Current Estrogen Use Research Articles

Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women.

Clinical profiles of women with recurrent urinary tract infection (RUTI) are correlated with their urinary microbes. This IRB-approved, cross-sectional study enrolled adult women with RUTI. Urine samples (catheterized and voided) underwent culture by expanded quantitative urine culture (EQUC) and standard urine culture (SUC) methods. A validated symptom questionnaire, relevant clinical variables, and EQUC were used to identify symptom clusters and detect associations with specific urinary microbes. Most (36/43) participants were postmenopausal; the average age was 67 years. 51% reported vaginal estrogen use; 51% reported sexual activity. Although single symptoms were not associated with specific urinary microbes, EQUC results were correlated with five distinct clinical profile clusters: Group A: odor, cloudiness, and current vaginal estrogen use (no culture result association). Group B: frequency, low back pain, incomplete emptying, and vaginal estrogen (significantly increased proportion of Lactobacillus-positive cultures). Group C: pain/burning, odor, cloudiness, and urgency (high proportions of UTI-associated microbe-positive cultures). Group D: frequency, urgency, pain/burning, and current vaginal estrogen use (increased number of no growth cultures). Group E: frequency, urgency, pain/burning, odor, overactive bladder, and sexually active (significantly increased proportion of Klebsiella-positive cultures). Distinct clinical profiles are associated with specific urinary microbes in women with RUTI. Refined assessments of clinical profiles may provide useful insights that could inform diagnostic and therapeutic considerations.

ICS 2019 Gothenburg Scientific Programme.

HYPOTHESIS/AIMS OF STUDY: Patients with overactive bladder syndrome (OAB) are treated according to a stepwise approach, with conservative treatments followed by more invasive ones (1). Since the efcacy of each step difers in patients and outcomes are poorly predictable, this approach often is time-consuming and disappointing from a patients' perspective. The aim of this study was to map the OAB-patient's pathway in a large teaching hospital. First, we evaluated the effect and duration of each of the ofered OAB treatments. Second, we questioned if derogation from the guideline afected treatment duration? Third, we tried to identify case-mix variables as predictors for treatment duration. STUDY DESIGN, MATERIALS AND METHODS: This study is retrospective cohort study of all female patients with idiopathic OAB that visited the outpatient clinic of a large teaching hospital. A search was done, using the search engine Ctcue, in the electronic patient records (EPR) of patients treated for OAB or urgency incontinence between January frst 2014 and September the 30th of 2016, allowing a follow-up period of at least one year. Patients younger than 18 years or women with OAB symptoms due to neurologic disorder, bladder tumor, bladder stones, urinary tract infection or interstitial cystitis were excluded from the analyses. OAB-treatment modalities provided in our hospital were pelvic foor muscle therapy (PFMT), anticholinergic drugs, alternative anticholinergic drugs, mirabegron, percutaneous tibial nerve stimulation (PTNS), intravesical injections with Onabotulinum Toxin A (Botox®) and sacral neuromodulation (SNM). All data were retrieved from the medical fles, using a structured case report form, and entered in Research Manager. Duration of the treatment was defined by the number of days from the frst to the last visit in our outpatient clinic per treatment modality. Treatment succes was defined as patient satisfaction and no need to start a new treatment. A survival analysis was done comparing patients that were treated according to the guideline with patients that were not treated according to the guideline. Case-mix variables that might affect OAB treatment outcomes as defined by the International Consortium for Health Outcome Measurement (ICHOM) were included in the analyses to allow for risk adjusted outcome comparisons (2). These variables were age, body mass index, bowel disease, diabetes, cognitive impairment, pelvic organ prolapse, stress urinary incontinence, current use of estrogens and history of pelvic surgery. Case-mix variables were analyzed using the Cox proportional hazards model for their predictive value of treatment duration. Statistical analysis was performed using IBM SPSS Statistics 24.0. RESULTS: Of 296 patients found with Ctcue, 119 patients met inclusion criteria, of which 81% reported urgency incontinence. Fourty-four percent of patients were treated according to the guidelines. About half of all women underwent PFMT, of which 35 were classifed as successful. About two-thirds of women received an anticholinergic drug (with 25% effect), and a small number received a second anticholinergic, whereas 15% of patients mirabegron was prescribed as second option after initial anticholinergic therapy. A total of 39 women received mirabegon, as frst, second or third step, showing around 30% effect. Of these patients, 22% did not receive an alternative anticholinergic. PTNS was ofered to 36% of patients, where in 6% PTNS was started before medication, mostly because of patient's preference. Mean age was 59.1(16.1) years. Prevalence of BMI>25 was 66%. Thirty seven percent of patients had bowel disease. Patients with pelvic organ prolapse were 33% and 47% of patients had previous pelvic surgery. None of the case-mix variables, as analyzed with Cox proportional hazards model, were predictive for treatment duration. INTERPRETATION OF RESULTS: This study shows that the OAB-patient's pathway is not an easy one. Especially conservative treatments have poor ef-fcacy and are time-consuming. We found no diference in treatment duration in relation to adherence to the guideline, and were unable to predict treatment duration by case-mix variables. Further research should aim at patient's expectations and experiences of the current stepwise approach, in order to optimize the OAB-treatment pathway to the patient's needs. CONCLUDING MESSAGE: This large retrospective cohort study shows that treatment of patients with OAB syndrome, especially with conservative therapy, is time-consuming and has poor outcomes. Derogation from the guideline did not afect treatment duration in this study. No case-mix variables could be identifed as predictors of duration of treatment.

