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 ( \u3c 40 (premature), 40-44 (early), 45-49, 50-51 (reference), and \u3e /=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 \u3c 0.001) and early menopause (1.80; 1.66-1.95) (p \u3c 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 \u3c 0.001) and early (6.55; 5.04-8.52; p \u3c 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p \u3c 0.001) and 3-fold (3.01; 2.15-4.21; p \u3c 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

Design and Methods for a Pilot Study of a Phone-Delivered, Mindfulness-Based Intervention in Patients with Implantable Cardioverter Defibrillators

Background. Meditation practices are associated with a reduction in adrenergic activity that may benefit patients with severe cardiac arrhythmias. This paper describes the design and methods of a pilot study testing the feasibility of a phone-delivered mindfulness-based intervention (MBI) for treatment of anxiety in patients with implantable cardioverter defibrillators (ICDs). Design and Methods. Consecutive, clinically stable outpatients (n = 52) will be screened for study eligibility within a month of an ICD-related procedure or ICD shock and will be randomly assigned to MBI or to usual care. MBI patients will receive eight weekly individual phone sessions based on two mindfulness practices (awareness of breath and body scan) plus home practice with a CD for 20 minutes daily. Patients assigned to usual care will be offered the standard care planned by the hospital. Assessments will occur at baseline and at the completion of the intervention (between 9 and 12 weeks after randomization). The primary study outcome is feasibility; secondary outcomes include anxiety, mindfulness, and number of administered shocks during the intervention period. Conclusions. If proven feasible and effective, phone-delivered mindfulness-based interventions could improve psychological distress in ICD outpatients with serious cardiovascular conditions

Advancing Stage of Female Reproductive Life Associated with Bipolar Illness Exacerbation

Introduction: Perimenopause confers an increased risk of depression in the general population, yet bipolar disorder mood course remains unknown. Methods: Clinic visits in 519 premenopausal, 116 perimenopausal including 13 women transitioning from peri- to postmenopause, and 133 postmenopausal women with bipolar disorder who received naturalistic treatment in the multisite STEP-Bipolar Disorder study over 19.8 +/- 15.5 months were analyzed for mood state. Results: Advancing female reproductive stage was associated with significant decline in mood elevation; significant decline in euthymia; no significant difference in major depression; and symptomatic significant increase. Conclusions: Advancing stage of female reproductive life was associated with bipolar illness exacerbation. Women transitioning from peri- to postmenopause had significantly greater depression than other female reproductive groups

Treatment and Management of Depression Symptoms in Pregnant Veterans: Varying Experiences of Mental Health Care in the Prenatal Period

Depression screening is recommended for all pregnant veterans; however, little is known on how often symptomatic women receive care, how depression treatment presents in practice, and whether women veterans are utilizing treatment during the appreciable perinatal period. Our sample included 142 pregnant veterans from 15 Veterans Health Administration (VA) medical facilities with Edinburgh Postnatal Depression Scale (EPDS) scores \u3e/=10. Sociodemographic characteristics, military service, health utilization, and pregnancy related factors were collected as part of a telephone survey. A majority of our sample (70%) had 1 or more mental health visits or antidepressant prescriptions during pregnancy. Women with a history of depression had more mental health visits and a higher percentage of antidepressant use before and during pregnancy than women without a history of depression. Pregnant women veterans without a history of depression may be less likely to receive care for depression during pregnancy. However, the majority of our veterans showing depression symptoms prenatally had at least one mental health visit or an antidepressant medication fill during their pregnancy window, suggesting that mental health care is readily available for women veterans

The Role of Multiple Sclerosis as a Risk Factor for the Development of Osteoporosis

