Late Postmenopause Research Articles

Menopause and accelerated aortic stiffness

BackgroundThe menopausal transition is widely believed to increase the risk of cardiovascular disease, based on the notion that estrogen is cardioprotective in women. While aortic stiffness is an independent predictor of cardiovascular disease, it has been unclear whether this risk increases during menopause. ObjectiveThis study aimed to determine the association between changes in menopausal status and aortic stiffness. Main outcome measuresMenopausal status was classified using the Stages of Reproductive Aging in Women criteria in a stratified random sample of Australian women aged 40–80 years, at three time-points over 14 years (n = 469 in 2001–02 and 2005, and n = 323 in 2014). Aortic stiffness was measured non-invasively via carotid-femoral pulse wave velocity at each time point. Mixed modeling was employed to determine the independent associations between menopausal status and aortic stiffness accounting for multiple covariates including age, systolic blood pressure, heart rate, medications, cholesterol, waist circumference, smoking and diabetes status. ResultsThere was no evidence to support an association between the menopausal transition and an acceleration of aortic stiffness. However, there was an acceleration of aortic stiffness in the late (8+ years) postmenopause phase, after accounting for age and traditional cardiovascular risk factors (0.122 [95%CI: 0.106, 0.139] m/s/year; p < 0.001). ConclusionsThe menopausal transition is not associated with major changes in aortic stiffness beyond normal age-related effects. However, the clinically significant acceleration in aortic stiffness observed in late postmenopause may contribute to greater cardiovascular risk in this later life phase.Study registered in the Australian and New Zealand Clinical Trials Registry, reference ACTRN12618000005257.

Plasma Ab42/40 levels differ by postmenopausal stage

AbstractBackgroundAlthough all women who live into late life experience reproductive aging (menopause), there is little understanding about how reproductive aging, as distinct from chronologic aging, influences the development of AD. Studies indicate that some AD biomarkers differ between peri‐ and postmenopausal women, but no studies to date have examined AD biomarkers across (sub)stages of the postmenopause. Here we compared plasma Ab42/40 levels in Early versus Late Postmenopausal women. We hypothesized that plasma levels of Ab42/40 would be lower in the Late versus Early Postmenopause group.MethodParticipants included women from the Human Connectome Aging Project who had plasma Ab42/40 and were either in the Early Postmenopause (i.e., Stages +1a, +1b or +1c; &gt;0 and &lt;6 years after the final menstrual period; FMP) or Late Postmenopause (Stage +2; &gt; 6 years after the FMP) according to the Stages of Reproductive Aging Workshop +10 criteria. Plasma Aβ42/40 was measured using an immunoprecipitation and liquid chromatography‐mass spectrometry assay. A univariate analysis of variance was conducted to compare plasma Ab42/40 in Early versus Late Postmenopause groups controlling for age, education, MOCA score, and ApoE carrier status.ResultThe sample included 42 women (mean age=66.2 years; mean MoCA=25.88; 73.8% white). Plasma Ab42/40 were significantly higher in the Early (n=10; mean age=55.77) versus Late Postmenopause (n=32; mean age=69.44) groups with mean values of 0.11 (SE=.002) and 0.103 (SE=.001), respectively, F(1,28)=7.23, p=.01. We restricted a second analysis to women age 60 years and under to optimally control for age differences between the groups (n=18, mean age=56.56 years; mean MOCA=26.04; mean education=17.17 years; 56% white, Early n=10). Again, plasma Ab42/40 were significantly higher in the Early (n=10; mean age=55.77) versus Late Postmenopause (n=32; mean age=57.56) groups with mean values of 0.11 (SE=.002) and 0.105 (SE=.003), respectively, F(1,13)=6.52, p =.025.ConclusionAdvanced reproductive stage, independent of chronologic age, may be associated with a lower plasma Ab42/40, a pattern shown to be predictive of the development of AD. These findings add to a body of AD biomarker studies showing differences between perimenopausal and postmenopausal women, and suggest that AD biomarkers also differ within distinct stages of the postmenopause.

Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause

The Early vs Late Intervention Trial with Estradiol showed that hormone therapy (HT) reduced progression of atherosclerosis when initiated in early but not in late postmenopause. This posttrial analysis examined the association between plasma estradiol (E2) levels and atherosclerosis determined by rate of change in carotid artery intima-media thickness (CIMT) and tested whether this association is equally evident in early (<6 years) vs late (≥10 years) postmenopause. Randomized controlled trial stratified by time since menopause (ClinicalTrials.gov no. NCT00114517). Mixed-effects linear models tested the association of E2 levels with CIMT rate of change. Los Angeles, California. Healthy women in postmenopause. Oral E2 with/without cyclic vaginal progesterone. Plasma E2 levels and CIMT assessed every 6 months over an average of 4.8 years. Among 596 women in postmenopause, higher E2 level was inversely associated with CIMT progression in those in early postmenopause (P = 0.041) and positively associated with CIMT progression in those in late postmenopause (P = 0.006) (P for interaction <0.001). CIMT progression rates for the lowest vs highest quartile of E2 levels among women in early postmenopause were 8.5 and 7.2 μm/y, respectively , whereas among women in late postmenopause they were 9.8 and 11.7 μm/y, respectively. E2 levels were differentially associated with atherosclerosis progression according to timing of HT initiation. With higher E2 levels, CIMT progression rate was decreased among women in early postmenopause but increased among women in late postmenopause. These results support the timing hypothesis of HT initiation on cardiovascular benefit, with reduced atherosclerosis progression for initiation during early postmenopause.

Correlation between allopregnanolone levels and depressive symptoms during late menopausal transition and early postmenopause

Objectives: This observational, cross-sectional study included 140 women with climacteric symptoms. The aim of the study was to evaluate the correlation between the presence and severity of depressive symptoms and allopregnanolone levels in women during late menopausal transition and early postmenopause.Methods: The study group was divided into two groups: 45 women in late menopausal transition and 95 early postmenopausal women. We evaluated Kupperman index, Hamilton scale and serum follicle-stimulating hormone, luteinizing hormone, 17β-estradiol, prolactin, total testosterone, dehydroepiandrosterone sulfate and allopregnanolone levels.Results: We found that serum allopregnanolone concentration was lower in early postmenopausal women compared to women in late menopausal transition; that there was a correlation between serum allopregnanolone levels in early postmenopausal women and time since last menstruation, intensity of climacteric symptoms, and intensity of depression symptoms and that there was a correlation between serum allopregnanolone levels and several depression symptoms presence (shallow sleep and symptoms of the digestive tract in women during late menopause transition; feelings of guilt, sleep disorders and general somatic symptoms in early postmenopausal women).Conclusion: We concluded that reproductive aging is characterized by a reduction of allopregnanolone circulating levels that correlate to Hamilton depression index in early postmenopause and presence of specific depressive symptoms during late menopausal transition and early postmenopause.

Impact of menopausal status on negative mood and depressive symptoms in a longitudinal sample spanning 20 years.

Studies examining depressive symptoms and negative mood across the postmenopause are lacking, particularly those that examine prevalence in early and late postmenopause. This study examines negative mood and depressive occurrence in the menopausal stages to provide a better understanding of prevalence of mood disturbance during this period. This study was a longitudinal assessment of variables drawn from an epidemiological prospective study of women's healthy aging. Scores were analyzed using general linear mixed models to determine whether there were reductions in negative mood across the stages of the menopausal transition, including the substages of the early and late postmenopause, as defined by Stages of Reproductive Ageing Workshop+10 criteria. Negative mood scores, derived from the Affectometer 2, were obtained at 11 time points between 1992 and 2012 in a group of 438 Melbourne-based, community-dwelling women aged between 45 and 55 years at baseline (n = 234; 53% retention in 2012). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale administered at three time points for 10 years. Women's experience of negative mood and depressive symptoms was highest during the menopausal transition and lowest in the late postmenopause. Increasing age was associated with a reduction in depressive symptoms F(1,559) = 14.83, P < 0.001 and negative mood F(1,935) = 14.97, P < 0.001. When controlling for age, there was no difference found between the early and late postmenopause stage mean scores. Although there were differences found between negative mood and depressive symptom scores in relation to categories of reproductive aging, age was found to be the driving influence to their association.

