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ABSTRACT: Context:The associations of serum sex steroid and FSH levels with change of bone mineral density (BMD) across the complete menopausal transition are incompletely understood.Objective:The objective of the study was to examine the associations of annual serum levels of FSH, estradiol (E(2)), T, and SHBG with the rates of bone loss in 3 phases: pretransmenopausal [baseline to 1 year before the final menstrual period (FMP)], transmenopausal (1 year before to 2 years after the FMP), later postmenopausal (≥ 2 years after the FMP).Design:The design of the study was a repeated-measures, mixed-effects regression.Setting:This was a community-based observational study, with a 10-year follow-up.Participants:A total of 720 participants of the Study of Women's Health Across the Nation Bone Study participated in the study.Outcome Measures:Annualized lumbar spine (LS) and femoral neck (FN) BMD decline was measured.Results:The mean annual change in BMD was slowest in pretransmenopause (0.27%/year in FN) and fastest in transmenopause (2.16%/year in LS). In the pretransmenopausal phase, for every doubling of FSH level, LS BMD change was faster by -0.32%/year (P < .0001). In the transmenopausal phase, for every doubling of FSH level, LS BMD change was -0.35%/year faster (P < .0001); for every doubling of SHBG level, LS BMD change was -0.36%/year faster (P < .0001). In the later postmenopausal phase, for each doubling of the E(2) level, the LS BMD change was slower by +0.26%/year (P = .049); for each SHBG doubling, the LS BMD change was 0.21%/year slower (P = .048). The FN associations were weaker and inconsistent.Conclusions:Higher E(2) levels and lower FSH levels were associated with lower rates of LS bone loss in some but not all menopausal transition phases.
The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
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ABSTRACT: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined.
The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories.
The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition.
Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits.
Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study.
Annual serum E2 and FSH levels anchored to final menstrual period were measured.
Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories.
E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition.
The Journal of clinical endocrinology and metabolism 06/2012; 97(8):2872-80. · 6.50 Impact Factor
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ABSTRACT: To quantify sources of night-to-night variability.
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.
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.
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.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2012; 8(1):87-96. · 3.23 Impact Factor
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ABSTRACT: 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).
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.
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.
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.
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.
The Journal of clinical endocrinology and metabolism 03/2011; 96(3):746-54. · 6.50 Impact Factor
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ABSTRACT: Examine associations of vasomotor and mood symptoms with visually scored and computer-generated measures of EEG sleep.
Cross-sectional analysis.
Community-based in-home polysomnography (PSG).
343 African American, Caucasian, and Chinese women; ages 48-58 years; pre-, peri- or post-menopausal; participating in the Study of Women's Health Across the Nation Sleep Study (SWAN Sleep Study).
None.
Measures included PSG-assessed sleep duration, continuity, and architecture, delta sleep ratio (DSR) computed from automated counts of delta wave activity, daily diary-assessed vasomotor symptoms (VMS), questionnaires to collect mood (depression, anxiety) symptoms, medication, and lifestyle information, and menopausal status using bleeding criteria. Sleep outcomes were modeled using linear regression. Nocturnal VMS were associated with longer sleep time. Higher anxiety symptom scores were associated with longer sleep latency and lower sleep efficiency, but only in women reporting nocturnal VMS. Contrary to expectations, VMS and mood symptoms were unrelated to either DSR or REM latency.
Vasomotor symptoms moderated associations of anxiety with EEG sleep measures of sleep latency and sleep efficiency and was associated with longer sleep duration in this multi-ethnic sample of midlife women.
Sleep 01/2011; 34(9):1221-32. · 5.05 Impact Factor
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ABSTRACT: Inflammation and pro-coagulation biomarkers may be a link between sleep characteristics and risk for cardiometabolic disorders. We tested the hypothesis that worse sleep characteristics would be associated with C-reactive protein (CRP), fibrinogen, factor VIIc, and plasminogen activator inhibitor (PAI)-1 in a multi-ethnic subsample of mid-life women enrolled in the Study of Women's Health across the Nation.
Cross-sectional.
African American, Chinese, and Caucasian women (N=340) participated in 3 days of in-home polysomnographic (PSG) monitoring and had measures of inflammation and coagulation. Regression analyses revealed that each of the biomarkers were associated with indicators of sleep disordered breathing after adjusting for age, duration between sleep study and blood draw, site, menopausal status, ethnicity, residualized body mass index, smoking status, and medications that affect sleep or biomarkers. Among African American women, those who had higher levels of CRP had shorter PSG-sleep duration and those who had higher levels of fibrinogen had less efficient sleep in multivariate models.
These results suggest that inflammation and pro-coagulation processes may be an important pathway connecting sleep disordered breathing and cardiometabolic disorders in women of these ethnic groups and that inflammation may be a particularly important pathway in African Americans.
Sleep 12/2010; 33(12):1649-55. · 5.05 Impact Factor
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ABSTRACT: Obesity and genetic variation in aromatase and type 1 17-β hydroxysteroid dehydrogenase (HSD) could influence the E2 trajectory of decline during the menopause transition.
