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PubMed2000

Influence of body composition on quantitative ultrasound parameters of the os calcis in a population-based sample of pre- and postmenopausal women.

Body mass is known to be related to measures of bone mineral density (BMD) as well as to parameters of quantitative ultrasound (US). To examine the effect of the body compartment's fat mass and lean body mass on quantitative ultrasonic bone parameters, data from a sample of 3241 German women were analyzed. Anthropometric measures, including skinfold thickness, were obtained from standardized measurements, and fat and lean body mass were derived from classical regression formulas based on skinfold measurements. Ultrasonic bone measurements were performed on the right os calcis, and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were determined. Women were grouped into pre- and postmenopausal status; postmenopausal women were further stratified into ever and never hormone-replacement user. Correlation analysis indicated lean body mass to be stronger correlated with BUA than fat mass in both pre- (r = 0.23; P = 0.0001) and postmenopausal women with (r = 0.19; P = 0.0001) and without hormone replacement therapy (HRT) (r = 0.26; p = 0.0001). SOS demonstrated very small or no associations with body mass or its components. Multiple linear regression models were used to describe the relationship among body weight, fat mass, and lean body mass on BUA after adjustment for confounding variables. Both in pre- and postmenopausal women lean body mass was more strongly related to BUA than fat mass. However, body mass measures explained only small amounts of the overall variance in BUA (R(2) = 1-3% in premenopausal women; R(2) = 1% postmenopausal with HRT; R(2) = 4-5% in postmenopausal women without HRT). In conclusion, the strong influence of body mass and its components previously reported for BMD was not observed for quantitative ultrasonic bone parameters.

Adult↗

PubMed2006

Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis.

Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The aim of this study was to evaluate the serum prolidase activity and its relationship between bone turnover markers and bone mineral density (BMD) in postmenopausal osteoporosis. The study included 45 postmenopausal osteoporotic, 55 postmenopausal nonosteoporotic and 38 premenopausal healthy women. BMD was measured at the femoral neck and lumbar spine with DEXA. T score was more than 2.5 SD below the normal at the lumbar spine or femoral neck in postmenopausal osteoporotic patients. Serum levels of prolidase, C-terminal telopeptide of type I collagen (C-telopeptide), total alkaline phosphatase (ALP), osteocalcin (OC), urinary deoxypyridinoline (Dpd) and urinary creatinine were also assayed. C-telopeptide, total ALP, OC, urinary Dpd levels were significantly higher in postmenopausal osteoporotic group compared with premenopausal women. However, there was no statistical difference in serum prolidase activity between the three groups. There were also no significant correlations between serum prolidase and any biomarkers of bone turnover as well as BMD. To conclude, in postmenopausal osteoporotic women with increased bone turnover, serum prolidase concentration was not correlated with the biomarkers of bone formation or bone resorption and with BMD.

Absorptiometry, Photon↗

PubMed2005

Effects of chronic liver disease on bone mineral density and bone metabolism markers in postmenopausal women.

OBJECTIVES: Patients with chronic liver disease (CLD) have an increased prevalence of osteoporosis. However, there is limited information about the effects of end-stage liver disease on bone metabolism and bone mineral density values in postmenopausal women. The aim of this study was to investigate the effects of chronic liver disease on bone mineral density (BMD) and bone metabolism markers in postmenopausal women. METHODS: We studied BMD by using dual-energy X-ray absorptiometry (DEXA), biochemical markers of bone turnover and calcium-parathyroid hormone (PTH)-Vitamin D axis in 22 postmenopausal women with CLD. Control group consisted of randomly recruited 30 healthy postmenopausal women. RESULTS: Based on WHO criteria, the prevalence of osteoporosis was significantly higher in patients with CLD (72 versus 33%) compared to healthy postmenopausal women. Bone loss was more significant at the lumbar spine than femur in the study group. Urinary excretion of bone resorption marker deoxypyridinoline was increased significantly in patients with CLD. There were no significant differences in bone formation markers (osteocalcin and bone alkaline phosphatase) between the groups. CONCLUSIONS: CLD increases the prevalence of osteoporosis in postmenopausal women, particularly in the lumbar spine. Increased bone resorption seems to be the main reason for osteoporosis in these patients. We suggest that treatment strategies should be improved in these women to protect them from subsequent fractures.

