BACKGROUND:Although many studies suggested the benefit of smoking cessation among pregnant women in reducing the risk of preterm birth (PTB), the timing of the effect of the cessation remains inconclusive. OBJECTIVES:To examine the association of trimester-specific smoking cessation behaviours with PTB risk. METHODS:We included 199,453 live births in Western New York between 2004 and 2018. Based on self-reported cigarette smoking during preconception and in each trimester, we created six mutually exclusive groups: non-smokers, quitters in each trimester, those who smoked throughout pregnancy, and inconsistent smokers. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression to examine the association between smoking cessation and PTB. Effect modification by illegal drug use, maternal age, race and ethnicity and pre-pregnancy body mass index (BMI) was investigated multiplicatively by ratio of relative risk and additively by relative excess risk due to interaction (RERI). RESULTS:Overall, 6.7% of women had a PTB; 14.1% smoked throughout pregnancy and 3.4%, 1.8% and 0.8% reported quitting smoking during the first, second and third trimesters, respectively. Compared to non-smokers, third-trimester cessation (RR 1.20, 95% CI 1.01, 1.43) and smoking throughout pregnancy (RR 1.27, 95% CI 1.21, 1.33) were associated with a higher PTB risk, while quitting smoking during the first or second trimester, or inconsistent smoking was not associated with PTB. A positive additive interaction was identified for maternal age and late smoking cessation or smoking throughout pregnancy on PTB risk (RERI 0.17, 95% CI 0.00, 0.36), and a negative interaction was observed for pre-pregnancy BMI ≥30 kg/m2 (ratio of relative risk 0.70, 95% CI 0.63, 0.78; RERI -0.42, 95% CI -0.56, -0.30). CONCLUSION:Compared to non-smokers, smoking throughout pregnancy and third-trimester smoking cessation are associated with an increased risk of PTB, while quitting before the third trimester may not increase PTB risk.

BACKGROUND: Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established.OBJECTIVE: This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women.STUDY DESIGN: The Women's Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low-birthweight (<2500 g) or high-birthweight (>4500 g) infants. Participants were fol-lowed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth.RESULTS: This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of >= 2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes.CONCLUSION: Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with >= 2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.

AbstractBackgroundPrevious animal model studies have highlighted a role for cholesterol and its oxidized derivatives (oxysterols) in uterine contractile activity, however, a lipotoxic state associated with hypercholesterolemia may contribute to labor dystocia. Therefore, we investigated if maternal mid-pregnancy cholesterol and oxysterol concentrations were associated with labor duration in a human pregnancy cohort.MethodsWe conducted a secondary analysis of serum samples and birth outcome data from healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22–28 weeks of gestation. Serum was analyzed for total-C, HDL-C, and LDL-C by direct automated enzymatic assay and oxysterol profile including 7α-hydroxycholesterol (7αOHC), 7β-hydroxycholesterol (7βOHC), 24-hydroxycholesterol (24OHC), 25-hydroxycholesterol (25OHC), 27-hydroxycholesterol (27OHC), and 7-ketocholesterol (7KC) by liquid chromatography-selected ion monitoring-stable isotope dilution-atmospheric pressure chemical ionization-mass spectroscopy. Associations between maternal second trimester lipids and labor duration (minutes) were assessed using multivariable linear regression adjusting for maternal nulliparity and age.ResultsAn increase in labor duration was observed for every 1-unit increment in serum 24OHC (0.96 min [0.36,1.56],p < 0.01), 25OHC (7.02 min [1.92,12.24],p = 0.01), 27OHC (0.54 min [0.06, 1.08],p < 0.05), 7KC (8.04 min [2.7,13.5],p < 0.01), and total oxysterols (0.42 min [0.18,0.06],p < 0.01]. No significant associations between labor duration and serum total-C, LDL-C, or HDL-C were observed.ConclusionsIn this cohort, mid-pregnancy concentrations of maternal oxysterols (24OHC, 25OHC, 27OHC, and 7KC) were positively associated with labor duration. Given the small population and use of self-reported labor duration, subsequent studies are required for confirmation.

