Estrogen Use Research Articles

14 Surgical management of mid- and upper-vaginal constriction rings

To review the diagnosis of mid- and upper-vaginal constriction rings and describe our technique for surgically correcting vaginal constriction rings. Causes of vaginal constriction include surgery, vaginal atrophy, conditions of the vulvovaginal skin, and radiation. It is imperative for the pelvic surgeon to be able to identify and adequately address vaginal constriction. In this video, we discuss the diagnosis and management of mid- and upper-vaginal constriction rings, an entity with an undefined etiology. Initial medical management may include vaginal dilation with use of vaginal estrogen. We present three techniques for surgical management: lysis of the constriction band, lysis of the band with use of a flap, and lysis of the band with use of a biologic graft. In our experience, lysis of the constriction ring perpendicular to its axis with immediate use of vaginal estrogen and vaginal dilators is sufficient for most cases. Cases of severe stenosis, prior failed surgical management, or a combination of stenosis and foreshortening may necessitate the use of a biologic graft or local flap. Pelvic surgeons should be familiar with the diagnosis and management of vaginal constriction rings. In this video, we review diagnosis and medical management and present 3 techniques for surgical correction of this condition.

ESTROgen use for complications in women treating pelvic organ prolapse with vaginal PESSaries (ESTRO-PESS)-a randomized clinical trial.

To evaluate the complications of new users' vaginal pessaries (VP), with and without the use of vaginal estrogen after a 6-month follow-up. A parallel, single-blinded, randomized, controlled trial. Symptomatic postmenopausal women (n = 98) with pelvic organ prolapse (POP) (stage 3/4) were recruited from August 2018 to October 2019. Patients were randomized into the local estrogen group (promestriene 3 × for a week) and the control group (no estrogen). They were evaluated for their vaginal symptoms at the baseline, after 3months, and after 6months, and a physical examination and vaginal sampling for microbiological analysis were done. Data were analyzed according to an intention-to-treat analysis (ITT). A 5% significance level was established for statistical analysis. Twenty women discontinued treatment (20.4%), mainly due to pessary extrusion (n= 15) and 5 for other reasons (lost to follow-up, pain, and surgery). Baseline characteristics were not statistically different between the estrogen and control groups. Regarding the presence of complications, the presence of erosion was 10% in the control group, but there was no significant difference between the groups (p= 0.175) after 6months. Bacterial vaginosis (BV) was more prevalent in the control group, according to the Nugent (p= 0.007) and Amsel (p= 0.014) criteria. Urinary urgency and increased urinary frequency were significantly improved in the estrogen group after 6months. There was no evident benefit related to complications such as ulcerations, itching, and vaginal discharge/odor from the use of vaginal estrogen in POP women using pessaries.

Spotlight on… urogynaecology

It is now nearly 5 years since Mohamed Abdel-Fattah wrote the last Spotlight on… urogynaecology (TOG 2016;18:7), highlighting relevant articles throughout the lifetime of The Obstetrician & Gynaecologist (TOG). That Spotlight concentrated on the emergence of urogynaecolgy as a subspecialty, and I would like to use this update to discuss, in these post-COVID-19 times, the emergence of pelvic floor medicine as a wider concept, again highlighting the most topical articles published in TOG. For much of the last 20 years, we have witnessed the living proof of Scott’s Parabola (BMJ 2001;323:1477) in the development and decline of the use of mesh in vaginal surgery. The publication of the Cumberlege report has largely closed the debate, but it does leave the question posed by George White more than 100 years ago1 as to the correction of the white line. TOG has sought to address this with the articles by Khasriya et al. (TOG 2020;18:101–8) on laparoscopic urogynaecology and by Loganathan et al. (TOG 2019;17:21–6) on the issue of whether to combine continence and prolapse surgery. The challenges of managing such problems have seen the debate revisit both Manchester repair2 and colpocleisis (TOG 2020;22:233–6). In stress urinary incontinence, there has been a return to interest in bulking agents (TOG 2020;22:137–46) and the more controversial topic of the role of lasers in vaginal therapy (TOG 2019;21:233–6). As with any period of controversy, there has also been a re-evaluation of how we assess patients. Key articles in TOG have highlighted this change with a guide to urodynamics from Taithongchai et al. (TOG 2019;21:193–202) and Lyttle and Fowler’s excellent article on cystoscopy (TOG 2017;19:236–40), as well as those that have concentrated on the conservative aspects of care, including the use of vaginal estrogen (TOG 2019;21:37–42) and the management of recurrent urinary tract infections (TOG 2020;22:115–21). As we look forward, I am sure we will see more articles on emerging topics, like that by Jones et al. on sports gynaecology (TOG 2019;21:85–94). We will need to think differently and perhaps challenge more paradigms: as pelvic floor medicine matures, we see more urogynaecologists running services for women who have sustained obstetric trauma, and perhaps we will see the emerging need for skilled vaginal surgeons to be increasingly involved with complex cervical cerclage.