Hot flashes: emerging cardiovascular risk factors in recent and late postmenopause and their association with higher blood pressure.

The aim of the study was to compare the endothelial function of symptomatic (self-reported hot flashes >3 on a scale of 0-10) versus asymptomatic (≤3) women in different postmenopause stages, and to examine if the association between hot flashes and endothelial function was independent of classical cardiovascular risk factors observed during the analysis. Noninvasive venous occlusion plethysmography within two groups: recent (recent postmenopause [RPM], <10 y, n = 63) and late (late postmenopause [LPM], ≥10 y, n = 67) postmenopause. Symptomatic women showed lower forearm blood flow and lower percentage increment of it during the reactive hyperemia response; higher systolic (P < 0.0001 in RPM and P = 0.0008 in LPM) and diastolic (P = 0.0005 in RPM and P = 0.0219 in LPM) blood pressure; highest score for perimenopausal hot flashes (P = 0.0007 in RPM and P < 0.0001 in LPM), longer duration of prior oral contraceptive use (P = 0.009 in RPM and P = 0.0253 in LPM), and higher current sleep disorders (P < 0.0001 in RPM and P = 0.0281 in LPM) compared with asymptomatic ones. In the LPM group, symptomatic women also had higher prevalence of previous hypertension diagnosis (P = 0.0092). During multivariate analysis, blood flow during the reactive hyperemia response was associated with hot flashes after adjusting for age, body mass index, and systolic blood pressure (odds ratio 0.55 [0.36-0.84] in RPM and odds ratio 0.7 [0.5-0.97] in LPM). In both phases, recent and late post menopause, hot flashes were associated with endothelial dysfunction and higher systolic and diastolic blood pressure, but the relationship between hot flashes and endothelial dysfunction was independent of blood pressure.

Cholesterol Efflux Capacity and Subclasses of HDL Particles in Healthy Women Transitioning Through Menopause.

Growing evidence challenges the concept that high-density lipoprotein-cholesterol (HDL-C) is cardioprotective after menopause. HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) might be better predictors of cardiovascular risk. Quantify alterations in HDL-P and CEC during menopause, correlating those changes with alterations in estradiol (E2) and FSH. Longitudinal study of HDL metrics before and after menopause as indexed by the final menstrual period (FMP). Forty-six women, mean baseline age 47.1 years, 33% black, 67% white. HDL-P concentration (HDL-PIMA) by calibrated ion mobility analysis (IMA); macrophage CEC with cAMP-stimulated macrophages; ATP-binding cassette transporter A1 (ABCA1)-specific CEC with BHK cells expressing human ABCA1. After a median of 2.1 years since FMP, both HDL-C (P = .03) and HDL-PIMA (P = .01) increased, with a selective increase in large HDL-PIMA (P = .01), whereas sizes of medium and small HDL-PIMA were decreased (P < .05). These changes were independent of race, body mass index, and time difference. Macrophage CEC and ABCA1-specific CEC increased after FMP (both P < .001). Greater declines in E2 correlated with larger increases in small HDL-PIMA (P = .01), whereas greater increases in FSH associated with greater reductions in the size of medium HDL-PIMA (P = .04). Macrophage CEC and ABCA1-specific CEC correlated positively with E2 levels only before menopause (P = .04 and .009, respectively). Large HDL-PIMA and CEC increased significantly in the early phase of the menopausal transition. Whether patterns of these alterations differ in late postmenopause is unknown. Further exploration is needed to assess that and to determine whether the reported changes in HDL metrics associate with increased cardiovascular risk after menopause.

Menopausal Symptoms and Sleep Quality During Menopausal Transition and Postmenopause.

Background:Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms and sleep quality in menopausal transition (MT) and postmenopause (PM) women in Taiyuan, Shanxi.Methods:A community-based survey of women's menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40–59 years was divided into four groups: early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0.Results:The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep.Conclusions:Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high.

