Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife women: study of Women's Health Across the Nation.

OBJECTIVE: During the menopausal transition, total testosterone (T) remains unchanged, whereas estrogen decreases markedly, creating a state of relative androgen excess. We hypothesized that change in the T-to-estradiol (T/E2) ratio during the menopausal transition would be associated with incident metabolic syndrome. METHODS: The association between incident metabolic syndrome and total E2, total T, sex hormone-binding globulin, the free androgen index, baseline total T/E2 ratio, and the change of this ratio over time was evaluated in a multiethnic cohort of 1,862 premenopausal and perimenopausal women without diabetes enrolled in the Study of Women's Health Across the Nation. RESULTS: New cases (n = 257) of metabolic syndrome were identified in the cohort during 6,296 woman-years of follow-up. The age-adjusted total T/E2 ratio increased by 10.1% per year during the 5 years of follow-up. Neither baseline nor change in E2 was associated with incident metabolic syndrome. Low sex hormone-biding globulin, free androgen index, and high total T at baseline all increased the risk of metabolic syndrome, but their change over time did not. Both baseline total T/E2 ratio (1.41; 95% CI = 1.17-1.69; P < 0.001) and its rate of change (1.24; 95% CI = 1.01-1.52; P < 0.04) were associated with increased incident metabolic syndrome independent of ethnicity. CONCLUSIONS: The interaction between T and E2 during the menopausal transition, rather than the individual change of each over time, is a factor in the determination of risk of developing metabolic syndrome during the menopausal transition. This relationship was independent of ethnicity and other factors associated with prevalent metabolic syndrome before the onset of the menopausal transition.

Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Our study evaluates the symptoms commonly attributed to adenomyosis in women undergoing the menopausal transition. We hypothesized that adenomyosis is more commonly seen in women with fibroids, pelvic pain, abnormal uterine bleeding, and in the presence of endometriosis. DESIGN: Retrospective cohort. SETTING: Multisite community-based study. PATIENT(S): Enrollees in the Study of Women's Health Across the Nation who had hysterectomies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relationship of adenomyosis to presenting symptoms and other patient characteristics. RESULT(S): Adenomyosis was found in 48% of 137 patients. Frequencies of presenting symptoms were similar in those with and without evidence of adenomyosis. The same prevalence of fibroids was seen in the presence or absence of adenomyosis: 37% versus 43%, endometriosis, 3% versus 5%, abnormal bleeding, 27% versus 33%, or chronic pelvic pain in the presence of fibroids 12% versus 17%. CONCLUSION(S): Adenomyosis is a common diagnosis seen in hysterectomized specimens from women undergoing the perimenopausal transition. Adenomyosis is equally common in women who also have fibroids, endometriosis, pelvic pain, or abnormal uterine bleeding, and women who do not. Therefore, adenomyosis is an incidental finding, not the source of the symptomatology. It appears not to be a "disease" per se but rather a normal variant.

Use of smoking-cessation treatments in the United States.

BACKGROUND: Health promotion efforts encourage smokers to quit and to use effective cessation treatments. Randomized controlled trials demonstrate that medications and behavioral treatments improve cessation rates, but retrospective surveys have been inconsistent. This study assessed frequency of quit attempts, use of treatments for cessation, and abstinence rates among treatment users and non-users. METHODS: Data were analyzed from the 2003 Tobacco Use Special Cessation Supplement to the Current Population Survey. Participants included 29,537 U.S. smokers aged > or =18 years who smoked daily 12 months before the survey. Outcome measures included past-year quit attempts; use of behavioral, pharmacologic, and alternative treatments; receipt of social support; and abstinence for > or =4 weeks at time of survey. RESULTS: Approximately 43.5% of smokers reported a quit attempt in the preceding year: 64.2% of attempters used no cessation treatments; 8.8% used behavioral treatment; 32.2% used medication; and 14.1% used more than one treatment. Social support was reported to have been received by 24.1%. More nicotine-dependent smokers were more likely to use medications (OR=3.58; 95% CI=3.04-4.20). At the time of the survey, 19.3% of attempters were abstinent > or =4 weeks. Smokers who sought treatment were less likely to be abstinent (OR=0.75; 95% CI=0.67-0.84), and those who sought multiple treatments were even less likely to be abstinent. CONCLUSIONS: Many U.S. smokers make quit attempts, but most do not use behavioral or pharmacologic treatments. More nicotine-dependent smokers were more likely to seek treatment. Smokers who sought treatment were less likely to report abstinence, probably due to biased self-selection and recall. Retrospective survey data are not well-suited to assess the effectiveness of treatment.

Individual differences in adoption of treatment for smoking cessation: demographic and smoking history characteristics.

