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PubMed1999

Prescription of hormone replacement therapy in postmenopausal women with renal failure.

UNLABELLED: Prescription of hormone replacement therapy in postmenopausal women with renal failure. BACKGROUND: Although patients with end-stage renal disease (ESRD) are at increased risk for early menopause, osteoporosis, cognitive dysfunction, and cardiovascular disease, few postmenopausal women are prescribed hormone replacement therapy (HRT). The reasons for the low prescription rate are not known. This study uses data from the United States Renal Data System (USRDS) to assess the prevalence and predictors of HRT use in postmenopausal women with ESRD. METHODS: Data were obtained from the USRDS Dialysis Morbidity and Mortality Study Wave 2. All women who were at least 45 years of age were considered postmenopausal and were selected for our analysis. Demographics, behavior and medical characteristics were abstracted from the database. Logistic regression was used to estimate the independent contribution of population characteristics in predicting the use of HRT. Linear regression models were used to estimate the relationship between HRT use and both triglycerides and total cholesterol. RESULTS: The overall prevalence of HRT prescription was 10.8%. Important predictors of HRT use included age (aOR = 0.74, 95% CI 0.13 to 0.88, P < 0.001), black ethnicity (aOR = 0.50, 95% CI, 0.31 to 0.78, P < 0.002), college education (aOR = 3. 00, 95% CI, 1.70 to 5.24, P < 0.001), and the ability to ambulate (aOR = 1.99, 95% CI, 1.01 to 3.91, P = 0.05). Serum triglyceride and total cholesterol levels were higher among women treated with HRT than among those not treated with HRT (264 +/- 155 vs. 217 +/- 159 mg/dl, P = 0.001 and 220 +/- 62 vs. 209 +/- 55 mg/dl, P = 0.02, respectively). CONCLUSIONS: HRT is prescribed less frequently in postmenopausal ESRD patients than in the general population. Younger age, higher education levels, white race, and the ability to ambulate were important predictors of HRT use. Targeting populations of patients who are likely to benefit from but less likely to be prescribed HRT may increase the prescription of HRT.

Aged↗

PubMed2005

Plasma leptin concentrations in postmenopausal women with osteoporosis.

Osteoporosis is less common in obese individuals with increased bone mineral density (BMD) and plasma leptin concentrations. The aim of this study was to determine the correlation between leptin levels and BMD in postmenopausal women. The study consisted of 90 postmenopausal women with a mean age of 53.45 +/- 0.87 years who visited our outpatient clinic for the evaluation of BMD. Thirty-six post-menopausal women with osteoporosis (mean age: 54.52 +/- 1.41 years and mean body mass index (BMI, kg/m2) 29.33 +/- 0.66), 30 age- and BMI-matched postmenopausal women with normal BMD, and 24 postmenopausal women (mean age: 52.79 +/- 1.48 years and mean BMI: 29.45 +/- 0.89) with osteopenic BMD were included in the study. Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DEXA) at the L2-L4 lumbar spine and femoral neck. The median spine BMD value in the patient group (0.67 +/- 0.08 g/cm2, mean +/- SEM) was significantly lower than that in the control group (1.02 +/- 0.25 g/cm2, mean +/- SEM) and osteopenic group (0.87 +/- 0.05 g/cm2, mean +/- SEM) (p < 0.005). The mean spine BMD value (T score -3.63 +/- 0.25, mean +/- SEM) and the mean femur neck BMD value (T score -2.55 +/- 0.18, mean +/- SEM) of the osteoporosis group were significantly lower than that in the normal BMD group (+ 0.33 +/- 0.14 and + 0.27 +/- 0.18, P < 0.001) and in the osteopenia group (-1.74 +/- 0,1 and -1.18 +/- 0.05, p < 0.005). The mean plasma leptin concentration in the osteoporotic group (17.03 +/- 1.40 ng/ml) was not significantly different from that in the normal BMD group and the osteopenia group (16.55 +/- 1.50 ng/ml; 16.16 +/- 1.60, respectively, p > 0.150). Plasma leptin concentrations were correlated with BMI in three groups (r(s) = 0.450, p = 0.025 in normal BMD group and r(s) = 0.4254, P = 0.009 in the osteoporotic group, and r(s) = 395, p = 0.015 in the osteopenia group. There was no correlation between plasma leptin concentrations and BMD values in three groups (r(s) = -0.89 in normal BMD group, r(s) = -0.124 in osteopenia group, and r(s) = -0.195 in osteoporosis group). From this study we conclude that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.