Alkaline Phosphatase↗

PubMed2006

Elevated arterial stiffness in postmenopausal women with osteoporosis.

OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are cardiovascular risk factors. We investigated the relationship between PWV and bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal women. The brachial-ankle PWV (baPWV) was measured using an automated device. The BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for age and years since menopause, women with osteoporosis had a significantly higher baPWV than those with normal BMD (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant differences in baPWV were seen between the osteoporotic and osteopenic groups or between the osteopenic and normal BMD groups. In univariate regression analysis, the baPWV was significantly negatively correlated with BMD (r = -0.450, P < 0.01), and significantly positively correlated with age (r = 0.601, P < 0.01), years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295, P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with other variables. In multivariate regression analysis, the baPWV was significantly correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS: Postmenopausal women with osteoporosis may have elevated arterial stiffness, suggesting that osteoporotic postmenopausal women may have a higher risk of cardiovascular disease.

Absorptiometry, Photon↗

PubMed1996

Serum insulin-like growth factor binding protein profiles in postmenopausal women: their correlation with bone mineral density.

OBJECTIVE: The objective of this study was to evaluate the relationship between serum insulin-like growth factor binding protein profiles and bone mineral density measurements and biochemical markers of bone turnover in postmenopausal women. STUDY DESIGN: Sera from 37 normal healthy postmenopausal women and 14 postmenopausal women with osteoporosis were analyzed for insulin-like growth factor binding proteins and osteocalcin by Western ligand blotting and radioimmunoassay, respectively. Bone mineral density measurements were performed by dual-energy x-ray absorptiometry. Urinary calcium and creatinine excretion were also determined. The data were analyzed statistically by analysis of variance and the least-squares method. RESULTS: The serum insulin-like growth factor binding protein-2 ratio (insulin-like growth factor binding protein-2 intensity/total insulin-like growth factor binding protein intensity) in postmenopausal women with osteoporosis was significantly higher (p < 0.02) than that in normal healthy postmenopausal women, but the serum insulin-like growth factor binding protein-3 ratio in women with osteoporosis was significantly lower (p < 0.01). The serum insulin-like growth factor binding protein-2 ratio correlated negatively with the bone mineral density of the lumbar spine (p < 0.0001), femoral neck (p < 0.05), trochanter (p < 0.01), and Ward's triangle (p < 0.05), but there was a significant positive correlation between the serum insulin-like growth factor binding protein-3 ratio and the bone mineral density of the lumbar spine (p < 0.001) and trochanter (p < 0.05). No correlations between serum insulin-like growth factor binding protein levels or serum ratios and biochemical markers of bone turnover were noted. CONCLUSION: The measurement of serum insulin-like growth factor binding protein profiles might be useful in identifying postmenopausal women at risk for osteoporosis.

Bone Density↗

PubMed2000

Prevention of postmenopausal bone loss by low and conventional doses of calcitriol or conjugated equine estrogen.

OBJECTIVES: Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss. Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear. In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of postmenopausal bone loss in Thais. METHODS: The subjects consisted of 146 Thai women no more than 6 years postmenopausal. The subjects were randomly allocated to receive 750 mg supplemental calcium alone, calcium and conjugated equine estrogen (CEE) at 0.3 or 0.625 mg, calcium and calcitriol at 0.25 or 0.5 microg daily. Those receiving CEE also took 5 mg medrogestone for 12 days each month. BMD at L2-4 and femoral neck were measured at baseline 1 year and 2 years after treatments. Data were expressed as mean +/- S.E. RESULTS: Subjects on supplemental calcium alone had approximately 2.5% decreases in L2-4 (P < 0.05) and femoral BMD (P < 0.01) at 2 years. CEE (0.3 mg) resulted in 3.20 +/- 1.2% increase in vertebral BMD (P < 0.05) while no significant change in BMD was demonstrated at the femoral neck. Likewise, 0.625 mg of CEE induced 5.4 +/- 1.4% increase in vertebral BMD at 2 years (P < 0.001) without change in the femoral BMD. In regard to calcitriol, no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol. CONCLUSION: We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais. It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement.