BACKGROUND:Although many studies have examined the association between prenatal air pollution exposure and gestational diabetes (GDM), the relevant exposure windows remain inconclusive. We aim to examine the association between preconception and trimester-specific exposure to PM2.5 and NO2 and GDM risk and explore modifying effects of maternal age, pre-pregnancy body mass index (BMI), smoking, exercise during pregnancy, race and ethnicity, and neighborhood disadvantage. METHODS:Analyses included 192,508 birth records of singletons born to women without pre-existing diabetes in Western New York, 2004-2016. Daily PM2.5 and NO2 at 1-km2 grids were estimated from ensemble-based models. We assigned each birth with exposures averaged in preconception and each trimester based on residential zip-codes. We used logistic regression to examine the associations and distributed lag models (DLMs) to explore the sensitive windows by month. Relative excess risk due to interaction (RERI) and multiplicative interaction terms were calculated. RESULTS:GDM was associated with PM2.5 averaged in the first two trimesters (per 2.5 μg/m3: OR = 1.08, 95% CI: 1.01, 1.14) or from preconception to the second trimester (per 2.5 μg/m3: OR = 1.10, 95% CI: 1.03, 1.18). NO2 exposure during each averaging period was associated with GDM risk (per 10 ppb, preconception: OR = 1.10, 95% CI: 1.06, 1.14; first trimester: OR = 1.12, 95% CI: 1.08, 1.16; second trimester: OR = 1.10, 95% CI: 1.06, 1.14). In DLMs, sensitive windows were identified in the 5th and 6th gestational months for PM2.5 and one month before and three months after conception for NO2. Evidence of interaction was identified for pre-pregnancy BMI with PM2.5 (P-for-interaction = 0.023; RERI = 0.21, 95% CI: 0.10, 0.33) and with NO2 (P-for-interaction = 0.164; RERI = 0.16, 95% CI: 0.04, 0.27). CONCLUSION:PM2.5 and NO2 exposure may increase GDM risk, and sensitive windows may be the late second trimester for PM2.5 and periconception for NO2. Women with higher pre-pregnancy BMI may be more susceptible to exposure effects.

Background An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes. Methods We conducted a secondary data analysis of healthy pregnant women ( N = 25) with mid-pregnancy fasting serum samples collected at 22–28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), and high-density lipoprotein (HDL), by nuclear magnetic resonance spectroscopy. Associations between maternal lipids and birth outcomes, including birth weight (g) and gestational age (weeks), were assessed using multivariable linear regression, adjusted for pre-pregnancy BMI. Results Although conventional lipids were not associated ( p > 0.05) with birth outcomes, every 1-unit increment in large VLDL/CM particles (nM) and VLDL/CM size (nm) was associated with an increase in birth weight (confounder-adjusted β-coefficient, 45.80 g [5.30, 86.20, p = 0.003] and 24.90 g [8.80, 40.90, p = 0.002], respectively). Among the HDL subclass parameters, a 1-unit (nM) increase in the concentration of total HDL-particles was associated with a reduced birth weight (confounder adjusted β-coefficient, -19.40 g [95% confidence interval, -36.70, -2.20]; p = 0.03) after adjustment for maternal pre-pregnancy BMI. Conclusion The preliminary results of this pilot study suggest that total particle concentrations of VLDL/CM and HDL in mid-pregnancy have divergent associations with birth weight, potentially reflecting the specific roles of these lipoprotein particles with respect to placental function and fetal growth.

BACKGROUND AND AIM: Smoking cessation during pregnancy is hypothesized to improve birth outcomes. However, the effect of the cessation time on birth weight among full-term infants merits further attention. We aimed to examine the association of maternal trimester-specific smoking cessation with term low birth weight (TLBW, 2500g). METHODS: We included 183,099 singleton, non-anomalous live births of 37-42 weeks gestation in Western New York between 2004-2018. Based on the self-reported average cigarettes per day during three months before pregnancy and during each trimester, we categorized pregnant women into six mutually exclusive groups: non-smokers; those who quit during the 1st, 2nd, or 3rd trimester; those who smoked throughout pregnancy; and inconsistent smokers. We examined the association between smoking cessation categories and TLBW using logistic regression, adjusting for potential confounders. We further explored the joint effect of smoking and illegal drug use during pregnancy on TLBW. RESULTS:Overall, 13.7% of pregnant women smoked throughout pregnancy; 3.4%, 1.8%, and 0.7% reported quitting smoking during the 1st, 2nd, or 3rd trimester, respectively. Compared to non-smokers, cessation during the 3rd trimester and smoking throughout pregnancy were associated with 1.73 (95% CI: 1.25, 2.39) and 2.28 (95% CI: 2.09, 2.49) times higher odds of TLBW, respectively. The associations were more pronounced for heavy smokers (≥10 cigarettes/day) than light smokers (1-9 cigarettes/day). Quitting smoking during the 1st trimester (OR=0.88, 95% CI: 0.71, 1.09), 2nd trimester (OR=1.22, 95% CI: 0.96, 1.56), or inconsistent smoking (OR=1.28, 95% CI: 0.71, 2.32) was not associated with TLBW. Infants of mothers who smoked throughout pregnancy and used illegal drugs had 2.84 (95% CI: 2.47, 3.25) times higher odds of TLBW compared to non-smokers without illegal drug use. CONCLUSIONS:Delayed smoking cessation, smoking throughout pregnancy, and the combination of smoking and illegal drug use were associated with an increased risk of TLBW. KEYWORDS: Cigarette smoking, Birth weight, Full-term infants, Illegal drug use