Urogynecology

Urogynecology

Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials.

Recurrent urinary tract infections (rUTIs) are commonly encountered in postmenopausal women. Optimal non-antimicrobial prophylaxis for rUTIs is an important health issue. The aim of this study was to evaluate the use of estrogen in the prevention of rUTIs versus placebo. Eligible studies published up to December 2019 were retrieved through searches of MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. We included randomized controlled trials of estrogen therapies versus placebo regarding the outcomes of preventing rUTIs. Changes in vaginal pH and estrogen-associated adverse events were also analyzed. Eight studies including 4702 patients (2367 who received estrogen and 2335 who received placebo) were identified. Five studies including 1936 patients evaluated the use of vaginal estrogen, which resulted in a significant reduction in rUTIs (relative risk, 0.42; 95% CI, 0.30-0.59). Three studies including 2766 patients evaluated the outcomes of oral estrogen in the prevention of UTIs and showed no significant difference in the number of rUTIs compared to treatment with placebo (relative risk, 1.11; 95% CI, 0.92-1.35). Two studies reviewed changes in vaginal pH and showed a lower pH (mean difference, -1.81; 95% CI, -3.10--0.52) after vaginal estrogen therapy. Adverse events associated with vaginal estrogen were reported, including vaginal discomfort, irritation, burning, and itching. There was no significance increase in the vaginal estrogen group (relative risk, 3.06; 95% CI, 0.79-11.90). Compared with placebo, vaginal estrogen treatment could reduce the number of rUTIs and lower the vaginal pH in postmenopausal women.

Effective Prevention of Recurrent UTIs With Vaginal Estrogen: Pearls for a Urological Approach to Genitourinary Syndrome of Menopause

ObjectiveTo review the available data related to the prevention of recurrent urinary tract infection (rUTI) in postmenopausal women with vaginal estrogen preparations and provide the urologic community with the confidence to identify and treat genitourinary syndrome of menopause (GSM). Materials and MethodsA literature search of MEDLINE and the Cochrane Central Register of Controlled Trials databases was performed to identify studies utilizing vaginal estrogen in the treatment of urological conditions related to rUTI and GSM. ResultsIn the setting of untreated GSM, the etiology of rUTIs (at least 3 episodes of UTIs in 12 months or at least 2 episodes in 6 months) is not fully elucidated, but estrogen deficiency is a contributing factor. The diagnosis of GSM is primarily a clinical diagnosis supported by other objective findings including: a vaginal pH >5, decreased content of superficial cells, and/or increased proportion of parabasal cells on vaginal maturation index. Local vaginal estrogen, dehydroepiandrosterone (prasterone), and ospemifene are commonly used GSM treatments. Thirty-one trials were identified utilizing estrogen preparations for rUTI in postmenopausal women. ConclusionOverall, multiple randomized clinical trials have successfully been completed to show the efficacy of local estrogen preparations for the treatment of rUTIs. This high yield review provides a framework for assessing GSM, prescribing recommendations for local vaginal hormone preparations, and a summary of the substantial evidence supporting the new 2019 American Urological Association/Canadian Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction Guidance for local vaginal estrogen use for rUTI.

Safety of vaginal estrogens: a systematic review.

