Reproductive cancer risk factors among Alaska Native women: the Alaska Education and Research Towards Health (EARTH) Study.

BACKGROUND: The purpose of this study was to provide estimates for the prevalence of reproductive cancer risk factors among Alaska Native (AN) women who enrolled in the Alaska Education and Research Towards Health (EARTH) Study from 2004 to 2006. METHODS: A total of 2,315 AN women 18 years or older completed reproductive health questions as part of a comprehensive health history questionnaire. The reproductive health section included menstrual status (age at menarche and menopause), pregnancy and live birth history, use of hormonal contraception, hormone replacement therapy, and history of hysterectomy and/or oophorectomy. RESULTS: A total of 463 (20%) of women experienced menarche before age 12 with a decline in mean age at menarche by age cohort. More than 86% had been pregnant (mean number of pregnancies, 3.8; mean number of live births, 2.9). More than one half of women (58%) had their first live birth between the ages of 18 and 24. Almost 28% of participants had completed menopause, of whom 24% completed menopause after age 52. Fewer than half (43%) reported ever using hormone replacement therapy. Almost two thirds (62%) reported ever using oral contraceptives, and fewer reported ever using birth control shots (30%) or implants (10%). CONCLUSIONS: This study is unique in reporting reproductive health factors among a large group of AN women. These data show that AN women have selective protective factors for reproductive cancers, including low nulliparity rates, low use of menopausal estrogens, and common use of contraceptive hormones. However, analysis by age cohorts indicates decreasing age at menarche that might increase the risk for reproductive cancers among AN women in the future.

Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition.

The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We analyzed data from 2283 participants of the Study of Women's Health Across the Nation, a longitudinal community-based cohort study of women aged 42 to 52 years at baseline. At baseline and annually through follow-up visit 8, participants provided questionnaire data, urine samples, serum samples, and anthropometric measurements. Using multivariable repeated-measures mixed models, we examined associations between annually assessed VMS frequency and annual NTX measurements. Our results show that mean adjusted NTX was 1.94 nM of bone collagen equivalents (BCE)/mM of creatinine higher among early perimenopausal women with any VMS than among early perimenopausal women with no VMS (p < .0001). Mean adjusted NTX was 2.44 nM BCE/mM of creatinine higher among late perimenopausal women with any VMS than among late perimenopausal women with no VMS (p = .03). Among premenopausal women, VMS frequency was not significantly associated with NTX level. When NTX values among women with frequent VMS (≥6 days in past 2 weeks) were expressed as percentages of NTX values among women without frequent VMS, the differences were 3% for premenopausal women, 9% for early perimenopausal women, 7% for late perimenopausal women, and 4% for postmenopausal women. Adjustment for serum follicle-stimulating hormone (FSH) level greatly reduced the magnitudes of associations between VMS and NTX level. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health.

Racial differences in women who have a hysterectomy for benign conditions.

OBJECTIVE: To evaluate if there are racial differences between African-American and Caucasian women who have hysterectomy for benign conditions in terms of (1) presenting symptoms (prolapse, vaginal bleeding, pain, and known history of leiomyomas), (2) serum estradiol and testosterone levels at the visit before hysterectomy, and (3) uterine weight. METHODS: A multi-ethnic, multisite, community-based longitudinal cohort study of 3,302 women ages 42-52 at enrollment was conducted. During 9 years of follow-up, 203 African-American and Caucasian women reported a hysterectomy, 90 with evidence of uterine leiomyomas. Women were surveyed regarding their overall perceived health before and after hysterectomy, presenting symptoms, and their motivations for surgery. Serum estradiol and testosterone levels were measured. Uterine weight at time of hysterectomy and clinical pathology were determined via medical record abstraction. RESULTS: Previously diagnosed leiomyomas were presenting symptoms more frequently in African-American women than Caucasian women (85% vs. 63%; p = .02). African-American women had less prolapse than Caucasian women (0% vs. 10%; p = 0.04). Chronic pain was a more frequent reason for hysterectomy in African-American women than in Caucasian women (49% vs. 29%; p = .05). There were no differences between the groups in levels of estradiol or testosterone. African-American women had almost twice the uterine weight as that of Caucasian women (448 vs. 240 g; p = .0005). CONCLUSION: Racial differences in frequency of hysterectomy for benign conditions are consistent with differences in presenting symptoms, where African-American women seemingly have larger, more symptomatic fibroids.