BACKGROUND AND AIM: Telomere length (TL) at birth determines TL in a later life and has been linked to midlife risk of cardiovascular disease, but its own determinants remain unclear. We aim to examine the association and to identify the sensitive window of pre-conception and prenatal exposures to fine particulate matter (PM2.5) with cord blood TL in a heavily air-polluted area in China. METHODS: In 2017, 107 pregnant women admitted for delivery at Anzhen Hospital in Beijing, China, were interviewed for demographics, addresses, and lifestyle factors. Weekly levels of ambient PM2.5 exposure from the three months before pregnancy to the end of pregnancy were estimated from a validated spatiotemporal model. PM2.5 exposure levels based on home and work addresses were combined by work routines. Cord blood leukocyte TL was measured using quantitative polymerase chain reaction. We used distributed lag models (DLMs) to analyze the association and to identify the sensitive window of ambient PM2.5 exposure with cord blood TL with adjusting for potential confounders. DLM analyses were also conducted in stratified subsamples by newborn sex. RESULTS:PM2.5 levels (median: 85 μg/m3) in the three months before LMP was positively (r=0.16) correlated with cord blood TL, while PM2.5 levels (median 78 μg/m3) in the whole pregnancy was inversely (r=-0.15) correlated with cord blood TL, although none of the correlation was significant (P0.05). From DLM, we found PM2.5 exposure was significantly associated with cord blood TL in three sensitive windows: 6-12 weeks before pregnancy (positive association), 6-18 weeks during pregnancy (inverse association), and 39-40 weeks during pregnancy (inverse association). These associations were more evident in female than male newborns. CONCLUSIONS:Preconception and prenatal exposure to ambient PM2.5 exposure may shorten cord blood TL, especially for female fetuses. Future studies with larger sample size are needed to replicate our findings. KEYWORDS: Particulate matter, Birth outcomes, Environmental epidemiology, Modeling

The WHI found an unexpected reduced breast cancer risk in women using CEE alone. We hypothesized CEE alone induces estrogen hydroxylation along the 2‐pathway rather than the competing 16‐pathway, a pattern linked to reduced postmenopausal breast cancer risk. One thousand eight hundred and sixty‐four women in a WHIOS case–control study of estrogen metabolism and ovarian and endometrial cancer were studied of whom 609 were current E + P users (351 used CEE + MPA), while 272 used E alone (162 used CEE). Fifteen EM were measured, and analyses were conducted for each metabolite, hydroxylation pathway (2‐, 4‐, or 16‐pathway) and ratios of pathway concentrations using inverse probability weighted linear regression. Compared to E + P users, all EM were higher in E alone users (significant for unconjugated estrone, total/conjugated estradiol, total/unconjugated 2‐methoxyestrone, 4‐methoxyestrone and unconjugated estriol). The relative concentrations of 2‐ and 4‐pathway EM did not differ between the MHT users (2‐pathway EM comprised 15% and 4‐pathway EM <2% of the total), but 16‐pathway EM were lower in E alone users ( p = 0.036). Ratios of 2‐ and 4‐pathway EM compared to 16‐pathway EM were significantly higher in E alone compared to E + P users. Similar but not significant patterns were observed in CEE‐alone and CEE + MPA users. Our data suggest that compared to E + P users, women using E alone have more extensive metabolism via the 2‐ vs. the competing 16‐pathway. This is consistent with epidemiologic evidence of reduced postmenopausal breast cancer risk associated with this metabolic profile and may provide a clue to the breast cancer risk reduction in CEE alone users during the WHI.

