Athletic activity and hormone concentrations in high school female athletes.

CONTEXT: Physical activity may affect the concentrations of circulating endogenous hormones in female athletes. Understanding the relationship between athletic and physical activity and circulating female hormone concentrations is critical. OBJECTIVE: To test the hypotheses that (1) the estradiol-progesterone profile of high school adolescent girls participating in training, conditioning, and competition would differ from that of physically inactive, age-matched adolescent girls throughout a 3-month period; and (2) athletic training and conditioning would alter body composition (muscle, bone), leading to an increasingly greater lean-body-mass to fat-body-mass ratio with accompanying hormonal changes. DESIGN: Cohort study. SETTINGS: Laboratory and participants' homes. PATIENTS OR OTHER PARTICIPANTS: A total of 106 adolescent girls, ages 14-18 years, who had experienced at least 3 menstrual cycles in their lifetime. MAIN OUTCOME MEASURE(S): Participants were prospectively monitored throughout a 13-week period, with weekly physical activity assessments and 15 urine samples for estrogen, luteinizing hormone, creatinine, and progesterone concentrations. Each girl underwent body-composition measurements before and after the study period. RESULTS: Seventy-four of the 98 girls (76%) who completed the study classified themselves as athletes. Body mass index, body mass, and fat measures remained stable, and 17 teenagers had no complete menstrual cycle during the observation period. Mean concentrations of log(estrogen/creatinine) were slightly greater in nonathletes who had cycles of <24 or >35 days. Mean log(progesterone/creatinine) concentrations in nonathletes were less in the first half and greater in the second half of the cycle, but the differences were not statistically significant. CONCLUSIONS: A moderate level of athletic or physical activity did not influence urine concentrations of estrogen, progesterone, or luteinizing hormones. However, none of the participants achieved high levels of physical activity. A significant number (17%) of girls in both activity groups were amenorrheic during the 3-month study period.

Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity.

OBJECTIVE: Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. METHODS: Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. RESULTS: Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. SUMMARY: During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.

Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women.

OBJECTIVE: Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB-R) in healthy midlife women. DESIGN AND METHODS: Cross-sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow-up visit of the multiethnic Study of Women's Health Across the Nation. RESULTS: T was weakly negatively associated with both HMW adiponectin and sOB-R (r = -0.12 and r = -0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB-R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = -0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB-R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB-R, independent of fat mass. CONCLUSIONS: These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

Bone resorption and fracture across the menopausal transition: the Study of Women's Health Across the Nation.

OBJECTIVE: Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women. METHODS: Women attended up to nine clinic visits for an average of 7.6 ± 1.6 years; all were aged 42 to 52 years and were premenopausal or early perimenopausal at baseline. Incident fractures were self-reported. Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were measured at baseline. NTX was measured at each annual follow-up. Interval-censored survival models or generalized estimating equations were used to test whether baseline BTMs and changes in NTX, respectively, were associated with fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs. RESULTS: Women who experienced fractures (n = 184) had about a 10% higher baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per liter per nanomole of creatinine per liter; P = 0.001), but there was no difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density (BMD) measured premenopausally was associated with a higher fracture risk during menopause (HR, 1.50; 95% CI, 1.28-1.68). Women with a baseline NTX greater than the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.46; 95% CI, 1.05-2.26). The HR of fracture among women with both the lowest spine BMD (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61-6.01), compared with women with lower NTX and higher BMD. Women whose NTX increased more than the median had a higher risk of fracture (odds ratio, 1.51; 95% CI, 1.08-2.10). Women who had baseline NTX greater than the median experienced greater loss of spine and hip BMD. CONCLUSIONS: A higher urinary NTX excretion measured before menopause and across menopause is associated with a higher risk of fracture. Our results are consistent with the pathophysiology of transmenopausal changes in bone strength.

Menopausal transition stage-specific changes in circulating adrenal androgens.

