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.

Objective: Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors.Methods: In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: <= 1 of the four components; at-risk phenotype: >= 2 components or diabetes).Results: Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77).Conclusions: Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

Premenopausal reproductive hormonal characteristics are a primary influence on the acquisition and maintenance of peak bone mass such that events associated with the reproductive lifespan and procreation have profound effects on subsequent risk for osteoporosis and fractures. A longer duration of menstruation, either from earlier menarche or later menopause, and the use of estrogen-containing hormonal contraception appear to increase bone mineral density and may reduce fracture risk. Pregnancy and lactation increase bone turnover and decrease bone density, but the effect is subsequently reversed with recovery of density and possible reduction in long-term fracture risk. Conditions that induce amenorrhea or early menopause, and nonestrogen-containing hormonal contraceptives such as depot medroxyprogesterone acetate, are associated with decreased bone density and possibly increased fracture risk. Mechanisms mediating these known or suggested effects are incompletely characterized.

Objectives: Circulating endogenous hormone levels may affect the susceptibility of female athletes to anterior cruciate ligament (ACL) injuries. This study tested the hypotheses that (1) the estradiol-progesterone profile of high school females participating in training, conditioning, and competition differs significantly from that of physically inactive age-matched females over a 3-month period; and (2) athletic training/conditioning alters body composition (muscle, bone), leading to an increasingly greater lean body mass to fat mass ratio and accompanying hormone change. Methods: One-hundred six women, ages 14-18 years, were prospectively monitored over a 13-week period with weekly physical activity assessments and 15 urine samples for estrogen (E1c), luteinizing hormone (LH) creatine (Cr), and progesterone (PdG) levels. Each underwent lower extremity strength tests and body composition measurements, both prior to and after the study period. Results: Seventy-four of the 98 women who completed the study classified themselves as athletes. Body-mass index, weight and fat measures remained stable over the course of the study. Seventeen women had no complete menstrual cycle during the observation period. Mean levels of log(E1c/Cr) were slightly higher in nonathletes in cycles <24 or >35 days. Mean log(PdG/Cr) levels in nonathletes were lower in the first half and higher in the second half of the cycle, but the differences were not statistically significant. Conclusion: In this cohort of high school females, the level of athletic or physical activity did not influence urine concentrations of estrogen, progesterone or luteinizing hormones. A significant number (17%) of women in both groups were amenorrheic during the 3-month study period.

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.

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/m(2) and smallest in women with BMI >30 kg/m(2). 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.

Background: It has been suggested that progestins may have an inflammatory component and/or increase in prostaglandin synthesis. Thus, extended progestin use may be associated with higher risk of periodontal diseases. This study investigates the association between depot medroxyprogesterone acetate (DMPA) injectable contraception and the prevalence of periodontal diseases among US premenopausal females.Methods: Data for this cross‐sectional analysis comes from the 1999 to 2004 National Health and Nutrition Examination Surveys. This analysis includes 4,460 US females (15 to 44 years of age) with complete DMPA usage and periodontal status data.Results: Current and past DMPA use was 4.1% and 12.0%, respectively. The prevalence of gingivitis was 53.9% for females who reported having used DMPA compared with 46.1% for DMPA never‐users. Females taking DMPA were more likely to be young, single, and non‐white, have a history of smoking, have lower levels of education and income, and have ≥1 live births and were less likely to visit the dentist. Using logistic regression, DMPA use was associated with an increased risk of gingivitis (odds ratio [OR] =1.7; 95% confidence interval [CI] = 1.09 to 1.67) and periodontitis (DMPA, OR = 1.49; 95% CI = 1.01 to 2.22) after adjusting for age, race, education, poverty income ratio, dental care use, and smoking status. A significant interaction between smoking status and DMPA use was also found (P = 0.029).Conclusions: This study suggests that DMPA use may be associated with periodontal diseases. Additional investigation is warranted as a result of the disproportionate usage of DMPA among low‐income populations who are at an increased risk for poor dental health.

