Ellen B. Gold

Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview‐based study of 1032 patients

Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC. We enrolled patients with PBC (n = 1032) from 23 tertiary referral centers for liver diseases in the United States and random‐digit‐dialed controls (n = 1041) matched for sex, age, race, and geographical location. Patients and controls were administered a modified version of the US National Health and Nutrition Examination Study (NHANES III) questionnaire by trained personnel to evaluate associations between PBC and social, demographic, personal and family medical histories, lifestyle, and reproductive factors and the rates of comorbidity in affected individuals. Data indicate that having a first‐degree relative with PBC (adjusted odds ratio [AOR] 10.736; 95% confidence interval 4.227‐27.268), history of urinary tract infections (AOR 1.511, 95% CI 1.192‐1.915), past smoking (AOR 1.569, 95% CI 1.292‐1.905), or use of hormone replacement therapies (AOR 1.548, 95% CI 1.273‐1.882) were significantly associated with increased risk of PBC. The frequent use of nail polish slightly increased the risk of having PBC. Other autoimmune diseases were found in 32% of cases and 13% of controls (P<0.0001). In conclusion, environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease. (HEPATOLOGY 2005;42:1194–1202.)

Longitudinal Analysis of the Association Between Vasomotor Symptoms and Race/Ethnicity Across the Menopausal Transition: Study of Women’s Health Across the Nation

OBJECTIVES We investigated whether vasomotor symptom reporting or patterns of change in symptom reporting over the perimenopausal transition among women enrolled in a national study differed according to race/ethnicity. We also sought to determine whether racial/ethnic differences were explained by sociodemographic, health, or lifestyle factors. METHODS We followed 3198 women enrolled in the Study of Womens Health Across the Nation during 1996 through 2002. We analyzed frequency of vasomotor symptom reporting using longitudinal multiple logistic regressions. RESULTS Rates of vasomotor symptom reporting were highest among African Americans (adjusted odds ratio [OR]=1.63; 95% confidence interval [CI]=1.21, 2.20). The transition to late perimenopause exhibited the strongest association with vasomotor symptoms (adjusted OR = 6.64; 95% CI = 4.80, 9.20). Other risk factors were age (adjusted OR=1.17; 95% CI=1.13, 1.21), having less than a college education (adjusted OR = 1.91; 95% CI = 1.40, 2.61), increasing body mass index (adjusted OR=1.03 per unit of increase; 95% CI=1.01, 1.04), smoking (adjusted OR=1.63; 95% CI=1.25, 2.12), and anxiety symptoms at baseline (adjusted OR=3.10; 95% CI=2.33, 4.12). CONCLUSIONS Among the risk factors assessed, vasomotor symptoms were most strongly associated with menopausal status. After adjustment for covariates, symptoms were reported most often in all racial/ethnic groups in late perimenopause and nearly as often in postmenopause.

SWAN: A Multicenter, Multiethnic, Community-Based Cohort Study of Women and the Menopausal Transition

Study of Womens Health Across the Nation (SWAN) is the first national study to describe women at midlife, an understudied age group. Its multidisciplinary approach provides the opportunity to consider the contributions of both culture and biology so that one may better understand health of women. The SWAN employs a prospective design that includes sufficient pre- and postmenopausal observations to ensure the separation of menopause-related and age-related physiological changes. Other attributes include the comprehensive standardized data collection related to biological, behavioral, physiological, social, environmental, and cultural factors; specialized data collection methodologies suitable to address the monthly and yearly variation in behavioral and biological patterns; general ability to community-dwelling populations recruited from major United States population centers; sufficiently large sample size and numbers of data points to ensure reliable estimates of associations and relevant effect sizes; and inclusion of sufficient numbers of racial/ethnic minorities to provide comparative information with the non-Hispanic Caucasian population. Because of these attributes, SWAN can contribute new and substantive knowledge about womens health in general and the menopause transition in particular.

A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study

The Womens Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

Longitudinal Change in Reproductive Hormones and Depressive Symptoms Across the Menopausal Transition: Results From the Study of Women’s Health Across the Nation (SWAN)