Does estrogen deprivation affect pelvic floor muscle contractility?

Pelvic floor muscle (PFM) function plays a role in pelvic organ support, and estrogen deprivation is commonly seen as a risk factor for pelvic floor dysfunction. This study investigated the association between estrogen deprivation and PFM contractility. This was a retrospective study on women attending a tertiary urogynecological unit. The assessment included an interview, POPQ assessment, Modified Oxford Scale (MOS) score, and 4D translabial ultrasound (US) on PFM contraction (PMFC). Hormonal status and details on hormone replacement therapy (HRT) were recorded. Corrected menopausal age was defined as the duration of systemic estrogen deprivation. Offline analysis of stored US volumes was performed to measure the reduction in anteroposterior hiatal diameter and bladder neck elevation on PFMC at a later date. Seven hundred thirty-nine women were seen during the study period. Fifty-three were excluded for missing data, leaving 686. Mean age was 56 (17-89, SD 13.3) years; average BMI was 29 (16-66, SD 6.6) kg/m²; 60.6% (n = 416) were menopausal at a mean duration of 16 (1-56, SD 10.2) years. Forty-nine (7.1%) were currently on systemic HRT, while 104 (15.2%) had used it previously. Mean corrected menopausal age (menopausal age - systemic HRT duration) was 7.4 (0-56, SD 10.0) years. Current local estrogen use ≥ 3months was reported by 31 (4.5%). Mean PFM contractility measured by MOS was 2 (0-5, SD 1.1,). On multivariate analysis there was no association between menopausal age and PFM contractility. Estrogen deprivation may not be an independent predictor of pelvic floor muscle contractility.

Abstract P1-08-07: Risk factors for high-grade and low-grade DCIS in the cancer prevention study-II nutrition cohort

Abstract Background: Nuclear grade, believed to be established early in carcinogenesis, is an indicator of ductal carcinoma in situ (DCIS) prognosis. Women with high-grade DCIS have a higher risk of local recurrence compared to women with low-grade DCIS. Risk factors for DCIS overall are well-characterized but risk factors by grade are not. Given the prognostic capabilities of grade for DCIS, it is of interest to identify whether risk factors by DCIS grade differ. Methods: Among 75,630 women enrolled in the Cancer Prevention Study-II Nutrition Cohort in 1992-1993, we identified 422 who were diagnosed with low-moderate grade DCIS (i.e. grades 1 or 2) and 355 who were diagnosed with high-grade DCIS (i.e. grade 3) during follow-up through 2013. Beginning in 1997, biennial questionnaires were administered to update exposure status, including screening mammography in the previous two years. For this analysis, these questionnaires were used to partition follow-up time into approximately two-year intervals. Because screening is strongly linked to diagnosis of DCIS, contribution of person-time within a specific interval was conditional on reporting a screening mammogram in the interval prior. Multivariate joint Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the associations of known breast cancer risk factors with DCIS overall, and with high-grade and low-grade DCIS individually. Results: Parity (HR=0.70; 95% CI: 0.63-0.78, parous vs. nulliparous), smoking status (HR=0.69; 95% CI: 0.58-0.82, current vs. never smoking) and menopausal status (HR=0.79; 95% CI: 0.73-0.87, natural menopause <50 years vs. natural menopause ≥ 50 years) were inversely associated with risk of DCIS overall. Whereas, positive family history of breast cancer (HR=1.46; 95% CI: 1.36-1.57), personal history of benign breast disease (BBD) (HR=1.73; 95% CI: 1.62-1.85), and current use of combination estrogen and progestin hormone replacement therapy (HR=1.15; 95% CI: 1.04-1.28) were associated with higher risk of DCIS. In analyses stratified on DCIS grade, history of BBD was more strongly associated with higher risk of low-grade (HR=2.21; 95% CI: 1.81-2.70) than with high-grade DCIS (HR=1.29; 95% CI:1.04-1.60) (p for heterogeneity=0.001). Current combination estrogen and progestin hormone replacement therapy use was associated with a higher risk of high-grade DCIS (HR=1.40; 95% CI:1.03-1.90) but not low-grade DCIS (HR=1.02; 95% CI: 0.75-1.40), but the difference by grade was not statistically significant (p=0.5). Conclusions: In this study, which is the first to comprehensively assess risk factors by DCIS grade, the association between personal history of BBD and risk of DCIS appeared to differ by grade. Due to limited power for some risk factor analyses, future studies using larger prospective cohorts or pooled data should be conducted to better identify these associations. Citation Format: Puvanesarajah S, Gapstur SM, Gansler T, Patel AV, Gaudet MM. Risk factors for high-grade and low-grade DCIS in the cancer prevention study-II nutrition cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-07.

