140 research outputs found
Urinary Nâ Telopeptide as Predictor of Onset of Menopauseâ Related Bone Loss in Preâ and Perimenopausal Women
The menopause transition (MT) is a period of rapid bone loss and has been proposed to be a timeâ limited window for early intervention to prevent permanent microarchitectural damage and reduce the risk of subsequent fracture. To intervene early, however, we first need to be able to determine whether menopauseâ related bone loss is about to begin, in advance of substantial bone loss. The objective of this study was, therefore, to assess whether urinary Nâ telopeptide (Uâ NTX) in preâ or early perimenopause can predict the onset of menopauseâ related bone loss. Repeated Uâ NTX measurements were obtained during preâ and early perimenopause in 1243 participants from the Study of Womenâs Health Across the Nation (SWAN). We examined the ability of Uâ NTX to predict the onset of significant menopauseâ related bone loss (categorical outcome, yes versus no) at the lumbar spine (LS) and femoral neck (FN), defined as annualized bone mineral density (BMD) decline at a rate faster than the smallest detectable change in BMD over the 3 to 4 years from the time of Uâ NTX measurement. Adjusting for age, race/ethnicity, body mass index, urine collection time, starting BMD, and study site in multivariable, modified Poisson regression, every standard deviation increment in Uâ NTX, measured at baseline in early perimenopausal women, was associated with an 18% and 22% greater risk of significant bone loss at the LS (pâ =â 0.003) and FN (pâ =â 0.003), respectively. The area under the receiverâ operator curve for predicting LS and FN bone loss was 0.72 and 0.72, respectively. In mixedâ effects analysis of all repeated measures of early perimenopausal Uâ NTX over followâ up, Uâ NTX predicted onset of bone loss at the LS (pâ =â 0.002) but not at the FN. We conclude that Uâ NTX can be used early in the MT to determine if a woman is about to experience significant LS bone loss before there has been substantial skeletal deterioration. ĂŠ 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/1/jbm410116_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149249/2/jbm410116.pd
Estradiol and Follicleâ Stimulating Hormone as Predictors of Onset of Menopause Transitionâ Related Bone Loss in Preâ and Perimenopausal Women
The menopause transition (MT) may be an opportunity for early intervention to prevent rapid bone loss. To intervene early, we need to be able to prospectively identify preâ and perimenopausal women who are beginning to lose bone. This study examined whether estradiol (E2), or follicleâ stimulating hormone (FSH), measured in preâ and perimenopausal women, can predict significant bone loss by the next year. Bone loss was considered significant if bone mineral density (BMD) decline at the lumbar spine (LS) or femoral neck (FN) from a preâ or early perimenopausal baseline to 1â year after the E2 or FSH measurement was greater than the least detectable change. We used data from 1559 participants in the Study of Womenâs Health Across the Nation and tested E2 and FSH as separate predictors using repeated measures modified Poisson regression. Adjusted for MT stage, age, race/ethnicity, and body mass index, women with lower E2 (and higher FSH) were more likely to lose BMD: At the LS, each halving of E2 and each doubling of FSH were associated with 10% and 39% greater risk of significant bone loss, respectively (pâ <â 0.0001 for each). At the FN, each halving of E2 and each doubling of FSH were associated with 12% (p = 0.01) and 27% (pâ <â 0.001) greater risk of significant bone loss. FSH was more informative than E2 (assessed by the area under the receiverâ operator curve) at identifying women who were more versus less likely to begin losing bone, especially at the LS. Prediction was better when hormones were measured in preâ or early perimenopause than in late perimenopause. Tracking withinâ individual change in either hormone did not predict onset of bone loss better than a single measure. We conclude that measuring FSH in the MT can help prospectively identify women with imminent or ongoing bone loss at the LS. ĂŠ 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/1/jbmr3856_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153118/2/jbmr3856.pd
Is there a positive association between mammographic density and bone mineral density? Authors' response
Melatonin Patterns and Levels During the Human Menstrual Cycle and After Menopause
Context: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging.