CONTEXT The contribution of reproductive hormones to mood has been the focus of considerable research. Results from clinical and epidemiological studies have been inconsistent. It remains unclear whether alterations in serum hormone levels across the menopausal transition are linked to depressive symptoms. OBJECTIVES To evaluate the relationship between serum hormone levels and high depressive symptoms and whether hormone levels or their change might explain the association of menopausal status with depressive symptoms previously reported in a national sample of midlife women. DESIGN A longitudinal, community-based, multisite study of menopause. Data were collected at baseline and annually from December 1995 to January 2008 on a range of factors. Early follicular phase serum samples were assayed for levels of estradiol, follicle-stimulating hormone, testosterone, and dehydroepiandrosterone sulfate. SETTING Seven communities nationwide. PARTICIPANTS A community-based sample of 3302 multiethnic women, aged 42 to 52 years, still menstruating and not using exogenous reproductive hormones. Main Outcome Measure Depressive symptoms assessed with the Center for Epidemiological Studies Depression Scale (CES-D). The primary outcome was a CES-D score of 16 or higher. RESULTS In multivariable random-effects logistic regression models, log-transformed testosterone level was significantly positively associated with higher odds of a CES-D score of 16 or higher (odds ratio = 1.15; 95% confidence interval, 1.01-1.31) across 8 years, and a larger increase in log-transformed testosterone from baseline to each annual visit was significantly associated with increased odds of a CES-D score of 16 or higher (odds ratio = 1.23; 95% confidence interval, 1.04-1.45). Less education, being Hispanic, and vasomotor symptoms, stressful life events, and low social support at each visit were each independently associated with a CES-D score of 16 or higher. No other hormones were associated with a CES-D score of 16 or higher. Being perimenopausal or postmenopausal compared with being premenopausal remained significantly associated with a CES-D score of 16 or higher in all analyses. CONCLUSIONS Higher testosterone levels may contribute to higher depressive symptoms during the menopausal transition. This association is independent of menopausal status, which remains an independent predictor of higher depressive symptoms.

Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition

IMPORTANCE The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS The Study of Womens Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

The Timing of the Age at Which Natural Menopause Occurs

The timing of natural menopause is a clinically important indicator of longevity and risk of morbidity and mortality. Demographic, menstrual, reproductive, familial, genetic, and lifestyle factors seem to be important in this timing. Smoking, lower parity and poor socioeconomic status are associated with earlier menopause. However, a number of relationships have been inconsistent; others remain largely unexplored. Much remains to be learned about factors that affect follicular atresia and the onset and duration of perimenopause and the timing of the natural menopause. Knowledge about these relationships offers women and their health care providers enhanced understanding and choices to deal with menopause.

Ethnic Differences in Use of Complementary and Alternative Medicine at Midlife: Longitudinal Results From SWAN Participants

OBJECTIVES We estimated the prevalence and longitudinal correlates of use of complementary and alternative medicine (CAM) at midlife among participants of the Study of Womens Health Across the Nation (SWAN). METHODS Multiple logistic regression was used to evaluate the relationship between baseline survey-reported symptoms and use of herbal, spiritual, and physical manipulation therapies 1 year later. RESULTS Almost half of all women had used CAM in the past year. Baseline psychological symptoms were associated with subsequent use of spiritual therapies among White and Chinese women. Baseline CAM use was a major predictor of subsequent use in White, Japanese, and Chinese women. CONCLUSIONS Baseline CAM use, rather than presence of symptoms, was the major predictor of subsequent CAM use. Premenopausal health behaviors are important determinants of choice of therapy during midlife.

Factors Related to Age at Natural Menopause: Longitudinal Analyses From SWAN

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Womens Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

Change in Follicle-Stimulating Hormone and Estradiol Across the Menopausal Transition: Effect of Age at the Final Menstrual Period

BACKGROUND AND OBJECTIVE To determine whether patterns of change in serum estradiol (E2) and FSH across the menopausal transition were associated with age at the final menstrual period (FMP). DESIGN AND SETTING The Study of Womens Health Across the Nation (SWAN) is a seven-site, multiethnic, longitudinal study of the menopausal transition being conducted in 3302 menstruating women who were aged 42-52 yr at the 1996 study baseline. MEASUREMENTS Annually collected serum was assayed for E2 and FSH levels. Patterns of hormone change were evaluated in the 1215 women with a documented natural FMP by follow-up visit 9 (2006) using semiparametric stochastic and piecewise linear mixed modeling. RESULTS The FSH pattern across the menopausal transition began with an increase 6.10 yr before the FMP, an acceleration 2.05 yr before the FMP, deceleration beginning 0.20 yr before the FMP, and attainment of stable levels 2.00 yr after the FMP, independent of age at the FMP, race/ethnicity, or smoking status. Obesity attenuated the FSH rise and delayed the initial increase to 5.45 yr before the FMP. The mean E2 concentration did not change until 2.03 yr before the FMP when it began decreasing, achieving maximal rate of change at the FMP, then decelerating to achieve stability 2.17 yr after the FMP. Obesity, smoking behavior, and being Chinese or Japanese were associated with some variation in E2 levels but not the pattern of E2 change. CONCLUSIONS Time spans and overall patterns of change in serum FSH and E2 across the menopausal transition were not related to age at FMP or smoking, whereas time spans but not overall patterns were related to obesity and race/ethnicity.