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PubMed2003

The effects of hormone replacement therapy on cortical bone in postmenopausal women. A histomorphometric study.

Investigations of the actions of estrogen on the skeleton have mainly focused on cancellous bone and there are no reported histomorphometric studies of the effects of oestrogen on cortical bone in humans. The aim of this study was to investigate the effects of both conventional hormone replacement therapy (HRT) and high-dose oestradiol on cortical bone in postmenopausal women. Transiliac biopsies were obtained from nine postmenopausal women aged 54-71 yr before and after 2 yr (mean, 23.5 months) of conventional HRT and in seven postmenopausal women aged 52-67 yr after long-term, high-dose oestradiol implant therapy (at least 14 yr). Indices of bone turnover, remodeling, and cortical structure were assessed by image analysis. Cortical width was highest in the women treated with high-dose oestrogen therapy (2.29 +/- 0.78 mm; mean +/- SD) and lowest in untreated women (1.36 +/- 0.60 mm; P=0.014). The proportion of canals with an eroded surface was significantly lower in the high-dose oestrogen group than in women before or after conventional HRT (3.03 +/- 3.7% vs. 11.1 +/- 7.1% and 10.5 +/- 8.6%; P=0.017 and 0.05, respectively). Bone formation rate (microm2/microm/day) in untreated women was significantly higher than in the high-dose oestrogen group (0.121 +/- 0.072 vs. 0.066 +/- 0.045, respectively; P=0.05), values in women treated with conventional HRT being intermediate. Our results provide the first histomorphometric evidence in postmenopausal women of dose-dependent oestrogen-induced suppression of bone turnover in iliac crest cortical bone. There was also a trend toward higher wall width with increasing dose of oestrogen, consistent with the previously reported anabolic effect in cancellous bone.

Aged↗

PubMed1997

Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and postmenopausal women.

In order to analyze the role of the estrogen receptor (ER) gene allelic polymorphisms on bone mineral density (BMD), 173 pre- and postmenopausal women were divided into four groups according to their menstrual status (group A: premenopausal women; group B: late premenopausal women; group C: postmenopausal women who had menopause for 5 years or less; and group D: postmenopausal women who had menopause for more than 5 years), and the relationship between ER gene polymorphism and lumbar spine BMD, the percent annual change in BMD and biochemical markers were studied. The restriction fragment length polymorphism (RFLPs) were represented as Xx (XbaI) and Pp (PvuII), with upper case and lower case letters signifying the absence or presence of restriction sites, respectively. In group A, the Xx genotype had significantly higher BMD (p < 0.01) than the xx genotype, but the difference was lost in groups B, C, and D. Because the percent annual change in BMD of group A was 0.052% and was not statistically different among genotypes, it is suggested that RFLP by Xba I is closely linked with peak bone mass that was attained during the subject's late thirties. In group B, serum N-region osteocalcin (N-OC) levels and the percent annual change in BMD showed a significantly larger increase than that of group A, indicating postmenopausal bone loss had commenced. Because the N-OC level of the Xx genotype was significantly higher than that of the xx genotype (p < 0.05), and the percent annual change in BMD of the Xx genotype showed a tendency to increase (p = 0.072), it is suggested that the high BMD of the Xx genotype is rapidly lost during menopausal transition. There were no significant relationships between RFLP and BMD in groups C and D, and between RFLP and BMD in groups C and D, and between RFLP by PvuII and BMD. The present study suggests that the Xx genotype is involved in accretion of BMD during young adulthood, but the effect was lost during menstrual transition.

Adult↗

PubMed1999

Intramuscular clodronate therapy in postmenopausal osteoporosis.