Objective: To assess the impact of discontinuing oral hormone therapy (HT) on sexual activity, vaginal symptoms, and sexual activity components among participants in the estrogen-progestin therapy (EPT) and estrogen therapy (ET) trial of the Women's Health Initiative. Methods: Surveys were sent postintervention to those who were still taking study pills and agreed to continue in the study when the trials were stopped. Comparisons between former HT and placebo users were accomplished with chi-square tests for categorical variables and t tests for continuous variables. Results: In all, 13,902 women with mean age at survey 69.9 years (EPT trial, women with intact uterus) and 71.7 years (ET trial, women with history of hysterectomy) responded. Prevalence of sexual activity postintervention was not significantly different between former EPT and placebo users (36.0% vs 34.2%; P = 0.37). Sexual activity of former ET users was 5.6% higher than placebo users (27.6% vs 22.0%; P = 0.001). The majority of sexually active women overall maintained orgasmic capacity and sexual satisfaction. Former EPT users were 10% to 12% more likely than former placebo users to report decreased desire, arousal, intercourse, climax, and satisfaction with sexual activity, and also increased dryness and dyspareunia upon discontinuing study drugs (P < 0.001). Former ET users were more likely than placebo users to report rare to no desire or arousal postintervention (P < 0.001). Conclusions: Postintervention ET trial participants formerly assigned to ET were significantly more likely to report sexual activity than those formerly assigned to placebo. Women who discontinued EPT were significantly more likely to report negative vaginal and sex-related effects.

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

BACKGROUND: The purpose of this study was to develop and utilize a clinical assessment tool to objectively measure robotic surgical skills and facilitate robotic surgery training and education. METHODS: This was a two-phase study. In phase I, the critical elements of a robotic hysterectomy were deconstructed into 6 key domains to assess technical skills for procedure completion. For each domain, anchor descriptions were developed to match a 5-point Likert scale. Delphi methodology was used for content validation. A panel of five expert robotic surgeons refined this scoring system using the Content Validity Index. In phase II, surgeons with varying degrees of experience performed a robotic hysterectomy. Video recordings were evaluated by blinded expert reviewers using the above scoring system. Descriptive statistics were evaluated for the total scores as well as each domain. Tests of both inter-rater (agreement between the assessors) and test-retest (consistency of scoring over time) reliability were performed with a threshold of significance at P <.05. RESULTS: Videos from 16 robotic hysterectomies, with two surgeons evaluated per case, were reviewed by the expert panel. The score for all surgeons was 4.36±0.49 (mean±SD). Scores varied according to surgical domain under assessment, however globally there was no difference between scores for trainees or attendings ( P =.83). There was excellent agreement between raters with respect to score in two domains, while disagreements occurred with respect to the other domains. DISCUSSION: This pilot study demonstrates the feasibility of utilizing a standardized rubric for clinical skills assessment in robotic hysterectomy.

BACKGROUND:Declines in endogenous estrogen levels after menopause can lead to systemic bone loss, including loss of oral bone and alveolar crest height (ACH). However, few studies have assessed both serum 17β-estradiol (E2) and exogenous hormone therapy (HT) use in relation to oral bone loss.METHODS:This study examines the associations among serum E2, HT use, and ACH in 613 postmenopausal women from the Buffalo OsteoPerio study. Baseline ACH levels and 5-year ACH were assessed for groups according to E2 level (undetectable, >5.00 to ≤18.00, >18.00 to ≤46.07, and >46.07 pg/mL) and among HT use (never, ever) using analysis of variance and analysis of covariance. Logistic regression was used to analyze the association of ACH loss with serum E2 and HT use.RESULTS:In cross-sectional analyses, no association was found of serum E2 with whole-mouth mean or worst-site ACH. However, history of HT use was associated with ACH. Women who had never used HT had more ACH loss assessed as a whole-mouth mean ACH (P = 0.01) and as worst-site ACH loss (P = 0.03). In logistic regression analyses of baseline ACH loss severity, HT never-users had two-fold higher odds of being in the severe ACH loss category compared to ever-users (odds ratio, 2.00; 95% confidence interval, 1.11 to 3.62). No association was observed of 5-year change in ACH with baseline serum E2 or HT use.CONCLUSION:Although this study did not detect an association with current serum E2 level and ACH, HT use was found to be associated with less ACH loss in postmenopausal women.