This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary objective of this systematic review was to examine the comparative safety of the Food and Drug Administration-approved vaginal estrogen preparations among postmenopausal women. We performed a PubMed search of the primary literature from January 1, 1966 to July 16, 2019 for English-language clinical trials. Manual review of retrieved citations identified additional citations. Of 882 retrieved citations, 75 clinical trials met inclusion criteria. Maximum trial duration was 52 weeks. None of the trials predesignated breast or endometrial cancer, cardiovascular events, or venous thromboembolism as primary outcomes. Studies were not designed to rule out an increase in endometrial carcinoma risk with long-term use of vaginal estrogen. There were few head-to-head comparisons. Fifty trials examined serum sex steroid and gonadotrophin levels; assay methodologies varied. Serum estradiol levels were 11 pg/mL at baseline or during placebo use and increased to a mean of 30 pg/mL after treatment. Estradiol levels were usually highest during the first 12 weeks of treatment, and were higher for estrogen creams than for inserts or rings. The 22 trials of endometrial thickness and the 15 trials of endometrial biopsy did not clearly demonstrate endometrial proliferation after vaginal estrogen treatment, but data were limited, and studies did not always perform systematic endometrial biopsy. Newer low-dose estradiol rings, tablets, and inserts appear to induce the least increases in serum hormones, possibly indicating greater safety. Limited evidence in trials lasting up to 52 weeks suggest endometrial safety of vaginal estrogen use. Long-term trials are needed. : Video Summary:http://links.lww.com/MENO/A513.

Systemic estradiol levels with low-dose vaginal estrogens.

Objectives:To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women.Methods:PubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens). Estradiol levels at baseline and during treatment, area under the curve, and maximum estradiol concentrations were summarized by dose within assay type. A proposed range of systemic estradiol in normal, untreated, postmenopausal women was estimated by conservatively pooling means and standard deviations from published studies.Results:Mean basal estradiol levels were 3.1 to 4.9 pg/mL using liquid or gas chromatography/mass spectroscopy (LC or GC/MS/MS) with a range of undetectable to 10.5 pg/mL using radioimmunoassay. Systemic estradiol levels with vaginal estrogens reflected their doses as measured with LC or GC/MS/MS in different studies: 7.1 to 9.1 pg/mL and 16.7 to 22.7 pg/mL with a 25-μg softgel capsule insert and a tablet insert, respectively; 4.6 to 7.4 pg/mL and 6.6 to 14.8 pg/mL with a 10-μg softgel capsule and a tablet insert, respectively; and 3.6 to 3.9 pg/mL with a 4-μg softgel capsule insert. A mean systemic estradiol concentration ranging from undetectable to 10.7 pg/mL is proposed as an estimate for basal estradiol levels in normal, untreated, postmenopausal women. Systemic estradiol absorption may be influenced by the placement of estradiol higher (as with an applicator) versus lower (as without an applicator) in the vagina, as estradiol transport to the uterus would be more likely further away than closer to the introitus.Conclusion:Serum estradiol concentrations were generally lower when measured with more specific and sensitive assays. Estradiol absorption was dose-dependent, and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow-dose vaginal estrogens may potentially decrease any adverse events that may be associated with higher doses of vaginal estrogens used for treating moderate to severe VVA due to less estradiol exposure.

20: Urinary tract infection following midurethral sling

Urinary tract infections (UTIs) are common in women following urogenital surgery and are associated with significant individual and societal burdens. Therefore, the need to further understand clinical risk factors and subsequent strategies for prevention is imperative. The purpose of this study is to identify risk factors for post-operative UTIs following midurethral sling (MUS). We also describe the bacterial species responsible for postoperative UTIs in our community and the antibiotics prescribed. This is a retrospective analysis of patients who underwent MUS from 2010-2018 within a FPMRS practice of 2 surgeons. Data was extracted from review of charts and UTIs were documented up to 12 months following MUS. Risk factors evaluated included patient factors (age, BMI, parity, medical comorbidities, urinary incontinence, post void residual (PVR), smoking history, prolapse stage, vaginal estrogen use, menopausal status, recurrent UTI history, sexual activity, pessary use, hormone replacement use, neurogenic bladder), surgical factors (operative time, antibiotic use, estimated blood loss, concomitant reconstructive surgery, bladder perforation) and postoperative factors (duration of voiding dysfunction, sling revision, urinary incontinence resolution, PVR at 6 week visit). Categorical variables were analyzed with the Chi-square test, and continuous variables were analyzed using Student’s t-tests. Statistically significant demographic and perioperative characteristics were studied in the Multiple Regression Analysis. 915 MUS cases were reviewed. 23% of patients developed at least 1 UTI in the 12-month period postoperatively. On a bivariate analysis, statistically significant associations were found between postoperative UTI and patients with higher age, greater BMI, stage 3 prolapse, recurrent UTI history, asymptomatic bacteriuria, and cardiovascular disease. Significant perioperative characteristics included concomitant reconstructive surgery, voiding dysfunction requiring catheterization, continued post-operative urinary incontinence, and elevated PVR. On a multivariate analysis, prior history of recurrent UTI and PVR >100mL at 6 weeks were associated with UTI postoperatively. A history of recurrent UTIs and UTI within the first 6 weeks postoperatively was both independently associated with development of recurrent UTI in the first year following MUS. Escherichia coli was the predominant bacterial species of both recurrent and nonrecurrent UTIs, and macrobid was the most common antibiotic utilized. This study provides additional power and confirmation of risk factors involved with postoperative UTIs following earlier studies of this topic. Local bacterial species and treatment patterns are described.