Background: Osteoporosis is the most common bone disease in the United States, and it is particularly common among women with multiple sclerosis (MS). However, despite this association, the temporal relationship between these two conditions has not been previously studied. Data from the Women’s Health Initiative provides a unique opportunity to examine the risk of developing osteoporosis over time in individuals diagnosed with MS. Objective: The purpose of this study is to refine the relationship between MS and osteoporosis, clarifying the impact of environmental and pharmacologic factors on each condition, as well as addressing treatment and preventative efforts for a patient population at a greater potential risk for osteoporosis. Methods: The study sample, derived from the Women’s Health Initiative, included 449 women who reported an MS diagnosis at baseline and 161,359 women without MS who comprised a control group. Baseline measures of self-reported osteoporosis, age, smoking status, steroid and anti-inflammatory use, and supplementary as well as dietary calcium and vitamin D were compared. MS patients reporting osteoporosis at baseline were removed, resulting in 355 women with MS to monitor for time to incident osteoporosis. Survival analyses were performed on follow-up data gathered annually between 1993 and 2005 to factor out significant associations of additional factors. Proportions of participants on osteoporosis-related medications as well as latency to use were compared between the multiple sclerosis and control cohorts. Results: At baseline, women with MS are nearly three times as likely to report osteoporosis (p Conclusions: A higher prevalence of osteoporosis at baseline suggests MS may significantly increase the risk of osteoporosis in premenopausal women. In contrast, environmental and pharmacologic variables appear to have a more significant role in the post-menopausal population. While osteoporosis was treated similarly between both groups, the point for intervention or prevention of osteoporosis in MS patients may be earlier in the disease course

Spiritual well-being may buffer psychological distress in patients with implantable cardioverter defibrillators (ICD)

Psychological distress is common in patients with implantable cardioverter defibrillators (ICDs) and has been associated with a worse prognosis. The authors examined whether spiritual well-being is associated with reduced psychological distress in patients with ICDs. The Functional Assessment of Chronic Illness Therapy-Spiritual Wellbeing (FACIT-SWB) questionnaire and the Hospital Anxiety and Depression Scale (HADS) were used to measure spiritual well-being and overall psychological distress. Multivariate linear regression was used to explore the relationship between these variables. The study sample included 46 ICD outpatients (32 M, 14 F; age range 43-83). An inverse association between HADS and FACIT-SWB scores was found, persisting after adjustment for demographics, anxiety/depression, medications, therapist support, and functional status (F = 0.001; β= -0.31, CI: -0.44, -0.19). In conclusion, spiritual well-being was independently associated with lower psychological distress in ICD outpatients. Spiritual well-being could act as a protective factor against psychological distress in these high-risk patients

Melatonin Patterns and Levels During the Human Menstrual Cycle and After Menopause

Context: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging. Objective: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging. Methods: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women\u27s Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and one postmenopausal collection with no evidence of luteal activity (NELA). Results: In addition to the organized patterns of hormone metabolites (estrone conjugates [E1c], and pregnanediol glucuronide [PdG]) and gonadotropins that characterized ovulatory menstrual cycles, there was a late luteal rise in aMT6s. In NELA collections, there was no periodicity of E1c, PdG, gonadotropins, or aMT6s. The strongest predictors of aMT6s levels were PdG values 11 to 12 days prior to aMT6s (beta = 1.46, P = .001 and beta = 1.44, P = .001, respectively). E1c and gonadotropins were not statistically significantly associated with aMT6s. Mean aMT6s in premenopause was 53.5 ng/mL, greater than the mean of 37.4 ng/mL in postmenopausal samples from the same women (P = .0002). Conclusions: This study confirms a late luteal melatonin rise, likely signaled by progesterone, which may influence menstrual cycle pacemaker control. Melatonin declined from premenopause to postmenopause. A high correlation between menopause transition stage and age precludes distinction between the influences of ovarian and chronological aging

Mid-gestation Angiogenic Biomarker Levels are Increased in Women at High Risk for Preeclampsia