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.

Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. DESIGN: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation. RESULTS: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenorrhea), and 27% were postmenopausal (>or=12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P=0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P=0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P=0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P=0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. CONCLUSIONS: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.

Adiposity and reporting of vasomotor symptoms among midlife women: the study of women's health across the nation.

It has long been hypothesized that increased adiposity would be associated with decreased vasomotor symptoms during menopause because of conversion of androgens to estrogens in body fat. However, recent thermoregulatory models have postulated that increased adipose tissue would be associated with a greater likelihood of vasomotor symptoms. The authors evaluated these hypotheses in the Study of Women's Health Across the Nation, a multiethnic, community-based observational study of US women transitioning through menopause. The sample included 1,776 women aged 47-59 years with an intact uterus and at least one ovary who completed bioelectrical impedance analysis for assessment of body composition at the sixth annual study visit (2002-2004). Assessments also included reported vasomotor symptoms (hot flashes, night sweats) and serum levels of follicle-stimulating hormone, estradiol, and sex hormone-binding globulin-adjusted estradiol (free estradiol index). Results indicated that a higher percentage of body fat was associated with increased odds of reporting vasomotor symptoms (per standard deviation increase in percent body fat, odds ratio = 1.27, 95% confidence interval: 1.14, 1.42) in age- and site-adjusted models. Associations persisted in fully adjusted models and were not reduced when models included reproductive hormones. These findings support a thermoregulatory model of vasomotor symptoms.

Menopause transition stage and endogenous estradiol and follicle-stimulating hormone levels are not related to cognitive performance: cross-sectional results from the study of women's health across the nation (SWAN).

BACKGROUND: By one estimate, 60% of women experiencing the menopause transition perceive that they have memory problems, but most studies that have used cognitive function tests have not substantiated a relation between menopause stage and cognitive performance. We sought to describe the cross-sectional relation between menopause status, estradiol (E(2)), follicle-stimulating hormone (FSH), and measured cognitive function. METHODS: Cross sectional analysis of a community-based cohort of midlife women was used. Cognitive tests were the East Boston Memory Test, Symbol Digit Modalities, and Digits Span Backward. Menopause categories (premenopausal, early perimenopausal, late perimenopausal, and postmenopausal) were defined based on menstrual patterns. One set of general linear models assessed the relations between each cognitive test and menopause transition category, initially adjusted for age, race/ethnicity, education, symptoms, self-rated general health, and body mass index (BMI); next, these were additionally adjusted for FSH and E(2). A second set of models, stratified by menopause status, examined the possible relations between each cognitive test and either E(2) or FSH, adjusted for age, race/ethnicity, education, symptoms, self-related general health, and BMI. RESULTS: The mean age of the analytical sample (n = 1657) was 49.7 years. Only 5% of the sample had less than a high school education, 16% graduated from high school, and the rest had at least some college. The percent of women in each menopause category was premenopausal (9.0%), early perimenopausal (57.0%), late perimenopausal (13.4%), postmenopausal (20.6%). Although clinical-site adjusted models showed moderate differences between menopause transition groups and cognitive performance, no association was found between each of the measured cognitive performance tests and menopause transition status when adjusting for covariates. Similarly, no association between each cognitive test and E(2) or FSH was found. CONCLUSIONS: This study does not support a cross-sectional relation between cognitive test performance and menopause stage, FSH, or E(2).

The association of bone mineral density with estrogen receptor gene polymorphisms.