Exogenous Hormone Use and Endometrial Cancer in U.S. Black Women.

Background: Although endometrial cancer risk differs among white and black women, few data on its associations with exogenous hormone use in the latter group are available. Studies have reported lower endometrial cancer risk among users of oral contraceptives (OCs), but higher risk among users of estrogen-only female menopausal hormones (FMHs). Evidence for the risk among estrogen plus progestin FMHs users is equivocal.Methods: We followed 47,555 Black Women's Health Study participants with an intact uterus from 1995 through 2013. Data on exogenous hormone use, covariates, and endometrial cancer were obtained biennially. Self-reported incident cases of endometrial cancer were confirmed by medical records or cancer registries whenever possible. We estimated incidence rate ratios (IRRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression.Results: We observed 300 endometrial cancer cases during 689,546 person-years of follow-up. Compared with never use, ≥10 years' duration of OC use was associated with lower risk (multivariable IRR = 0.45, 95% CI, 0.27-0.74), but risk was higher among current users of estrogen-only (IRR = 3.78, 95% CI, 1.69-8.43) and estrogen plus progestin FMH (IRR = 1.55, 95% CI, 0.78-3.11). Risk was not increased among former users of estrogen-only (IRR = 0.87, 95% CI, 0.44-1.72) or estrogen plus progestin FMH (IRR = 0.63, 95% CI, 0.36-1.09).Conclusions: Current use of estrogen-only and estrogen plus progestin FMH was associated with increased risk of endometrial cancer. Risk appeared lower among former users of estrogen plus progestin FMH. Long-term OC use was associated with reduced risk.Impact: Our results are generally consistent with those among white women. Cancer Epidemiol Biomarkers Prev; 27(5); 558-65. ©2018 AACR.

Pelvic organ prolapse: does hormone therapy use matter?

To determine the effect of hormone therapy (HT) use on pelvic organ support. A retrospective observational study involving postmenopausal women with pelvic floor dysfunction attending a tertiary urogynecology center between January 2012 and March 2015. All underwent a clinical examination including International Continence Society Pelvic Organ Prolapse Quantification and 4D translabial ultrasound imaging. Information on current or former use of systemic HT and current local estrogen use was collected. Main outcome measure was pelvic organ support. One thousand four hundred forty-three women were seen during the study period. On univariate analysis, current HT was significantly associated with sonographically determined descent of the rectal ampulla (β [95% confidence interval] 3.4 mm [0.4-6.5], P = 0.03) and Gh + Pb (-0.45 mm [-0.8 to -0.1], P = 0.005). Past HT use, duration of HT use, or current vaginal estrogen use was not associated with pelvic organ support. On multivariate analysis controlling for age, parity, body mass index, history of forceps delivery, and avulsion, the association between current HT on the one hand and Gh + Pb as well as increased descent of the rectal ampulla on ultrasound, remained significant (P = 0.008 and P = 0.012, respectively). HT may have a minor negative effect on pelvic organ support; however, the effect is likely too small to be clinically relevant.

Abstract 4237: Estrogen metabolism in menopausal hormone users: Does it differ between estrogen plus progestin and estrogen alone users in the Women’s Health Initiative Observational Study

