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PubMed1998

Fat distribution and plasma lipid-lipoprotein concentrations in pre- and postmenopausal women.

OBJECTIVE: In the postmenopausal years, women develop a central pattern of fat distribution and an increased risk of developing cardiovascular disease (CVD). The possibility that these events are related has not been extensively investigated. The object of the present study was to test the hypotheses that, 1) menopause-related differences in lipids are associated with greater estimated intra-abdominal adiposity, and 2) the relationship between individual adipose depots and plasma lipids differs with menopausal status. DESIGN: Cross-sectional. SUBJECTS: 141 healthy pre- and postmenopausal women aged 35-65 y. MEASUREMENTS: Total body fat by hydrodensitometry was used as an index of whole-body adiposity, the sum of five central skinfold measurements as an index of subcutaneous upper-body adiposity, and estimated intra-abdominal adipose tissue (IAF) as an index of visceral adiposity. Fasting plasma concentrations of total cholesterol (total-C), high- and low-density-lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides were used as indices of CVD risk. RESULTS: Postmenopausal women had greater total body fat (P < 0.001), summed central skinfolds (P < 0.01), estimated IAF (P < 0.001), higher plasma concentrations of total-C (P < 0.001), LDL-C (P < 0.001) and triglycerides (P < 0.001), than premenopausal women. The relationship between central skinfolds and LDL-C differed with menopausal status, being significant in pre- but not postmenopausal women. Adjustment for estimated IAF with analysis of covariance decreased menopause-related differences in levels of total-C, LDL-C and triglycerides by approx 40-70%. CONCLUSION: These observations suggest that, 1) menopause-related changes in IAF may adversely affect the plasma lipid profile, and 2) menopausal status affects the relationship between central subcutaneous fat and LDL-C. Studies with measured IAF are needed to confirm present results.

Adipose Tissue↗

PubMed2001

Waist circumference vs body mass index for prediction of disease risk in postmenopausal women.

OBJECTIVE: To test the sensitivity of waist circumference (central adiposity) as an index of disease risk in postmenopausal women. DESIGN: Retrospective analysis of postmenopausal women tested at Washington University School of Medicine. SUBJECTS: A total of 323 healthy postmenopausal (66+/-5 y; mean+/-s.d.) women not using any hormone replacement. MEASUREMENTS: Body composition, hyperinsulinemia (insulin area), triglycerides and HDL-cholesterol. RESULTS: Excess waist size had a stronger association with hyperinsulinemia and hypertriglyceridemia than body mass index (BMI; kg/m(2)) in otherwise healthy, postmenopausal women. After adjusting for BMI, a strong relation existed between waist circumference and insulin area, HDL-cholesterol and triglycerides (P<0.01). Conversely, after adjusting for waist circumference, no relation was apparent between BMI and the dependent variables of interest. The strength of the association between waist circumference and disease risk became most apparent when analyses were restricted to normal-weight women (BMI 24--28 kg/m(2)). When BMI was held constant, hyperinsulinemia and triglyceridemia increased dose-dependently with changes in waist size. CONCLUSION: Waist circumference, an easily obtained index of central adiposity, is a more sensitive measure of relative disease risk than is BMI in middle-aged and older women, particularly in normal-weight individuals.

Adipose Tissue↗

PubMed2002

Insulin resistance and hypertension in postmenopausal women.

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

Area Under Curve↗

PubMed2006

Hormone treatment gives no benefit against cognitive changes caused by acute sleep deprivation in postmenopausal women.

The objective was to evaluate whether hormone therapy (HT) gives any benefit against the possible impairment of cognitive performance when challenged by acute sleep deprivation. Twenty postmenopausal women volunteered (age range 59-72 years, mean=64.4 years, SD=4.4): 10 HT users and 10 nonusers. Eleven young women served as a control group for the cognitive age effect (age range 20-26 years, mean age 23.1 years, SD=1.6). The subjects spent four consecutive nights at the sleep laboratory and were exposed to acute sleep deprivation of 40 h. Measures of attention (reaction speed and vigilance), alertness, and mood were administered every 2 h during the daytime and every hour during the sleep deprivation night. Postmenopausal women performed slower than young controls, whereas young controls made more errors. In HT users, the recovery night did not fully restore the performance in the simple and two-choice reaction time tasks, but in nonusers it did so. Sleep deprivation had a detrimental, yet reversible effect on vigilance in all groups. In all groups, sleepiness started to increase after 15 h of sleep deprivation and remained elevated in the morning after the recovery night. Prolonged wakefulness or HT had no effect on mood. In conclusion, sleep deprivation impaired cognitive performance in postmenopausal as well as young women. Postmenopausal women kept up their performance at the expense of reaction speed and young women at the expense of accuracy. One night was not enough for HT users to recover from sleep deprivation. Thus, HT gave no benefit in maintaining the attention and alertness during sleep deprivation.