Background: Pre-pregnancy hypertension and diabetes mellitus, multiple gestations, prior preeclampsia, are significant risk factors for preeclampsia. Whether altered maternal levels of angiogenic factors contribute to increased preeclampsia risk in these conditions is unknown. Our objective was to compare maternal serum angiogenic biomarker levels in women with major risk factors for preeclampsia and healthy controls. Methods: Women presenting for prenatal care were enrolled if they had one of the following preeclampsia risk factors: pre-pregnancy hypertension and/or diabetes mellitus, nulliparity with pre-pregnancy BMI\u3e30, multiple gestations, or prior preeclampsia. Healthy control pregnancies without these risk factors were enrolled for comparison. Maternal serum samples were collected at 3 pre-specified gestational windows between 23 and 36 weeks gestation. sFlt1, sEng, and PlGF were measured by ELISA. The (sFlt1+sEng):PlGF ratio was calculated and compared for each risk group at each gestational window. Results: Gestational patterns of angiogenic biomarkers differed in high-risk groups vs. healthy control subjects. The angiogenic ratio (sFlt1+sEng):PlGF was higher for all high risk groups except obesity/nulliparity as compared with healthy control subjects after 28 weeks gestation. Biomarker ratio levels were highest in subjects with MG and prior PE, and differences from the health control group became more pronounced as gestation progressed. Women with hypertension/diabetes had more subtle differences as compared with healthy control subjects. Conclusion: Women with preeclampsia risk factors had higher angiogenic ratios compared with healthy control women. This study illuminates the interplay between risk factors and placental angiogenic biomarkers in the pathogenesis of preeclampsia

Predictors of irritability symptoms in mildly depressed perimenopausal women

OBJECTIVE: Irritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with depressive symptoms during perimenopause, more insight is needed into reproductive hormone dynamics and other factors that predispose perimenopausal women to irritable mood. METHODS: Among 50 mildly depressed perimenopausal women (mean (SD) age 48.4 (3.9) years), severity of irritability symptoms (on Symptom Questionnaire Hostility subscale, range 0-23) was assessed weekly for eight weeks, concurrent with potential predictors. Associations between these were examined using generalized estimating equating models. RESULTS: Most women (82.0%) reported having moderate to severe irritability at least once. However, the severity of irritability was highly variable from week-to-week (between-subject mean coefficient of variation [CV] 72.9% and within-subject mean CV 63.7%). In multivariate analyses, less variable serum estradiol levels (standardized beta within-person CV -0.23 95%CI [-0.32, -0.14], p \u3c 0.001), greater depression severity (0.45 [0.35, 0.56], p \u3c 0.001), younger age (-0.23, [-0.28, -0.09], p \u3c 0.001), and more frequent vasomotor symptoms (0.14 [0.05, 0.23], p=0.002) were associated with more irritability. Depression severity explained the largest portion of the variance in irritability, but still not more than 20.3%. Neither crude values, weekly change in, or variability of progesterone or FSH levels were associated with irritability. CONCLUSIONS: Irritability was highly prevalent among mildly depressed perimenopausal women. In contrast to depressive symptoms, decreased rather than increased variability in estradiol levels was associated with more irritability. This highlights that irritable mood can be disentangled from depressive symptoms in perimenopausal women and might be linked with different estradiol dynamics

An exploration of the role of religion/spirituality in the promotion of physicians\u27 wellbeing in Emergency Medicine

BACKGROUND: Burnout is highly prevalent among Emergency Medicine (EM) physicians and has significant impact on quality of care and workforce retention. The objective of this study was to determine whether higher religion/spirituality (R/S) is associated with a lower prevalence of burnout among EM physicians (primary outcome). A history of malpractice lawsuits and maladaptive behaviors were the secondary outcomes. METHODS: This was a cross-sectional, survey-based study conducted among a random sample of physicians from the Massachusetts College of Emergency Physicians mailing list. Burnout was measured using a validated 2-item version of the Maslach Burnout Inventory. Maladaptive behaviors (smoking, drinking, and substance use) and medical malpractice were self-reported. R/S measures included organized religiosity, religious affiliation, private R/S practice, self-rated spirituality, religious rest, and religious commitment. Logistic regression was used to model study outcomes as a function of R/S predictors. RESULTS: Of 422 EM physicians who received the invitation to participate, 138 completed the survey (32.7%). The prevalence of burnout was 27%. No significant associations were observed between burnout and R/S indicators. Maladaptive behaviors (adjusted OR = 0.42, CI: 0.19 to 0.96; p = 0.039) and history of medical malpractice (adjusted OR = 0.32; CI: 0.11 to 0.93; p = 0.037) were less likely among physicians reporting to be more involved in organized religious activity and to observe a day of rest for religious reasons, respectively. CONCLUSION: This study provides preliminary evidence for a possible protective association of certain dimensions of R/S on maladaptive behaviors and medical malpractice among EM physicians