Objective: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging.
Methods: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women\u27s Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and one postmenopausal collection with no evidence of luteal activity (NELA).
Results: In addition to the organized patterns of hormone metabolites (estrone conjugates [E1c], and pregnanediol glucuronide [PdG]) and gonadotropins that characterized ovulatory menstrual cycles, there was a late luteal rise in aMT6s. In NELA collections, there was no periodicity of E1c, PdG, gonadotropins, or aMT6s. The strongest predictors of aMT6s levels were PdG values 11 to 12 days prior to aMT6s (beta = 1.46, P = .001 and beta = 1.44, P = .001, respectively). E1c and gonadotropins were not statistically significantly associated with aMT6s. Mean aMT6s in premenopause was 53.5 ng/mL, greater than the mean of 37.4 ng/mL in postmenopausal samples from the same women (P = .0002).
Conclusions: This study confirms a late luteal melatonin rise, likely signaled by progesterone, which may influence menstrual cycle pacemaker control. Melatonin declined from premenopause to postmenopause. A high correlation between menopause transition stage and age precludes distinction between the influences of ovarian and chronological aging
Duration of menopausal vasomotor symptoms over the menopause transition
IMPORTANCE: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments.
OBJECTIVES: To determine total duration of frequent VMS ( \u3e /= 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence.
DESIGN, SETTING, AND PARTICIPANTS: The Study of Women\u27s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS.
MAIN OUTCOMES AND MEASURES: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause.
RESULTS: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, \u3e 11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS.
CONCLUSIONS AND RELEVANCE: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women
Sex steroid metabolism polymorphisms and mammographic density in pre- and early peri-menopausal women
Abstract Introduction We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17β-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women. Methods The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI). Results After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01). Conclusions SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density.http://deepblue.lib.umich.edu/bitstream/2027.42/78273/1/bcr2340.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78273/2/bcr2340.pdfPeer Reviewe
Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study
INTRODUCTION: Mammographic breast density is a strong independent risk factor for breast cancer. We hypothesized that demonstration of an association between mammographic breast density and bone mineral density (BMD) would suggest a unifying underlying mechanism influencing both breast density and BMD. METHODS: In a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64 years and were at least 1 year postmenopausal. Mammographic breast density (percentage of the breast composed of dense tissue), the outcome, was assessed with a computer-assisted percentage-density method. BMD, the primary predictor, was measured with dual-energy X-ray absorptiometry. Women quitting menopausal hormone therapy to join PEPI were designated recent hormone users. RESULTS: The mean age of the 594 women was 56 years. The average time since menopause was 5.6 years. After adjustment for age, body mass index, and cigarette smoking, in women who were not recent hormone users before trial enrollment (n = 415), mammographic density was positively associated with total hip (P = 0.04) and lumbar (P = 0.08) BMD. Mammographic density of recent hormone users (n = 171) was not significantly related to either total hip (P = 0.51) or lumbar (P = 0.44) BMD. In participants who were not recent hormone users, mammographic density was 4% greater in the highest quartile of total hip BMD than in the lowest. In participants who were not recent hormone users, mammographic density was 5% greater in the highest quartile of lumbar spine BMD than in the lowest. CONCLUSION: Mammographic density and BMD are positively associated in women who have not recently used postmenopausal hormones. A unifying biological mechanism may link mammographic density and BMD. Recent exogenous postmenopausal hormone use may obscure the association between mammographic density and BMD by having a persistent effect on breast tissue
Active, but not passive cigarette smoking was inversely associated with mammographic density
The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism.
We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Womenâs Health Across the Nation (SWAN).
We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked âĽ20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked âĽ20 cigarettes/day was associated with 23.8% lower density, compared to having smoked â¤9 cigarettes/day (p < 0.001).
Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density
Mammographic density and breast cancer risk: current understanding and future prospects
Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making
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