Genitourinary Syndrome of Menopause: Prevalence and Predictors.

The genitourinary syndrome of menopause (GSM) has been proposed as a diagnosis by a consensus of clinicians and investigators. Our purpose for this paper is to review extant evidence about: 1) the breadth of symptoms and symptom clusters as related to the syndrome; 2) the prevalence of GSM (includes vulvar and vaginal atrophy); 3) factors that are associated with, predict, or explain the syndrome; and 4) what should be pursued for expanding meaningful evidence. Within recent literature, we found a wide range of prevalence estimates, likely a function of the differing populations studied, study design, and methods of data collection. Factors related to the prevalence of GSM included age and aging; reproductive aging stage; hormones, especially estrogen; and culture and language. We recommend further specification of diagnostic criteria for GSM; clarification of urinary symptoms in GSM; use of longitudinal study designs; validation of GSM-related measures; exploration of cultural equivalence of GSM measures; and assessing biases in completed research.

Association Between Insomnia, Stress Events, and Other Psychosocial Factors and Incident Atrial Fibrillation in Postmenopausal Women: Insights From the Women's Health Initiative.

Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks (P for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. Conclusions Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.

Social isolation and health among family caregivers of older adults: Less community participation may indicate poor self-reported health.

Social isolation is associated with adverse health outcomes in the general older adult population, but little is known about indicators of social isolation in family caregiver populations. This cross-sectional study examined the prevalence of social isolation in the 2015 National Survey of Caregiving. Using the Convoy Model of social relations, a life-course social support framework, we also examined associations between social isolation and caregiver self-reported health. Using multiple ordinal logistic regression models, we examined social isolation - operationalised with a five-item summative measure and, alternatively, with each social isolation item - as a predictor of self-reported general health status. On the dichotomised summative measure, 24.74% (n = 2,175) were more isolated. Younger caregivers were more isolated (M = 56.77 years, SE = 0.76) compared with those who were not (M = 60.86 years, SE = 0.41). Self-reported general health was as follows: 4.93% poor; 15.67% fair; 25.62% good; 34.81% very good and 18.97% excellent. Less social isolation was associated with higher odds of better self-reported health (Adjusted odds ratio [AOR] = 1.19; CI = 1.05-1.35). Of the individual social isolation indicators, only a lack of community participation was associated with higher odds of worse self-reported health (AOR = 1.57; CI = 1.25-1.97). Social isolation and particularly community participation were associated with caregiver health status. It may be necessary for healthcare providers to consider these factors in caregiver health assessments. Future research is recommended to understand the consequences of various social isolation indicators in diverse samples including younger caregivers.

Racial/Ethnic Disparities in Alzheimer's Disease Risk: Role of Exposure to Ambient Fine Particles.

BACKGROUND: Whether racial/ethnic disparities in Alzheimer's disease (AD) risk may be explained by ambient fine particles (PM2.5) has not been studied. METHOD: We conducted a prospective, population-based study on a cohort of Black (n = 481) and White (n = 6 004) older women (aged 65-79) without dementia at enrollment (1995-1998). Cox models accounting for competing risk were used to estimate the hazard ratio (HR) for racial/ethnic disparities in AD (1996-2010) defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition and the association with time-varying annual average PM2.5 (1999-2010) estimated by spatiotemporal model. RESULTS: Over an average follow-up of 8.3 (±3.5) years with 158 incident cases (21 in Black women), the racial disparities in AD risk (range of adjusted HRBlack women = 1.85-2.41) observed in various models could not be explained by geographic region, age, socioeconomic characteristics, lifestyle factors, cardiovascular risk factors, and hormone therapy assignment. Estimated PM2.5 exposure was higher in Black (14.38 ± 2.21 µg/m3) than in White (12.55 ± 2.76 µg/m3) women, and further adjustment for the association between PM2.5 and AD (adjusted HRPM2.5 = 1.18-1.28) slightly reduced the racial disparities by 2%-6% (HRBlack women = 1.81-2.26). The observed association between PM2.5 and AD risk was ~2 times greater in Black (HRPM2.5 = 2.10-2.60) than in White (HRPM2.5 = 1.07-1.15) women (range of interaction ps: <.01-.01). We found similar results after further adjusting for social engagement (social strain, social support, social activity, living alone), stressful life events, Women's Health Initiative's clinic sites, and neighborhood socioeconomic characteristics. CONCLUSIONS: PM2.5 may contribute to racial/ethnic disparities in AD risk and its associated increase in AD risk was stronger among Black women.