Long-term daily administration of oral bisphosphonates has been effective in the treatment of postmenopausal osteoporosis, but the duration, mode and cost of the therapy may sometimes affect patient compliance. In Italy, the bisphosphonate clodronate is also available via the intramuscular (i.m.) route of administration, and the present study was performed to test its efficacy in postmenopausal osteoporosis. Ninety osteoporotic postmenopausal women were enrolled in a randomized, controlled 3 year study. The diet of all patients was adjusted to provide 1200-1300 mg of calcium daily, eventually by administration of supplements. Patients were randomly assigned to no therapy (30 patients) or to receive clodronate 100 mg i.m. either every 2 weeks (30 patients) or 1 week (30 patients). The i.m. injection caused substantial pain at the site of injection, which led to treatment withdrawal in almost 50% of the patients receiving weekly dosing. In control patients, a progressive, slow decline in spine and femoral bone mineral density (BMD), which became statistically significant at the end of the second year of observation, was observed. In the patients given weekly i.m. clodronate, spinal BMD rose by 3.8% (+/-7.3 SD) within 6 months. A slight, nonsignificant increase was observed thereafter, such that, at the completion of 3 years of observation, the mean gain was 4.5% (+/-6.3). In the patients treated with injections of 100 mg of clodronate every two weeks the increase in BMD was somewhat lower and slower, becoming significant only at month 24 (2.9+/-4.6%). In none of the two active groups was the femoral neck BMD changed significantly during the 3 years of the study. A significant increase in trochanter and Ward's triangle BMD was observed at month 12 only in the patients on the highest dose of clodronate. In both groups treated, the hip BMD changes were significantly different from those observed in control patients. The biochemical markers of bone turnover were suppressed in both clodronate groups. These results indicate that intermittent i.m. clodronate administration can provide clinically relevant benefits to skeletal bone density in osteoporotic postmenopausal women, but the in situ pain may limit its extensive use.

Aged↗

PubMed1999

Does estrogen stimulate osteoblast function in postmenopausal women?

How estrogen therapy influences bone metabolism in postmenopausal women has previously been studied using several approaches, including bone densitometry, measurement of biochemical markers of bone turnover, and histomorphometry. Taken together, these investigations suggest that conventional doses of estrogen protect from bone loss predominantly through suppression of bone resorption, with little evidence to suggest that a stimulatory action on osteoblasts is also involved. In contrast, studies of patients treated with estradiol implants suggest that, following prolonged exposure to relatively high estrogen levels, an additional stimulatory effect on osteoblast function is observed. The suggestion that estrogen stimulates osteoblast activity in postmenopausal women under certain circumstances is consistent with other evidence that estrogen is an important physiological regulator of osteoblast activity. Furthermore, these findings raise the possibility that it may be useful to develop strategies for treating postmenopausal osteoporosis that aim to reproduce the stimulatory action of relatively high estrogen levels on bone formation in postmenopausal women.

Aged↗

PubMed2000

Cytokine RNA levels in transiliac bone biopsies from healthy early postmenopausal women.

The cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6 induce osteoclast formation and may contribute to the development of postmenopausal osteoporosis. Cross-sectional studies have suggested that both IL-1 and IL-1ra secretion increase on estrogen withdrawal, and that postmenopausal osteoporosis is associated with an inadequate increase in monocyte IL-1ra secretion with age. We measured cytokine mRNA (IL-1beta, IL-1ra, IL-6, and TNF-alpha) directly in bone biopsies from early postmenopausal women to determine if a lower compensatory increase in IL-1ra mRNA could be demonstrated in women with rapid bone loss after the menopause. Biopsies were obtained from 23 early postmenopausal women (mean age 53.9 years) who participated in a randomized study of hormone replacement therapy (HRT) and risk factors for osteoporosis. Bone mineral density was assessed by duel energy X-ray absorptiometry at 0, 1, 2, and 5 years. Women in the control group were recruited to the biopsy study based on their observed rate of bone loss (upper or lower tertile). Consent was also obtained from 11 participants receiving HRT. Biopsies were taken at 2 years, frozen in nitrogen, and homogenized. Cytokine mRNA was measured by competitive reverse transcriptase polymerase chain reaction. The IL-1ra/IL-1beta mRNA slope for the slow-loss group was steeper (deltaF = 23.3, p < 0.01) than that observed in the fast-loss group, indicating that slower bone loss was associated with higher IL-1ra mRNA levels relative to IL-1beta. During HRT, the IL-1beta mRNA level was inversely correlated with serum estradiol (log r2 = 0.77, p < 0.01), and women with a serum estradiol below 200 pmol/L during HRT had IL-1beta, mRNA levels identical to the control group. In contrast, IL-1ra mRNA was independent of serum estradiol. Histomorphometric analysis revealed weak correlations between IL-1beta mRNA and activation frequency (r2 = 0.26, p = 0.06) and between IL-1ra and volume referent bone resorption rate (r2 = 0.19, p = 0.11). TNF-alpha was not associated with the bone loss rates or with serum estradiol, and only three samples were positive for IL-6 mRNA. The findings support the hypothesis that IL-1beta production within bone increases with declining estrogen levels, and that an increase in II-1ra protects against accelerated bone loss.