Adult↗

PubMed1997

Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine.

OBJECTIVE: The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover. DESIGN: A prospective study over 2 years of post-menopausal women treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND MEASUREMENTS: Sixty-four post-menopausal women, ages 47 to 74 (61 +/- 9, mean +/- SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n = 23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n = 23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2. RESULTS: The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = -0.41 P < 0.001, r = -0.29 P = 0.01 and r = -0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow-up (ANOVA, P > 0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t-test, P = 0.0021, 0.034, 0.0017, 0.011 and < 0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P < 0.05). CONCLUSIONS: In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.

Aged↗

PubMed1998

Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women.

BACKGROUND: Patients with subclinical hyperthyroidism (reduced serum TSH and normal free T4 and T3 concentrations) have slightly increased bone turnover and might have reduced bone mass, especially among postmenopausal women (due to concomitantly reduced oestrogen production), as also seen during suppressive L-T4 treatment. OBJECTIVE: We have evaluated whether normalization of serum TSH using radioiodine treatment (RAI) in postmenopausal women with a nodular goitre and subclinical hyperthyroidism, protects against bone loss? DESIGN: Prospective, non-randomized study, outpatients 2 years follow-up. PATIENTS: Postmenopausal women with a nodular goitre, biochemically subclinical hyperthyroidism (TSH < 0.2 mU/I, and signs of a growing goitre or compression symptoms. Sixteen were treated with RAI (median dose 555 MBq) (+RAI), whereas 12 were followed without treatment (-RAI). MEASUREMENTS: Serum TSH (third generation technology), free T4 and T3 indices, and bone mass (BMD) as measured by Dual Photon Absorptiometry (4 in each group) (only spine) or Dual X-ray Absorptiometry (DEXA) (both spine and hip), were measured yearly for up to 2 years. RESULTS: The two groups did not differ regarding age, thyroid hormone parameters, and absolute levels of BMD at spine and hip. RAI resulted in normalization of TSH in all 16 women, and FT4I as well as FT3I decreased to 78% after one year (P < 0.01). These parameters did not change in the untreated group, thus serum TSH remained reduced. BMD at the spine tended to increase (n.s.) after RAI to (median) 101.9% after one year, and 101.5% after 2 years. In contrast the -RAI group experienced a continued fall in BMD to 97.3% after one year, and 95.5% after 2 years, both reduced as compared to the +RAI group (P < 0.02). BMD of the hip also increased after RAI, to 102.3% after one year, and 101.7% after 2 years. In contrast BMD in the -RAI group decreased to 94.8% after one year, and 98.0% after 2 years, both lower than in the +RAI group (P < 0.01). CONCLUSIONS: Subclinical hyperthyroidism due to a nodular goitre in postmenopausal women resulted in a continued loss of bone mass of about 2% per year. Radioiodine treatment resulting in normalization of serum TSH prevented this continued bone loss for at least 2 years. Our study supports earlier intervention in such patients.

Aged↗

PubMed2001

Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy.

OBJECTIVE: Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated. DESIGN: Randomised, double-blind placebo controlled study. PATIENTS: Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). MEASUREMENTS: Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin. RESULTS: In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024). CONCLUSIONS: The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.

Analysis of Variance↗

PubMed2001

A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function.