Associations Between Changes in Loneliness and Social Connections, and Mental Health During the COVID-19 Pandemic: The Women's Health Initiative.

BACKGROUND: Older women have faced significant disruptions in social connections during the coronavirus disease 2019 pandemic. Whether loneliness increased or whether a change in loneliness from pre- to intrapandemic period was associated with mental health during the pandemic is unknown. METHODS: Older women (n = 27 479; mean age 83.2 [SD: 5.4] years) completed surveys in mid-2020, including questions about loneliness, living arrangements, changes in social connections, and mental health. Loneliness was also previously assessed in 2014-2016. We examined whether loneliness changed from the pre- to intrapandemic period and explored factors associated with this change. In multivariable models, we investigated the association of changes in loneliness and social connections with mental health. RESULTS: Loneliness increased from pre- to intrapandemic levels. Factors associated with worsening loneliness included older age, experiencing stressful life events, bereavement, histories of vascular disease and depression, and social connection disruptions. Factors associated with a decrease in loneliness included identifying as Black, engaging in more frequent physical activity, being optimistic, and having a higher purpose in life. A 3-point increase in loneliness scores was associated with higher perceived stress, higher depressive, and higher anxiety symptoms. Social connection disruptions showed modest or no associations with mental health. CONCLUSIONS: Loneliness increased during the pandemic in older women and was associated with higher stress, depressive, and anxiety symptoms. Our findings point to opportunities for interventions targeting lifestyle behaviors, well-being, disrupted social connections, and paying closer attention to those with specific medical and mental health histories that may reduce loneliness and improve mental health.

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

OBJECTIVE: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects on menopause-related QOL relative to control in women with VMS. METHODS: We pooled individual-level data from 1,005 peri- and postmenopausal women with 14 or more VMS/week across the four RCTs. Interventions included escitalopram 10 to 20 mg/d; yoga/aerobic exercise; 1.8 g/d omega-3-fatty acids; oral 17-beta-estradiol 0.5 mg/d; venlafaxine XR 75 mg/d; and cognitive behavioral therapy for insomnia (CBT-I). Outcomes measures were the Menopause-specific Quality of Life scale and its subscales. RESULTS: Significant improvements in total Menopause-specific Quality of Life from baseline were observed with estradiol, escitalopram, CBT-I, and yoga, with mean decreases of 0.3 to 0.5 points relative to control. The largest improvement in the vasomotor subscale was observed with estradiol (-1.2 points), with more modest but significant effects seen with escitalopram, yoga, and CBT-I. Significant improvements in the psychosocial subscale were observed for escitalopram, venlafaxine, and CBT-I. For the physical subscale, the greatest improvement was observed for CBT-I and exercise, whereas for the sexual subscale, the greatest improvement was observed for CBT-I, with yoga and estradiol demonstrating smaller effects. CONCLUSIONS: These results suggest that for menopause-related QOL, women have a variety of treatment strategies to choose from and can select an approach based on most bothersome symptoms and individual preferences.

Healthy aging through the lens of community-based practitioners: a focus group study.

BACKGROUND: Nearly one in every seven Americans is 65 years and older, facing day-to-day challenge of aging. Although interest in healthy aging is growing, most of the efforts are directed towards understanding the perceptions of older adults. Little is known about the perspectives of community-based practitioners who work with older adults and deliver programs to promote healthy aging. The purpose of this project was to expand knowledge on healthy aging by exploring the perspectives of community-based practitioners working directly with older adults. METHODS: We purposively sampled community-based practitioners (n = 12, including nurses, physician, social workers, and other community services professionals) working with older adults, who then participated in one of three in-depth focus group discussions conducted between March and June 2016. Each focus group discussion lasted for about 2 h. Verbatim transcript data were analyzed in Atlas.ti 7 using a conventional content analysis with an inductive approach, and consensual validation of coding was achieved. RESULTS: Three core categories of healthy aging were identified: (1) characteristics of healthy aging; (2) healthy aging attainment; and (3) programs and activities for healthy aging. Practitioners identified a number of characteristics of healthy aging under person-specific (physiological, basic, psych-emotional, and cognitive needs), social aspects (creating community and contributing to the community), and spiritual dimensions (cultural views and beliefs) of healthy aging. Healthy aging attainment was represented as facilitators and barriers both with respect to care recipients and care providers, and programs and activities through promoting fitness and wellness. CONCLUSIONS: The rapidly changing demographics and aging population in the United States and their various needs suggest the implications for recognizing opportunities and developing and implementing programs to promote healthy aging. Although practitioners' perspectives had some overlap with traditional research and medical views on healthy aging, the unique and holistic conceptual framework derived in the study might provide a more refined foundation for delivering appropriate health care services to the American aging population.