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-βHSD single-nucleotide polymorphisms (SNPs) and obesity.
(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-βHSD 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-β 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.
Clinical Endocrinology 12/2010; 74(5):618-23. · 3.17 Impact Factor
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ABSTRACT: 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.
Social Science [?] Medicine 10/2010; 71(7):1259-67. · 2.70 Impact Factor
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Fertility and sterility 07/2010; · 3.97 Impact Factor
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ABSTRACT: The objective of the study was to describe bone loss rates across the transmenopause related to FSH staging and the final menstrual period (FMP).
This was a population-based cohort of 629 women (baseline age 24-44 yr) with annual data points over 15 yr.
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.
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.
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.
The Journal of clinical endocrinology and metabolism 03/2010; 95(5):2155-62. · 6.50 Impact Factor
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ABSTRACT: To describe anti-Müllerian hormone (AMH) variation across normal menstrual cycles.
Cohort study.
Academic environment.
Twenty regularly menstruating women.
Serum AMH and inhibin B assayed daily during one normal menstrual cycle.
Intracycle variability of AMH and inhibin B.
Data were classified into quartiles of AMH area-under-the-curve (AUCs). Mean AMH AUC was 15.7 ng/mL for quartile 1 versus 43.5, 80.9 and 144.9 ng/mL for quartiles 2, 3, and 4. Mean AMH levels (ng/mL) were 0.67, 1.71, 3.02, and 5.33, respectively. There was no variation in quartile 1 AMH rate of change from stochastic modeling, but in quartiles 2 to 4, there were increased rates of change in days 2 to 7. Women in quartile 1 had the lowest mean inhibin B (24.2 pg/mL vs. 44.3, 43.2, and 42.2 pg/mL), and had shorter menstrual cycles (24.6 days) than women in quartiles 3 and 4 (28.2 and 28.4 days).
There were two menstrual cycle patterns of AMH. The "aging ovary" pattern included low AMH levels with little variation, lower inhibin B, and shorter cycle lengths. The "younger ovary" pattern included higher AMH levels with significant variation days 2 to 7, suggesting that for women with AMH>1 ng/mL, the interpretation of AMH levels is contingent upon the day of the menstrual cycle on which the specimen is obtained.
Fertility and sterility 12/2009; 94(4):1482-6. · 3.97 Impact Factor
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ABSTRACT: To relate reproductive hormones (and the preceding 7-year rates of their change) to objectively and subjectively assessed sleep measures, independent of age, vasomotor symptom frequency, depressive symptoms, and body size.
A cross-sectional sleep substudy nested in the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the menopausal transition.
Community-based.
365 Caucasian, African American, and Chinese women.
Sleep duration, continuity, and architecture were measured during two nights of in-home polysomnography (PSG) studies. Participants completed the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, sleep diaries for medication, vasomotor symptoms, lifestyle information and questionnaires for depressive symptoms. Blood collected annually in the years prior to sleep study was assayed for follicle stimulating hormone (FSH), estradiol (E2), and total testosterone (T). More rapid rate of FSH change was significantly associated with higher delta sleep percent, longer total sleep time (TST), but less favorable self-reported sleep quality (PSQI). Baseline E2 was modestly and negatively associated with sleep quality. Women in the lowest total testosterone quartile at baseline had more wake time after sleep onset (WASO) than women in the highest quartile. Lower E2/T ratio, an index reflecting the increasing androgenic environment with the menopause transition, was associated with less WASO.
More rapid rate of FSH change was associated with longer sleep duration but poor sleep quality. Women with higher T or who were closer to the completion of the transition process (as indexed by a lower E2/T) had less sleep discontinuity (less WASO).
Sleep 11/2008; 31(10):1339-49. · 5.05 Impact Factor
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ABSTRACT: The aim was to characterize rates of change in serum estradiol (E2) levels across the menopausal transition and into early postmenopause.
We studied the Michigan Bone Health and Metabolism Study cohort of 629 women with median age of 38 yr (interquartile range, 7) at the 1992-1993 baseline with annual assessment of E2 levels over the subsequent 15-yr period. DESIGN/MAIN OUTCOME MEASURES: The purpose was to describe patterns of acceleration/deceleration in (log)E2 rates of change before and after the final menstrual period (FMP) using nonparametric and piecewise regression modeling.
Between -10 to -2 yr to the FMP, mean fitted serum E2 population values were relatively stable. The 95% confidence bands around the slight increase in E2 rate of change 5 yr prior to the FMP included the value of no change. The fitted population mean E2 value declined 67% from 64.5 pg/ml (se = 3.6) to 21 pg/ml (se = 1.2) in the 4 yr between -2 < FMP < +2. A second significant mean E2 rate of change was identified from 6-8 yr after FMP. Fitted population mean E2 values declined 18% from 18.1 pg/ml (se = 1.3) at FMP = 6 to 14.8 pg/ml (se = 1.3) at FMP = 8. In nonobese women, the mean E2 percent decline was 42% from FMP = 6 to FMP = 8, whereas in obese women, the mean E2 percent decline over this time was 31%.