Vaginal estrogen use for genitourinary symptoms in women with a history of uterine, cervical, or ovarian carcinoma

ObjectiveMenopausal symptoms may adversely affect quality of life and health in women diagnosed with a gynecologic malignancy. The aim of this study was to determine the incidence of adverse outcomes,...

8 versus 12weeks of percutaneous tibial nerve stimulation and response predictors for overactive bladder.

The primary objective is to compare weekly success rates after 8 vs 12 weekly percutaneous tibial nerve stimulation (PTNS) sessions for treatment of overactive bladder (OAB) in women and the secondary objective is to identify treatment response predictors. A retrospective study of 470 women was performed with the primary definition of success a Patient Global Impression-Improvement (PGI-I) score of 1 ("very much better") or 2 ("much better") and a ≥ 10-point improvement in both subscales of the Overactive Bladder Questionnaire-Short Form (OABq-SF). Additional analyses were performed to include a success definition of a PGI-I score of 3 ("a little better"). Categorical variables were compared using the Chi-squared test. Multivariate logistic regression was performed to identify factors associated with response. One hundred and thirty-six out of 470 (29%) discontinued treatment before 12weeks. One hundred out of 334 (29.9%) were successes at 8weeks vs 138 out of 334 (41.3%) at 12weeks (p = 0.002). Including a PGI-I score of 3 as an indicator of success, 181 out of 334 (54.2%) at 8weeks and 202 out of 334 (60.5%) at 12weeks were successes (p = 0.10). Factors associated with treatment response were neurological disorder (OR 4.32 [1.10-16.04]), prolapse surgery history (OR 3.89 [1.12-14.49]), and vaginal estrogen use (OR 1.76 [1.01-3.08]). Recurrent UTI was associated with failure (OR 0.42 [0.21-0.86]). The PTNS treatment success rate for OAB in women is greater at 12weeks than at 8weeks based on two validated questionnaires, the PGI-I and the OABq-SF. However, the success rates were equivalent if women who are "a little better" are also considered successes; with this definition, clinicians may consider shortening treatment duration to 8weeks. Four clinical factors were significantly associated with response and may help to guide patient selection.

Surgeon volume and reoperation risk after midurethral sling surgery

Emerging research supports that fewer complications occur in patients who undergo surgery by higher surgical volume surgeons. The midurethral sling surgery has been involved in recent warnings and litigation, which further supports a need to understand features that enhance its safety and efficacy. The purpose of this study was to measure the impact of a surgeon's volume on their patient's rate of reoperation after midurethral sling surgery. This was a retrospective cohort study that evaluated all surgeons who performed synthetic mesh midurethral sling surgery for stress urinary incontinence at a large managed care organization with >4.5 million members from 2005-2016. Physicians Current Procedural Terminology and International Classification of Diseases, version 9/10, codes were used to identify the procedures and the reoperations that were performed. The system-wide medical record was queried for demographic and perioperative data. The primary outcome was the overall reoperation rate after midurethral sling surgery. Concentration curves were used to identify the impact of a surgeon's surgical volume on their rate of reoperation. Demographics, characteristics, and reoperation of patients were compared with the use of chi-square test for categoric variables and Wilcoxon rank sum test for continuous variables. Poisson regression models with a robust error variance were used to calculate the unadjusted and the adjusted risk ratios of reoperation with the use of age, body mass index, marital status, race, parity, vaginal estrogen use, sling type, smoking, diabetes mellitus, and menopausal status as covariates. Two hundred twenty-seven surgeons performed 13,404 midurethral sling surgeries over the study period; patients had a mean of 4.4 years of follow up. Higher-volume surgeons (>40 procedures/year, ≥95th percentile) performed 47% of the surgeries in this cohort and had an overall lower rate of reoperation (3.6% vs 4.2%; 95% confidence interval, 0.67-0.94; P=.04) compared with lower-volume surgeons. Higher-volume surgeons had a lower rate of reoperation for surgical failure (2.7% vs 3.6%; 95% confidence interval, 0.55-0.92; P<.01). Rates of reoperation for complications were similar between the 2 groups (1.1% vs 0.9%; 95% confidence interval, 0.82-1.13; P=.32). For patients whose condition required a reoperation secondary to complication, the rates of reoperation for urinary retention (0.9% vs 0.6%; P=.06), mesh exposure (0.2% vs 0.3%; P=.31), hemorrhage/bleeding (0.1% vs 0.0%; P=.11), pain (0.1% vs 0.1%; P=.52), and infection (0.0% vs 0.0%; P=.37) did not differ between higher- and lower-volume surgeons. The risk ratio for reoperation that compared higher- and lower-volume surgeons was 0.83 (95% confidence interval, 0.67-0.98; P=.01) in the adjusted model. Although the reoperation rates were low for both higher- and lower-volume surgeons, higher-volume surgeons had lower overall rates of reoperation after midurethral sling surgery. This effect is seen most dramatically in reoperation for surgical failure, in which patients who have surgery with a higher-volume surgeon are 25% less likelytohave postoperative stress urinary incontinence that leads to reoperation.