Obesity, smoking, and risk of vasomotor menopausal symptoms: a pooled analysis of eight cohort studies.

BACKGROUND: Frequent and severe vasomotor symptoms during menopause are linked with adverse health outcomes. Understanding modifiable lifestyle factors for the risk of vasomotor menopausal symptoms is important to guide preventive strategies. OBJECTIVE: We investigated the associations between body mass index and smoking, their joint effects with the risk of vasomotor symptoms, and whether the associations differed by menopausal stage. STUDY DESIGN: The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events pooled data on 21,460 midlife women from 8 studies (median age, 50 years; interquartile range, 49-51 years) for the cross-sectional analysis. Four studies provided data for the prospective analysis (n=11,986). Multinomial logistic regression models with 4 categories of frequency/severity for the outcome of vasomotor symptoms were used to estimate relative risk ratios and 95% confidence intervals that were adjusted for within-study correlation and covariates. RESULTS: At baseline, nearly 60% of the women experienced vasomotor symptoms. One-half of them were overweight (30%) or obese (21%), and 17% were current smokers. Cross-sectional analyses showed that a higher body mass index and smoking more cigarettes with longer duration and earlier initiation were all associated with more frequent or severe vasomotor symptoms. Never smokers who were obese had a 1.5-fold (relative risk ratio, 1.52; 95% confidence interval, 1.35-1.73) higher risk of often/severe vasomotor symptoms, compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of often/severe vasomotor symptoms was much greater among smokers who were obese (relative risk ratio, 3.02; 95% confidence interval, 2.41-3.78). However, smokers who quit at <40 years of age were at similar levels of risk as never smokers. Prospective analyses showed a similar pattern, but the association attenuated markedly after adjustment for baseline vasomotor symptoms. Furthermore, we found that the association between body mass index and vasomotor symptoms differed by menopausal status. Higher body mass index was associated with increased risk of vasomotor symptoms in pre- and perimenopause but with reduced risk in postmenopause. CONCLUSION: High body mass index (≥25 kg/m2) and cigarette smoking substantially increased women's risk for experiencing frequent or severe vasomotor symptoms in a dose-response manner, and smoking intensified the effect of obesity. However, the effect of body mass index on the risk of vasomotor symptoms was opposite among postmenopausal women. Maintaining a normal weight before the menopausal transition and quitting smoking at <40 years of age may mitigate the excess risk of vasomotor symptoms in midlife.

A systematic review and meta-analysis of postpartum contraceptive use among women in low- and middle-income countries.

BACKGROUND: Short birth intervals increase risk for adverse maternal and infant outcomes including preterm birth, low birth weight (LBW), and infant mortality. Although postpartum family planning (PPFP) is an increasingly high priority for many countries, uptake and need for PPFP varies in low- and middle-income countries (LMIC). We performed a systematic review and meta-analysis to characterize postpartum contraceptive use, and predictors and barriers to use, among postpartum women in LMIC. METHODS: PubMed, EMBASE, CINAHL, PsycINFO, Scopus, Web of Science, and Global Health databases were searched for articles and abstracts published between January 1997 and May 2018. Studies with data on contraceptive uptake through 12 months postpartum in low- and middle-income countries were included. We used random-effects models to compute pooled estimates and confidence intervals of modern contraceptive prevalence rates (mCPR), fertility intentions (birth spacing and birth limiting), and unmet need for contraception in the postpartum period. RESULTS: Among 669 studies identified, 90 were selected for full-text review, and 35 met inclusion criteria. The majority of studies were from East Africa, West Africa, and South Asia/South East Asia. The overall pooled mCPR during the postpartum period across all regions was 41.2% (95% CI: 15.7-69.1%), with lower pooled mCPR in West Africa (36.3%; 95% CI: 27.0-45.5%). The pooled prevalence of unmet need was 48.5% (95% CI: 19.1-78.0%) across all regions, and highest in South Asia/South East Asia (59.4, 95% CI: 53.4-65.4%). Perceptions of low pregnancy risk due to breastfeeding and postpartum amenorrhea were commonly associated with lack of contraceptive use and use of male condoms, withdrawal, and abstinence. Women who were not using contraception were also less likely to utilize maternal and child health (MCH) services and reside in urban settings, and be more likely to have a fear of method side effects and receive inadequate FP counseling. In contrast, women who received FP counseling in antenatal and/or postnatal care were more likely to use PPFP. CONCLUSIONS: PPFP use is low and unmet need for contraception following pregnancy in LMIC is high. Tailored counseling approaches may help overcome misconceptions and meet heterogeneous needs for PPFP.