Abstract Background: The Women’s Health Initiative (WHI) provided divergent results regarding the effects of menopausal hormone therapy (MHT) on breast cancer risk, with women in the conjugated equine estrogen plus medroxyprogesterone (CEE+MPA) arm at elevated risk, and women in the CEE alone arm at reduced risk. Although direct progestin-mediated effects may largely explain the elevated risk, we hypothesize that in addition, these MHT treatments may differentially influence patterns of estrogen metabolism, with CEE alone preferentially inducing metabolism along the 2-hydroxylation pathway, a pattern previously linked to reduced breast cancer risk. Study methods/population: Women in a case-control study of estrogen metabolites (EM) and ovarian and endometrial cancer from the WHI Observational Study were identified for this analysis. Unlike the WHI trial, no medication restrictions were applied. At enrollment, serum, anthropometric measures, and self-administered questionnaires which ascertained reproductive history, lifestyle factors and health behaviors including MHT use, were obtained. 615 women reported current use of estrogen plus progestin formulations (E+P), of whom 343 used CEE+MPA; 266 used estrogens alone (E alone), with 148 using CEE. Fifteen EM were measured by liquid chromatography/mass spectrometry and analyses were conducted separately for each EM. EM differences between E alone and E+P users were assessed using inverse probability weighted linear regression. Primary analyses included women using any MHT formulation; secondary analyses were restricted to CEE users. Results: Compared to users of E+P, concentrations of all EM were higher in E alone users, and significantly so for unconjugated estrone, estradiol, 2-methoxyestrone, 4-methoxyestrone and unconjugated estriol. Relative to total EM, concentrations of 2- and 4-pathway EM did not differ by MHT group (for E alone and E+P users, 2-pathway EM were ~14% of the total EM; 4-pathway EM were <2% of the total), but E+P users had a significantly higher proportion of 16-pathway EM compared to E alone users (32% vs. 30%, p=0.025). Similar patterns were observed in analyses comparing users of CEE alone to CEE+MPA, albeit not significant. Conclusion: Our data suggest that women using E alone may preferentially metabolize estrogens along the 2- and 4-hydroxylation pathways, whereas in E+P users, more extensive metabolism occurs along the 16-pathway. However, we did not observe these effects in the smaller groups of women using CEE alone or CEE+MPA, the MHT formulations administered in the treatment arms of the WHI trial. Our findings in E alone users are consistent with epidemiologic investigations demonstrating reduced breast cancer risk in postmenopausal women with more extensive 2-pathway estrogen metabolism, and may provide a clue to the breast cancer risk reduction observed in these women. Citation Format: Roni T. Falk, Garnet L. Anderson, Vanessa M. Barnabei, Louise A. Brinton, Jane A. Cauley, Chu Chen, Rowan T. Chlebowski, Sally B. Coburn, JoAnn E. Manson, Ruth M. Pfeiffer, Kerryn W. Reding, Thomas E. Rohan, Gloria E. Sarto, Nicolas Wentzensen, Britton Trabert. Estrogen metabolism in menopausal hormone users: Does it differ between estrogen plus progestin and estrogen alone users in the Women’s Health Initiative Observational Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4237. doi:10.1158/1538-7445.AM2017-4237

Bias from depletion of susceptibles: the example of hormone replacement therapy and the risk of venous thromboembolism.

The data on the association between hormone replacement therapy and the increased risk of venous thromboembolism (VTE) in postmenopausal women are conflicting. The observed differences between oral estrogen and oral estrogen-progestogen combination formulations may be the result of bias from depletion of susceptibles. We used United Kingdom's Clinical Practice Research Datalink to identify the cohort of all women aged 50 to 79 during 1987-2008, with all incident cases of VTE occurring during the study period identified. Using a nested case-control approach, the rate ratios (RRs) of VTE with current use of oral estrogen and oral estrogen-progestogen combinations were estimated as a function of duration of use using conditional logistic regression with cubic splines. The cohort of 955582 postmenopausal women included 23505 cases of VTE matched to 231562 controls. The risk of VTE was increased with current use of oral estrogen (RR 1.49; 95% confidence interval: 1.37 to 1.63) and oral estrogen-progestogen (RR 1.54; 95% confidence interval: 1.44 to 1.65), relative to non-use. When assessed by duration of use, the risks with oral formulations were particularly elevated during the first year of use and were reduced subsequently. The phenomenon of depletion of susceptibles should be considered in cohort studies evaluating acute side effects of medications. This can be achieved by estimating the risk as a function not only of current use but also of duration of use. Copyright © 2017 John Wiley & Sons, Ltd.

Abstract P019: Low Ovarian Reserve is Associated with Cardiovascular Disease Risk