Establishment of new ELISA system for HLA-G

s for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20 15 Different circulating levels of monocyte chemoattractant protein-1 and interleukin-8 during the menopausal transition A. Tani1,2, T. Yasui2, K. Kasai3, K. Keyama2, S. Matsui2, T. Kato2, M. Irahara2 1 Department of Obstetrics and Gynecology, The Veritas Hospital, USA 2 Department of Obstetrics and Gynecology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan 3 Department of Obstetrics and Gynecology, Takamatsu Municipal Hospital, Japan 554 women were recruited for the outpatient clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. We divided the women into seven stages by menstrual regularity and FSH level: midreproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause, early postmenopause and late postmenopause. We measured serum concentrations of nine cytokines (IL-1 , IL-5, IL-6, IL-7, IL-8, IL-10, TNF, MIP-1 andMCP-1). IL-8 levels in postmenopausal women were significantly (p=0.001) higher than those in women in the midor reproductive stage and women in early or late menopausal transition. MCP-1 levels in women in late menopausal transition and postmenopause were significantly (p<0.001) higher than those in women in the midor late reproductive stage and women in early menopausal transition. MCP-1 level showed a significant positive correlation (r=0.215, p<0.01) with FSH level in women in menopausal transition. By using a detailed classification of menopausal transition, it was found that the features of IL-8 and MCP-1 levels were differed during the menopausal transition. IL-8 level showed a high level after menopause, while MCP-1 level showed a high level in menopausal transition. MCP-1 may be sensitive to hormonal change andmay be involved in the development of estrogen deficiency diseases. http://dx.doi.org/10.1016/j.jri.2014.09.036 Establishment of new ELISA system for HLA-G N. Ouji-Sageshima1,∗, M. Akasaki2, D.E. Geraghty3, E. Kita4, A. Ishitani5, K. Hatake5, T. Ito1 1 Department of Immunology, Nara Medical University, Japan 2 Akasaki Clinic, Japan 3 Fred Hutchinson Cancer Research Center, USA 4 Department of Microbiology and Infectious Disease Medicine, Nara Medical University, Japan 5 Department of Legal Medicine, Nara Medical University,

Sexual function in the late postmenopause: a decade of follow-up in a population-based cohort of Australian women.

There is a paucity of longitudinal studies assessing sexual function of women in the late postmenopause. This study aims to describe sexual function of women in the late postmenopause and to investigate change from early postmenopause. Cross-sectional analysis of 2012/13 and longitudinal analysis from 2002/04 of the population based, Australian cohort of the Women's Healthy Ageing Project, applying validated instruments: Short Personal Experience Questionnaire (SPEQ), Female Sexual Distress Scale (FSDS), Hospital Anxiety and Depression Scale, Geriatric Depression Scale, and California Verbal Learning Test. Sexual activity, SPEQ, and FSDS. Two hundred thirty women responded (follow-up rate 53%), mean age was 70 years (range 64-77), 49.8% were sexually active. FSDS scores showed more distress for sexually active women (8.3 vs. 3.2, P<0.001). For 23 (23%) sexually active and for five (7%) inactive women, the diagnosis of female sexual dysfunction could be made. After adjustment, available partner (odds ratio [OR] 4.31, P<0.001), no history of depression (OR 0.49, P=0.036), moderate compared with no alcohol consumption (OR 2.43, P=0.019), and better cognitive function score (OR1.09, P=0.050) were significantly predictive for sexual activity. Compared with early postmenopause, 18% more women had ceased sexual activity. For women maintaining their sexual activity through to late postmenopause (n=82), SPEQ and FSDS scores had not changed significantly, but frequency of sexual activity had decreased (P=0.003) and partner difficulties had increased (P=0.043). [Correction added on 10 July 2014, after first online publication: Mean age of respondents was added.] In late postmenopause, half of the women were sexually active. Most important predictors were partner availability and no history of depression. However, being sexually active or having a partner were associated with higher levels of sexual distress. Compared with early postmenopause, sexual function scores had declined overall but were stable for women maintaining sexual activity. Further research into causes of sexual distress and reasons for sexual inactivity at this reproductive stage is warranted.