Absorptiometry, Photon↗

PubMed2004

The relationship between serum dehydroepiandrosterone sulfate concentration and bone mineral density, lipids, and hormone replacement therapy in premenopausal and postmenopausal women.

OBJECTIVE: To investigate the relationship between serum dehydroepiandrosterone sulfate (DHEAS) concentration and bone mineral density (BMD), lipids, and hormone replacement therapy (HRT) in postmenopausal women. METHODS: Two hundred twenty-seven women aged >40 years were admitted to the study and divided into three groups: 61 premenopausal normally menstruating women, 108 postmenopausal women who were not receiving HRT, and 58 postmenopausal women receiving HRT. DHEAS levels and lipid patterns were measured. BMD measurements of the lumbar spine (L1-L4) were performed by dual-energy x-ray absorptiometry (DXA). RESULTS: A positive correlation between DHEAS levels and BMD was found in all three groups. A linear regression model was used to assess the effect of age, body mass index (BMI), parity, and BMD of lumbar vertebrae (L1-L4) on changes in the serum level of DHEAS and found that aging and BMD at the spine had a significant association with serum level of DHEAS and only aging after adjustment for age, BMI, parity, and lipid patterns among the three groups. Age (RR 0.80), DHEAS (RR 0.98), and osteoporosis/osteopenia rate (RR 24.94) were also found to be independent influencing factors for HRT use. CONCLUSIONS: A positive correlation between DHEAS levels and BMD was found in all three groups. Our study confirms earlier reports that DHEAS levels decrease with age in premenopausal and, especially, postmenopausal women regardless of estrogen treatment. DHEAS levels in postmenopausal women were not associated with atherogenic lipid patterns in the present study.

Absorptiometry, Photon↗

PubMed2003

Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women.

BACKGROUND: Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets. Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures. OBJECTIVE: We assessed relations between postmenopausal hip fracture risk and calcium, vitamin D, and milk consumption. DESIGN: In an 18-y prospective analysis in 72 337 postmenopausal women, dietary intake and nutritional supplement use were assessed at baseline in 1980 and updated several times during follow-up. We identified 603 incident hip fractures resulting from low or moderate trauma. Relative risks (RRs) from proportional hazards models were controlled for other dietary and nondietary factors. RESULTS: Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37% lower risk of hip fracture (RR = 0.63; 95% CI: 0.42, 0.94) than did women consuming < 3.5 microg/d. Total calcium intake was not associated with hip fracture risk (RR = 0.96; 95% CI: 0.68, 1.34 for > or = 1200 compared with < 600 mg/d). Milk consumption was also not associated with a lower risk of hip fracture (P for trend = 0.21). CONCLUSIONS: An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women. Neither milk nor a high-calcium diet appears to reduce risk. Because women commonly consume less than the recommended intake of vitamin D, supplement use or dark fish consumption may be prudent.

Animals↗

PubMed2001

The role of calcium in peri- and postmenopausal women: consensus opinion of The North American Menopause Society.

OBJECTIVE: The North American Menopause Society (NAMS) established a goal to review the published medical data and develop an evidence-based consensus opinion regarding the role of calcium in peri- and postmenopausal women. DESIGN: In building this consensus opinion, NAMS followed the general principles established for evidence-based guidelines. As part of that process, NAMS appointed a panel of clinicians and researchers acknowledged to be experts in the field of calcium. Their advice was used to assist the NAMS Board of Trustees in developing this consensus opinion. RESULTS: Adequate calcium intake (in the presence of adequate vitamin D intake) has been shown to prevent bone loss and reduce fracture risk in peri- and postmenopausal women. Although calcium is not as effective as antiresorptive agents (e.g., estrogen, selective estrogen-receptor modulators, or bisphosphonates), it is an essential component of antiresorptive agent therapy for osteoporosis. 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 and mechanisms involved have not been fully explored. Estimates of adequate intakes of calcium for peri- and postmenopausal women are based on evidence relating to osteoporosis prevention. At least 1,200 mg/day of calcium is required for most women; levels greater than 2,500 mg/day are not recommended. To ensure adequate calcium absorption, a daily intake of 400-600 IU of vitamin D is recommended, either through sun exposure or through diet or supplementation. Since no accurate test to determine calcium deficiency exists, clinicians should focus instead on ensuring that a woman consumes enough calcium to meet the recommended levels. CONCLUSION: Although the most definitive role for calcium in peri- and postmenopausal women is in bone health, it is clear that adequate calcium intake has implications that encompass a woman's overall health. Based on the available evidence, a strong statement can be made regarding the importance of ensuring adequate calcium intake in all women, particularly those in peri- or postmenopause.