OBJECTIVE: To study the effects of long-term combined continuous oral hormone replacement therapy (HRT) on vascular function in healthy postmenopausal women. BACKGROUND: The cardiovascular effects of HRT are controversial. Improvement in vascular function is a proposed mechanism of oestrogen action but there are no long-term controlled human trials in this area. In this study, we examined the effects of HRT on lipid profiles and vascular function, encompassing both biomechanical arterial properties [systemic arterial compliance (SAC) and pulse wave velocity (PWV)] and endothelial function [flow-mediated vasodilation (FMD)]. METHODS: In this 2-year, double-blind, placebo-controlled study, 59 healthy postmenopausal women were randomized to oral combined continuous oestrogen and progesterone [Kliogest, oestradiol (2 mg), norethisterone (1 mg)] or placebo, with end-points measured at baseline, 6 weeks and after 6,12 and 24 months of treatment. RESULTS: Oral combined HRT reduced lipoprotein a [Lp(a)], although other lipid benefits were not observed. There were no significant changes in SAC, PWV or FMD with oral combined HRT, compared to placebo. CONCLUSION: In this long-term, randomized placebo-controlled trial, oral continuous HRT with combined oestradiol and norethisterone in healthy postmenopausal women did not improve a spectrum of indices of arterial function compared to placebo. These results suggest that HRT might not be of cardiovascular benefit in postmenopausal women.

Analysis of Variance↗

PubMed2001

The contribution of IGF-I to skeletal integrity in postmenopausal women.

OBJECTIVES: The pathogenic role of the decline in serum concentrations of IGF-I in postmenopausal osteoporosis is not fully elucidated. We investigated the associations among IGF-I, bone mineral density (BMD), ultrasound parameters and prevalence of vertebral fractures in postmenopausal women. DESIGN: A cross-sectional study. PATIENTS: One hundred and fifty-four ambulatory postmenopausal women (61 +/- 7 years) referred for osteoporosis screening. MEASUREMENTS: IGF-I was measured by radioimmunoassay and BMD using dual-energy X-ray absorptiometry. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at calcaneus were measured by a quantitative ultrasound system. RESULTS: IGF-I was significantly lower in osteoporotic subjects and correlated positively with BMD, BUA and SOS. After adjusting for age, years since menopause and body mass index, IGF-I accounted for 8.5% of the variance at lumbar spine BMD, 4.6% at femoral neck and 7.1% at calcaneal BUA. BUA was associated with IGF-I independently of BMD. IGF-I was lower in women with vertebral fractures (91 +/- 39 microg/l vs. 114 +/- 44 microg/l; P = 0.003). The osteoporosis densitometric criteria (t-score < or = -2.5 SD) was the most strongly independent associated variable with prevalent vertebral fractures [odds ratio (OR): 3.3 (1.4-7.6)], followed by IGF-I levels below 75th percentile [OR: 3 (1-8.8)]. CONCLUSIONS: Our study shows that IGF-I is strongly associated with bone mineral density and reflects aspects of bone quality. The contribution of IGF-I to skeletal integrity in postmenopausal women is clinically relevant.

Aged↗

PubMed2002

Relationships of urinary phyto-oestrogen excretion to BMD in postmenopausal women.

OBJECTIVE: Phyto-oestrogens are plant compounds with both oestrogenic and anti-oestrogenic properties. However, it is not known whether natural phyto-oestrogens are beneficial or harmful in human osteoporosis. This study was performed to investigate the relationships between urinary phyto-oestrogens and bone mineral density (BMD) in Korean postmenopausal women. DESIGN: The subjects were classified into osteoporotic, osteopenic and normal groups according to their BMD as defined by WHO criteria. We compared the urinary phyto-oestrogens of each group and studied whether urinary phyto-oestrogens correlate with BMD. PATIENTS: The subjects were 75 Korean postmenopausal women with ages ranging from 52 to 65 years (mean 58 +/- 1.1 years). Mean number of years after menopause was 7.3 +/- 1.3. MEASUREMENTS: Twenty-four-hour urinary phyto-oestrogens were measured by gas chromatography-mass spectrometry (GCMS) and BMD by dual-energy X-ray absorptiometry (DXA, Lunar Expert-XL, Lunar Co., WI, USA). RESULTS: In Korean postmenopausal women, urinary enterolactone (1.46 +/- 1.11 micromol/day) was lower and daidzein (2.59 +/- 3.25 micromol/day) was higher than in western women, and both levels were comparable to those in Japanese women. Daily urinary excretion of genistein and apigenin were 1.09 +/- 0.912 and 0.48 +/- 0.40 micromol/day, respectively. In subjects with osteoporosis, urinary enterolactone was lower (P < 0.05) but apigenin was significantly higher (P < 0.05) than in the controls. BMD of L2-L4 correlated positively with urinary enterolactone (r = 0.388, P < 0.01), and BMD of the femoral neck and Ward's triangle correlated positively with urinary enterolactone (r = 0.271, P < 0.05 and r = 0.322, P < 0.05) but negatively with apigenin (r = -0.412, P < 0.01 and r = -0.395, P < 0.01). By multiple stepwise regression, the variables associated with spinal BMD were age, the amount of urinary apigenin and body mass index (BMI). The variables associated with femoral neck BMD were age and urinary apigenin. CONCLUSIONS: From these results, we conclude that urinary phyto-oestrogens, especially enterolactone and apigenin, are related to BMD in Korean postmenopausal women. Our results also suggest the possibility that phyto-oestrogens have differential effects on bone density. Further studies are needed to clarify the exact biological roles of phyto-oestrogenic components on bone metabolism.