Depression und Östrogene

Through their brain receptors, estrogens modulate mood, mental function, and cognition. The incidence of depression is significantly greater in women than in men. In particularly vulnerable women, the menopausal transition might trigger a depressive disorder. There is suggestive evidence from clinical trials that estrogen therapy improves mood in the menopausal transition, particularly in women suffering from vasomotor symptoms. In women with climacteric symptoms, estrogens might therefore be considered as a treatment for mild depressive symptoms. There are data suggesting that estrogens given as adjuvant therapy potentiate the effect of antidepressants in depressive disorders during the peri- and early postmenopause, and, in special situations, in severe depression in the late postmenopause. Estrogens do not improve even milder forms of depression in the late postmenopause. Estrogens have not been shown to improve severe depression. Estrogen therapy might improve cognition, which is still a controversial issue.

Sexual Desire During the Menopausal Transition and Early Postmenopause: Observations from the Seattle Midlife Women's Health Study

To describe levels of sexual desire across the menopausal transition (MT) and early postmenopause (PM), including effects of age, MT-related factors, health, stress, symptoms (hot flash, sleep, mood), and social opportunity factors. A subset of Seattle Midlife Women's Health Study (SMWHS) participants who provided data during the early reproductive, early and late menopausal transition stages, or postmenopause (n = 286), including menstrual calendars for staging the MT, annual health reports between 1990 and 2005, and morning urine samples assayed for estrone glucuronide (E(1)G), testosterone (T), and follicle-stimulating hormone (FSH) was included. Multilevel modeling using the R program was used to test factors related to sexual desire. Women experienced a significant decrease in sexual desire during the late MT stage (p < 0.01) and early PM (p < 0.0001). Those with higher urinary E(1)G and T reported significantly higher levels of sexual desire, whereas those with higher FSH levels reported significantly lower sexual desire (p < 0.0001, 0.06, and 0.0002, respectively). Women using hormone therapy also reported higher sexual desire (p = 0.02). Those reporting higher perceived stress reported lower sexual desire (p < 0.0001), but history of sexual abuse did not have a significant effect. Those most troubled by symptoms of hot flashes, fatigue, depressed mood, anxiety, difficulty getting to sleep, early morning awakening, and awakening during the night also reported significantly lower sexual desire (p range from <0.03 to 0.0001), but there was no effect of vaginal dryness. Women with better perceived health reported higher sexual desire (p < 0.0001), and those reporting more exercise and more alcohol intake also reported greater sexual desire (p < 0.0001). Having a partner was associated with lower sexual desire. Clinicians working with women traversing the MT should be aware that promoting healthy sexual functioning among midlife women requires consideration of their changing biology as well as ongoing life challenges.

Circulating Dehydroepiandrosterone Sulfate Concentrations during the Menopausal Transition

A previous report from the Study of Women Across the Nation indicated a rise in dehydroepiandrosterone sulfate (DHEAS) during the menopausal transition using data from three annual visits. Our objective was to examine changes in DHEAS with chronological and ovarian aging, expanding the original analyses to include 10 yr of annual data. A longitudinal observational study and cross-sectional analyses of baseline data were conducted. OUTCOME MEASURES AND SUBJECTS: DHEAS, age, menopause status, ethnicity, smoking, weight, and height were assessed in 2886 women from five ethnic groups aged 42-52 yr at entry. Hysterectomy, bilateral oophorectomy, and hormone use were excluded. Cross-sectional analysis at baseline showed a linear decline in circulating log-transformed DHEAS with increasing age for either the entire cohort (2.81% per year) or for individual ethnicities. A similar negative association with baseline age (2.44% decline per year) was seen in longitudinal linear mixed modeling including observations from premenopause through late postmenopause, an additional 0.33% decline/year. In contradistinction, a late-transition rise in DHEAS was detected when the same women were analyzed by ovarian status. The average increase in mean circulating DHEAS level between early and late menopause transition, beyond changes predicted by aging, was 3.95%, followed by an average decline of 3.96% during the late postmenopause. Approximately 84.5% of the women had an estimated within-woman increase in DHEAS from premenopause/early perimenopause to late perimenopause/early postmenopause. These observations underscore differences between cross-sectional and longitudinal studies and the importance of considering ovarian status. Additional investigations regarding adrenal contribution to sex steroids in mid-aged women are warranted.