Abdominal pain during the menopause transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: To assess the relationship between abdominal pain severity during the menopausal transition (MT) and age, MT stage, reproductive biomarkers, stress biomarkers, and stress perceptions. METHODS: Women ages 35-55 were recruited from multiethnic neighborhoods in the greater Seattle area from 1990 to 1992, for an original study cohort of 508. From 1990 to 2013, a subset of this cohort consented to ongoing annual data collection by annual health questionnaire, health diary, and daily menstrual calendar. Beginning in 1997, a portion of these women also provided a first morning voided urine specimen to be assayed for levels of estrone glucuronide (E1G), follicle stimulating hormone (FSH), testosterone, cortisol, norepinephrine, and epinephrine. To identify how changes in abdominal pain severity changed over time in relation to age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions, mixed effects modeling was used. RESULTS: In a univariate model, E1G (p = 0.02) and testosterone (p = 0.02) were significantly and negatively related to abdominal pain severity, while perceived stress (p = 0.06), tension (p <  0.001), and anxiety (p <  0.001) were significantly and positively associated. In a multivariate model, increasing age (p = 0.001) and E1G (p = 0.04) were negatively associated with abdominal pain severity, and anxiety (p = 0.00) positively associated. Testosterone did not improve the fit to the final model, nor did tension or perceived stress. CONCLUSIONS: These results suggest that age, anxiety, and E1G each show a significant association with abdominal pain severity in the MT. In contrast, stress perception, tension, testosterone, stress biomarkers, and MT stage do not. These factors should be evaluated further in research on abdominal pain experienced during the MT and early postmenopause years.

Is Interpersonal Abuse Associated with Sexual (Dis)satisfaction among Postmenopausal Women?

PURPOSE: To investigate associations between past-year verbal and/or physical abuse (VA/PA) and sexual (dis)satisfaction, that is, global or frequency-related (dis)satisfactions with sexual activity, among postmenopausal women in the Women's Health Initiative. PROCEDURES: A cross-sectional analysis of archival data was performed from the subset of 83,329 Women's Health Initiative participants (clinical trial and/or observational study components) who reported sexual activity in the year before baseline. Associations between VA/PA and global frequency (dis)satisfactions were modeled using logistic regression. MAIN FINDINGS: Most participants reported sexual satisfaction (global, 77%; frequency related, 66%). Disappointment with sexual frequency, specifically a desire for more frequent sex, was the most common dissatisfaction expressed. Past-year VA/PA exposure was reported by 9,410 participants (11%). In regression models adjusted for sociodemographic, health and health risk, and menopausal symptom variables, VA/PA was associated with higher rates of global (35% VA/PA exposed vs. 22% non-exposed; adjusted odds ratio, 1.66; 95% confidence interval, 1.53-1.80) and frequency-related dissatisfactions (50% of VA/PA exposed vs. 32% of non-exposed; adjusted odds ratio, 1.73; 95% confidence interval, 1.57-1.90). CONCLUSIONS: Sexual satisfaction was common, but not universally reported by study participants. Sexual dissatisfactions were overrepresented in VA/PA-exposed participants and associated with a desire for more frequent sexual activity. Opportunities for postmenopausal women to receive clinician-led education about safe and healthy ways to increase sexual activity are needed. Further research on this topic, particularly efforts to characterize safety concerns as well as modifiable barriers to satisfying sexual activity among postmenopausal women with recent VA/PA, would ensure that these interventions are evidence based.