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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Objective The aim of this study was to determine whether postmenopause status is associated with self-reported limitations in physical function. Methods The Study of Women's Health Across the Nation is a multisite, multiethnic, longitudinal study of midlife women. Women aged 45 to 57 years (N = 2,566) completed the physical function scale of the Medical Outcomes Study Short-Form 36 on visit 4 (2000-2001). Scores created a three-category variable of physical function limitations: none (86-100), moderate (51-85), and substantial (0-50). In the Study of Women's Health Across the Nation, menopause status is a five-category list variable based on menstrual bleeding patterns and gynecological surgery. Premenopausal and perimenopausal women using hormones (n = 284) or missing physical function scores (n = 46) were excluded. Multinomial logistic regression was used to relate physical function and menopause status after adjustment for age, ethnicity, site, education, body mass index (BMI), and self-reported diabetes, hypertension, arthritis, depressive symptoms, smoking, and hormone use among postmenopausal women. Results Of 2,236 women, 8% were premenopausal, 51% were early perimenopausal, 12% were late perimenopausal, 24% were naturally postmenopausal, and 5% were surgically postmenopausal. In the full model, substantial limitations in physical function were higher in postmenopausal women, whether naturally postmenopausal (odds ratio, 3.82; 95% CI, 1.46-10.0) or surgically postmenopausal (odds ratio, 3.54; 95% CI, 1.15-10.84), than in premenopausal women. These associations were attenuated by higher BMI and depressive symptoms but remained significant. Moderate limitations in physical function were not significantly related to menopause status. Conclusions Women experiencing surgical or naturally occurring postmenopause report greater limitations in physical function compared with premenopausal women, independent of age and only partly explained by higher BMI and depressive symptoms. This suggests that physiological changes in menopause could contribute directly to limitations in physical function.

Study Objectives: We evaluated associations among subjective and objective measures of sleep and the metabolic syndrome in a multi-ethnic sample of midlife women.Design: Cross-sectional study.Setting: Participants' homes.Participants: Caucasian (n = 158), African American (n = 125), and Chinese women (n = 57); mean age = 51 years. Age range = 46-57 years.Interventions: None.Measurements and Results: Metabolic syndrome was measured in the clinic and sleep quality was assessed by self-report. Indices of sleep duration, continuity/fragmentation, depth, and sleep disordered breathing were assessed by in-home polysomnography (PSG). Covariates included sociodemographics, menopausal status, use of medications that affect sleep, and self-reported health complaints and health behaviors known to influence metabolic syndrome risk. Logistic regression was used to test the hypothesis that the metabolic syndrome would be associated with increased subjective sleep complaints and PSG-assessed sleep disturbances. In univariate analyses, the metabolic syndrome was associated with decreased sleep duration and efficiency and increased NREM beta power and apnea-hypopnea index (AHI). After covariate adjustment, sleep efficiency (odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.08-3.93), NREM beta power (OR = 2.09, 95% CI: 1.09-3.98), and AHI (OR = 1.86, 95% CI: 1.40-2.48) remained significantly associated with the metabolic syndrome (odds ratio values are expressed in standard deviation units). These relationships did not differ by race.Conclusions: Objective indices of sleep continuity, depth, and sleep disordered breathing are significant correlates of the metabolic syndrome in midlife women, independent of race, menopausal status and other factors that might otherwise account for these relationships.