Introduction: Age at menopause and the postmenopausal state are frequently linked to cardiovascular disease (CVD) risk. Anti-Müllerian hormone (AMH) is produced by ovarian antral follicles and its concentration in peripheral blood is a quantitative estimation of the size of the antral follicle pool, thereby providing a measure of ovarian reserve before the end of the reproductive lifespan. We and others have shown that AMH is related to age at menopause. Literature on whether AMH is related to CVD risk is still scarce and heterogeneous. Hypothesis: We hypothesized that a low ovarian reserve, measured by low levels of AMH, is associated with higher risk of CVD risk in premenopausal women. Methods: We used data from 2,338 premenopausal women who participated in the second follow-up round of the population-based Doetinchem Cohort Study. In a cross-sectional analysis, CVD risk was compared between women in different AMH level-based categories. AMH was measured in stored serum samples using a Gen-II ELISA assay (Beckman-Coulter, Sinsheim, Germany) in a single laboratory. CVD risk was assessed in three ways: levels of single cardiovascular risk factors (systolic and diastolic blood pressure, total and HDL cholesterol, glucose), a metabolic risk factor score, and predicted 10- and 30-year risk using Framingham prediction rules. The association of AMH categories with CVD risk outcomes was studied using linear regression models, adjusted for age, age-squared, current estrogen use, current smoking, parity, menstrual cycle regularity, current pregnancy and BMI. Results: AMH was unmeasurable in 456, and measurable, but below the limit of quantification (0.16 μg/L) in 186 women. In the remaining 1,696 women AMH level could be quantified and the median [IQR] AMH was 1.34 [0.24-5.14] μg/L. After adjustment, women with quantifiable AMH had 0.11 mmol/l (95% CI -0.23; 0.01) lower total cholesterol level than women with unmeasurable and unquantifiable AMH levels. Women with quantifiable AMH had on average 0.11 (95% CI 0.01-0.21) fewer metabolic risk factors compared to women with unmeasurable AMH, adjusted for confounders. Women with quantifiable AMH also had a 5% (95% CI -0.01; 11.0) lower hazard of 10- and 30-year CVD occurrence compared to women with unmeasurable AMH. Conclusions: This study indicates that premenopausal women with very low ovarian reserve, expressed by unmeasurable serum AMH levels, may have an increased CVD risk. Longitudinal research with clinical endpoints and more sensitive AMH assays are necessary to confirm a relationship between AMH and CVD risk.

Concurrent use of statins and hormone therapy and risk of venous thromboembolism in postmenopausal women

Statins and hormone therapy (HT), often used concurrently in postmenopausal women, have antagonist effects on the risk of venous thromboembolism (VTE). This study aims to determine whether statins attenuate the increased VTE risk associated with HT. We conducted a nested case-control study within a population-based cohort of women aged 50 to 79 years between January 1, 1987 and March 1, 2008, who were identified from the UK General Practice Research Database. Cases of VTE occurring during follow-up were identified and each matched with up to 10 controls from the cohort. Odds ratios (ORs) for the effects of concurrent HT and statin use on the risk of VTE were estimated using conditional logistic regression with interaction terms. The cohort included 955,582 postmenopausal women, with 23,505 cases of VTE matched with 231,562 controls. Regardless of any HT use, current use of statins was associated with a decreased risk of VTE (OR, 0.83; 95% CI, 0.78-0.87). The interaction between statin use and HT use was of borderline significance (P = 0.053). Consequently, among nonusers of statins, the risk of VTE was elevated with current use of oral estrogen and progestogen combinations (OR, 1.55; 95% CI, 1.45-1.66) but this risk was not elevated among users of statins (OR, 0.98; 95% CI, 0.56-1.73). There was no such modification of the OR with statins and other HT types and formulations. Statins could potentially attenuate the increased risk associated with HT combinations of oral estrogens and progestogens. This observation needs further confirmation in other large cohorts.

Abstract P378: Risk Factors for Incident Venous Thrombosis and their Associations with Recurrence

Background: Risk factors for incident venous thrombosis (VT) have been studied extensively, yet less is known about risk factors for recurrent VT in population-based settings. Objective: To evaluate whether established risk factors for incident VT are associated with recurrent VT in women. Methods: In a population-based, case-control study, we identified 1575 incident VT cases in 2002-2010 among women aged 18-89 and 3254 matched controls. Incident VT cases were followed for VT recurrence, defined by physician diagnosis with clinical and/or imaging evidence of a new or expanded clot. We used separate Cox proportional hazards models to evaluate the association of risk factors, assessed at the time of the incident VT, with the hazard of VT recurrence. Established risk factors for incident VT included: age, race, body mass index (BMI), hospitalization or inpatient surgery ≤30 days prior to event, recent cancer diagnosis or treatment, history of cardiovascular disease, and current estrogen use (oral contraceptive or hormone therapy). Incident VT characteristics (distal vs. proximal deep vein thrombosis [DVT] and pulmonary embolism [PE] with or without DVT) were also evaluated. Models were adjusted for all factors simultaneously and were run with and without adjustment for time-dependent oral anticoagulation therapy (OAT). Risk factors were assessed by chart review, telephone interview, and computerized pharmacy records. Results: For these interim analyses, follow-up data were available for 1285 women who were followed for a mean of 39.6 months with a 13% probability of a recurrent VT at 3 years. Higher BMI and recent cancer were associated with an increased risk of recurrent VT. When time-dependent OAT was included in the models, estimates were essentially unchanged. Conclusions: In our population-based study, most risk factors for incident VT were poor predictors of recurrence. However, we provide further evidence that BMI and recent cancers are associated with modestly increased hazards of VT recurrence in women.