Topical vaginal estrogen use and risk of endometrial hyperplasia or cancer

Topical vaginal estrogen use and risk of endometrial hyperplasia or cancer

Endometrial safety of low-dose vaginal estrogens in menopausal women: a systematic evidence review.

The aim of the study was to systematically review studies that evaluated endometrial hyperplasia or cancer incidence with unopposed vaginal estrogens. PubMed and EMBASE were searched from inception to August 2017 for relevant articles and abstracts. Bibliographies of review articles and abstracts of major women's health medical meetings were examined. Eligible studies (independently reviewed by 4 authors) had to report menopausal vaginal estrogen use and endometrial histology, or incidence of endometrial hyperplasia or cancer. Of 5,593 abstracts from the literature search and 47 articles from other sources, 36 articles and 2 abstracts were eligible, describing 20 randomized controlled studies, 8 interventional studies, and 10 observational studies. Collectively, the studies did not support an increased risk of endometrial hyperplasia or cancer with low-dose vaginal estrogens. Rates of endometrial cancer and hyperplasia were 0.03% and 0.4%, respectively, from 20 randomized controlled trials (2,983 women) of vaginal estrogens. Overall, reports of endometrial hyperplasia were observed with various doses and durations and appeared sporadic (except 1.25 mg conjugated equine estrogens), consistent with endometrial hyperplasia rates in the general population. A Denmark registry study was an exception and may be of limited applicability to the United States. The Women's Health Initiative Observational Study showed no association (1.3 cases/1,000 women-years with vaginal estrogens versus 1.0/1,000 women-years for nonuse). This systematic review supports the use of low-dose vaginal estrogens for treating vulvar and vaginal atrophy in menopausal women without a concomitant progestogen. This review does not support increased endometrial hyperplasia or cancer risk with low-dose, unopposed vaginal estrogens; however, longer-term, real-world data are needed.

13: Short-, mid-, and long-term incontinence outcomes in women undergoing mid-urethral sling procedures