Base Sequence↗

PubMed1997

Administration of long-term tamoxifen therapy modifies the plasma lipoprotein-lipid concentration and lipid transfer protein I activity in postmenopausal women with breast cancer.

Tamoxifen remains one of the most effective agents in the treatment of breast cancer. However, the development of persistent side effects from chronic administration of tamoxifen remains a concern. The objective of this project was to investigate the effect of long-term tamoxifen therapy (2 years) on the plasma lipoprotein concentration and lipid transfer activity in postmenopausal women diagnosed with breast cancer. Two distinct populations of breast cancer patients were recruited for this study: postmenopausal women diagnosed with breast cancer that have never been on tamoxifen and postmenopausal women diagnosed with breast cancer that have been on tamoxifen (20 mg once daily) for 2 years (n = 18 each group). Blood was collected for total and lipoprotein cholesterol (C) and triglyceride (TG) analysis by established enzymatic assays prior to and 2 years following the initial tamoxifen dose. To determine the effect of tamoxifen administration on lipid transfer between lipoprotein fractions, lipid transfer protein (LTP I) activity was measured. A significant decrease in total and low-density lipoprotein (LDL) cholesterol levels and a moderate increase in high-density lipoprotein (HDL) triglyceride levels were observed in plasma samples from postmenopausal women with breast cancer who were administered tamoxifen for 2 years. No significant differences in total and lipoprotein C and TG plasma levels were observed in samples from women with breast cancer that never received tamoxifen. LTP I activity was significantly decreased in patients receiving tamoxifen compared to patients who never received tamoxifen. These specific tamoxifen-induced effects may be important for a number of reasons. Although the apparent decrease in total C and LDL-C levels are favorable for reducing the risk of cardiovascular disease, the elevated levels of HDL-TG have been related to the increased risk of ischemic heart disease. Furthermore, understanding how tamoxifen influences LTP I activity provides valuable insight into how the administration of tamoxifen modifies plasma lipoprotein-lipid levels.

Aged↗

PubMed1999

Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer.

The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well-established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin-releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well-tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical-pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.

Adult↗

PubMed2000

Mammographic density changes in perimenopausal and postmenopausal women: is effect of hormone replacement therapy predictable?

BACKGROUND: Mammographic density adversely affects diagnostic accuracy and may be a risk factor for breast cancer. Mammographic density is affected by hormone replacement therapy (HRT). OBJECTIVE: To assess mammographic density in postmenopausal women with and without HRT. METHOD: Part I. Mammographic density was determined in 1232 postmenopausal women attending a breast screening clinic. Density was compared between HRT users and nonusers in three age groups. When available, previous mammograms were assessed for interval density change. Part II. Density change in 162 women during transition from premenopause to postmenopause was recorded. HRT effect was assessed. RESULTS: Part I. There was no density difference between postmenopausal HRT-users and nonusers younger than age 55. Thereafter, the density was significantly less in nonusers. In the majority of HRT-users the density remained at pretreatment levels but density increased in 8% of women after HRT was started. Part II. Of 117 HRT nonusers followed over menopause 38% had a density decrease before age 55. Of those started on HRT, 80% had no density change, 18% decreased density and 2% increased density. CONCLUSIONS: The density decreases significantly after age 55 with the greatest change occurring between age 55 and 64. This decrease does not occur in the majority of HRT-users. Usually HRT maintains the density present at the time HRT is started. Density decreases after HRT is started in some women suggesting refractoriness to hormones. In fewer than 8% of women density increases commensurate with HRT. Any adverse effect of HRT may depend on the receptivity of the epithelial elements which, in turn, may be reflected by the mammographic density at the time HRT is started.