Aged↗

PubMed1995

Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism.

To elucidate the role of PTH in postmenopausal bone loss, we studied 33 postmenopausal patients who received total thyroidectomy due to thyroid carcinoma. Among these patients, 13 were patients with hypoparathyroid function (HPf), and 20 retained normal parathyroid function (NPf) after thyroidectomy. Bone mineral density (BMD), the rate of BMD loss, and incidence of spinal deformity as well as varying bone metabolic markers were analyzed in all patients. The age-matched BMD was clearly higher, and the incidence of spinal deformity was significantly lower in HPf than in NPf. The rate of BMD loss in HPf was significantly lower than in NPf during the early postmenopausal period (within 5 yr after menopause; mean +/- SD, -0.567 +/- 3.05% vs. -2.49 +/- 1.86%/yr, P < 0.05). In contrast, the rates were similar between the two groups during the late postmenopausal period (> 5 yr after menopause). Bone metabolic markers indicated that an accelerated bone turnover occurred during the early postmenopausal period in NPf, but not in HPf. These results suggest that the hypoparathyroid condition provides protection against age-related bone loss. This is due in part to attenuation of the high turnover bone loss that occurs early in menopause.

Adult↗

PubMed1998

A defect in renal calcium conservation may contribute to the pathogenesis of postmenopausal osteoporosis.

Although all postmenopausal women are estrogen deficient, women who have postmenopausal osteoporosis may have a defect, in addition to estrogen deficiency, that accounts for their higher rates of bone resorption and greater bone loss, relative to those who do not. To test the hypothesis that one defect is an impairment in renal calcium conservation, we measured renal calcium transport in 19 osteoporotic and 19 normal postmenopausal women, whose ages (median and 25th-75th percentile range) were 70 yr (range, 67-72) and 72 yr (range, 69-74), respectively. There was no difference between groups in values for serum ionized calcium and PTH concentrations or in renal filtered load of calcium. However, before PTH infusion, the osteoporotic women had lower (P = 0.0046) values for tubular reabsorption of calcium (TRCa) of 96.8% (range, 96.0-97.1) vs. 98.0% (range, 97.2-98.3) and higher (P = 0.0154) urinary calcium excretion of 0.194 mg/dL of glomerular filtrate (GF) (0.154-0.239) vs. 0.125 mg/dL of GF (0.103-0.173) than the normal women. After infusion of 200 U of synthetic PTH (synthetic 1-34 analog of human PTH), TRCa increased and calcium excretion decreased comparably in both groups, so that the differences between groups after intervention remained: for TRCa, 98.3% (97.7-98.6) vs. 98.9% (98.4-99.3; P = 0.0042); and for calcium excretion, 0.099 mg/dL of GF (0.080-0.138) vs. 0.066 mg/dL of GF, (0.045-0.097, P = 0.0180). In conclusion, postmenopausal women with osteoporosis have a PTH-independent defect in renal calcium conservation. This defect is of sufficient magnitude to contribute to the greater negative calcium balance in post-menopausal women with osteoporosis vs. their postmenopausal peers.

Absorption↗

PubMed2004

Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial.