OBJECTIVE: It is now recognized that mean circulating dehydroepiandrosterone sulfate (DHEAS) concentrations in most midlife women exhibit a positive inflection starting in early perimenopause, continuing through early postmenopause and returning to early perimenopausal levels by late postmenopause. This rise in mean DHEAS is accompanied by concomitant rises in testosterone (T), dehydroepiandrosteone (DHEA), and androstenedione (Adione) and an equal rise in androstenediol (Adiol). These observations suggest that there is a specific relationship between the circulating levels of steroids emanating from the adrenal glands, declining ovarian function, and the stages of the menopausal transition. This study was designed to test the hypothesis that the menopausal stage-specific change in circulating DHEAS is associated with concomitant changes in the circulating pattern of adrenal steroids and that some of these adrenal androgens could influence the circulating estrogen/androgen balance. METHODS: Stored annual serum samples (N = 120) were first selected to represent four longitudinal DHEAS profiles of individual women to assess and compare changes in the adrenal contribution to circulating steroids. RESULTS: Changes in mean circulating DHEAS levels in midlife women during the menopausal transition is associated with changes in mean circulating T, Adione, and Adiol. Mean Adione and T concentrations changed the least, whereas mean DHEAS and Adiol changed the most. CONCLUSIONS: Changes in circulating steroid hormone emanating from the adrenal during the menopausal transition may be more important than the decline in ovarian function in terms of altering the estrogen/androgen balance.

Race-ethnic differences in adipokine levels: the Study of Women's Health Across the Nation (SWAN).

Differences in adipose tissue secretory profile, as measured by adipokine levels, may play a role in race-ethnic disparities in cardiovascular disease (CVD). We examined race-ethnic differences in adipokine levels in a group of mid-life Caucasian, African American (AA), Chinese and Japanese women, after accounting for adiposity. Data on 1876 women from the Study of Women's Health Across the Nation were analyzed. In multivariable adjustment, including total fat mass, differences in total and high molecular weight (HMW) adiponectin, leptin and soluble leptin receptor (sOB-R) levels were examined. Despite intermediate levels of adiposity, Caucasian women had higher levels of both total and HMW adiponectin, when compared to both AA and Chinese and Japanese women. After multivariable adjustment, compared to Caucasian women, AA women had significantly lower total (ß: -3.40; 95% CI: -4.29, -2.52; P<.001) and HMW adiponectin (ß: -0.53; 95% CI: -0.64, -0.43; P<.001) levels, higher leptin levels (ß: 3.26; 95% CI: 1.36, 5.16; P<.001) and lower sOB-R levels (ß: -0.07; 95% CI: -0.11, -0.03; P<.001). Compared to Caucasian women, both Chinese and Japanese women had lower total (Chinese: ß: -5.50; 95% CI: -7.07, -3.93; P<.001; Japanese: ß: -5.48; 95% CI: -6.95, -4.02; P<.001) and HMW adiponectin (Chinese: ß: -0.57; 95% CI: -0.75, -0.38; P<.001; Japanese: ß: -0.61; 95% CI: -0.78, -0.44; P<.001) levels and lower sOB-R levels (Chinese: ß: -0.13; 95% CI: -0.20, -0.06; P<.001; Japanese: ß: -0.09; 95% CI: -0.15, -0.02; P=.008). Significant race-ethnic differences exist in circulating adipokines, even after accounting for adiposity. Further research is needed to explicitly determine if such differences contribute to known racial differences in CVD risk.

Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS).

OBJECTIVE: To examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women. METHODS: Women screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n=650). RESULTS: Higher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r=0.21 and 0.19, respectively; P<0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides=-0.16, 0.11, and 0.11, respectively, P<0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4-1.6], 1.5 [0.8-2.9], and 1.8 [1.0-3.4]; p for linear trend=0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat. CONCLUSION: While hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC.

The relationship of birth weight with longitudinal changes in body composition in adult women.