Absorptiometry, Photon↗

PubMedDate not supplied

The role of calcium in peri- and postmenopausal women: 2006 position statement of the North American Menopause Society.

OBJECTIVE: To update the evidence-based consensus opinion published by The North American Menopause Society (NAMS) in 2001 on the role of calcium in peri- and postmenopausal women. DESIGN: NAMS followed the general principles established for evidence-based guidelines to create this document. A panel of clinicians and researchers acknowledged to be experts in the field of calcium and women's health was enlisted to review the previous position statement and data published since then, compile supporting statements, and make recommendations. Their advice was used to assist the NAMS Board of Trustees in publishing this position statement. RESULTS: Adequate calcium intake (in the presence of adequate vitamin D status) has been shown to reduce bone loss in peri- and postmenopausal women and reduce fractures in postmenopausal women older than age 60 with low calcium intakes. Adequate calcium is considered a key component of any bone-protective therapeutic regimen. Calcium has also been associated with beneficial effects in several nonskeletal disorders, primarily hypertension, colorectal cancer, obesity, and nephrolithiasis, although the extent of those effects has not been fully elucidated. The calcium requirement rises at menopause. The target calcium intake for most postmenopausal women is 1,200 mg/day. Adequate vitamin D status, defined as 30 ng/mL or more of serum 25-hydroxyvitamin D (usually achieved with a daily oral intake of at least 400 to 600 IU), is required to achieve the nutritional benefits of calcium. The best source of calcium is food, and the best food source is dairy products. High-quality calcium supplements (taken in divided doses) are alternative sources for women unable to consume enough dietary calcium. There are no reported cases of calcium intoxication from food sources, and cases associated with supplements are rare (high intake levels of 2,150 mg/day have resulted in a 17% increase in renal calculi in one recent study, but not others). Because no accurate test to determine calcium deficiency exists, clinicians should focus instead on encouraging women to consume enough calcium to meet the recommended levels. CONCLUSIONS: The most definitive role for calcium in peri- and postmenopausal women is in bone health, but, like most nutrients, calcium has beneficial effects in many body systems. Based on the available evidence, there is strong support for the importance of ensuring adequate calcium intake in all women, particularly those in peri- or postmenopause.

Calcium↗

PubMed2005

[Prevalence of osteopenia and osteoporosis in postmenopausal women].

OBJECTIVE: To know the osteoponia and osteoporosis prevalence in postmenopausal women determined with broadband ultrasonic attenuation (BUA). DESIGN: Descriptives cross-sectional study of prevalence. SETTING: Salvador Allende Health Center. Valencia, Spain. PARTICIPANTS: A total of 115 postmenopausal women aged 49 at 85 years old was studied, initiated in September to December 2003. Iatrogenic menopause or women with calcium, vitamin D, estrogen replacement therapy, estrogen receptor modulators, and biphosphonates therapy were considered criteria for exclusion. We measured bone mineral density with BUA at right calcaneus. MAIN MEASUREMENTS: We analyzed the age, height, and weight, the result of BUA, tobacco and diuretics consumption and years of amenorrhea. RESULTS: . The prevalence of osteoporosis was 50.4%. Other 29.6% had osteopenia. Of the postmenopausal women with osteoporosis, 27.6% were 70 to 75 years old. The 82.8% of postmenopausal women with osteoporosis were younger than 75 years old. The 66.7% postmenopausal women with body mass index lesser than 25 had osteoporosis. CONCLUSIONS: The osteoporosis prevalence in our patients was greater than other studies (30%). Emphasis may be placed on screening osteoporosis with BUA in primary health care. We suggested that educational community programs should start at an earlier age to identify factors that contribute to maintaining bone mineral density among postmenopausal women.