The purpose of this investigation was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and bone mineral density (BMD) of the lumbar spine (LS-BMD) or total hip (hip BMD) in women of 4 races/ethnicities who were premenopausal or in early perimenopause. The sample consisted of 1,301 participants from the Study of Women's Health Across the Nation (SWAN) with measures of BMD and genotyping; of these, 295 were African American, 693 were Caucasian, 151 were Chinese, and 162 were Japanese. We evaluated the potential association of LS-BMD or hip BMD with 4 SNPs from the ESR1 gene (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 SNPs from the ESR2 gene (ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Unadjusted mean LS-BMD values ranged from 1.141+/-0.14 g/cm(2) in African American women to 1.031+/-0.11 g/cm2 in Japanese women; unadjusted mean hip BMD values ranged from 1.053+/-0.14 g/cm2 in African American women to 0.862+/-0.10 g/cm2 in Chinese women. African American and Japanese women with the ESR1 rs2234693 (PvuII) CC genotype had higher LS-BMDs than did their peers with the TT genotype (P=0.009 and P=0.04, respectively). Japanese women with the ESR1 rs3798577 CC or TC genotypes had lower LS-BMD than did Japanese women with the TT genotype (P=0.02 and P=0.01, respectively). Caucasian women with the TC genotype for ESR2 rs1256030 had lower LS-BMDs than did those with the CC genotype (P=0.02). Chinese women who were heterozygous for ESR2 rs1256030 or ESR2 rs1256065 had significantly higher LS-BMDs and hip BMDs than did the referent groups for each of these SNPs (CC and AA, respectively). Associations between BMD and ESR1 and ESR2 genotypes varied by race/ethnicity and by bone site. Our results differ from those previously reported for 2 ESR1 genotypes (ESR1 rs2234693 [PvuII] and ESR1 rs9340799 [XbaI]). Moreover, 2 ESR1 and 3 ESR2 SNPs we studied have not previously been examined with respect to BMD. Among these, ESR2 rs1256030 and ESR2 rs1256065 appear to have an effect at both the lumbar spine and hip in Chinese women and may warrant further study.

One-year clinical outcomes of protected and unprotected left main coronary artery stenting.

AIMS: To evaluate outcomes for left main coronary artery (LMCA) stenting and compare results between protected (left coronary grafted) and unprotected LMCA stenting in the current bare-metal stent era. METHODS: We reviewed outcomes among 142 consecutive patients who underwent protected or unprotected LMCA stenting since 1997. All-cause mortality, myocardial infarction (MI), target-lesion revascularization (TLR), and the combined major adverse clinical event (MACE) rates at one year were computed. RESULTS: Ninety-nine patients (70%) underwent protected and 43 patients (30%) underwent unprotected LMCA stenting. In the unprotected group, 86% were considered poor surgical candidates. Survival at one year was 88% for all patients, TLR 20%, and MACE 32%. At one year, survival was reduced in the unprotected group (72% vs. 95%, P<0.001) and MACE was increased in the unprotected patients (49% vs. 25%, P=0.005). CONCLUSIONS: In the current era, stenting for both protected and unprotected LMCA disease is still associated with high long-term mortality and MACE rates. Stenting for unprotected LMCA disease in a high-risk population should only be considered in the absence of other revascularization options. Further studies are needed to evaluate the role of stenting for unprotected LMCA disease.

Improved outcomes for women undergoing contemporary percutaneous coronary intervention: a report from the National Heart, Lung, and Blood Institute Dynamic registry.

OBJECTIVES: The goal of this study was to determine whether women undergoing contemporary percutaneous coronary intervention (PCI) remain at increased risk in comparison with men and whether the outcomes in women have improved. BACKGROUND: Previous studies have shown that women treated with coronary angioplasty have a higher incidence of procedural morbidity and mortality than men. METHODS: Gender differences in wave 1 of the National Heart, Lung and Blood Institute (NHLBI) Dynamic registry were evaluated. Baseline characteristics and outcomes in women in the Dynamic registry were compared with those in women in the 1985-1986 and 1993-1994 NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) registries. RESULTS: Women were older with a higher prevalence of diabetes mellitus, hypertension, congestive heart failure, unstable angina and single vessel disease in comparison with men. Although procedural success and in-hospital death (2.2% vs. 1.3%), myocardial infarction (MI) (2.3% vs. 3.0%) and coronary artery bypass graft surgery (CABG) (1.3% vs. 1.4%) were similar in women and men, respectively, one-year mortality (6.5% vs. 4.3%, p = 0.02) and combined end point of death/MI/CABG (18.3% vs. 14.4%, p = 0.03) were higher in women than in men. After controlling for other factors, gender was not a significant predictor of death or death plus MI at one year. Despite a higher risk profile in women in the Dynamic registry in comparison with women in the 1985-1986 NHLBI PTCA registry, in-hospital death/MI/CABG was lower (6.0% vs. 11.6%, p < 0.001). CONCLUSIONS: Despite persistent high-risk characteristics in women, gender differences in outcomes in patients undergoing contemporary PCI have decreased, and outcomes in women have improved.