UNLABELLED: NO regulates bone remodeling in cellular and animal models. We examined the effect of administering ISMO, a NO donor, on bone turnover in 144 postmenopausal women. After 3 months, women randomized to ISMO had a greater decrease in bone resorption and a greater increase in bone formation compared with placebo. NO donors may prevent postmenopausal bone loss. INTRODUCTION: NO both stimulates bone formation and inhibits bone resorption in vitro. NO donors (nitrates) are inexpensive and widely available, but their value for postmenopausal osteoporosis has never been evaluated in a randomized trial. MATERIALS AND METHODS: We randomly assigned 144 healthy postmenopausal women with a hip BMD T score between 0 and -2.5 to 5 or 20 mg/day of isosorbide mononitrate (ISMO) or placebo for 12 weeks. We measured urine N-telopeptide (NTx), a marker of bone resorption, and serum bone-specific alkaline phosphatase (BSALP), a marker of bone formation. Markers were measured immediately before randomization and after 12 weeks of treatment. We calculated the percent change in NTx and BSALP for each of the treatment groups (placebo, 5 mg ISMO, and 20 mg ISMO). Our primary outcome was the percent change in NTx and BSALP in the 5- and 20-mg ISMO groups compared with placebo. RESULTS AND CONCLUSIONS: Compared with women randomized to placebo, women randomized to 20 mg of ISMO had a 45.4% decrease in NTx (95% CI, 25.8-64.9) and a 23.3% increase (95% CI, 8.9-37.8) in BSALP. Women randomized to 5 mg of ISMO had a 36.3% decrease in NTx (95% CI, 14.8-57.8) and a 15.9% increase in BSALP (95% CI, 1.1-30.7). ISMO decreases bone resorption and increases bone formation. These findings suggest that nitrates may be useful for the prevention of postmenopausal osteoporosis.

Aged↗

PubMed2005

Rate of forearm bone loss is associated with an increased risk of fracture independently of bone mass in postmenopausal women: the OFELY study.

UNLABELLED: BMD is a major determinant of the risk of fragility fractures, but the role of the rate of postmenopausal bone loss is still unclear. In 671 postmenopausal women from the OFELY cohort, we found that the rate of bone loss was significantly associated with fracture risk independently of other well-known predictors including BMD and previous fractures. INTRODUCTION: The level of BMD is a major determinant of the risk of fragility fractures, but the role of the rate of postmenopausal bone loss is still unclear. MATERIALS AND METHODS: In the OFELY study, we analyzed the risk of fracture in 671 postmenopausal women (mean age, 62.2 +/- 9 years), according to the rate of bone loss. BMD was measured annually by DXA at the forearm, with a mean number of measurements of 10.3 +/- 2.6. Peripheral fractures, all confirmed by radiographs, were prospectively registered, and vertebral fractures were evaluated with spine radiographs every 4 years. RESULTS: During a median (interquartile range [IQ]) of 11.2 years (11-12.3 years) of follow-up, 183 incident fragility fractures including 53 vertebral and 130 nonvertebral fractures were recorded in 134 women. The annual median +/- IQ rate of bone loss, calculated from the slope, was -0.30 +/- 0.76% at the mid-radius, -0.55 +/- 0.79% at the distal radius, and -0.40 +/- 0.96% at the ultradistal radius. Women with incident fracture had a rate of bone loss (before fracture) higher by 38-53% than those without fracture (p = 0.0003-0.016). Using multivariate Cox regression models, we found that bone loss in the highest tertile at the mid-radius, distal radius, and ultradistal radius was associated with a significant increased risk of all fractures with an hazard ratio from 1.45 to 1.70 (p = 0.02 to p = 0.009 after adjusting for age, previous fractures, maternal history of fracture, physical activity, grip strength, falls, and baseline BMD). CONCLUSIONS: The rate of bone loss in postmenopausal women is significantly associated with fracture risk independently of other well-known predictors such as BMD and history of fractures.

Adult↗

PubMed2005

Relationship between osteoporosis and cardiovascular disease in postmenopausal women.