Performance of Five Phalangeal QUS Parameters in the Evaluation of Gonadal-Status, Age and Vertebral Fracture Risk Compared with DXA

The aim of this cross-sectional study was to study the value of five different quantified ultrasound (QUS) parameters—amplitude-dependent speed of sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), fast-wave amplitude (FWA), bone transmission time (BTT) and signal dynamic (SDY)—measured at the phalanges of the hand in discriminating women with vertebral fracture and their relationship with some determinants of bone mass, in particular age and gonadal status compared with lumbar spine and hip dual-energy x-ray absorptiometry (DXA). We included 791 women aged 35–84 y, divided into premenopause, early menopause and late postmenopause groups on the basis of gonadal status and years since menopause (YSM). The presence of vertebral fracture was evaluated radiographically. All QUS parameters were very sensitive to changes in early postmenopause, with a doubled decrease in early postmenopausal with respect to late postmenopause. In particular AD-SoS and BTT decreases were markedly high in the early postmenopause group. In the late menopause group, similar decreases were observed for AD-SoS, UBPI and hip bone mineral density (BMD). In the multiple logistic model, DXA and QUS significantly discriminate women with and without fractures ( p < 0.0001); odds ratio (OR) was higher at lumbar spine BMD (OR 4.01), FWA (OR 3.88), AD-SoS (OR 3.81) and total hip BMD (OR 3.77). Even adjusting the logistic model for age, height, weight, lumbar spine and total hip BMD, all QUS parameters remained significantly predictive of vertebral fracture. AD-SoS showed the best performances both in terms of OR and ROC analysis. QUS parameters show a different behavior in evaluating the effect on bone mass of the time since menopause; AD-SoS and BTT showed a high sensitivity to first changes in bone tissue after menopause. After correction for potential confounders, AD-SoS showed the same ability of lumbar spine BMD in discriminating women with or without vertebral fractures and in the prediction of fracture risk. (E-mail: carlina.albanese@uniroma1.it)

Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment

Throughout the life cycle the skeleton requires optimum development and maintenance of its integrity to prevent fracture. Bones break because the loads placed on them exceed the ability of the bone to absorb the energy involved. It is now estimated that one in three women and one in twelve men aged >55 years will suffer from osteoporosis in their lifetime and at a cost in the UK of > 1.7 pounds x 10(9) per year. The pathogenesis of osteoporosis is multifactorial. Both the development of peak bone mass and the rate of bone loss are determined by key endogenous and exogenous factors. Ca supplements appear to be effective in reducing bone loss in women late post menopause (>5 years post menopause), particularly in those with low habitual Ca intake (<400 mg/d). In women early post menopause (<5 years post menopause) who are not vitamin D deficient, Ca supplementation has little effect on bone mineral density. However, supplementation with vitamin D and Ca has been shown to reduce fracture rates in the institutionalised elderly, but there remains controversy as to whether supplementation is effective in reducing fracture in free-living populations. Re-defining vitamin D requirements in the UK is needed since there is evidence of extensive hypovitaminosis D in the UK. Low vitamin D status is associated with an increased risk of falling and a variety of other health outcomes and is an area that requires urgent attention. The role of other micronutrients on bone remains to be fully defined, although there are promising data in the literature for a clear link between vitamin K nutrition and skeletal integrity, including fracture reduction.

Spinal trabecular bone loss and fracture in American and Japanese women.

This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the K2HPO4 liquid phantom in 538 Americans aged 20-85 years, and with the B-MAS200 phantom in 577 Japanese aged 20-83 years. These BMD were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111 postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1 mg/cm3 in women aged 20-24 years, 40-44 years, 60-64 years, respectively. In premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion, Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women.