Inflammatory and Tissue Remodeling Urinary Biomarkers before and after Mid Urethral Sling Surgery for Stress Urinary Incontinence

Urinary biomarkers were measured in women at baseline and 1 year after surgery for stress urinary incontinence, and associations with clinicodemographic covariates and outcomes were analyzed. Preoperative and postoperative urine specimens from 150 women were assayed for inflammatory biomarkers (tumor necrosis factor-α, interferon-γ, interleukin-1β, interleukin-6, interleukin-10, interleukin-12p70, interleukin-17 and nerve growth factor) and tissue remodeling biomarkers (collagenase activity, matrix metalloproteinases-1, 2, 9 and 13, and NTx [N-telopeptide cross-linked collagen], epidermal growth factor and heparin-binding epidermal growth factor-like growth factor). Paired t-tests were used to compare changes in biomarkers during 1 year (significance p <0.05). Linear regression models correlated baseline and changes in biomarker levels with covariates (significance p ≤ 0.001). Logistic regression models, controlling for age, were used to analyze associations of baseline and changes in biomarker levels with surgical failure (significance p <0.05). During 1 year interleukin-12p70 decreased (mean ± SD 0.53 ± 1.4 to 0.28 ± 0.62 pg/mg creatinine, p = 0.04) and nerve growth factor increased (0.034 ± 0.046 to 0.044 ± 0.060 pg/ml/mOsm, p = 0.03). Baseline NTx level per mg creatinine was positively associated with age and postmenopausal status (p = 0.001), and negatively associated with current estrogen use (p = 0.0001). Baseline collagenase activity per mg creatinine was positively associated with age (p = 0.001). Epidermal growth factor per mOsm, NTx per mOsm and interferon-γ per mOsm were negatively correlated with age, current estrogen use and UDI (Urogenital Distress Inventory)-irritative subscale score, respectively (p ≤ 0.001). Subjects with lower baseline NTx per mg creatinine were less likely to experience surgical failure (OR 0.49, 95% CI 0.26-0.93, p = 0.03). Changes in biomarker levels were not associated with any covariates or surgical failure. Stress urinary incontinence surgery was significantly less likely to fail in women with lower baseline NTx levels. Studies are needed to validate NTx as a possible independent biomarker for stress urinary incontinence surgery outcomes.

Postmenopausal unopposed estrogen and estrogen plus progestin use and risk of non-Hodgkin lymphoma in the American Cancer Society Cancer Prevention Study-II Cohort

Results of epidemiologic studies on postmenopausal hormone (PMH) use and non-Hodgkin lymphoma (NHL) are inconsistent. To help clarify this issue, PMH and NHL incidence was examined in the Cancer Prevention Study-II Nutrition Cohort. Between 1992 and 2007, 616 cases of NHL were identified among 67 980 postmenopausal women who were cancer-free at baseline. PMH use was updated during follow-up. Using extended Cox regression, we observed a statistically significant 29% higher risk of NHL for ever unopposed estrogen use compared to never use, which was restricted to follicular lymphoma (current estrogen compared to never use, hazard ratio [HR] = 2.25, 95% confidence interval [CI]: 1.17–4.33) and diffuse large B-cell lymphoma (DLBCL, HR = 1.95, 95% CI: 1.13–3.35). There was no association between current estrogen plus progestin (E + P) use and NHL incidence overall, but a suggested positive association between current E + P use and DLBCL, as well as former E + P use and follicular lymphoma. These results suggest that postmenopausal hormones might play a role in NHL etiology, particularly for follicular lymphoma and DLBCL.

Surgical menopause and nonvertebral fracture risk among older US women.

The aim of this study was to determine whether older postmenopausal women with a history of bilateral oophorectomy before natural menopause (surgical menopause) have a higher risk of nonvertebral postmenopausal fracture than women with natural menopause. We used 21 years of prospectively collected incident fracture data from the ongoing Study of Osteoporotic Fractures, a cohort study of community-dwelling women without previous bilateral hip fracture who were 65 years or older at enrollment, to determine the risk of hip, wrist, and any nonvertebral fracture. χ(2) and t tests were used to compare the two groups on important characteristics. Multivariable Cox proportional hazards regression models stratified by baseline oral estrogen use status were used to estimate the risk of fracture. Baseline characteristics differed significantly among the 6,616 women within the Study of Osteoporotic Fractures who underwent either surgical (1,157) or natural (5,459) menopause, including mean age at menopause (44.3 ± 7.4 vs 48.9 ± 4.9 y, P < 0.001) and current use of oral estrogen (30.2% vs 6.5%, P < 0.001). Fracture rates were not significantly increased for surgical versus natural menopause, even among women who had never used oral estrogen (hip fracture: hazard ratio [HR], 0.87; 95% CI, 0.63-1.21; wrist fracture: HR, 1.10; 95% CI, 0.78-1.57; any nonvertebral fracture: HR, 1.11; 95% CI, 0.93-1.32). These data provide some reassurance that the long-term risk of nonvertebral fracture is not substantially increased for postmenopausal women who experienced premenopausal bilateral oophorectomy, compared with postmenopausal women with intact ovaries, even in the absence of postmenopausal estrogen therapy.