Most research on birth weight and adult health status has reported adult measures at a single time point. This study examined the relationship of self-reported birth weight to longitudinal changes in adult body composition in 587 women of the Michigan Bone Health and Metabolism Study, followed from 1992 to 2007 and aged 24-50 years at baseline. Linear mixed models were used to estimate the association between three birth weight categories and women's 15-year changes in adult weight, height, BMI, waist and hip circumference, waist-to-hip ratio, and fat, lean, and skeletal muscle mass. Body composition measures increased in all women over the 15-year study period. At their adult baseline, high birth weight women weighed 13% more and had waist circumference and lean mass measures that were 5.51 cm and 3.91 kg larger, respectively, than normal birth weight women. No differences were observed in adult body composition between low and normal birth weight women and rates of change in the adult measures did not vary across the birth weight groups. Women heavier at birth continued to be heavier through adulthood, corroborating previous reports based on single measures of adult body composition. Research to address whether higher adult body composition in high birth weight women increases the longitudinal risk for obesity-related chronic diseases is needed.

Urinary bisphenol A and type-2 diabetes in U.S. adults: data from NHANES 2003-2008.

OBJECTIVE: Bisphenol A (BPA) is found in plastics and other consumer products; exposure may lead to insulin resistance and development of type-2 diabetes mellitus (T2DM) through over-activation of pancreatic ß-cells. Previous studies using data from the National Health and Nutrition Examination Survey (NHANES) showed an inconsistent association between prevalence of self-reported T2DM and urinary BPA. We used a different diagnosis method of T2DM (hemoglobin A1c (HbA1c)) with a larger subset of NHANES. METHODS AND FINDINGS: We analyzed data from 4,389 adult participants who were part of a sub-study of environmental phenol measurements in urine from three NHANES cycles from 2003 to 2008. T2DM was defined as having a HbA1c ≥ 6.5% or use of diabetes medication. The weighted prevalence of T2DM was 9.2%. Analysis of the total sample revealed that a two-fold increase in urinary BPA was associated with an odds ratio (OR) of 1.08 of T2DM (95% confidence interval (CI), 1.02 to 1.16), after controlling for potential confounders. However, when we examined each NHANES cycle individually, we only found a statistically significant association in the 2003/04 cycle (n = 1,364, OR = 1.23 (95% CI, 1.07 to 1.42) for each doubling in urinary BPA). We found no association in either the NHANES cycle from 2005/06 (n = 1,363, OR = 1.05 (95% CI, 0.94 to 1.18)); or 2007/08 (n = 1,662, OR = 1.06 (95% CI, 0.91 to 1.23)). Similar patterns of associations between BPA and continuous HbA1c were also observed. CONCLUSIONS: Although higher urinary BPA was associated with elevated HbA1c and T2DM in the pooled analysis, it was driven by data from only one NHANES cycle. Additional studies, especially of a longitudinal design with repeated BPA measurements, are needed to further elucidate the association between BPA and T2DM.

Adiposity and the menopausal transition.

This review summarizes the published literature on the potentially circular relationship between adiposity and the menopause. Although data are limited, current information suggests there are substantial effects of obesity and adiposity on the magnitude of hormone changes experienced during the transition, as well as on the risks of chronic disease resulting from the menopause transition. However, evidence regarding the reverse, namely, effects of the menopause transition and its associated hormone changes on weight gain and redistribution of body fat, are inconclusive.

Genetic polymorphisms and obesity influence estradiol decline during the menopause.