The Role of Calcium Intake in Preventing Bone Fragility, Hypertension, and Certain Cancers ,

This paper examines the evidence that connects calcium intake and vitamin D status to bone fragility, hypertension, colon cancer, and breast cancer. Human calcium physiology, with an intestinal absorptive barrier and inefficient conservation, reflects the abundance of calcium in the primordial human food supply. The calcium intake of stone-age adults is estimated at 50 to 75 mmol/d, three to five times the median calcium intake of present-day U.S. adults. Long-term calcium restriction and/or insufficient vitamin D may promote the development of bone fragility, high blood pressure, colon cancer, and breast cancer in susceptible individuals. Conversely, improvement in calcium intake and/or in vitamin D status may help to prevent these serious health problems. At least 12 intervention studies have established the skeletal benefit of increased calcium intake among women in the late postmenopause. Other reports suggest that adequate calcium may protect against salt-sensitive and pregnancy-associated hypertension. High intakes of both dietary calcium and vitamin D are associated with reduced development of precancerous changes in colonic mucosa. Preliminary findings also suggest that vitamin D has a protective effect against breast cancer.

Low Calcium Intake: The Culprit in Many Chronic Diseases

Calcium is the fifth most abundant element in the earth's crust and is necessary for both plant and animal life today. Moreover, the natural diets of all mammals are rich in calcium. The diet of Stone Age human adults is estimated to have contained from 50 to 75 mmol of calcium (2000 to 3000mg)/d, three to five times the median calcium intake of present-day US adults. Human physiology has adapted to this environmental abundance with an intestinal absorptive barrier and inefficient renal conservation of calcium. Although mammalian physiology contains mechanisms by which organisms can adjust to temporary environmental shortages, chronic calcium retention has a number of health consequences, most notably bone fragility, high blood pressure, and colon cancer. Evidence indicates that improvement in calcium intake (or in vitamin D status) prevents some portion of each of these multifactorial problems. At least 14 intervention studies have established the skeletal benefit of increased calcium intake during growth and among women in the late postmenopause. Other evidence suggests that adequate calcium may protect against salt-sensitive and pregnancy-associated hypertension and that high intakes of both dietary calcium and vitamin D reduce development of precancerous changes in colonic mucosa.

Endogenous sex hormones and bone mineral density among community-based postmenopausal women

In order to describe the relationships between endogenous sex hormones and bone mineral density in healthy postmenopausal women, we carried out a cross-sectional study of 90 community-based women, all at least one year since their last menstrual period (mean 9.6 +/- 4.9 years, range 1-22) and with a serum oestradiol level less than 100 pmol/l. None was currently using hormone replacement therapy. Serum oestradiol, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, and androstenedione were measured using standard techniques. Free oestradiol and testosterone indices were derived as the ratio of total hormone to sex hormone binding globulin, respectively. Total body, spine and hip bone mineral density (g/cm2) were measured by dual energy X-ray absorptiometry. Significant positive correlations were found between the free oestradiol and testosterone indices and bone mineral density at all sites. These relationships remained significant for the free oestradiol index after adjustment for age and body mass index. By stepwise multiple regression analysis, the free oestradiol index was an independent predictor of total body, spine and hip bone mineral density, accounting for 4-17% of the variance. These findings suggest an independent positive relationship between endogenous free oestradiol and total body, spine and hip bone mass even in the late postmenopause.

Persistence of increased bone resorption and possible role of dehydroepiandrosterone as a bone metabolism determinant in osteoporotic women in late post-menopause

Specific data on bone metabolism in the late post-menopause are relatively scarce. This study presents data on the biochemical, hormonal and bone mineral status of a selected group of 22 osteoporotic women with at least 1 vertebral fracture who had been post-menopausal for a minimum of 5 yr. Bone resorption parameters were elevated in over two-thirds of these patients. The serum levels of dehydroepiandrosterone and its sulphate were negatively correlated with age and years since menopause but positively correlated with bone mineral content, bone turnover parameters (urinary calcium/creatinine, osteocalcin), 1,25-dihydroxy-vitamin D levels and the 1,25-dihydroxy-vitamin D/ 25-hydroxy-vitamin D ratio. These findings indicate that careful evaluation of the bone turnover rate in the late post-menopause can still have an important bearing on therapeutic decisions. They also support the theory that adrenal androgens play a role in bone mineral metabolism in the late post menopause.