Aged↗

PubMed2004

Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women.

UNLABELLED: We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants. There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures. INTRODUCTION: Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures, potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy. We prospectively tested this hypothesis in the Study of Osteoporotic Fractures (SOF). MATERIALS AND METHODS: We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline. Hip fracture analyses included 708 hip fractures; vertebral fracture analyses included 267 incident vertebral fractures. Baseline serum estradiol and free testosterone values were available in a small subset of participants. RESULTS AND CONCLUSION: There were no significant differences in age, weight, or BMD between the women who underwent postmenopausal oophorectomy (n = 583) and those who did not (n = 5712). Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy. A history of postmenopausal oophorectomy was not associated with an increased risk of hip (hazard ratio [HR] = 1.1; 95% CI = 0.9-1.5) or vertebral fracture (HR = 0.7; 95% CI = 0.5-1.2). The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level (HR = 1.3; 95% CI = 0.5-3.2) or serum free testosterone level (HR = 1.7; 95% CI = 0.8-3.7) to the model. In summary, postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort. These results are in contrast to previous findings, suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully elucidated and that incidental oophorectomy after menopause should still be considered carefully in each potential patient.

Aged↗

PubMed2005

Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women.

UNLABELLED: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. INTRODUCTION: We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. MATERIALS AND METHODS: Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. RESULTS: Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. CONCLUSIONS: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.

Acromegaly↗

PubMed2000

The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women.

To examine the predictive value of biochemical markers of bone turnover for bone loss pre- and postmenopausally, we measured two markers of bone formation, bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OC); four markers of bone resorption, urinary cross-linked N-telopeptides of type I collagen (NTx), type I collagen C-telopeptide breakdown products (CTx), hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP); serum OC N-terminal (OC-N); and two serum cytokines, soluble interleukin-6 receptor (sIL-6R) and IL-1r antagonist at baseline and 1 year, as well as lumbar spine bone mineral density (BMD) at baseline and 1, 2, 3, 4, and 5 years after trial in 82 premenopausal (44.8 +/- 5.4 years old) and 325 postmenopausal (60.2 +/- 6.1 years old) healthy Japanese women. In premenopausal women, stratification of the baseline value of each biochemical marker into quartiles did not cause any significant difference in the change in BMD. Stratification of the NTx baseline value in postmenopausal women showed significant differences in rate of bone loss to the first year among those subjects with each quartile (Q1 [0.28 +/- 0.28%], Q2 [-0.32 +/- 0.34%], Q3 [-1.50 +/- 0.31%], and Q4 [-2.43 +/- 0.35%]) except for the difference between Q1 and Q2. The predictive value of NTx for BMD was greater in early postmenopausal women within 5 years after menopause than in late postmenopausal women with more than 5 years since menopause (YSM). Quartile analysis of the other biochemical markers and serum cytokines did not show any significant capacity for differentiating between bone loss rates. Moreover, when the changes in the lumbar spine BMD to the second and third years were stratified into quartiles by the baseline NTx, the ratios of bone loss to the second and the third years were significantly higher in those women with higher NTx (Q4; -3.15 +/- 0.56% and -4.06 +/- 0.57%, respectively) than in those with lower NTx (Q1; -0.74 +/- 0.44% and -1.03 +/- 0.51%, respectively). In conclusion, baseline urinary NTx was the most sensitive predictor of bone loss in the lumbar spine after 1, 2, and 3 years. Markers of bone resorption can be used clinically to predict future BMD in postmenopausal women.

Adult↗

PubMed2001

Inhaled corticosteroids reduce bone mineral density in early postmenopausal but not premenopausal asthmatic women.