CONTEXT:Cognitive decline is prevalent in aging populations, and cognitive complaints are common during menopause. However, the extent of hormonal influence is unclear, particularly when considered independent of the aging process.OBJECTIVE:We sought to determine differences in cognitive function attributable to menopause, hypothesizing that differences would be associated with reproductive rather than chronological age.DESIGN AND SETTING:In this cross-sectional study at a university hospital, we combined neuropsychological measures with functional magnetic resonance imaging to comprehensively assess cognitive function.PARTICIPANTS:Sixty-seven menopausal women, aged 42-61 yr, recruited from a population-based menopause study, grouped into menopause stages based on hormonal and cycle criteria (premenopause, perimenopause, and postmenopause), participated in the study.MAIN OUTCOME MEASURES:Neuropsychological and functional magnetic resonance imaging measures of verbal, visual, and executive cognitive function.RESULTS:We found age-independent menopause effects on verbal function. Menopause groups differed in phonemic verbal fluency (F = 3.58, P < 0.019) and regional brain activation (inferior frontal cortex: corrected P < 0.000 right, P < 0.036 left; left prefrontal cortex: P < 0.012); left temporal pole: P < 0.001). Verbal measures correlated with estradiol and FSH (phonemic fluency: R = 0.249, P < 0.047 estradiol, R = -0.275, P < 0.029 FSH; semantic fluency: R = 0.318, P < 0.011 estradiol, R = -0.321, P < 0.010 FSH; right inferior frontal cortex: R = 0.364, P < 0.008 FSH; left inferior frontal cortex: R = -0.431, P < 0.001 estradiol, left prefrontal cortex: R = 0.279, P < 0.045 FSH; left temporal pole: R = -0.310, P < 0.024 estradiol, R = 0.451, P < 0.001 FSH; left parahippocampal gyrus: R = -0.278, P < 0.044 estradiol; left parietal cortex: R = -0.326, P < 0.017 estradiol).CONCLUSIONS:Results suggest that verbal fluency mechanisms are vulnerable during the menopausal transition. Targeted intervention may preserve function of this critical cognitive domain.

OBJECTIVE:To examine the relationship of knee osteoarthritis (OA) with cardiovascular and metabolic risk factors by obesity status and gender.METHODS:Data from 1,066 National Health and Nutrition Examination Survey III participants (≥60 years of age) was used to examine relationships of osteophytes-defined radiographic knee OA and cardiovascular and metabolic measures. Analyses were considered among obese [body mass index (BMI)≥30 kg/m(2)] and non-obese (BMI<30 kg/m(2)) men and women.RESULTS:The prevalence of osteophytes-defined radiographic knee OA was 34%. Leptin levels and homeostatic model assessment-insulin resistance (HOMA-IR), a proxy measure of insulin resistance, were significantly associated with knee OA; those with knee OA had 35% higher HOMA-IR values and 52% higher leptin levels compared to those without knee OA. The magnitude of the association between HOMA-IR and knee OA was strongest among men, regardless of obesity status; odds ratios (ORs) for HOMA-IR were 34% greater among non-obese men (OR=1.18) vs obese women (OR=0.88). Among obese women, a 5-μg/L higher leptin was associated with nearly 30% higher odds of having knee OA (OR=1.28). Among men, ORs for the association of leptin and knee OA were in the opposite direction.CONCLUSIONS:Cardiometabolic dysfunction is related to osteophytes-defined radiographic knee OA prevalence and persists within subgroups defined by obesity status and gender. A sex dimorphism in the direction and magnitude of cardiometabolic risk factors with respect to knee OA was described including HOMA-IR being associated with OA prevalence among men while leptin levels were most important among women.

STUDY OBJECTIVE:To quantify sources of night-to-night variability. METHODS:This project was conducted in 285 middle-aged African American, Caucasian, and Chinese women from the Study of Women's Health Across the Nation (SWAN) Sleep Study living in Chicago, the Detroit area, Oakland, and Pittsburgh. The study used 3 repeated nights of in-home polysomnography (PSG) measures. Night 1 data included assessment of sleep staging, sleep apnea, and periodic limb movements, while Nights 2 and 3 focused on sleep staging. RESULTS:Mean total sleep time (TST) increased substantially from 365 minutes on Night 1 to 391 minutes and 380 minutes, respectively, on Nights 2 and 3. Mean percent sleep efficiency (SE%) for the 3 nights were 83%, 85%, and 85%, respectively. Night 1 sleep values were significantly different than Nights 2 and 3 measures except for S2 (%), S1 (min), and Delta (S3+4)%. Nights 2 and 3 differences in variability were negligible. Obesity, past smoking, and financial strain measures were associated with greater Night 1 vs. Night 2 or Night 3 differences. We concluded that there was significant Night 1 vs. Nights 2 and 3 variability and, though relatively modest, it was sufficient to bias estimates of association. Additionally, personal characteristics including smoking, obesity, and financial strain increased night-to-night variability. CONCLUSIONS:This reports adds new information about between and within person sources of variation with in-home PSG and identifies elements that are essential in the design and planning of future sleep studies of multi-ethnic groups in social and physiological transition states such as the menopause.