OBJECTIVES: Obesity and genetic variation in aromatase and type 1 17-ß hydroxysteroid dehydrogenase (HSD) could influence the E2 trajectory of decline during the menopause transition. DESIGN AND PARTICIPANTS: E2 trajectories during the menopause transition (phenotype) were identified using 5934 data points acquired annually from 681 women in Study of Women's Health across the Nation (SWAN), a multiethnic study of the mid-life. E2 trajectories were related to CYP19 and type I 17-ßHSD single-nucleotide polymorphisms (SNPs) and obesity. RESULTS: (log) E2 trajectories began to decline precipitously 2 years before the final menstrual period (FMP). The trajectory of the (log) E2 decline varied with genotypes and obesity. (log) E2 rates of decline were greater in nonobese women than in obese women, P < 0·05. Women with the CYP19rs936306 CT variant had (log) E2 rate of decline that was 54% as rapid as the rate of decline of women with the TT variant, P < 0·05. (log) E2 rate of decline in women with the CYP19rs749292 GG variant was two-thirds the rate of (log) E2 decline in women with the AG variant, P < 0·05. (log) Rates of E2 decline with 17-ßHSD SNPs (rs2830, rs592389, and rs615942) varied according to genotype within obesity groups. Within each obesity group, (log) E2 rate of decline was greater in heterozygous variants and much less in homozygotes (P < 0·05). Obese women with selected CYP19 and 17-ß HSD gene variants had remarkably different E2 trajectories around the FMP, resulting in different postmenopausal E2 levels. The rate of the E2 decline and the subsequent postmenopausal E2 levels may be relevant to oestrogen-sensitive chronic diseases including cancers.

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 Women's 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.

Cardiovascular disease risk of abdominal obesity vs. metabolic abnormalities.

It remains unclear whether abdominal obesity increases cardiovascular disease (CVD) risk independent of the metabolic abnormalities that often accompany it. Therefore, the objective of this study was to evaluate the independent effects of abdominal obesity vs. metabolic syndrome and diabetes on the risk for incident coronary heart disease (CHD) and stroke. The Framingham Offspring, Atherosclerosis Risk in Communities, and Cardiovascular Health studies were pooled to assess the independent effects of abdominal obesity (waist circumference >102 cm for men and >88 cm for women) vs. metabolic syndrome (excluding the waist circumference criterion) and diabetes on risk for incident CHD and stroke in 20,298 men and women aged ≥45 years. The average follow-up was 8.3 (s.d. 1.9) years. There were 1,766 CVD events. After adjustment for demographic factors, smoking, alcohol intake, number of metabolic syndrome components, and diabetes, abdominal obesity was not significantly associated with an increased risk of CVD (hazard ratio (HR) (95% confidence interval): 1.09 (0.98, 1.20)). However, after adjustment for demographics, smoking, alcohol intake, and abdominal obesity, having 1-2 metabolic syndrome components, the metabolic syndrome and diabetes were each associated with a significantly increased risk of CVD (2.12 (1.80, 2.50), 2.82 (1.92, 4.12), and 5.33 (3.37, 8.41), respectively). Although abdominal obesity is an important clinical tool for identification of individuals likely to possess metabolic abnormalities, these data suggest that the metabolic syndrome and diabetes are considerably more important prognostic indicators of CVD risk.

Vitamin D and subsequent systolic hypertension among women.

BACKGROUND: We examined data from a cohort of Caucasian women for evidence of an association between serum vitamin D (25-hydroxyvitamin D (25(OH)D)) insufficiency and greater risk of systolic hypertension in the population-based longitudinal Michigan Bone Health and Metabolism Study (MBHMS). METHODS: The cohort includes 559 women aged 24-44 years in 1992; annual blood pressure (BP) measurements and data collection began in 1992 and is ongoing. A single-time serum 25(OH)D level was measured in 1993. Using logistic regression, vitamin D insufficiency (<80 nmol/l) was related to systolic hypertension (≥140 mm Hg) measures identified in 1993 and in 2007. Further, the relationship between vitamin D at baseline and the trajectory of systolic BP across the ensuing 14 years was assessed using longitudinal mixed modeling. RESULTS: Vitamin D insufficiency was not significantly associated with concurrent systolic hypertension in 1993 (odds ratio (OR) 1.3; 95% confidence interval (CI) (0.32, 5.1)). However, vitamin D insufficiency was associated with increased risk of systolic hypertension in 2007 (OR 3.0; 95% CI (1.01, 8.7)) after adjusting for age, body fat percentage, antihypertensive medication use, and smoking. Baseline vitamin D status was not associated with rate of BP change over the 14-year period. CONCLUSIONS: Consistent with previous animal and human studies, we found a single-time measure of vitamin D among young adult women was associated with systolic hypertension 14 years later. These prospective results suggest the need for further study of the role vitamin D insufficiency in early adulthood as a risk factor in subsequent hypertension among women.