Background and aims: Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction.Methods and results: The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63,815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (<6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR = 1.086, p = 0.009). LBW was a significant covariate in the BMI-based model (HR = 1.128, p < 0.0001) but not in the lipid-based models.Conclusion: LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease. (C) 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

OBJECTIVE:Endometrial spotting or bleeding is a common adverse effect among women taking continuous-combined estrogen-progestin therapy. The renin-angiotensin-aldosterone system plays a major role in hypertension and is present in the endometrium. We hypothesized that postmenopausal women with hypertension would have a higher incidence of bleeding compared with postmenopausal women without hypertension.METHODS:A multivariate mixed-effects logistic model estimated the odds ratios for the relationship of hypertension status or use of antihypertensive drugs with endometrial bleeding using the Women's Health Initiative database.RESULTS:The incidence of spotting or bleeding in the first 12 months of estrogen-progestin use was 42% in women aged 50 to 79 years. Women with hypertension were more likely to experience bleeding than women without hypertension (odds ratio, 1.07; 95% CI, 1.02-1.13). Overall antihypertensive medication use increased bleeding with an odds ratio of 1.24, whereas angiotensin II receptor antagonists had a reduced odds ratio (0.53).CONCLUSIONS:Postmenopausal women with hypertension are more likely to bleed than postmenopausal women without hypertension when taking continuous estrogen-progestin, with less bleeding in women using angiotensin II receptor antagonists. This finding is novel and supports our hypothesis that the endometrial renin-angiotensin-aldosterone system may contribute to endometrial bleeding.

OBJECTIVE: To evaluate the economic benefit of prophylactic negative pressure wound therapy on a closed laparotomy incision after cesarean delivery in comparison with standard postoperative dressing.METHODS: We designed a decision-analytic model from a third-party payer's perspective to determine the cost-benefit of prophylactic application of negative pressure wound therapy compared with standard postoperative dressing on a closed laparotomy incision after cesarean delivery. Our primary outcome measure was the expected value of the cost per strategy. Baseline probabilities and cost assumptions were derived from published literature. We conducted sensitivity analyses using both deterministic and probabilistic models. Cost estimates reflect 2014 U. S. dollars.RESULTS: Under our baseline parameters, standard postoperative dressing was the preferred strategy. Standard postoperative dressing and prophylactic negative pressure wound therapy cost $547 and $804 per strategy, respectively. Sensitivity analyses showed that prophylactic negative pressure wound therapy can be cost-beneficial if it is priced below $192; standard postoperative dressing is the preferred strategy among patients with surgical site infection rate of 14% or less. If surgical site infection rates are greater than 14%, prophylactic negative pressure wound therapy could be cost-beneficial depending on the degree of reduction in surgical site infections. At a surgical site infection rate of 30%, the rate must be reduced by 15% for negative pressure wound therapy to become the preferred strategy. Monte Carlo simulation of 1,000 patients in 1 million trials showed that standard postoperative dressing was the preferred cost-beneficial strategy with a frequency of 85%.CONCLUSION: Our cost-benefit analysis provides economic evidence suggesting that negative pressure wound therapy should not be used on closed laparotomy incisions of patients with low risk of postcesarean delivery surgical site infections. However, among patients with a high risk of surgical site infections, prophylactic negative pressure wound therapy is potentially cost-beneficial.

Objective: The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI). Methods: Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. Results: Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). Conclusions: Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.

OBJECTIVE:To determine whether menstrual abnormalities, multiple personal behaviors and some contraceptive methods, all of which have been described as potential causes of single episodes of bacterial vaginosis (BV), are associated with recurrent bacterial vaginosis (RBV). STUDY DESIGN:This was a retrospective, case-controlled study performed in an urban setting. Women with RBV and matched controls were mailed a survey that included multiple questions about potential risk factors for BV. Four-to-one matching of age groups was performed, with 28 RBV cases matched to 112 controls. RESULTS:Among multiple possible predisposing factors, only African American ethnicity (p < 0.001) and > 1 male sex partner in the previous 2 years (p = 0.007) were strongly associated with RBV. Abnormal uterine bleeding, frequent intercourse without a condom or withdrawal, anal intercourse, menstrual hygiene product use, tub baths, back-to-front wiping after using the toilet, smoking, choice of contraceptive method (including condoms, the combination oral contraceptive, injectable medroxyprogesterone acetate or an intrauterine device) and douching were not associated with RBV. CONCLUSION:Providers should counsel women with RBV to minimize their number of male sex partners. There are few data to support the recommendation of other behavioral changes.

OBJECTIVE:The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.METHODS:Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.RESULTS:Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).CONCLUSIONS:CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.