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.

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.

Objectives: No longitudinal studies have examined how iron measures change over menopause. Our objectives were to examine iron measures in individual women at premenopause and at postmenopause and, secondarily, to determine if any changes contributed to insulin resistance. Methods: In a subset of participants (n=70) in a longitudinal study of menopause, we measured ferritin, transferrin, and soluble transferrin receptor (sTfR) once in the premenopause and once in the postmenopause. We also examined associations between menopausal status and change in iron markers after adjustment for age at menopause, race/ethnicity, and waist circumference. In linear regression models, we examined associations between premenopause iron measures and changes in iron markers over menopause with homeostasis model assessment of insulin resistance (HOMA-IR) changes over menopause, before and after adjustment for age at menopause, race/ethnicity, changes in waist circumference, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) levels. Results: Women had lower ferritin (p<0.01), higher sTfR:ferritin levels (p<0.01), lower HOMA-IR (p=0.022), and lower glucose (p=0.05) in premenopause compared to postmenopause. After adjustment, lower premenopausal iron levels (sTfR:ferritin levels β=11.0, 95% confidence interval [CI] 0.017-22.0) and larger increases in iron over menopause (changes in sTfR:ferritin β=13.6, 95% CI 0.93-26.3) were associated with larger increases in HOMA-IR. Conclusions: From premenopause to postmenopause, women on average have increases in measures of iron stores. Women who had the greatest changes in iron over menopause (lower measures of premenopausal iron and greater increases in iron measures over the menopause) had the strongest associations between changes in iron and changes in insulin resistance.

Motivated by the study of the longitudinal development and progression of knee osteoarthritis (OA) over a 15-year period, this study developed non-parametric mixed-effect models for ordinal outcomes. A stochastic mixed-effect model was used to evaluate the similarity of trajectories associated with increasing disease severity of OA in both knees. Then, a non-parametric mixed-effects model, based on cubic B-splnes, was developed to characterize the unknown nonlinear trend of logits as a function of time1-order. A Markov Transition Model was developed to characterize the transitions among multi-states of knee OA. This newly developed approach allows more flexible functional dependence of the ordinal outcome, levels of increasing knee OA severity, on the covariates.

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.

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 (beta: -3.40; 95% CI: -4.29, -2.52; P<.001) and HMW adiponectin (beta: -0.53; 95% CI: -0.64, -0.43; P<.001) levels, higher leptin levels (beta. 3.26; 95% CI: 1.36, 5.16; P<.001) and lower sOB-R levels (beta: -0.07; 95% CI: -0.11, -0.03; P<.001). Compared to Caucasian women, both Chinese and Japanese women had lower total (Chinese: beta: -5.50; 95% CI: -7.07, -3.93; P<.001; Japanese: beta: -5.48; 95% CI: -6.95, -4.02; P<.001) and HMW adiponectin (Chinese: beta: -0.57; 95% CI: -0.75, -0.38; P<.001; Japanese: beta: -0.61; 95% CI: -0.78, -0.44; P<.001) levels and lower sOB-R levels (Chinese: beta: -0.13; 95% CI: -0.20, -0.06; P<.001; Japanese: beta: -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. (C) 2012 Elsevier Inc. All rights reserved.

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.