Adult↗

PubMed2001

Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom).

OBJECTIVE: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer. METHODS: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance. RESULTS: SHBG decreased with increasing body mass index and increasing waist-hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women. CONCLUSIONS: Certain factors such as obesity and perhaps waist-hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.

Adult↗

PubMed2000

Weight change and risk of postmenopausal breast cancer (United States).

OBJECTIVE: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case-control study of postmenopausal breast cancer. METHODS: Participants included women aged 50 79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (<45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84 0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95 1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06-1. 11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. CONCLUSIONS: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.

Aged↗

PubMed2001

Association of family history and other risk factors with breast cancer risk among Japanese premenopausal and postmenopausal women.

OBJECTIVES: To determine the impact of family history (FH) on anthropometric and reproductive risk factors for breast cancer, a case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. METHODS: In total, 1584 breast cancer cases were included and 15,331 women, confirmed as free of cancer, were recruited as the referents. Odds ratios and 95% confidence intervals were determined by logistic regression analysis. Separate analyses were performed for premenopausal and postmenopausal women. RESULTS: Height, weight, and current body mass index (BMI) were positively associated with postmenopausal breast cancer regardless of FH, while these anthropometric factors did not alter risk in premenopausal women. The impacts of height and weight on postmenopausal breast cancer were more pronounced among FH women. There was little association with reproductive risk factors for premenopausal or postmenopausal breast cancer in FH cases, in clear contrast to the non-FH cases. CONCLUSIONS: These findings suggest some differences in risk impact of common etiologic factors between familial breast cancer and sporadic cases that may give pointers to further analysis of host-specific factors. They imply that avoidance of obesity after menopause may reduce the risk of breast cancer, regardless of FH.

Adult↗

PubMed2002

Developing profiles of postmenopausal women being prescribed estrogen therapy to prevent osteoporosis.

Postmenopausal women with estrogen deficiency are at high risk for osteoporosis. Estrogen therapy has been shown to be effective in preventing postmenopausal bone loss and maintaining bone mineral density. The increasing number of women at risk for osteoporosis and the high cost of treating this condition emphasizes the importance of preventing osteoporosis. This study was designed to identify trends and predictors of estrogen use for osteoporosis prevention among postmenopausal women. A retrospective, cross-sectional study was conducted using Behavioral Risk Factor Surveillance System data (1997-1999). Women 35 years and older who had passed menopause or were currently going through menopause were identified from the states including the BRFSS module that asked questions about estrogen use. Results showed an increasing prevalence in estrogen use from 1997 to 1999 for osteoporosis prevention. In 1999, almost a third of the postmenopausal women surveyed used estrogen to prevent osteoporosis. Prevalence was higher among women 45-64 years of age, whites, and those with higher education levels. Physician counseling on the benefits and risks of estrogen therapy was the strongest predictor of estrogen use for prevention of osteoporosis. Insurance coverage and compliance with other preventive behaviors such as mammograms and Pap smears were also strongly associated with greater estrogen use. However, women who were at risk for acute drinking, not married, overweight or obese, and diabetic were all less likely to receive estrogen therapy for osteoporosis prevention. The relationships demonstrated between estrogen use and demographic characteristics, lifestyle behaviors and health care access and utilization factors underline the importance of targeting specific groups of women for promoting its protective effect against osteoporosis.

Adult↗

PubMed2002

Progesterone receptor quantification as a strong prognostic determinant in postmenopausal breast cancer women under tamoxifen therapy.