Acceptability, feasibility and utility of a Mobile health family planning decision aid for postpartum women in Kenya.

BACKGROUND: Unmet need for contraception is high during the postpartum period, increasing the risk of unintended subsequent pregnancy. We developed a client facing mobile phone-based family planning (FP) decision aid and assessed acceptability, feasibility, and utility of the tool among health care providers and postpartum women. METHODS: Semi-structured in-depth interviews (IDIs) were conducted among postpartum women (n = 25) and FP providers (n = 17) at 4 Kenyan maternal and child health clinics, 2 in the Nyanza region (Kisumu and Siaya Counties) and 2 in Nairobi. Stratified purposive sampling was used to enroll postpartum women and FP providers. Data were analyzed using an inductive content analysis approach by 3 independent coders, with consensual validation. RESULTS: FP providers stated that the Interactive Mobile Application for Contraceptive Choice (iMACC) tool contained the necessary information about contraceptive methods for postpartum women and believed that it would be a useful tool to help women make informed, voluntary decisions. Most women valued the decision aid content, and described it as being useful in helping to dispel myths and misconceptions, setting realistic expectations about potential side effects and maintaining confidentiality. Both women and providers expressed concerns about literacy and lack of familiarity with smart phones or tablets and suggested inclusion of interactive multimedia such as audio or videos to optimize the effectiveness of the tool. CONCLUSIONS: The iMACC decision aid was perceived to be an acceptable tool to deliver client-centered FP counseling by both women and providers. Counseling tools that can support FP providers to help postpartum women make informed and individualized FP decisions in resource-limited settings may help improve FP counseling and contraceptive use in the postpartum period.

Sexual frequency and pain in a randomized clinical trial of vaginal estradiol tablets, moisturizer, and placebo in postmenopausal women.

OBJECTIVE: To evaluate the efficacy of two common interventions for bothersome postmenopausal vaginal symptoms on improving sexual frequency and pain. METHODS: This is a post-hoc analysis of data from a 12-week double-blind placebo-controlled trial that randomized postmenopausal women (ages 45-70 years) with moderate-severe genitourinary discomfort to vaginal 10 µg estradiol tablet plus placebo gel (n = 102), placebo tablet plus vaginal moisturizer (n = 100), or dual placebo (n = 100). Outcomes were proportion of sexually active women at 12 weeks, frequency of sexual activity, and pain severity with sexual activity (0-3 scale). Consistent with the original study design, comparisons were made between each active arm and the dual placebo arm. RESULTS: Most women enrolled in the trial, 294/302 (97%), had sufficient data to be included in this analysis. Mean age of participants was 61 years, most were white (88%), college educated (66%), and most reported sexual activity in the month before enrollment (81%). After 12 weeks of treatment, a similar proportion of women in the vaginal estrogen and dual placebo groups reported sexual activity in the past week (50% and 40%; P = 0.10) and the past month (78% and 84%, P = 0.52). Mean (standard deviation) pain with sexual activity scores at 12 weeks were similar between vaginal estrogen (1.0 [1.0]) and placebo (0.9 [0.9], P = 0.52] groups. The proportion sexually active at 12 weeks (35%) and mean (standard deviation) pain severity in the vaginal moisturizer group (1.1 [0.9]) did not differ from placebo (P = 0.36). CONCLUSIONS: Compared to placebo, neither low-dose vaginal estradiol nor vaginal moisturizer treatment over 12 weeks resulted in significantly greater increases in the proportions of women reporting sexual activity or improvement in pain scores with sexual activity. TRIAL REGISTRATION: Clinical trials.gov: NCT02516202.

Soy intake and vasomotor menopausal symptoms among midlife women: a pooled analysis of five studies from the InterLACE consortium.