BACKGROUND: Behavioral and pharmacological treatments have been shown to improve smoking cessation rates, but treatments are under-utilized. AIMS: To examine the demographic and smoking history characteristics associated with adoption of treatment for cessation. DESIGN: Analysis of the 2003 tobacco use special cessation supplement to the current population survey. PARTICIPANTS: Representative sample of 12,027 U.S. daily smokers ages 18 and older who made a quit attempt in the past year. MEASUREMENTS: Use of behavioral, pharmacological or alternative treatments for cessation; demographic variables (age, gender, ethnicity, education and income) and measures of nicotine dependence. RESULTS: Females, Whites, older, more educated and wealthier smokers were more likely to adopt treatment in a quit attempt, as were more nicotine dependent smokers. Females were more likely than males to use behavioral treatments. Females and more educated smokers were more likely to combine behavioral and pharmacological treatment. Among those who used only one treatment, males, older and more nicotine dependent smokers were more likely to adopt pharmacological treatments. CONCLUSIONS: The majority of smokers make quit attempts without the benefit of proven behavioral or pharmacological treatments. Efforts are needed to increase use of smoking cessation treatments among all smokers, particularly combination treatment.

Helping midlife women predict the onset of the final menses: SWAN, the Study of Women's Health Across the Nation.

OBJECTIVE: Women approaching menopause often ask their doctors, "When are my periods going to end?" The objective of this study was to predict time to the final menstrual period (FMP). DESIGN: This multiethnic, observational cohort study, the Study of Women's Health Across the Nation, has been ongoing since 1996. Data collected from seven annual study visits were used. The community-based cohort from seven national sites included 3,302 white, African American, Hispanic, Chinese, and Japanese women aged 42 to 52 years at baseline with a uterus and at least one ovary, who were not pregnant or taking reproductive hormones, and had at least one menstrual period within the past 3 months at baseline. The time to the FMP was defined retrospectively after 12 months of amenorrhea. Uni- and multivariable Cox proportional hazard models, hazard ratios (HRs), and 95% CIs were computed for variables of interest. RESULTS: A total of 2,662 women, of whom 706 had an observed FMP, were included. Age, menstrual cycles that had become farther apart (HR = 2.56, 95% CI = 1.94-3.39) or more variable (HR = 1.79, 95% CI = 1.45-2.21), and current smoking (HR = 1.68, 95% CI = 1.35-2.08) were all associated with shorter time to the FMP. Higher (log) follicle-stimulating hormone (HR = 2.32, 95% CI = 2.02-2.67) was related to a shorter time to the FMP, but the highest estradiol category (>or=100 pg/mL [367 pmol/L]) was associated with an earlier onset of the FMP (HR = 2.16, 95% CI = 1.63-2.89). The number of vasomotor symptoms was related to an earlier FMP, whereas higher physical activity and educational levels were associated with a later FMP. CONCLUSIONS: Age, menstrual cycle recall, smoking status, and hormone measurements can be used to estimate when the FMP will occur, allowing for more precise estimates for older midlife women: in the most extreme cases, ie, age 54, high estradiol level, current smoking, and high follicle-stimulating hormone level, the FMP can be estimated to within 1 year.

The association of genetic polymorphisms in sex hormone biosynthesis and action with insulin sensitivity and diabetes mellitus in women at midlife.

We evaluated associations of insulin sensitivity, metabolic syndrome, and diabetes mellitus with single nucleotide polymorphism (SNP) variants from sex hormone biosynthesis and action in women of 4 races/ethnicities. DNA was extracted from transformed cell samples of 1,538 women in the Study of Women's Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women in SWAN enrolled in the Sex Steroid Hormone Genetics Protocol from whom fasting glucose and insulin measures (for estimating insulin sensitivity), diabetes status, and metabolic syndrome classification were obtained. SNPs from the genes encoding aromatase (CYP 19), 17beta-hydroxysteroid dehydrogenase (17HSD) type 1, and the estrogen receptors-alpha (ESR1) and -beta (ESR2) were measured. The prevalence of metabolic syndrome was 20% in Chinese women, 22% in Japanese women, 28% in Caucasian women, and 43% in African American women. The prevalence of diabetes was 3% in Chinese women, 4% in Japanese women, 7% in Caucasian women, and 19% in African American women. Significant associations of CYP 19 genotypes and insulin sensitivity were observed in African American, Caucasian, and Japanese women. Selected ESR1 and ESR2 genotypes were associated with insulin sensitivity and metabolic syndrome only in Japanese and Chinese women. The strongest associations related 17HSD genotypes to diabetes in Caucasian women, with odds ratios ranging from 4.4 to 7.5 and confidence intervals that excluded the null value. We observed strong associations between variations in sex hormone biosynthesis and function genes with insulin sensitivity, the metabolic syndrome, and diabetes that varied by race/ethnicity. The strong association of 17HSD and diabetes in Caucasian women has not been previously reported and should be further investigated.