4-Butyrolactone↗

PubMed2002

Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy.

OBJECTIVE: To prospectively assess bone density and the factors determining the rate of bone loss over a 10-year period of postmenopausal life. DESIGN: Prospective, observational study. METHODS: One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47-71 years) completed the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual-energy X-ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed. RESULTS: Twenty-four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow-up. The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT was associated with significant gains in bone density (total body + 3.0%, trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non-HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow-up bone densities in the non-HRT users were highly correlated (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted for the majority of the variance in the 10-year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow-up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health). CONCLUSIONS: Bone density is highly predictable over an extended period of time in normal postmenopausal women. Maintenance of body weight and good health reduce bone loss. HRT is effective for treating osteoporosis, with improvement in bone density and reduction in vertebral fractures. Good compliance with HRT long-term is achievable. These findings are relevant to deciding the frequency of bone density measurement, and in advising women regarding prevention and treatment of postmenopausal bone loss.

Aged↗

PubMed2002

Transdermal oestradiol replacement therapy enhances platelet constitutive nitric oxide synthase activity in postmenopausal women with type 2 diabetes mellitus.

OBJECTIVE: To determine whether treatment with transdermal oestrogen replacement therapy (TERT) in postmenopausal women with type 2 diabetes mellitus was able to increase the activity of constitutive nitric oxide synthase (cNOS) in platelets. RESEARCH DESIGN AND METHODS: Eighteen postmenopausal women with type 2 diabetes mellitus (group A) were studied in basal conditions (A1) and on the 10th day of the third month of a sequential opposed TERT (A2) evaluating platelet cNOS activity measured by the conversion of radiolabelled l-arginine to l-citrulline. As a control group (B) 25 normal postmenopausal women underwent the same treatment (B1 and B2 before and during treatment, respectively). RESULTS: Basal values of platelet cNOS activity were superimposable (0.6 +/- 0.1 vs. 0.7 +/- 0.1 fmol/min/109 plts, NS). During TERT, platelet cNOS activity rose in A and B (0.6 +/- 0.1 vs. 1.8 +/- 0.1 fmol/min/109 plts, P < 0.05 and 0.7 +/- 0.1 vs. 2.4 +/- 0.2, P < 0.001, A1 vs. A2 and B1 vs. B2, respectively). However, platelet cNOS activity of A2 did not reach the values of B2 (1.8 +/- 0.1 vs. 2.4 +/- 0.2 fmol/min/109 plts, P < 0.05; A2 vs. B2, respectively). CONCLUSIONS: Sequential opposed transdermal oestrogen replacement therapy was able to increase platelet cNOS activity in postmenopausal women with type 2 diabetes mellitus, suggesting that its use might be positive in preventing cardiovascular pathologies.

Administration, Cutaneous↗

PubMed2004

Oestrogen receptor alpha genotype, and interactions between vitamin D receptor and transforming growth factor-beta1 genotypes are associated with quantitative calcaneal ultrasound in postmenopausal women.