Abstract LB-60: Long-term use of hormone therapy and breast cancer incidence and mortality

Abstract Background: The risk of breast cancer associated with longer-term use of both estrogen (ET) or estrogen + progesterone (E+P) hormone therapy (HT) cannot be determine from existing randomized controlled trials. Methods: The Nurses’ Health Study included 121,700 female registered nurses aged 30-55 in 1976 who have been followed with biennial questionnaires to medication use, risk factors and cancer incidence. Only postmenopausal women were included in this analysis. The main outcome was incidence of invasive breast cancer. We additionally evaluated the risk of fatal breast cancer (breast cancer diagnosis that resulted in breast cancer death). Results: During 1.57 million person-years of follow-up from 1980 through 2008, 5631 incident invasive breast cancers were diagnosed and 884 died of breast cancer. Breast cancer risk increased with duration of current E+P use without evidence for a plateau (e.g. RR 1.88 (95% CI 1.64-2.16) for 10-14.9 years and RR 2.35 (95% CI 1.90-2.92) for 15-19.9 years of use). More than 10 years of current ET use was also associated with increased breast cancer risk (RR 1.22 (95% CI 1.06-1.40) for 10-14.9 years and RR 1.43 (95% CI 1.22-1.68) for 15-19.9 years of use). Past E+P was also weakly associated with breast cancer risk. When the population was restricted to the same entry criteria as the Women's Health Initiative trial, we also observed a non-significant deceased risk of breast cancer HT with current ET use similar in magnitude to that seen in the trial (RR 0.61 (95% CI 0.63-1.05) for &amp;lt; 5 years and RR 0.93 (95% CI 0.76-1.14) for 5-9.9 years), but still observed an increased risk with current ET users of 15-19.9 years (RR 1.30 (95% CI 1.07-1.59). Effects were stronger for ER positive tumors and among thinner women. Results were similar when limited to women who underwent regular screening. Although breast cancer incidence was increased in these groups, there was no increase in the risk of fatal breast cancer with either E+P or ET use (RR 1.05 (95% CI 0.67-1.68) and RR 1.08 (0.80-1.46) for 10-19.9 years of current use respectively). Conclusions: Both past and current E + P users and current long-term ET users were at increased breast cancer risk. We did not observe an increase in fatal breast cancer with HT use. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-60. doi:1538-7445.AM2012-LB-60

Uterine development in patients with Turner syndrome: Relation to hormone replacement therapy and karyotype

Our study aimed to assess uterine development in Turner syndrome patients and its relation to dose and type of estrogen therapy; and karyotype. Pelvic ultrasound was used to assess uterine size and shape, and ovarian volume in 40 Turner syndrome patients. Information on hormone replacement therapy was collected from patients' notes. Among the 40 patients studied, 57.5% started estrogen therapy and 30% were taking progestins. Sixty-five per cent had immature uterus, 17.5% had fully mature uterus and 17.5% had transitional uterus. Uterine volume was associated with age (p < 0.001), height (p = 0.002), weight (p = 0.001), years of estrogen use (p < 0.001), estrogen dose (p = 0.016), current estrogen use ( p =0.001) and Tanner breast stage ( p <0.001). Uterine volume was not affected by the type of estrogen used ( p =0.40) and karyotype ( p =0.40). Patients with Turner syndrome treated with estrogen (of adequate dose and duration) may attain a normal, mature uterine size and configuration, even at a late start of hormone replacement therapy and regardless of karyotype.

An Approach to Identify Rural Women Aged 60 to 64 for Osteoporosis Treatment

The US Preventive Services Task Force recently recommended that women younger than 65 years undergo a bone mineral density screening if clinical risk factors (CRFs) of a major osteoporotic fracture are ≥9.3% for a period of 10 years. We sought the most cost-effective approach to identify older, rural women who are eligible for osteoporosis treatment. We evaluated CRFs and peripheral forearm densitometry (pDXA) in 277 rural women aged 60 to 64 years for treatment eligibility. We compared three strategies of universal screening-pDXA, CRFs, and exclusion of pDXA in specific situations (prior fracture and CRFs ≥20%)-followed by CRF evaluation with pDXA confirmation in the residual population. Our sample showed that 37.5% of women had CRFs at a ≥9.3% cutoff threshold. Only osteoporotic pDXA values were significantly higher at this threshold. Current estrogen use was significantly associated with diminished treatment eligibility (P = 0.001). Body mass index correlated poorly with pDXA values (r = 0.12) and CRFs (r = 0.21). Although a cost-savings strategy nonsignificantly identified more women who were eligible for treatment using the three strategies (P = 0.25), significantly fewer pDXA examinations were required (P < 0.001). Initiating treatment in rural women aged 60 to 64 years who had a prior fracture or CRFs ≥20% without pDXA confirmation, followed by pDXA evaluations in the residual population with CRFs between ≥9.3% and 20%, significantly reduced the number of pDXA examinations and the cost of screening.