Physical functioning among mid-life women: associations with trajectory of depressive symptoms.

During midlife, physical functioning limitations emerge and depressive symptoms are highly prevalent. We examined the relationship between physical functioning and depressive symptoms in the Michigan Study of Women's Health Across the Nation (SWAN) cohort of mid-life women (n = 377). Seven performance-based physical functioning measures quantifying strength, balance, coordination, flexibility and range of motion and perceived physical functioning, assessed with the SF-36 physical functioning sub-score, were included. The Center for Epidemiological Studies Depression Scale (CES-D) identified concurrent depressive symptom trajectory from 2000/2001 through 2005/2006 and history of depressive symptoms from 1996/1997 through 1999/1900. Longitudinal mixed-effects regression modeling was used to evaluate relationships. Median age of participants was 50 years. As age increased, higher CES-D scores were associated with performance-based functions including slower timed walk sit-to-stand, and stair climb after adjusting for five-year history of depressive symptoms and relevant covariates. As age increased, those with higher CES-D scores were more likely to have perceived limitations in physical functioning, though the association was weak. History of depressive symptoms was not significant in any model. These findings suggest that higher concurrent depressive symptoms are modestly associated with slower movement and a perception of poorer functioning. In contrast, history of depressive symptoms played little or no role in current physical functioning of mid-life women. When evaluating physical function, women's current mental health status should be considered.

Relating smoking, obesity, insulin resistance, and ovarian biomarker changes to the final menstrual period.

To determine if smoking, obesity, and insulin resistance mediated age at final menstrual period (FMP), we examined anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH) as biomarkers of changing follicle status and ovarian aging. We performed a longitudinal data analysis from a cohort of premenopausal women followed to their FMP. Our results found that smokers had an earlier age at FMP (P < 0.003) and a more rapid decline in their AMH slope relative to age at FMP (P < 0.002). Smokers had a lower baseline inhibin B level relative to age at the FMP than nonsmokers (P = 0.002). Increasing insulin resistance was associated with a shorter time to FMP (P < 0.003) and associations of obesity and time to FMP were observed (P = 0.004, in model with FSH). Change in ovarian biomarkers did not mediate the time to FMP. We found that smoking was associated with age at FMP and modified associations of AMH and inhibin B with age at FMP. Insulin resistance was associated with shorter time to FMP independent of the biomarkers. Interventions targeting smoking and insulin resistance could curtail the undue advancement of reproductive aging.

American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer.

PURPOSE: To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. METHODS: A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. RESULTS: An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. CONCLUSION: The Update Committee recommends that postmenopausal women with hormone receptor-positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy.

The evolving role of obesity in knee osteoarthritis.