Population mean serum E2 levels were sustained until approximately 2 yr prior to the FMP. In the ensuing 4-yr period, E2 levels declined 67%. A secondary E2 decline, commencing about 6 yr after the FMP, was observed in nonobese but not obese women.
Journal of Clinical Endocrinology & Metabolism 10/2008; 93(10):3847-52. · 6.50 Impact Factor
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ABSTRACT: The objective of the study was to identify menopause transition stages using acceleration or deceleration patterns of FSH rates of change from the late reproductive years to postmenopause.
Participants were the Michigan Bone Health and Metabolism Study cohort of 629 women, aged 24-44 yr (in 1992/3), with 5757 annual FSH data points over a 14-yr period. DESIGN/MAIN OUTCOME MEASURES: The study was designed to relate acceleration/deceleration patterns in FSH rate of change to time to final menstrual period (FMP) and chronological age using nonparametric and piecewise regression modeling.
Four major FSH stages, based on rate of FSH change patterns, were identifiable in relation to the FMP. In FSH stage 1, the rate of FSH change increased modestly up to -7 yr prior to the FMP; in FSH stage 2 (-7 to -2 yr prior to FMP), there was a major acceleration in FSH rate of change. FSH stage 3 had an acute increase in FSH rate of change (-2 to +1 yr around the FMP), with average FSH level of 34 mIU/ml. The fourth, or plateau, FSH stage began at 1 yr after FMP when the average FSH level was 54 mIU/ml. During the yr 28-60, there were eight age-specific epochs defined by significant changes of FSH trajectory accelerations or decelerations and rate of change.
Four menopause transition stages bounding the FMP and eight epochs in chronological aging from age 28 to 60 yr were defined by changes of FSH trajectory accelerations/decelerations and rates of change. This timing information, combined with knowledge of FSH levels and menstrual cycle characteristics, can help discern the likely status of women with respect to their reproductive viability and menopause transition stage.
Journal of Clinical Endocrinology & Metabolism 10/2008; 93(10):3958-64. · 6.50 Impact Factor
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ABSTRACT: Understanding the menopause association with body weight is important because excess weight increases risk for stroke, incident cardiovascular disease, cardiovascular mortality, and all-cause mortality among the middle-aged.
The objective of this study was to examine chronological age and ovarian age and consider how these could influence body size and composition in midlife women.
The Study of Women's Health Across the Nation is a longitudinal, community-based study. This report uses data from the Michigan Study of Women's Health Across the Nation site.
Participants were 543 premenopausal or early perimenopausal African-American and Caucasian women aged 42-52 yr at baseline examination.
Waist circumference, fat mass and skeletal muscle mass, from bioelectrical impedance, were assessed in seven annual serial measures. Annual FSH values were assayed by ELISA. The final menstrual period was defined retrospectively after 12 months of amenorrhea.
There was an absolute cumulative 6-yr increase in fat mass of 3.4 kg and a 6-yr decrease in skeletal muscle mass of approximately 0.23 kg. There was an absolute cumulative 6-yr increase of approximately 5.7 cm in waist circumference. The (log)FSH change was positively correlated with (log)(fat mass) change. Waist circumference increased over the time period, but 1 yr after final menstrual period, the rate of increase slowed. Fat mass continued to increase with no change in rate.
Both time (chronological aging) and ovarian aging contributed to substantial changes in body composition (fat and skeletal muscle mass) and waist circumference. These changes have important ramifications for establishing a metabolic environment that can be healthy or unhealthy.
Journal of Clinical Endocrinology & Metabolism 04/2007; 92(3):895-901. · 6.50 Impact Factor
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ABSTRACT: We investigated whether subclinical inflammatory markers high-sensitivity C-reactive protein (CRP) and fibrinogen are related to measures of physical functioning in mid-life women.Our sample included 543 participants in the Michigan site of Study of Women’s Health Across the Nation (SWAN). Predictors included CRP from serum and fibrinogen from plasma. Performance-based outcomes included measures of gait, hand grip strength, flexibility, stair climb, 40-foot walk, and chair rise. Perception of physical functioning was assessed with the Medical Outcomes Study Short-Form 36 questionnaire. Regression analyses adjusted for relevant covariates. Cross-sectional associations were identified between higher CRP and more time spent in double support (with both feet on the floor while walking), shorter forward reach, slower 2-lb lift, and slower stair climb. Higher CRP and fibrinogen were associated with worse perceived functioning in cross-sectional analyses. Predictive associations across time were found between higher CRP and increased time spent in double support, diminishing forward reach distance and grip strength and worse perceived physical functioning. Predictive associations across time were also found between higher fibrinogen and greater time spent in double support, slower stair climb and worse perceived physical functioning. Our results suggest that inflammatory processes are associated with poor physical functioning in mid-life women.
Experimental Gerontology.