BACKGROUND/OBJECTIVES: Phytoestrogen rich-foods such as soy may be associated with less frequent/severe vasomotor menopausal symptoms (VMS), although evidence is limited. We thus investigated the associations between the consumption of soy products and soy milk and the frequency/severity of VMS. SUBJECTS/METHODS: We pooled data from 19,351 middle-aged women from five observational studies in Australia, UK, USA, and Japan that contribute to the International Collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on soy consumption, VMS and covariates were collected by self-report. We included 11,006 women who had complete data on soy consumption, VMS and covariates at baseline for the cross-sectional analysis. For the prospective analysis, 4522 women who were free of VMS at baseline and had complete data on VMS at follow-up were considered. Multinomial logistic regression and binary logistic regression models were used. RESULTS: No statistically significant evidence of an association was found between soy products (relative risk ratio (RRR): 0.92, 95% CI: 0.76-1.11) or soy milk (RRR: 1.24, 95% CI: 0.93-1.65) and the likelihood of reporting frequent or severe VMS cross-sectionally. Prospective results indicated that frequent consumption of soy products (odds ratio (OR): 0.63, 95% CI: 0.45-0.89) but not soy milk (OR: 1.11, 95% CI: 0.85-1.45) was associated with lower likelihood of reporting subsequent VMS, after adjustment for socio-demographic and reproductive factors. CONCLUSIONS: These are the first ever findings from pooled observational data of association between consumption of soy products and VMS.

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BACKGROUND: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. METHODS AND FINDINGS: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40-44 (early), 45-49, 50-51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. CONCLUSIONS: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial.

OBJECTIVE: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. METHODS: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. RESULTS: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. CONCLUSIONS: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.

Outcome Measures in Interventions That Enhance Breastfeeding Initiation, Duration, and Exclusivity: A Systematic Review.

OBJECTIVE: The purpose of this review was to examine outcome measures used in interventions focusing on enhancement of breastfeeding initiation, duration, and exclusivity. METHODS: A literature search guided by search terms on outcome measures of breastfeeding interventions was conducted using PubMed, CINAHL Plus, & PsycINFO databases on publications between 2006 and 2017. RESULTS: Nine studies were included in this review, using PRISMA guidelines. Rates of breastfeeding initiation, duration, and exclusivity were measured during specific points in time. Data collection methods involve interviews, self-report, observations, and/or feeding logs. Although breastfeeding types (exclusive breastfeeding, predominant breastfeeding, and complementary breastfeeding) were measured, methods of infant feeding (breastfeeding and bottle feeding) were rarely assessed, ignoring significant mediators or moderators of breastfeeding. CONCLUSIONS: There were methodological limitations to the reviewed studies: (1) a 24-hour recall bias, (2) misclassification of breastfeeding categories, (3) lack of consistency in breastfeeding definitions, and (4) few reports of the reason for breastfeeding discontinuation. Future studies should focus on the modifiable cause of the problem: outcome measures attributed to the targets of the intervention, followed by breastfeeding initiation, duration, and/or exclusivity.

Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children.

Lead (Pb) is neurotoxic and children are highly susceptible to this effect, particularly within the context of continuous low-level Pb exposure. A current major challenge is identification of children who may be uniquely susceptible to Pb toxicity because of genetic predisposition. Learning and memory are among the neurobehavioral processes that are most notably affected by Pb exposure, and modification of N-methyl-D-aspartate receptors (NMDAR) that regulate these processes during development are postulated to underlie these adverse effects of Pb. We examined the hypothesis that polymorphic variants of genes encoding glutamate receptor, ionotropic, NMDAR subunits 2A and 2B, GRIN2A and GRIN2B, exacerbate the adverse effects of Pb exposure on these processes in children. Participants were subjects who participated as children in the Casa Pia Dental Amalgam Clinical Trial and for whom baseline blood Pb concentrations and annual neurobehavioral test results over the 7 year course of the clinical trial were available. Genotyping assays were performed for variants of GRIN2A (rs727605 and rs1070503) and GRIN2B (rs7301328 and rs1806201) on biological samples acquired from 330 of the original 507 trial participants. Regression modeling strategies were employed to evaluate the association between genotype status, Pb exposure, and neurobehavioral test outcomes. Numerous significant adverse interaction effects between variants of both GRIN2A and GRIN2B, individually and in combination, and Pb exposure were observed particularly among boys, preferentially within the domains of Learning & Memory and Executive Function. In contrast, very few interaction effects were observed among similarly genotyped girls with comparable Pb exposure. These findings support observations of an essential role of GRIN2A and GRIN2B on developmental processes underlying learning and memory as well as other neurological functions in children and demonstrate, further, modification of Pb effects on these processes by specific variants of both GRIN2A and GRIN2B genes. These observations highlight the importance of genetic factors in defining susceptibility to Pb neurotoxicity and may have important public health implications for future strategies aimed at protecting children and adolescents from potential health risks associated with low-level Pb exposure.