The relationship of longitudinal change in reproductive hormones and vasomotor symptoms during the menopausal transition.

CONTEXT: The relationship of reproductive hormones to vasomotor symptoms (VMS) has been incompletely explored, although an increase in such symptoms at midlife and their reduction with hormone therapy suggest a strong and direct relationship. Vasomotor symptoms are reported by 65-76% of women traversing the menopausal transition and are a primary reason for medical intervention during this life stage. OBJECTIVE: The purpose of this report was to relate longitudinal serum concentrations of the reproductive hormones estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), and SHBG and the free hormone indices free E2 index (FEI) and free T index (FTI) with the occurrence of VMS in women traversing the menopausal transition. DESIGN AND SETTING: The Study of Women's Health Across the Nation is a multisite, longitudinal, cohort study of the menopausal transition being conducted in community-based groups of women. PARTICIPANTS AND MAIN OUTCOME MEASURES: At baseline, 3302 menstruating women who belonged to one of five ethnic/racial groups were recruited and followed up with annual visits. Frequencies of symptoms (hot flashes, night sweats) for the prior 2 wk and measures of other covariates as well as potentially confounding variables were self-reported in the annual interview. Serum was obtained annually, on d 2-5 of a spontaneous cycle in cycling women or within 90 d of the anniversary of the baseline study visit in noncycling women and assayed for FSH, E2, T, SHBG, and DHEAS. FTI and FEI were calculated. This analysis incorporated available longitudinal data from 3293 women, excluding information collected at or after first report of hormone therapy use or hysterectomy. Data were analyzed using longitudinal marginal logistic regression models and a partial proportional odds model. RESULTS: After adjusting for age, body mass index, and other related covariates, VMS prevalence increased with higher (log)FSH concentrations, and the increase was greater when blood was drawn more than 5 d after menses began. FSH concentrations were positively associated with the frequency of either hot flashes or night sweats, and higher FSH concentrations were associated with greater odds of reporting more frequent symptoms. Vasomotor symptom prevalence decreased with higher (log)E2, (sqrt)SHBG, and (log)FEI but only when these hormone values were modeled independently of (log)FSH values and the specimens were obtained outside the d 2-5 window. When modeled simultaneously with (log)FSH, (log)E2, (sqrt)SHBG, and (log)FEI were no longer significantly associated with symptom prevalence. (Cubic root)T and (sqrt)DHEAS concentrations and (log)FTI were not associated with the prevalence of VMS. CONCLUSIONS: Annual serum FSH concentrations, but not E2, T, DHEAS, FTI, or FEI when collectively modeled longitudinally, are associated with both the prevalence and frequency of VMS in women at midlife.

Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN).

BACKGROUND: Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife. METHODS AND RESULTS: The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E2) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P<0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. CONCLUSIONS: Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.

Segment-specific effects of cardiovascular risk factors on carotid artery intima-medial thickness in women at midlife.

OBJECTIVE: We investigated associations between segment-specific carotid intima-medial thickness (IMT) and cardiovascular risk factors collected before menopause for insight into mechanisms of atherosclerosis development. METHODS AND RESULTS: Participants were 453 healthy women (aged 46 to 58 years) enrolled in a dietary and physical activity randomized clinical trial. Ultrasound scan measures were taken approximately 2.7 years after baseline in the common carotid artery (CCA), bifurcation (bulb), and internal carotid artery (ICA) segments. When scanned, 84% remained premenopausal. In linear regression models adjusted for age, menopausal status, and intervention group, measures independently (P<0.05) and positively associated were as follows: baseline weight (beta=0.007 per 5 kg), systolic blood pressure (SBP; beta=0.008 per 10 mm Hg), and age (beta=0.02 per 5 years) with CCA IMT; smoking (beta=0.08), weight (beta=0.009), and SBP (beta=0.02) with bulb IMT; and apoprotein B (beta=0.01 per 0.1 g/L) with ICA IMT. Differential effects in a repeated measures model with all 3 IMT locations showed these risk factors to have segment-specific positive associations. The effect of weight was strongest in the CCA, smoking and SBP were specific to the bulb, and apoprotein B was strongest in the ICA segment. CONCLUSIONS: Analyses indicate that cardiovascular risk factors may differentially affect IMT in the CCA, bulb, and ICA segments of healthy middle-aged women.