There is now an emerging body of evidence that shows there is a relationship between the survival of breast cancer patients and the expression level of steroid receptors. The aim of this study was to determine the relationship existing between estrogen receptors (ER) and progesterone receptors (PR) cytosolic content and the prognosis of postmenopausal breast cancer women under tamoxifen therapy. Two hundred and nineteen postmenopausal patients, without neoadjuvant chemotherapy and treated postoperatively with tamoxifen for at least 2 years, were followed up in our Cancer Center. We used flexible regression modeling and log likelihood methods for determining optimum cut-off values for steroid receptors, which allows the separation of patients into significantly different categories in term of survival. For PR, 3 categories were defined (category 1: PR < 10, category 2: 10 < or = PR < 60 and category 3: PR > or = 60 fmol/mg P). Univariate analysis at 8 years indicated that significant differences in event-free survival (EFS) were found for tumor size (T) (p = 0.005), lymph node status (N) (p = 0.003), histological Scarff, Bloom and Richardson grade (p = 0.003), ER values divided into 5 categories (p = 0.02) and PR values divided into 3 categories (p = 1 x 10(-5)). Eight-year EFS rate for the 3 PR categories, adjusted for N, were 39, 66 and 81%, respectively. Multivariate Cox analysis indicated that only T, N and PR values were significant variables for EFS. Patients with PR values > or = 60 present significantly greater EFS rates than patients with PR < 60 (p < 0.001). Our results show that the PR level in ER positive postmenopausal women is a strong prognostic marker in postmenopausal breast cancer women under tamoxifen therapy.

Aged↗

PubMed2004

Alterations in gallbladder emptying and bile retention in the absence of changes in bile lithogenicity in postmenopausal women on hormone replacement therapy.

The role of female sex hormones in the pathogenesis of gallstones is well established. Pregnancy, contraceptive use, estrogen replacement therapy in postmenopausal women, and estrogen therapy in men for the treatment of prostatic carcinoma have been found to be associated with increased risk of cholesterol gallstones. Alterations in gallbladder emptying and in bile lithogenicity in postmenopausal women receiving hormone replacement therapy (HRT) have not been studied to date. The present study was undertaken to study the effect of HRT on gallbladder emptying and bile lithogenicity. Sixteen postmenopausal women were included in the study. None of the patients had gallstone disease and none had received prokinetic drugs, such as, erythromycin, metoclopramide, domperidone or cisapride, aspirin, and nonsteroidal antiinflammatory drugs. Gallbladder emptying (n = 16), bile microscopy (n = 7), cholesterol saturation index (CSI) (n = 7), and nucleation time (n = 7) were studied before and 3 months after HRT (conjugated estrogen, 0.625 mg, + medroxyprogesterone acetate, 2.5 mg, everyday). Fasting and residual volumes increased (fasting volume, 18.2 +/- 2.2 mL pre-HRT vs 27.6 +/- 3.2 mL post-HRT, P = 0.0003; residual volume, 3.9 +/- 0.6 mL pre-HRT vs 10.3 +/- 2.0 mL post-HRT, P = 0.00009) and ejection fraction decreased (78.2 +/- 2.5% pre-HRT vs 62.2 +/- 3.8% post-HRT; P = 0.0017) after 3 months of HRT. There was no change in CSI (2.32 +/- 0.36 pre-HRT vs 2.60 +/- 0.51 post-HRT; P = NS) or in nucleation time (19.0 +/- 1.2 days pre-HRT vs 17.6 +/- 1.3 days post-HRT; P = NS). None of the bile samples either pre-HRT or post-HRT showed cholesterol monohydrate crystals. Though impairment of gallbladder emptying occurs in the short term with HRT in postmenopausal women, there is no change in CSI and nucleation time.

Bile↗

PubMed2003

Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women.

OBJECTIVES: To test the hypothesis that both raloxifene and estrogen would improve insulin sensitivity in postmenopausal women and that the magnitude of the effect would be similar for both drugs. DESIGN: Placebo-controlled, double-blind, randomized study. SETTING: The General Clinical Research Center of the University of Michigan Medical Center, a university hospital. PARTICIPANTS: Forty-four healthy postmenopausal women 73 +/- 7 years old (mean age +/- standard deviation) who were not receiving hormone replacement therapy. INTERVENTION: Eight weeks of drug therapy with randomization to raloxifene (n = 16), estrogen (n = 14), or placebo (n = 14). MEASUREMENTS: These subjects underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (SI) and total and regional (central) body composition measurements by dual-energy x-ray absorptiometry at baseline and after 8 weeks of drug therapy. RESULTS: There were no statistically significant differences in age, body mass index, total or central fat mass, or SI between the three groups at baseline. The major outcome variable was SI. After 8 weeks of drug therapy, there was no significant change in SI in the placebo group or in the estrogen group and a significant decrease in SI in the raloxifene group, P =.003. CONCLUSION: In contrast to estrogen's ability to maintain insulin sensitivity, raloxifene decreases insulin sensitivity in healthy nondiabetic postmenopausal women. The clinical significance of this effect of raloxifene to impair insulin sensitivity in postmenopausal women warrants further evaluation in future studies.