The primary aim was to compare short-, mid-, and long-term subjective treatment success in women undergoing MUS for stress urinary incontinence (SUI). Women undergoing a primary MUS between 2001 and 2009 were identified by CPT code. Eligible patients were mailed the Urinary Distress Inventory (UDI-6), Pelvic Floor Impact Questionnaire (PFIQ-7), Patient Global Impression of Improvement (PGI-I), and Patient Satisfaction Questionnaire (PSQ). Patients in the long-term cohort were asked whether to undergo a MUS procedure again. Follow-up intervals were categorized as short-term (≤ 36 months), mid-term (36-70 months), and long-term (119 -200 months). Treatment success was defined as responses of “not at all” or “somewhat” to both SUI subscales on the UDI-6. Chi-squared tests for categorical variables, and analysis of variance (ANOVA) or Kruskal-Wallis for continuous variables were utilized. Logistic regression was used to examine the association between follow-up group and subjective treatment success, between short- and combined mid- and long-term follow-up groups after adjustment for covariates. Of N=896 respondents, 361 were assessed short-term (mean: 23.3±7.2 months), 251 mid-term (49.8±9.1 months), and 284 in long-term (147.9±20.6 months) follow-up. Differences were significant for age (short: 60.9±11.6, mid: 60.3 ± 12.5, long: 58.4±10.5, p=0.03), smoking status, prior prolapse surgery, and perioperative vaginal estrogen use (all p<0.05). Treatment success differed among groups: 75.4% in the short-, 62.3% mid-, and 67.0% long-term groups, p<0.01. Logistic regression showed that women with mid- or long-term follow up were nearly half as likely as their short-term counterparts to report subjective treatment success, adjusted Odds Ratio OR 0.51, 95% Confidence Interval CI, 0.36, 0.74. Median UDI-6 and PFIQ-7 scores revealed significant differences among short-, mid- and long-term follow-up, all p<0.01 (Table). Findings were similar for the PGI-I, p<0.01. Patient satisfaction was similar: “completely” and “somewhat satisfied” in 83.3% short-, 76.6% mid-, 78.2% long-term (p = 0.09) follow-up. In the long-term group, 73.1% reported they would undergo a MUS again. Subjective treatment success, post-operative symptom severity, and condition-specific QOL differed among short-, mid-, and long-term groups, with higher success and improved symptoms in the short-term group in women undergoing MUS. There is a drop to mid- and long-term success which is stable and sustained to 12 years; high satisfaction was sustained across the follow-up groups. Given the paucity of data on long-term outcomes of MUS, this information is valuable and informs to patient expectations.

Vaginal estrogen use and chronic disease risk in the Nurses' Health Study.

To examine the associations between vaginal estrogen use and multiple health outcomes including cardiovascular disease (total myocardial infarction, stroke, and pulmonary embolism/deep vein thrombosis), cancer (total invasive, breast, endometrial, ovarian, and colorectal cancer), and hip fracture. We included postmenopausal women from the Nurses' Health Study (1982-2012) who were not current users of systemic hormone therapy at the start of the study or during follow-up. Vaginal estrogen use was self-reported on the biennial questionnaires. Information on incident health outcomes were self-reported and confirmed by medical records. We used Cox proportional hazards regression to model the multivariable adjusted hazard ratios and the 95% confidence intervals for vaginal estrogen use and multiple health outcomes. Over 18 years of follow-up, after adjusting for covariates, risks for cardiovascular disease, cancer, and hip fracture were not different between users and nonusers of vaginal estrogen. No statistically significant increase in risk of any health outcome was observed with vaginal estrogen use. In sensitivity analyses, when we examined associations by hysterectomy status, the stratified results were generally similar to those for the total cohort. Vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer. Our findings lend support to the safety of vaginal estrogen use, a highly effective treatment for genitourinary syndrome of menopause.

Moderate to severe vasomotor and sexual symptoms remain problematic for women aged 60 to 65 years.

This study aims to determine the prevalence and severity of menopausal symptoms in older postmenopausal women and, hence, the need for treatment options for women of this age. This is a cross-sectional questionnaire-based study conducted between October 2013 and March 2014 among 2,020 women aged 40 to 65 years and living independently across Australia. The main outcome measures were the prevalence of moderate to severe vasomotor symptoms (VMS), as measured by the Menopause-Specific Quality of Life Questionnaire, and the current use of prescription therapy for menopausal symptoms. The prevalence of moderate to severe VMS was as follows: 2.8% in premenopausal women, 17.1% in perimenopausal women, 28.5% in postmenopausal women younger than 55 years, 15.1% in postmenopausal women aged 55 to 59 years, and 6.5% in postmenopausal women aged 60 to 65 years. Prescription therapy for menopausal symptoms was used by 135 women: 120 (5.9%) women using hormone therapy and 15 (0.7%) women using nonhormonal medication. The factors positively associated with moderate to severe VMS were smoking (odds ratio, 1.6; 95% CI, 1.1-2.3; P < 0.05) and a body mass index of 25 to 29.9 kg/m (odds ratio, 1.7; 95% CI, 1.1-2.5; P < 0.05); education beyond high school was inversely associated (odds ratio, 0.7; 95% CI, 0.5-0.9; P < 0.05). In this large, representative, community-based sample of women, there is a high prevalence of untreated moderate to severe VMS even in women aged 60 to 65 years. The use of vaginal estrogen and nonhormonal prescription therapy with proven efficacy for treatment of menopausal symptoms is strikingly low, suggesting that menopause remains an undertreated condition.

WISDOM survey: attitudes and behaviors of physicians toward vulvar and vaginal atrophy (VVA) treatment in women including those with breast cancer history.