PURPOSE OF REVIEW: The frequency of knee osteoarthritis continues to accelerate, likely because of the increasing proliferation of obesity, particularly in men and women 40-60 years of age at the leading edge of the 'baby boom' demographic expansion. The increasing pervasiveness of obesity and the growing appreciation of obesity's accompanying metabolic/inflammatory activities suggest rethinking the knee osteoarthritis paradigm. RECENT FINDINGS: Whereas once knee osteoarthritis was considered a 'wear-and-tear' condition, it is now recognized that knee osteoarthritis exists in the highly metabolic and inflammatory environments of adiposity. Cytokines associated with adipose tissue, including leptin, adiponectin, and resistin, may influence osteoarthritis though direct joint degradation or control of local inflammatory processes. Further, pound-for-pound, not all obesity is equivalent for the development of knee osteoarthritis; development appears to be strongly related to the co-existence of disordered glucose and lipid metabolism. Additionally, obesity loads may be detected by mechanoreceptors on chondrocyte surfaces triggering intracellular signaling cascades of cytokines, growth factors, and metalloproteinases. SUMMARY: This review summarizes recent literature about obesity, knee osteoarthritis and joint pain. Consideration of adipocytokines, metabolic factors, and mechanical loading-metabolic factor interactions will help to broaden the thinking about targets for both prevention and intervention for knee osteoarthritis.

High-molecular-weight adiponectin and incident ischemic stroke in postmenopausal women: a Women's Health Initiative Study.

BACKGROUND AND PURPOSE: Although low levels of adiponectin are associated with coronary heart disease and cardiovascular disease risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke. METHODS: We examined the relationship between baseline high-molecular-weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case-control study nested within the Women's Health Initiative Observational Study. Included were 855 incident ischemic stroke cases and 855 control subjects matched for age, race-ethnicity, date of entry into the cohort, and follow-up time. ORs of incident ischemic stroke associated with baseline HMW adiponectin levels were calculated using conditional logistic regression modeling adjusting for body mass index, type 2 diabetes, hypertension, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, physical activity, C-reactive protein, and aspirin use. RESULTS: Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher body mass index, waist circumference, glucose, and insulin levels and lower high-density lipoprotein cholesterol levels. The distribution of incident stroke cases by HMW adiponectin quartiles was 49.9%, 50.5%, 50.7%, and 48.9%, respectively (P=0.96). Multivariable-adjusted ORs of stroke associated with the top 3 quartiles of HMW adiponectin versus the first quartile were 0.99 (95% CI, 0.71 to 1.37), 1.37 (0.99 to 1.91), and 1.25 (0.88 to 1.79), respectively (P trend=0.14). CONCLUSIONS: Despite moderate associations between HMW adiponectin and cardiovascular disease risk factors, we found no evidence of an association between HMW adiponectin levels and incident ischemic stroke in these postmenopausal women.

Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause.

BACKGROUND AND OBJECTIVE: The objective of the study was to describe bone loss rates across the transmenopause related to FSH staging and the final menstrual period (FMP). DESIGN AND SETTING: This was a population-based cohort of 629 women (baseline age 24-44 yr) with annual data points over 15 yr. MEASUREMENTS: Measures were bone mineral density (BMD), FSH to define four FSH stages, and menstrual bleeding cessation to define the FMP. Bone loss rates were reported by obesity status. RESULTS: Annualized rates of lumbar spine bone loss began in FSH stage 3, which occurs approximately 2 yr prior to the FMP (1.67%/yr); bone loss continued into FSH stage 4 (1.21%/yr). Mean spine BMD in FSH stage 4 was 6.4% less than spine BMD value in FSH stage 1. Annualized rates of femoral neck (FN) bone loss began in FSH stage 3 (0.55%/yr) and continued into FSH stage 4 (0.72%/yr). The FN difference between mean values in FSH stage 1 and FSH stage 4 was 5%. Annualized rates of spine bone loss in the 2 yr prior to the FMP were 1.7%/yr, 3.3%/yr in the 2 yr after the FMP, and 1.1%/yr in the 2- to 7-yr period after the FMP. Nonobese women had lower BMD levels and greater bone loss rates. CONCLUSIONS: Spine and FN bone loss accelerates in FSH stage 3. Bone loss also began to accelerate 2 yr before the FMP with the greatest loss occurring in the 2 yr after the FMP. Bone loss rates in both spine and FN BMD were greater in nonobese women than obese women.