UNLABELLED: In the placebo group of the MORE study, including 2576 postmenopausal women (mean age, 66.5 years), the authors describe a strong linear association between the severity grade of osteoporosis (from low BMD to presence of severe vertebral fractures) and the future risk of cardiovascular events. Accordingly, treatment of postmenopausal osteoporosis should include consideration of measures to prevent adverse cardiovascular outcomes. INTRODUCTION: Observations indicate an inverse association between BMD and the severity of peripheral atherosclerosis in postmenopausal women. The predictive value of osteoporosis and its different severity stages for the risk of acute cardiovascular events remains unknown. MATERIALS AND METHODS: Participants were 2576 women (mean age, 66.5 years) assigned to placebo and followed for 4 years in an osteoporosis treatment trial. Those with at least one vertebral fracture or total hip BMD T score < or = -2.5 at baseline were defined as having osteoporosis, whereas those without vertebral fracture and total hip BMD T score between -2.5 and -1 were defined as having low bone mass. The primary outcome for these posthoc analyses was the incidence of adjudicated fatal or nonfatal cardiovascular events. RESULTS: After adjustment for potential confounders, women with osteoporosis had a 3.9-fold (95% CI, 2.0-7.7; p < 0.001) increased risk for cardiovascular events compared with women with low bone mass. Under the same boundaries, a total hip BMD T score < or = -2.5 versus a T score between -2.5 and -1 was associated with a 2.1-fold (95% CI, 1.2-3.6; p < 0.01) increase in risk, whereas presence of at least one vertebral fracture versus no vertebral fracture at baseline was associated with a 3.0-fold (95% CI, 1.8-5.1; p < 0.001) increase in risk. The risk of cardiovascular events increased incrementally with the number and increasing severity of baseline vertebral fractures (both p < 0.001). CONCLUSIONS: Postmenopausal women with osteoporosis are at an increased risk for cardiovascular events that is proportional to the severity of osteoporosis at the time of the diagnosis. Treatment of postmenopausal osteoporosis should include consideration of measures to prevent cardiovascular outcomes.

Aged↗

PubMed2005

Use of clinical prediction rules in detecting osteoporosis in a population-based sample of postmenopausal women.

BACKGROUND: Osteoporosis clinical prediction rules attempt to identify the postmenopausal women in whom, on the basis of individual risk factors, bone densitometry will detect low bone mass. We assessed and compared the diagnostic properties of the following 3 osteoporosis clinical prediction rules: the Simple Calculated Osteoporosis Risk Estimation, Osteoporosis Risk Assessment Instrument, and National Osteoporosis Foundation practice guidelines. METHODS: Secondary data analysis of an existing population-based sample of postmenopausal women 45 years or older (N = 202) in Rochester, Minn. RESULTS: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and positive (LR+) and negative (LR-) likelihood ratios were calculated using the World Health Organization diagnosis of osteoporosis as the reference standard. The Simple Calculated Osteoporosis Risk Estimation had a sensitivity of 100%, specificity of 29%, PPV of 27%, NPV of 100%, LR+ of 1.4, and LR- of 0. The Osteoporosis Risk Assessment Instrument had a sensitivity of 98%, specificity of 40%, PPV of 29%, NPV of 77%, LR+ of 1.4, and LR- of 0.4. The National Osteoporosis Foundation practice guidelines had a sensitivity of 100%, specificity of 10%, PPV of 27%, NPV of 100%, LR+ of 1.1, and LR- of 0. The Simple Calculated Osteoporosis Risk Estimation and Osteoporosis Risk Assessment Instrument were much more specific in postmenopausal women younger than 65 years compared with those 65 years or older. CONCLUSIONS: Our results suggest that these clinical prediction rules do not perform well as a general screening method to identify postmenopausal women who are more likely to have osteoporosis; however, the Osteoporosis Risk Assessment Instrument and Simple Calculated Osteoporosis Risk Estimation may be useful in identifying some women who need not undergo testing, especially younger postmenopausal women.

Absorptiometry, Photon↗

PubMed1994

Hypercholesterolemia in postmenopausal women. Metabolic defects and response to low-dose lovastatin.

OBJECTIVE: To determine the metabolic mechanisms underlying hypercholesterolemia in postmenopausal women and to determine whether a low dose of lovastatin will correct this abnormality. DESIGN: In the first part of the study, turnover rates of autologous low-density lipoprotein (LDL) were measured in hypercholesterolemic and control women. In the second part, hypercholesterolemic women participated in a placed-controlled, randomized, double-blind study using lovastatin as the therapeutic agent. SETTING: The General Clinical Research Center of the University of Texas Southwestern Medical Center, Dallas, utilizing inpatient and outpatient facilities, and the Veterans Affairs Medical Center, Dallas, Tex. PATIENTS: For the LDL turnover study, 26 postmenopausal women with moderate hypercholesterolemia (mean +/- SD LDL cholesterol, 4.78 +/- 0.59 mmol/L [185 +/- 23 mg/dL]) and 13 postmenopausal women with normal levels of plasma lipids and lipoproteins (mean +/- SD LDL cholesterol, 3.31 +/- 0.39 mmol/L [128 +/- 15 mg/dL]) were studied. Sixteen postmenopausal women participated in the drug study. INTERVENTIONS: In the drug study, patients received blindly both lovastatin (10 mg/d) and placebo. MAIN OUTCOME MEASURES: In the first study, kinetic parameters of LDL metabolism; in the second study, response in lipids and lipoproteins to lovastatin therapy. RESULTS: In the LDL turnover study, mean (+/- SD) input (production) rates for LDL apolipoprotein B (apo B) were similar for hypercholesterolemic women and control women (12.4 [+/- 3.2] mg/kg per day and 11.1 [+/- 2.2] mg/kg per day, respectively). In contrast, mean (+/- SD) fractional catabolic rates for LDL apo B in hypercholesterolemic women (0.29 [+/- 0.04] pools per day) were significantly lower than those in normolipidemic women (0.35 [+/- 0.03] pools per day). In the drug trial, lovastatin therapy reduced mean (+/- SD) total cholesterol and LDL cholesterol from 7.03 (+/- 1.16) mmol/L (272 [+/- 45] mg/dL) and 4.42 (+/- 0.80) mmol/L (171 [+/- 31] mg/dL, respectively, to 5.70 (+/- 1.03) mmol/L (221 [+/- 40] mg/dL) and 3.46 (+/- 0.85) mmol/L (134 [+/- 33] mg/dL). CONCLUSIONS: The turnover data suggest that hypercholesterolemia in post-menopausal women is primarily attributable to a reduced activity of LDL receptors. In accord, the hypercholesterolemia in these women was effectively lowered by low doses of lovastatin. Thus, a low dose of lovastatin appears highly effective for treatment of moderate hypercholesterolemia in most postmenopausal women, presumably because it reverses the reduction in LDL receptor activity associated with menopause.

Aged↗

PubMed1998

Estrogen therapy in postmenopausal women: effects on cognitive function and dementia.

CONTEXT: Several studies have suggested that estrogen replacement therapy in postmenopausal women improves cognition, prevents development of dementia, and improves the severity of dementia, while other studies have not found a benefit of estrogen use. OBJECTIVE: To determine whether postmenopausal estrogen therapy improves cognition, prevents development of dementia, or improves dementia severity. DATA SOURCES: We performed a literature search of studies published from January 1966 through June 1997, using MEDLINE, manually searched bibliographies of articles identified, and consulted experts. STUDY SELECTION: Studies that evaluated biological mechanisms of estrogen's effect on the central nervous system and studies that addressed the effect of estrogen on cognitive function or on dementia. DATA EXTRACTION: We reviewed studies for methods, sources of bias, and outcomes and performed a meta-analysis of the 10 studies of postmenopausal estrogen use and risk of dementia using standard meta-analytic methods. DATA SYNTHESIS: Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition: promotion of cholinergic and serotonergic activity in specific brain regions, maintenance of neural circuitry, favorable lipoprotein alterations, and prevention of cerebral ischemia. Five observational studies and 8 trials have addressed the effect of estrogen on cognitive function in nondemented postmenopausal women. Cognition seems to improve in perimenopausal women, possibly because menopausal symptoms improve, but there is no clear benefit in asymptomatic women. Ten observational studies have measured the effect of postmenopausal estrogen use on risk of developing dementia. Meta-analysis of these studies suggests a 29% decreased risk of developing dementia among estrogen users, but the findings of the studies are heterogeneous. Four trials of estrogen therapy in women with Alzheimer disease have been conducted and have had primarily positive results, but most have been small, of short duration, non-randomized, and uncontrolled. CONCLUSIONS: There are plausible biological mechanisms by which estrogen might lead to improved cognition, reduced risk for dementia, or improvement in the severity of dementia. Studies conducted in women, however, have substantial methodologic problems and have produced conflicting results. Large placebo-controlled trials are required to address estrogen's role in prevention and treatment of Alzheimer disease and other dementias. Given the known risks of estrogen therapy, we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed.

Alzheimer Disease↗

PubMed1999

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Adult↗

PubMed2002

Walking and leisure-time activity and risk of hip fracture in postmenopausal women.

CONTEXT: Physical activity can reduce the risk of hip fractures in older women, although the required type and duration of activity have not been determined. Walking is the most common activity among older adults, and evidence suggests that it can increase femoral bone density and reduce fracture risk. OBJECTIVE: To assess the relationship of walking, leisure-time activity, and risk of hip fracture among postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Prospective analysis begun in 1986 with 12 years of follow-up in the Nurses' Health Study cohort of registered nurses within 11 US states. A total of 61,200 postmenopausal women (aged 40-77 years and 98% white) without diagnosis of cancer, heart disease, stroke, or osteoporosis at baseline. MAIN OUTCOME MEASURES: Incident hip fracture resulting from low or moderate trauma, analyzed by intensity and duration of leisure-time activity and by time spent walking, sitting, and standing, measured at baseline and updated throughout follow-up. RESULTS: From 1986 to 1998, 415 incident hip fracture cases were identified. After controlling for age, body mass index, use of postmenopausal hormones, smoking, and dietary intakes in proportional hazards models, risk of hip fracture was lowered by 6% (95% confidence interval [CI], 4%-9%; P<.001) for each increase of 3 metabolic equivalent (MET)-hours per week of activity (equivalent to 1 h/wk of walking at an average pace). Active women with at least 24 MET-h/wk had a 55% lower risk of hip fracture (relative risk [RR], 0.45; 95% CI, 0.32-0.63) compared with sedentary women with less than 3 MET-h/wk. Even women with a lower risk of hip fracture due to higher body weight experienced a further reduction in risk with higher levels of activity. Risk of hip fracture decreased linearly with increasing level of activity among women not taking postmenopausal hormones (P<.001), but not among women taking hormones (P =.24). Among women who did no other exercise, walking for at least 4 h/wk was associated with a 41% lower risk of hip fracture (RR, 0.59; 95% CI, 0.37-0.94) compared with less than 1 h/wk. More time spent standing was also independently associated with lower risks. CONCLUSION: Moderate levels of activity, including walking, are associated with substantially lower risk of hip fracture in postmenopausal women.

Adult↗

PubMed2004

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.

CONTEXT: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. MAIN OUTCOME MEASURES: The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. RESULTS: In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

Aged↗

PubMed2001

Risk factors of endometrial polyps resected from postmenopausal patients with breast carcinoma treated with tamoxifen.

BACKGROUND: Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure. Up to 3% of these polyps may show malignant changes. However, to the authors' knowledge no one has described any risk factor for the development of this pathology in postmenopausal patients with breast carcinoma treated with tamoxifen. OBJECTIVE. The objective of this study was to evaluate whether risk factors can be identified for the development of endometrial polyps in postmenopausal patients with breast carcinoma treated with tamoxifen. METHODS: The authors reviewed the medical records of 54 postmenopausal patients with breast carcinoma in whom endometrial polyps were resected by hysteroscopy after at least 6 months of tamoxifen treatment (Group I). Demographic characteristics, health habits, risk factors for endometrial carcinoma, and clinical factors related to the primary breast disease were examined. The results were compared with those obtained from 210 similar patients in whom hysteroscopy did not reveal any endometrial pathology (Group II). RESULTS: Age at menopause was significantly older, duration of breast disease was significantly longer, and body weight was significantly heavier among Group I patients compared with Group II patients (P = 0.0162, P = 0.0026, and P = 0.0364, respectively). Endometrial thickness, measured by transvaginal ultrasonography, was significantly thicker in Group I patients (16.3 +/- 7.2 mm) compared with that detected in Group II patients (11.8 +/- 6.3; P = 0.0001). CONCLUSIONS: Various factors, such as older age at menopause, longer duration of breast disease, heavier weight, and thicker endometrium may contribute to the prediction of increased risk of development of endometrial polyps in postmenopausal patients with breast carcinoma treated with tamoxifen.

Antineoplastic Agents, Hormonal↗

PubMed2026

Long-term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women. SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024. SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms. AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.

Humans↗