Objective:To evaluate and compare physicians’ behaviors and attitudes regarding vulvar and vaginal atrophy (VVA) treatment in menopausal women, including women with breast cancer, using an internet-based survey.Methods:The WISDOM survey queried obstetricians and gynecologists (OB/GYNs) and primary care physicians (PCPs) with 23 multipart questions assessing behaviors and attitudes towards VVA treatment.Results:Of 2,424 surveys sent, 945 (39%) responded and 644 (27%) were completed. Of the menopausal women seen by OB/GYNs and PCPs, 44% to 55% reported having VVA symptoms. Physicians prescribed VVA treatments primarily because of effectiveness. Only 34% of OB/GYNs and 17% of PCPs felt comfortable prescribing VVA therapies to women with a personal history of breast cancer. In general, the most common VVA treatment recommended by all was prescription therapy (49%; with or without other therapies) in the form of US Food and Drug Administration-approved vaginal estrogen creams. More OB/GYNs (72%) than PCPs (47%) disagreed that VVA was best treated with over the counter than prescription products. Out-of-pocket cost and fear of risks associated with estrogens were believed to be the main barriers for why women choose not to get treated and why they discontinue treatment.Conclusions:More OB/GYNs than PCPs prescribed VVA treatment, especially vaginal estrogens, for menopausal women, but both groups generally had similar attitudes and behaviors regarding VVA treatment. Physician comfort was low when prescribing to women with a history of breast cancer, despite women's health medical societies supporting vaginal estrogen use in women with a history of estrogen-dependent breast cancer who were unresponsive to nonhormonal therapies when offered in consultation with their oncologist.

Vaginal estrogen and mammogram results: case series and review of literature on treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors.

To examine mammographic density before and after at least 1 year of vaginal estrogen use in a small cohort of healthy postmenopausal women and women with a personal history of breast cancer. We extracted data via chart review of patients from a single practitioner's menopause specialty clinic in Baltimore, MD. Mammographic change was primarily determined via the Bi-RADS scoring system, including the Bi-RADS density score. In addition, we conduct a narrative review of the current literature on the usage of local estrogen therapy, and systemic and local alternatives in the treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors. Twenty healthy postmenopausal women and three breast cancer survivors fit our inclusion criteria. Amongst these two groups, we did not find an increase in mammographic density after at least 1 year and up to 18 years of local vaginal estrogen. Ospemifene use in one patient did not appear to be associated with any change in Bi-RADS score. Our narrative review found little data on the effects of vaginal estrogen therapy or newer alternative systemic therapies such as ospemifene on mammographic density. Low-dose vaginal estrogen use for 1 or more years in a small cohort of women with GSM did not appear to be associated with any changes in breast density or Bi-RADS breast cancer risk scores in the majority of study participants, including three breast cancer survivors. Larger long-term controlled clinical trials should be conducted to examine the effects of low-dose vaginal estrogen on mammographic density in women with and without a personal history of breast cancer. Furthermore, relative efficacy and risk of vaginal estrogen compared with other forms of treatment for GSM should also be studied in long-term trials.

Endometrial Safety of Low Dose Vaginal Estrogens in Menopausal Women [39P

INTRODUCTION: 2.3 million women use low dose vaginal estrogen products to treat symptomatic vulvar and vaginal atrophy (VVA) in the US. Most women do not take a concomitant progesterone. A systematic literature search was conducted on the risk of endometrial hyperplasia/cancer and the use of unopposed vaginal estrogen products. METHODS: PubMed and EMBASE were searched for journal articles related to the use of vaginal estrogens in postmenopausal women published in the English language. A total of 5,593 abstracts were reviewed; 37 articles reported vaginal estrogen use and endometrial histology. RESULTS: There were 20 randomized studies with a total of 2,747 women exposed to vaginal estrogen for up to one year; there was no evidence of an increased risk of endometrial hyperplasia/cancer in association with vaginal estrogen products. Other interventional and observational studies identified during the systematic review do not support an increased risk of endometrial hyperplasia or endometrial cancer with low dose vaginal estrogen. The exception is a registry from Denmark that was inconsistent with other studies evaluated and of limited applicability to the US. CONCLUSION: The available evidence from systematic review does not support an increased risk of endometrial hyperplasia or endometrial cancer with low dose vaginal estrogen; however, there are limitations with the applicability of current reports to new lower dose products.