Absorptiometry, Photon↗

PubMed2002

Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women.

The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45-0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12-2.38) and 1.35 (95% CI 1.02-1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60-1.04), 0.69 (95% CI 0.54-0.88), 0.66 (95% CI 0.51-0.85) and 0.64 (95% CI 0.48-0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer.

Abortion, Spontaneous↗

PubMed1997

The effect of dietary sodium on calcium metabolism in premenopausal and postmenopausal women.

OBJECTIVE: To investigate the effects of high and low sodium diets on urinary calcium, bone turnover and calcium absorption in pre and postmenopausal women. DESIGN: Experimental, prospective and longitudinal study. SETTING: Samples were taken at the hospital and the diets were followed at home. SUBJECTS: Volunteers were recruited from the hospital and were either hospital staff or post-graduate students. No volunteers failed to complete the study but one was omitted from analysis due to lack of compliance. INTERVENTIONS: Eleven healthy premenopausal women aged 22-47 y and 11 healthy postmenopausal women ages 45-70 y followed a high (300 mmol/d) and a low (50 mmol/d) sodium diet for one week each. On the 7th day of each diet, blood and urine samples were taken. RESULTS: On the high sodium diet 24 h urinary sodium and calcium values relative to creatinine were significantly higher for all subjects (P < 0.05). Postmenopausal women on the high sodium diet had biochemical evidence of increased bone resorption in relation to the low sodium diet. However in premenopausal women there was no such change. Calcium absorption did not change significantly in either group. CONCLUSIONS: It appears that postmenopausal, but not premenopausal, women respond to a high sodium diet by an increase in bone resorption which may lead to reduced bone density. SPONSORSHIP: Arthritis and Rheumatism Council Project Grant R44.

Absorption↗

PubMed1998

Leptin in overweight postmenopausal women: no relationship with metabolic syndrome X or effect of exercise in addition to diet.

OBJECTIVE: To examine the effect of diet with exercise on serum leptin and whether leptin is associated with the metabolic syndrome X in a high risk population such as overweight postmenopausal women. STUDY DESIGN AND SUBJECTS: 121 healthy overweight, postmenopausal women (aged 49-58y, body mass index (BMI) 25-42 kg/m2) were randomized to: A low-energy-diet, 4.2 MJ/d (n = 51), low-energy-diet + standardized physical exercise (n=49) or no intervention (control: n=21) for 12 weeks, followed by 6 months follow-up without intervention. MEASUREMENTS: S-leptin was measured by Radio Immuno Assay (RIA), body composition and fat distribution by dual energy X-ray absorptiometry (DEXA) and anthropometry. Factors associated with the metabolic syndrome X and sex hormones were measured. RESULTS: S-leptin was two-fold higher than in normal-weight postmenopausal women and S-leptin was normalized after weight loss induced by the 12-week low-energy-diet, without any additive effect of the exercise. Of the factors associated with the metabolic syndrome X, serum-leptin correlated significantly only with sex-hormone-binding-globulin and plasminogen-activator-inhibitor-1, whereas factors associated with obesity per se correlated significantly with leptin. Changes in S-leptin correlated with changes in fat tissue mass during the follow-up, but not during the intervention. S-leptin at baseline did not correlate with either short term or long term weight loss. CONCLUSION: There is no effect of exercise added to diet on S-leptin in overweight postmenopausal women. Leptin does not seem to be associated with the metabolic syndrome X, but rather with fatness. S-leptin is probably associated with both dynamic and static effects of adipose tissue. S-leptin did not predict weight loss.

Body Composition↗