Inhaled corticosteroids are widely used in the treatment of bronchial asthma, but it is still uncertain whether long-term use of the inhaled corticosteroids affects bone metabolism in asthmatic patients. In this study, we examined the effect of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD) and biochemical markers of bone metabolism in pre- and early postmenopausal asthmatic women. Thirty-six (17 premenopausal and 19 early postmenopausal) asthmatic women and 45 healthy control (24 premenopausal and 21 early postmenopausal) women were investigated. All the asthmatic patients were treated with BDP (542 +/- 298 microg/day; 100-1200 microg/day) without any systemic administration of corticosteroids for at least 1 year. In premenopausal women, BMD as well as the biochemical markers of bone metabolism did not differ between control subjects and BDP-treated asthmatic patients. By contrast, in early postmenopausal women, BMD was significantly lower in BDP-treated asthmatic patients than in control subjects. In these early postmenopausal women, serum intact osteocalcin concentration was lower in the BDP-treated asthmatic patients than in the control subjects whereas urinary free pyridinoline (F-PYD) and free deoxypyridinoline (F-DPD) concentrations did not differ between the groups. Thus, early postmenopausal, but not premenopausal, asthmatic patients who were treated with inhaled BDP had reduced BMD, which was associated with a decreased level of the bone formation marker. Ovarian hormones may be protective against the adverse effect of inhaled BDP on bone metabolism in the premenopausal patients.

Absorptiometry, Photon↗

PubMed2004

[Bone mineral density and 17 beta-estradiol correlation in postmenopausal women].

BACKGROUND: With the increased life-expectancy reached during 20th century, women will spend a very important part of their lives in the estrogenic deficiency state accompanying menopause. OBJECTIVES: To detect serum 17beta-estradiol levels, bone mineral density values, and to see the correlation between both parameters as well as with postmenopausal period. MATERIAL AND METHODS: A transversal study with ambulatory, community-dwelling postmenopausal women from Oaxaca de Juárez, Oax. was performed. RESULTS: We studied 70 women with spontaneous menopause, medium values were: age, 55.9 +/- 5.4 yr; menopause age, 48 +/- 3 yr; postmenopausal period, 7.9 +/- 5.3 yr; body mass index, 28.3 +/- 5.4, and serum 17beta-estradiol by radioimmunoassay, 62.78 +/- 25.83 pg/mL. Quantitative calcaneous ultrasound was used to measure bone mineral density and we found 30 women with normal level (-1.0 to 1.4 SD), 29 with osteopenia (-1.1 to -2.3 SD) and only 2 subjects with osteoporosis (-2.7 to 2.8 SD). CONCLUSIONS: Statistical analysis shows that bone mineral density and postmenopausal period were significantly correlated (p<0.05) as well as serum 17beta-estradiol levels with postmenopausal period; nevertheless, no correlation between bone mineral density and serum 17beta-estradiol or body mass index (p>0.05) was found. On the other hand, it is remarkable high serum 17beta-estradiol levels found in this group, related with postmenopausal status. These latter results are different from those reported in the literature.

Aged↗

PubMed2004

Postmenopausal estrogen use affects risk for Parkinson disease.

BACKGROUND: Although estrogen therapy has been associated with improved cognitive functioning, a reduced risk of dementia in women with Parkinson disease (PD), and a decreased risk of Alzheimer disease, estrogen therapy has not affected the risk of PD per se. OBJECTIVE: To determine whether postmenopausal women with PD differed from control subjects with regard to estrogen exposure.Design, Setting, and Patients A case-control design was used, abstracting questionnaire data obtained via interview from 133 female PD cases and 128 female controls during routine outpatient clinic visits in 1999 at a mid-Atlantic tertiary care referral center. There were 140 subjects (68 PD cases and 72 controls) who met the inclusion criteria. Main Outcome Measure Use of postmenopausal estrogen therapy. RESULTS: More women in the control group than in the PD group took postmenopausal estrogen (36 [50%] of 72 women vs 17 [25%] of 68 women; P<.003), and women who had taken postmenopausal estrogen were less likely to develop PD than those who had not (odds ratio, 0.40 [95% confidence interval, 0.19-0.84]; P<.02). Among PD cases only, postmenopausal estrogen use was not associated with age of onset. CONCLUSION: Postmenopausal estrogen therapy may be associated with a reduced risk of PD in women.

Adult↗

PubMed2002

Hormone replacement therapy for cognitive function in postmenopausal women.

BACKGROUND: As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline. OBJECTIVES: To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in randomized controlled trials (RCTs) on cognitive function in postmenopausal women. SEARCH STRATEGY: The CDCIG Specialized Register was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* on 16 May 2002. In addition MEDLINE (1966-2002/01); EMBASE (1985-2000/11); PsycINFO (1967-2002/01) and CINAHL (1982-2001/12) were searched as the CDCIG Register does not contain all trials with healthy volunteers. SELECTION CRITERIA: All double-blind randomized controlled trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the resulting lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. Two reviewers (EH and KY) assessed the quality of other aspects including design and assessment of outcomes. One reviewer (EH) extracted the data from the studies. MAIN RESULTS: In total, 15 trials involving 566 postmenopausal women were included, but 6 studies did not have adequate data for analysis. Meta-analyses showed a positive effect of 10 mg of estradiol (E2) bolus injections intramuscularly monthly in relatively young surgically menopausal women on the Paired Associate learning test immediate recall (z=2.40, p<0.05, chi-square test=1.12, p=0.29, SMD=1.02, 95% C.I.=0.19-1.85), on a test of abstract reasoning (z=10.45, p<0.0001, WMD=6.80, 95% C.I.=5.52-8.08) and a test of speed and accuracy (z=9.16, p<0.0001 WMD=6.00, 95% C.I.=4.72-7.28). However, most studies showed no evidence of an effect on verbal or visuospatial memory, mental rotations, speed or accuracy measures. There was little evidence that Premarin, the most widely prescribed estrogen for postmenopausal use, had positive effects on cognitive function. The one effect of 9 months of treatment with Premarin (and a progestagen) on a measure of complex speed of information processing (the TMT-B) was probably explained by baseline differences, as it was not reported by the authors. REVIEWER'S CONCLUSIONS: There was little evidence regarding the effect HRT or ERT on overall cognitive function in healthy postmenopausal women. There was an effect on some verbal memory functions (immediate recall), on a test of abstract reasoning and a test of speed and accuracy in relatively young (47 years of age) surgically menopausal women who had been given a bolus intramuscular injection of 10 mg E2 every month for 3 months. These effects were from small studies from a single research group. It remains to be determined whether factors such as an older age (> 69 years of age), type of menopause (surgical or natural) and type of treatment (E2 with or without a progestagen), mode of delivery (transdermal, oral or intramuscular), dosage and duration (> 3 months) could alter the effect on memory functions to a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Longitudinal RCTs currently underway in the U.S.A., U.K. and Canada will be able to test these hypotheses by the year 2010.

Cognition↗

PubMed2002

Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre- and postmenopausal women.