Soy milk and dairy consumption is independently associated with ultrasound attenuation of the heel bone among postmenopausal women: the Adventist Health Study–2

Soy milk has become a popular substitute for dairy milk with important health claims. We hypothesized that soy milk, based on its nutrient composition, is comparable to dairy products and, therefore, beneficial for bone health. To test this hypothesis, we examined the benefit of soy milk and dairy products intake on bone health using broadband ultrasound attenuation of the calcaneus. Postmenopausal white women (n = 337) who had completed a lifestyle and dietary questionnaire at enrollment into the Adventist Health Study-2 had their calcaneal broadband ultrasound attenuation measured 2 years later. The association between osteoporosis (defined as a T-score <-1.8) and some dietary factors (soy milk, dairy) and selected lifestyle factors was assessed using logistic regression. In a multivariable model adjusted for demographics, hormone use, and other dietary factors, osteoporosis was positively associated with age (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.06-1.12) and inversely associated with body mass index (OR = 0.91; 95% CI, 0.86-0.97) and current estrogen use (OR = 0.27; 95% CI, 0.13-0.56). Compared with women who did not drink soy milk, women drinking soy milk once a day or more had 56% lower odds of osteoporosis (OR = 0.44; 95% CI, 0.20-0.98; P(trend) = .04). Women whose dairy intake was once a day or more had a 62% reduction in the likelihood of having osteoporosis (OR = 0.38; 95% CI, 0.17-0.86; P(trend) = .02) compared with women whose dairy intake was less than twice a week. Among individual dairy products, only cheese showed an independent and significant protection (OR = 0.28; 95% CI, 0.12-0.66; P(trend) = .004) for women eating cheese more than once per week vs those who ate cheese less than once a week. We concluded that osteoporosis is inversely associated with soy milk intake to a similar degree as dairy intake after accounting for age, body mass index, and estrogen use.

A cross-sectional and 10-year prospective study of postmenopausal estrogen therapy and blood pressure, renal function, and albuminuria

Blood pressure, urine albumin-to-creatinine ratio, and estimated glomerular filtration rate (GFR) are highly correlated conditions. The longitudinal effect of exposure to postmenopausal estrogen therapy on these traits studied together has not been reported. This was a cross-sectional study of 1,044 older postmenopausal community-dwelling women from the Rancho Bernardo Study (1992-1996); 443 women were reevaluated ∼ 10 years later (2002-2005). We determined the cross-sectional and prospective association of baseline postmenopausal estrogen therapy and blood pressure, urine albumin-to-creatinine ratio, GFR, and the odds of categorical hypertension (physician diagnosis, medication, or blood pressure ≥ 140/≥ 90 mm Hg), chronic kidney disease (GFR ≤ 60 mL/min per 1.73 m2), and albuminuria (urine albumin-to-creatinine ratio ≥ 25 mg/g). At baseline, the mean age was 68.3 years for current estrogen users, 75.4 years for past users, and 74.3 years for never users. In the cross-sectional analyses, current users had lower diastolic blood pressure and lower odds of having chronic kidney disease, independent of covariates. In the ∼ 10-year follow-up, comparisons between never, past, and current estrogen use (91% continuous use since baseline), the mean diastolic blood pressure declined over time in current users, whereas systolic blood pressure increased among never users. Urine albumin-to-creatinine ratio also increased in never users and decreased in current users; GFR did not differ by estrogen use. In cross-sectional analyses, estrogen users had better GFR and blood pressure than nonusers did, but the 10-year follow-up showed improved blood pressure and decreased urine albumin-to-creatinine ratio among mostly long-term current users, without differences in GFR by estrogen use. This study suggests no association of GFR with 10 years of continuous estrogen use and an inverse association with albuminuria.

Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Menopausal hormone therapy (HT) may influence colorectal cancer risk. A total of 136,275 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition were followed for an average of 9 years, during which time 1,186 colorectal cancers were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by center and age, and adjusted for body mass index, smoking, diabetes, physical activity and alcohol consumption. Compared to never use of HT at study enrollment, current use of estrogen-only (HR, 1.02; 95% CI, 0.79-1.31) or estrogen plus progestin (HR, 0.94; 95% CI, 0.77-1.14) was not significantly associated with the risk of colorectal cancer, and these associations did not vary by recency, duration, route of administration, regimen or specific constituent of HT. Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk.