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PubMed2006

Adult weight change and risk of postmenopausal breast cancer.

CONTEXT: Endogenous hormones are a primary cause of breast cancer. Adiposity affects circulating hormones, particularly in postmenopausal women, and may be a modifiable risk factor for breast cancer. OBJECTIVE: To assess the associations of adult weight change since age 18 years and since menopause with the risk of breast cancer among postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study within the Nurses' Health Study. A total of 87,143 postmenopausal women, aged 30 to 55 years and free of cancer, were followed up for up to 26 years (1976-2002) to assess weight change since age 18 years. Weight change since menopause was assessed among 49,514 women who were followed up for up to 24 years. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Overall, 4393 cases of invasive breast cancer were documented. Compared with those who maintained weight, women who gained 25.0 kg or more since age 18 years were at an increased risk of breast cancer (relative risk [RR], 1.45; 95% confidence interval [CI], 1.27-1.66; P<.001 for trend), with a stronger association among women who have never taken postmenopausal hormones (RR,1.98; 95% CI, 1.55-2.53). Compared with weight maintenance, women who gained 10.0 kg or more since menopause were at an increased risk of breast cancer (RR, 1.18; 95% CI, 1.03-1.35; P = .002 for trend). Women who had never used postmenopausal hormones, lost 10.0 kg or more since menopause, and kept the weight off were at a lower risk than those who maintained weight (RR, 0.43; 95% CI, 0.21-0.86; P = .01 for weight loss trend). Overall, 15.0% (95% CI, 12.8%-17.4%) of breast cancer cases in this population may be attributable to weight gain of 2.0 kg or more since age 18 years and 4.4% (95% CI, 3.6%-5.5%) attributable to weight gain of 2.0 kg or more since menopause. Among those who did not use postmenopausal hormones, the population attributable risks are 24.2% (95% CI, 19.8%-29.1%) for a weight gain since age 18 years and 7.6% (95% CI, 5.9%-9.7%) for weight gain since menopause. CONCLUSIONS: These data suggest that weight gain during adult life, specifically since menopause, increases the risk of breast cancer among postmenopausal women, whereas weight loss after menopause is associated with a decreased risk of breast cancer. Thus, in addition to other known benefits of healthy weight, our results provide another reason for women approaching menopause to maintain or lose weight, as appropriate.

Adiposity↗

PubMed2006

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

BACKGROUND: Strontium ranelate is a new anti-osteoporosis therapy therefore, its benefits and harms need to be known. OBJECTIVES: To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors and industry sponsors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life and/or safety outcomes in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. DATA COLLECTION AND ANALYSIS: Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. MAIN RESULTS: A total of four trials met our inclusion criteria, three of which investigated the effects of strontium ranelate compared to placebo in a treatment population (doses ranged from 0.5 to 2 g daily) and one, in a prevention population (doses 0.125, 0.5 and 1 g daily). In osteoporotic, postmenopausal women a 37% reduction in vertebral fractures (two trials, n = 5082, RR 0.63, 95% CI 0.56 to 0.71) and a 14% reduction in non-vertebral fractures (two trials, n = 6572, RR 0.86, 95% CI 0.75 to 0.98) was demonstrated over a three year period with 2 g of strontium ranelate daily. An increase in BMD at all sites was shown with the same dose: lumbar spine BMD (two trials, n = 1614, WMD adjusted for strontium content 5.44, 95% CI 3.41 to 7.46 and WMD not adjusted 11.29, 95% CI 10.22 to 12.37 over two years), femoral neck and total hip (two trials, n = 4230, WMD 8.25, 95% CI 7.84 to 8.66 and WMD 9.83, 95% CI 9.39 to 10.26 respectively over three years). One gram of strontium ranelate daily in postmenopausal women without osteoporosis increased BMD at all sites over a two year period: lumbar spine (one trial, n = 59, WMD adjusted for strontium content 2.39, 95% CI 0.15 to 4.63 and WMD not adjusted 6.68, 95% CI 5.16 to 8.20), femoral neck (one trial, n= 60, WMD 2.52, 95%CI 0.96 to 4.09) and total hip (one trial, n = 60, WMD 1.02, 95% CI 0.48 to 1.56). In both the treatment and prevention populations, lower doses of strontium ranelate were superior to placebo with the highest dose of strontium ranelate demonstrating the greatest reduction in vertebral fractures and increase in BMD. There is some evidence to suggest that 2 g of strontium ranelate daily compared to placebo may have a beneficial effect on health related quality of life in postmenopausal women after three years of treatment. Two grams of strontium ranelate daily increased the risk of diarrhea (RR 1.38%, 95% CI 1.02 to 1.87); however, adverse events did not affect the risk of discontinuing strontium ranelate nor did it increase the risk of serious side effects, gastritis or death. Additional data obtained suggests that the risk of vascular system disorders including venous thromboembolism (two trials, n = 6669, 2.2% versus 1.5%, OR 1.5, 95% CI 1.1 to 2.1) and pulmonary embolism (two trials, n = 6669, 0.8% versus 0.4%, OR 1.7, 95% CI 1.0 to 3.1) as well as nervous system disorders such as headaches (3.9% versus 2.9%), seizures (0.3% versus 0.1%), memory loss (2.4% versus 1.9%) and disturbance in consciousness (2.5% versus 2.0%) is slightly increased with taking 2 g of strontium ranelate daily over a 3 to 4 year period. AUTHORS' CONCLUSIONS: There is silver level evidence to support the efficacy of strontium ranelate for the reduction of vertebral fractures (and to a lesser extent non-vertebral fractures) in postmenopausal osteoporotic women and an increase in BMD (all sites) in postmenopausal women with and without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased in the strontium ranelate group. Potential risks to the vascular and neurological system associated with taking 2 g of strontium ranelate daily need to be further explored and quantified.

Bone Density↗

PubMed2001

Clinical relevance of benign endometrial cells in postmenopausal women.

Our objective was to determine if the finding of benign endometrial cells on a Papanicolaou (Pap) smear of a postmenopausal woman is associated with endometrial/uterine pathology, independent of symptomatology and hormone replacement therapy (HRT) status. The medical records of 146 postmenopausal patients who had a Pap smear showing normal-appearing endometrial cells between January 9, 1997 and January 12, 2000 were reviewed. Uterine pathology for each patient was determined by reviewing the results of endometrial sampling (endometrial biopsy or dilatation and curettage), hysterectomy, or pelvic sonogram, which were performed within 24 mo of the cytologic smear. The results were then correlated with clinical symptomatology and HRT status of each patient at the time the cytologic smear was obtained. Of the 146 Pap smears coded with "endometrial cells in a postmenopausal woman," 50 were excluded due to prior hysterectomy, perimenopausal status, and absence of further follow-up. Of the remaining 96 women, 27 (28%) had benign pathologic findings including polyps, leiomyomata, and simple hyperplasia without atypia, whereas 11 (12%) had significant pathologic findings including hyperplasia with atypia, adenocarcinoma, mixed Mullerian tumor, and leiomyosarcoma. Of the 11 patients with significant pathology, only one patient did not have abnormal vaginal bleeding but instead had a 30-wk-size irregular uterus on examination, and only 2 patients received hormone replacement therapy. In conclusion, Reporting endometrial cells on Pap smears in postmenopausal women did not lead to the diagnosis of any cases of significant pathology that would have gone unsuspected clinically. Moreover, HRT status did not affect the incidence of normal endometrial cells on Pap smears in postmenopausal women, nor did it aid in distinguishing which postmenopausal women had endometrial/uterine pathology. This calls into question the usefulness of the current Bethesda guideline to report "benign endometrial cells in a postmenopausal woman."

Aged↗

PubMed1994

Analysis of gene expression in human bone biopsies by polymerase chain reaction: evidence for enhanced cytokine expression in postmenopausal osteoporosis.

It has been suggested that one of the mechanisms by which estrogen protects against postmenopausal osteoporosis is by modulating the production of cytokines, such as interleukin-1 (IL-1), tumor necrosis factors (TNF), and interleukin-6 (IL-6), in the bone microenvironment. In this study, reverse transcription/polymerase chain reaction (RT/PCR) was used to analyze expression of the mRNAs encoding these cytokines in freshly isolated human bone biopsy samples. Marked differences were found in the prevalence with which certain cytokines were expressed in different patient subgroups. Specifically, IL-1 alpha, IL-1 beta, and IL-6 mRNAs were expressed significantly more often in bone samples from postmenopausal women with osteoporotic fractures than in postmenopausal women with normal bone density or postmenopausal women on hormone replacement therapy (HRT). The prevalence of IL-1 alpha expression was 54% in bone samples from patients with osteoporotic fractures (n = 22), compared with 30% in nonosteoporotic postmenopausal patients (n = 10) and 10% in postmenopausal patients on HRT (difference between groups by chi 2 test = 7.0; DF = 2, p < 0.05). Corresponding figures for IL-1 beta were 54 versus 30 versus 0% (chi 2 = 8.6; DF = 2, p < 0.01) and, for IL-6, 94 versus 51 versus 40%; chi 2 = 13.5; DF = 2, p < 0.01). TNF-alpha was expressed in a similar proportion of osteoporotic (63%) and normal postmenopausal patients (60%), whereas only 10% of HRT-treated patients showed expression of TNF-alpha (chi 2 = 8.2; DF = 2, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMed2004

How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding.

OBJECTIVE: Transvaginal sonography (TVS) is routinely performed as part of a pelvic sonogram in postmenopausal women, and images of the endometrium are frequently obtained. In women without vaginal bleeding, the threshold separating normal from abnormally thickened endometrium is not known. The aim of this study was to determine an endometrial thickness threshold that should prompt biopsy in a postmenopausal woman without vaginal bleeding. METHODS: This was a theoretical cohort of postmenopausal women aged 50 years and older who were not receiving hormone therapy. We determined the risk of cancer for a postmenopausal woman with vaginal bleeding when the endometrial thickness measures > 5 mm, and then determined the endometrial thickness in a woman without vaginal bleeding that would be associated with the same risk of cancer. We used published and unpublished data to determine the sensitivity and specificity of TVS, the incidence of endometrial cancer, the percentage of women symptomatic with vaginal bleeding, and the percentage of cancer that occurs in women without vaginal bleeding. Ranges for each estimate were included in a sensitivity analysis to determine the impact of each estimate on the overall results. RESULTS: In a postmenopausal woman with vaginal bleeding, the risk of cancer is approximately 7.3% if her endometrium is thick (> 5 mm) and < 0.07% if her endometrium is thin (< or = 5 mm). An 11-mm threshold yields a similar separation between those who are at high risk and those who are at low risk for endometrial cancer. In postmenopausal women without vaginal bleeding, the risk of cancer is approximately 6.7% if the endometrium is thick (> 11 mm) and 0.002% if the endometrium is thin (< or = 11 mm). The estimated risk of cancer was sensitive to the percentage of cancer cases that were estimated to occur in women without vaginal bleeding. For the base case we estimated that 15% of cancers occur in women without vaginal bleeding. When we changed the estimate to project that only 5% of cancers occur in women without vaginal bleeding, the projected risk of cancer with a thick measurement was only 2.2%, whereas when we estimated that 20% of endometrial cancers occur in women without bleeding, the projected risk of cancer with a thick measurement was 8.9%. As a woman's age increases, her risk of cancer increases at each endometrial thickness measurement. For example, using the 11 mm threshold, the risk of cancer associated with a thick endometrium increases from 4.1% at age 50 years to 9.3% at age 79 years. Varying the other estimates used in the decision analysis within plausible ranges had no substantial effect on the results. CONCLUSIONS: In a postmenopausal woman without vaginal bleeding, if the endometrium measures > 11 mm a biopsy should be considered as the risk of cancer is 6.7%, whereas if the endometrium measures < or = 11 mm a biopsy is not needed as the risk of cancer is extremely low.

Aged↗

PubMed1998

Determination of a normal level of serum CA125 in postmenopausal women as a tool for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

In an attempt to determine a normal level of CA125 in postmenopausal women, CA125 levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8 +/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was found in postmenopausal women without HRT and was significantly lower than that of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the cutoff level of CA125 in postmenopausal women or women without reproductive organs should be estimated at a level lower than that conventionally accepted. A receiver operating characteristic (ROC) curve for a preoperative evaluation of myometrial invasion was analyzed in postmenopausal women with endometrial cancer (n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial invasion to more than one-half of the myometrium with sensitivity of 69.0%, specificity of 74.1%, positive predictive value of 58.8%, and negative predictive value of 81.6%. In addition, the distribution of CA125 levels was analyzed in patients who had undergone an operation for endometrial cancer more than 2 years earlier and as yet had no clinical evidence of recurrence of the disease. Ninety-six point two percent of 619 measurement values were lower than 20 U/ml. These results suggest that the novel CA125 level of 20 U/ml is clinically useful for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

Aged↗

PubMed1999

Adipose tissue distribution in postmenopausal women with adenomatous hyperplasia of the endometrium.

OBJECTIVE: To investigate body fat distribution in postmenopausal women with adenomatous and atypical hyperplasia of the endometrium. METHODS: A prospective population-based case control study was performed in a health care county in Sweden. General obesity, as reflected by body mass index (BMI), and adipose tissue distribution, expressed as waist to hip circumference ratio (WHR), were evaluated in a cohort of 367 postmenopausal women who underwent dilatation and curettage because of uterine bleeding. The study group consisted of 29 women with adenomatous or atypical hyperplasia of the endometrium. The controls consisted of 49 age-matched postmenopausal women randomly selected from the computerized population register of the same region. RESULTS: The frequency of endometrial adenomatous and atypical hyperplasia in postmenopausal women with bleeding was 7.2%. In the total population of postmenopausal women the incidence of these endometrial lesions was 44 per 100,000 per year. Body weight (P = 0.039), BMI (P = 0.007), and WHR (P = 0.022) were higher in postmenopausal women with endometrial adenomatous and atypical hyperplasia than in controls. In multivariate analysis only BMI remained statistically associated with adenomatous hyperplasia (P = 0.012). CONCLUSIONS: General obesity, but neither upper nor lower body fat distribution, was characteristic of postmenopausal women with adenomatous and atypical hyperplasia of the endometrium. Overall obesity is a risk factor for these endometrial precancerous lesions, as it is also claimed to be for endometrial cancer.

Adipose Tissue↗

PubMed1999

Malignant endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients.

BACKGROUND: Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure. It is generally accepted that the occurrence of malignancy in endometrial polyps among healthy women is up to 0.5%. However, no one has yet described the incidence of this malignant transformation among postmenopausal breast cancer tamoxifen-treated patients. Objective. The aim of this study was to study the exact rate of malignant changes in endometrial polyps recovered from postmenopausal breast cancer tamoxifen-treated patients. METHODS: We reviewed the pathological results and medical records of all postmenopausal breast cancer patients in whom endometrial polyps were recovered following at least 6 months of tamoxifen treatment in our institute. We also looked for the rate of malignant changes in polyps recovered from all healthy postmenopausal controls with endometrial polyps in our institute during the period of the study. RESULTS: Two (3.0%) of 67 endometrial polyps recovered from postmenopausal breast cancer tamoxifen-treated patients revealed malignant features. None of the clinical variables tested, including risk factors for endometrial cancer, was significantly different between the groups. In the controls only 5 (0.48%) of 1034 polyps were malignant. CONCLUSION: Up to 3.0% of endometrial polyps recovered from postmenopausal breast cancer tamoxifen-treated patients may show malignant changes. This rate is higher than that found in our controls as well as that reported in the general female population.

Aged↗

PubMed1998

Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis.

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1-84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1-84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1-84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1-84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1-84) and serum phosphate was absent and PTH (1-84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1-84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1-84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest that normal dynamics of PTH (1-84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.

Adult↗

PubMed2006

Strategies for the prevention and treatment of osteoporosis during early postmenopause.

During the perimenopause, both the quantity and quality of bone decline rapidly, resulting in a dramatic increase in the risk of fracture in postmenopausal women. Although many factors are known to be associated with osteoporotic fractures, measures to identify and treat women at risk are underused in clinical practice. Consequently, osteoporosis is frequently not detected until a fracture occurs. Identification of postmenopausal women at high risk of fracture therefore is a priority and is especially important for women in early postmenopause who can benefit from early intervention to maintain or to increase bone mass and, thus, reduce the risk of fracture. Most authorities recommend risk-factor assessment for all postmenopausal women, followed by bone mineral density measurements for women at highest risk (ie, all women aged > or =65 years, postmenopausal women aged <65 years with > or =1 additional risk factors for osteoporosis, and postmenopausal women with fragility fractures). All postmenopausal women can benefit from nonpharmacologic interventions to reduce the risk of fracture, including a balanced diet with adequate intake of calcium and vitamin D, regular exercise, measures to prevent falls or to minimize their impact, smoking cessation, and moderation of alcohol intake. Several pharmacologic agents, including the bisphosphonates (eg, alendronate, risedronate, and ibandronate) and the selective estrogen receptor modulator, raloxifene, have been shown to increase bone mass, to reduce fracture risk, and to have acceptable side-effect profiles. Women who have discontinued hormone therapy are in particular need of monitoring for fracture risk, in light of the accelerated bone loss and increased risk of fracture that occurs after withdrawal of estrogen treatment.

Accidental Falls↗

PubMed2001

Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women.

OBJECTIVE: To evaluate the effects of dietary isoflavones in soy products on menopausal symptoms, lipid profiles, and bone mineral densities in postmenopausal Japanese women. METHODS: We estimated the daily intakes of isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption. We recorded serum values of fasting total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoproteins. Bone mineral density was measured at the lumbar spine (L2-L4) by dual energy x-ray absorptiometry. Women were assigned to two groups according to years since menopause (early and late postmenopausal groups), and each group was subcategorized into four groups according to dietary isoflavone intake. Relationships between isoflavone intake, menopausal symptoms, lipid profiles, and bone mineral density were examined in each group. RESULTS: The mean estimated intake of isoflavones among 478 women was 54.3 mg/day. With stepwise regression analysis we found that weight and years since menopause were significant independent predictors of bone mineral density. Bone mineral densities adjusted to years since menopause and weight were significantly different in the highest intake compared with lowest intake category (P <.001) within the early and late postmenopausal groups. In the early postmenopausal group, significant differences were found in palpitation and backaches between the high and low intake categories but were not significant in the late postmenopausal group. CONCLUSION: High consumption of soy products is associated with increased bone mass in postmenopausal women and might be useful for preventing hypoestrogenic effects.

Adult↗

PubMed2001

Bladder neck circulation by Doppler ultrasonography in postmenopausal women with urinary stress incontinence.

OBJECTIVE: To investigate the effect of hormone replacement therapy (HRT) on bladder neck circulation in postmenopausal women with genuine urinary stress incontinence (USI). METHODS: A total of 227 women were enrolled in the study, including 114 postmenopausal women with USI (n = 57) or without USI (n = 57) and 113 premenopausal women with USI (n = 55) or without USI (n = 58). The bladder neck circulation was measured in 31 postmenopausal women with USI and in 12 without USI, all of whom received 0.625 mg conjugated equine estrogen plus 5 mg medroxyprogesterone acetate daily for 6 months. Bladder neck blood flow data detected by perineal color Doppler ultrasonography and weekly urinary diary data were collected before HRT and then 3 and 6 months after beginning HRT. Two-way analysis of variance and repeated measures of variance were used for statistical analysis. Power analysis was done by a two-sided test with a significance level at.05. RESULTS: The pulsatility index (PI) was significantly higher in the postmenopausal than in the premenopausal women. The postmenopausal women with USI had the highest PI level. The presence of USI did not change the PI values in the premenopausal women. After 3 months of HRT, the PI levels decreased significantly (P <.001) in the postmenopausal women with USI. The subjective improvement of USI appeared after 3 months of HRT. CONCLUSION: The blood flow around the bladder neck in women can be measured by perineal color Doppler ultrasonography. Hormone replacement therapy increases the blood flow around the bladder neck in postmenopausal women with USI. The clinical improvement of USI can be seen with HRT after 3 months.

Female↗

PubMed2001

Comparison of quantitative ultrasound parameters with dual energy X-ray absorptiometry in pre- and postmenopausal women.

BACKGROUND: Quantitative ultrasound (QUS) has been claimed as an alternative technique for risk assessment of hip fractures associated with osteoporosis. However, reports concerning modest correlations between QUS parameters and dual energy X-ray absorptiometry (DXA) in women raise questions about the reliability of QUS technology to predict bone mineral density (BMD). Partially, the lack of stronger correlations may be due to heterogeneity in bone architecture deterioration which may be more pronounced in older than in younger women. Therefore, it was thought important to study QUS/DXA interrelationships in subgroups of pre- and postmenopausal women. METHODS: We studied 217 pre- and postmenopausal women between the ages of 25 and 75 years, who were referred for a BMD measurement because of osteoporosis in at least one family member either in the first or in the second degree. All women had a calcaneal QUS and a DXA measurement at the lumbar spine, total hip and femoral neck. RESULTS: The linear regression coefficients between the QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) and DXA at the various sites in the group as a whole were 0.53 to 0.54 (P<0.0001). Significantly lower regression coefficients between BUA and DXA at the total hip and the femoral neck were found in premenopausal women (r=0.31 and 0.38, P<0.0001) compared to postmenopausal women (r=0.56 and 0.53, P<0.0001). For SOS there was no significant difference between the regression coefficients in the pre- and postmenopausal group. The overall prevalence of osteoporosis as assessed by DXA in the total group was 25% (6% in the pre- and 36% in the postmenopausal group). BUA failed to detect osteoporosis in all five premenopausal women but also in 20 out of 50 postmenopausal women with osteoporosis according to DXA measurements. SOS measurements were even worse in this respect. CONCLUSIONS: Linear regression coefficients between calcaneal QUS parameters and DXA are only modest considering a group of 25--75-year-old Dutch women. In the subgroup of premenopausal women correlations between BUA and BMD at the hip and femoral neck are worse compared to those in postmenopausal women. The predictive value of QUS parameters for BMD is limited, therefore it is not appropriate to use QUS as a surrogate for DXA.

Absorptiometry, Photon↗

PubMed2000

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy.

OBJECTIVE: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. METHODS: premenopausal women with normal cycles (n=30; mean ages, 35.4+/-8.3 years) and postmenopausal women (n=45; mean ages, 49.5+/-4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m(2)) and as non-obese (BMI<27 kg/m(2)). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. RESULTS: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18. 60+/-5.0; 3.67+/-2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60+/-7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50+/-4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05+/-10.53; 14.78+/-6.76 ng/ml, respectively, P<0.001). CONCLUSION: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.

Adult↗

PubMed2000

The influence of hormone replacement therapy (HRT) on serum leptin concentration in postmenopausal women.

OBJECTIVE: This study aimed to evaluate the influence of hormone replacement therapy (HRT), the estradiol concentration and body mass index (BMI, kg/m(2)) on the serum leptin concentration in postmenopausal women. SUBJECTS AND METHODS: 352 healthy postmenopausal women (mean age, 60.9 +/- 8.5 years) participated in this comparative study. 71 (30%) women (mean age 55.9 +/- 8.3 years) had taken HRT, while 281 (70%) women (mean age, 59.1 +/- 10.6 years) had not. Baseline characteristics -age, weight, height, BMI (greater than or = 25 or <25), follicle stimulating hormone, estradiol, and leptin values-were compared in the two groups. In a second analysis to evaluate the influence of HRT, estradiol concentrations, and BMI on leptin concentrations, these data were analysed in women allocated to one of four groups: (a) postmenopausal women not on HRT with a BMI <25 (n = 130); (b) postmenopausal women not on HRT with a BMI greater than or = 25 (n = 151); (c) postmenopausal women on HRT with a BMI<25 (n = 48); and (d) postmenopausal women on HRT with a BMI greater than or = 25 (n = 23). Leptin concentrations were subsequently analysed in relation to BMI and age and BMI and estradiol concentrations to determine any independent effect of these variables. RESULTS: The women taking HRT had a significantly lower mean age, weight, BMI and follicle stimulating hormone concentration than those who were not taking HRT. Furthermore, they had a higher mean height and serum estradiol value, but a significantly lower serum leptin concentration. After controlling for BMI, neither the use of HRT nor the estradiol concentration was found to be related to the leptin value (group (a) versus (c) and group (b) versus (d)), but there were significant differences in leptin concentrations between HRT users with BMI greater than or = 25 and BMI <25 and between women not taking HRT with BMI greater than or = 25 and BMI <25 (groups (a) versus (b) and (c) versus (d)). Furthermore, women with a BMI greater than or = 25 had significantly higher leptin concentrations than women with a BMI<25, irrespective of the HRT use. CONCLUSIONS: Leptin concentrations are significantly higher in obese postmenopausal women than in their non-obese counterparts. Serum leptin concentrations are not influenced by HRT use or estradiol concentrations. Further studies are needed to elucidate the role of HRT and estrogen on serum leptin concentrations.

Age Distribution↗

PubMed2000

No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women.

The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.

Aged↗

PubMed2001

Proliferative effects of combination estrogen and progesterone replacement therapy on the normal postmenopausal mammary gland in a murine model.

OBJECTIVE: The aim of the study was to analyze the proliferative response of the normal mammary gland to combination hormone replacement therapy with estrogen and progesterone in a murine model of early versus late postmenopausal states. STUDY DESIGN: Ovariectomized mice were injected daily for up to 56 days with estrogen plus progesterone, starting at either 1 or 5 weeks after ovariectomy to simulate early and late menopausal periods, respectively. At various times after treatment, proliferation was analyzed by deoxyribonucleic acid histoautoradiography and whole-mount preparations. The induction of progesterone receptor by estrogen was also analyzed. To distinguish between estrogen- and progesterone-specific responses, we tested the effects of the antiprogesterone mifepristone (RU 486) and the antiestrogen ICI 182,780. RESULTS: The acute response to estrogen-progesterone therapy in the early postmenopausal period resulted in duct-end enlargement, ductal side branching, alveolar bud formation, and a 100-fold increase in epithelial cell proliferation. This was caused by the dominant effect of progesterone acting through the progesterone receptor. In the late postmenopausal period the acute response produced only duct-end enlargement; the 100-fold increase in epithelial cell proliferation resulted from the dominant effect of estrogen. After long-term treatment, both early and late postmenopausal glands exhibited similar morphologic features and a 9-fold higher steady-state proliferation rate than was found in control-treated groups. CONCLUSIONS: Starting combined estrogen and progesterone hormone replacement therapy in either early or late postmenopause produced a persistent, steady-state 9-fold increase in epithelial cell proliferation, which could be a contributing factor to increased breast cancer risk. The acute response in the late postmenopausal period mimics the hormonal response of the pubertal mammary gland, which in rodents is the stage most susceptible to carcinogen-induced mammary tumorigenesis. These observations raise questions about increased susceptibility of the late postmenopausal gland to carcinogenesis and a role for hormone replacement therapy in the promotion of tumorigenesis.

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PubMed1998

Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study.

High dietary fiber intake has been hypothesized to lower blood estrogen concentrations, an effect thought to be beneficial for decreasing breast cancer risk. This study investigated the association between dietary supplementation of wheat bran and circulating estrogen levels in postmenopausal African-American women participating in a community intervention trial. Seventeen postmenopausal women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was assessed and blood and 24-hour urine samples were collected before and after five to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin confirmed that all postmenopausal participants adhered to the intervention protocol. Nine of the 17 postmenopausal women were taking some form of estrogen replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs. 113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml), and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l) levels remained constant. In the eight postmenopausal women who were not receiving exogenous hormones (PM), wheat bran consumption was not associated with predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml), estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/- 0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/- 6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and postintervention levels of estradiol and SHBG significantly higher and androstenedione significantly lower than those not receiving ERT. No association between wheat bran supplementation and hormone levels was found in PM or PM-ERT African-American participants. These results in postmenopausal women are in contrast to findings of earlier studies in premenopausal women indicating that wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal women are only 5-10% of those in premenopausal women; therefore, a high wheat bran fiber diet alone may not be sufficient to depress these low levels even further.

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