Breast cancers in younger, premenopausal women are more likely to exhibit an adverse prognostic profile (including negative steroid hormone receptors and a high rate of cellular proliferation) and poor outcome than breast cancers in postmenopausal women. It has been hypothesized that this adverse prognostic profile is a result of the higher histologic grade of breast cancers in pre- compared with post-menopausal women. To assess the association of expression of steroid hormone receptors and indicators of proliferation while controlling for histologic grade, we identified 100 infiltrating ductal carcinomas from premenopausal women 45 years of age or younger and 100 from postmenopausal women 65 years of age or older. The carcinomas were selected so that the histologic grades (low versus high) were distributed equally between the 2 groups. Estrogen receptors (ER), progesterone receptors (PR), p27(Kip1) and Ki-67 (to measure rate of proliferation) were assessed by immunohistochemistry and compared between groups. Clinical information and survival data were also analyzed. ER content was lower and proliferation was higher in carcinomas in premenopausal women (p = 0.048 and p = 0.005, respectively). By univariate analysis, p27(Kip1) and PR were not different between the groups; however, in multivariate analysis, p27(Kip1) was higher in postmenopausal women, but only in a subgroup with highly proliferative carcinomas. Overall survival was similar in the pre- and postmenopausal women. Furthermore, low p27(Kip1) and African-American ethnicity predicted a poorer overall survival in the premenopausal, but not in the postmenopausal, women in our study. After controlling for histologic grade, a lower expression of ER and a higher proliferative index were detected in breast carcinomas in premenopausal women. Therefore, some prognostic indicators, such as ER and proliferative rate, may be more closely associated with menopausal status than histologic grade. Our data also suggest that some prognostic factors are not equally effective as predictors of survival in pre- and postmenopausal women.

Age Factors↗

PubMed2001

Involvement of up-regulation of 17beta-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers.

Estradiol (E2) and estrone (E1) levels as well as mRNA expression levels of aromatase, sulfatase and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) in breast cancer tissues were studied to elucidate the mechanism involved in the maintenance of the intratumoral high E2 levels in postmenopausal patients with very low serum E2 levels. Intratumoral E2 levels of postmenopausal patients (127.2 +/- 17.5 pg/g) (mean +/- SE) were not significantly different from those of premenopausal patients (110.1 +/- 10.1 pg/g) (p = 0.36). The mRNA expression levels of aromatase and sulfatase, determined by a quantitative real-time PCR, were not significantly different between premenopausal and postmenopausal breast cancers, but 17beta-HSD1 mRNA expression levels were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.05). Intratumoral E2/E1 ratios were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.01). These results demonstrate that the increased conversion from E1 to E2 catalyzed by 17beta-HSD1 may play an important role in the maintenance of the intratumoral high E2 levels in postmenopausal patients.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

Premenopausal levels of circulating insulin-like growth factor I and the risk of postmenopausal breast cancer.

Increased levels of insulin-like growth factor I (IGF-I) may directly stimulate breast cell proliferation and promote growth and survival of transformed cells. Higher levels of IGF-I have been associated with increased risk of premenopausal breast cancer but not postmenopausal breast cancer. We investigated whether circulating levels of IGF-I prior to menopause are associated with breast cancer diagnosed after menopause in a population-based nested case-control study. Female cohort participants were enrolled in 1974 (n = 15,192) and 1989 (n = 18,724) and blood was drawn. Cases were women diagnosed with primary breast cancer at ages > or =50, of whom 152 were premenopausal at blood draw. One control was matched to each case on cohort participation, age, ethnic group, menopausal status and date of blood draw. Levels of IGF-I and IGF binding protein 3 (IGFBP-3) were measured using enzyme-linked immunoabsorbent assays. The association between IGF-I and breast cancer was determined using conditional logistic regression, adjusting for IGFBP-3. IGF-I levels decreased with age (p = 0.0001). Prior to age-stratification, IGF-I levels neither measured before nor after menopause were associated with postmenopausal breast cancer. After age-stratification, associations were suggested in the youngest premenopausal age group (upper vs. lowest third: odds ratio (OR) = 5.31, 95% confidence intervals (CI) = 0.85-33.13; p trend = 0.06) and oldest postmenopausal age group (upper vs. lowest third: OR = 3.41, 95% CI = 0.66-17.71; p trend = 0.13). The association between circulating levels of IGF-I and postmenopausal breast cancer risk may be modified by age. Increased levels of circulating IGF-I may be of particular interest in the younger premenopausal women and older postmenopausal women. Age-stratification should be undertaken in larger investigations of IGF-I levels as predictors of postmenopausal breast cancer.

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