OBJECTIVE: Quantitative ultrasound (QUS) of bone is a new radiation-free, low-cost method that measures both bone mass and quality. We investigated associations between QUS parameters and polymorphisms of vitamin D receptor (VDR), oestrogen receptor alpha (ERalpha) and transforming growth factor-beta1 (TGF-beta1) genes in postmenopausal women residing in a community. DESIGN: QUS and anthropometric characteristics were measured in postmenopausal women, and compared with regard to the VDR, ERalpha and TGF-beta1 genotypes. PATIENTS: Among the 552 women who participated in the population-based Chung-Up osteoporosis prevalence study, 206 postmenopausal women, aged 60-69 years, were included. MEASUREMENTS: Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the left calcaneus using QUS measurement of bone, and a stiffness index (SI) was calculated. We determined the BsmI and FokI polymorphisms of VDR gene and the XbaI and PvuII polymorphisms of ERalpha gene using the polymerase chain reaction-restriction fragment length polymorphism method, and Tau29 --> C polymorphism of TGF-beta1 gene using an allele-specific polymerase chain reaction assay. RESULTS: The XbaI polymorphism of ERalpha gene was significantly associated with SI (T-score) and BUA (P = 0.040 and P = 0.024, respectively). There were no significant differences in any QUS parameters among the genotypes of VDR and TGF-beta1. However, significant genetic interactions between the VDR and TGF-beta1 genotypes, were noted (P = 0.017 for SI and P = 0.028 for BUA between the BsmI and Tau29 --> C polymorphisms; P = 0.038 for SI and P = 0.035 for BUA between the FokI and T29 --> C polymorphisms). The combined genotypes between the BsmI and T29 --> C polymorphisms or between the FokI and T29 --> C polymorphisms, were significantly associated with the QUS parameters. CONCLUSIONS: This study indicates that the XbaI polymorphism of ERalpha gene may influence the Quantitative ultrasound parameters in postmenopausal women, and suggests the need for further investigations about the interactions between the VDR and TGF-beta1 genes.

Aged↗

PubMed1996

Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women.

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.

Administration, Cutaneous↗

PubMed1997

The anti-oestrogen tamoxifen produces haemodilution in normal postmenopausal women.

OBJECTIVES: To report the effects of the anti-oestrogen tamoxifen on biochemical and haematological parameters. DESIGN: Randomized, double-blind comparison of tamoxifen 20 mg per day and placebo, over two years. SETTING: A university hospital. SUBJECTS: Forty-six healthy late-postmenopausal women (mean, SD time since menopause; 11, seven years). MAIN OUTCOME MEASURES: Blood specimens were drawn in the fasting state at baseline, six months and two years for measurement of haemoglobin, haematocrit, erythrocyte mean cell volume, mean erythrocyte haemoglobin, leucocyte count, platelet count, urea, electrolytes, creatinine and albumin. RESULTS: There was a significant decline in the haemoglobin concentration in the tamoxifen group (-4.4, 1.2 g/L; mean, SE) and its levels were lower in this group than in those receiving placebo (P = 0.004). Similarly, haematocrit, erythrocyte count and total leucocyte count were lower in those on placebo (P = 0.002, P = 0.01 and P = 0.01, respectively) and platelet count showed a similar trend (P = 0.08). In the tamoxifen group, the level of serum albumin fell significantly (-2.2, 0.4 g/L) and was lower throughout the study than that in the placebo group (P = 0.006). That of serum urea tended to fall (-0.4, 0.2 mmol L) but the between-groups comparison was not significant (P = 0.18). CONCLUSIONS: These data suggest that tamoxifen exerts a haemodilutory effect in normal postmenopausal women. Since a similar effect has been reported in response to postmenopausal oestrogen therapy, it is likely that the observed changes represent another oestrogenic effect of tamoxifen in postmenopausal women. Haemodilution may contribute to the reduced incidence of cardiovascular disease reported in tamoxifen-treated women, and, therefore, its assessment in the new oestrogen agonists/antagonists being developed for cardiovascular disease prevention may be important.

Antineoplastic Agents, Hormonal↗

PubMed2003

Oestrogen receptor alpha gene polymorphism is related to aortic valve sclerosis in postmenopausal women.

OBJECTIVES: Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor alpha (ORalpha) gene and in the transforming growth factor beta (TGF-beta1) gene were related to the presence of AS in postmenopausal women. DESIGN: Case-control study. SUBJECTS AND METHODS: Relationships were tested between polymorphisms in the ORalpha gene defined by the restriction enzymes PvuII and XbaI, and in the TGF-beta1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age- and sex-matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 +/- 1.2 years. RESULTS: In the postmenopausal patients and age-matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13-10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF-beta1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68-12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low-density lipoprotein cholesterol (LDL) (P = 0.04). CONCLUSIONS: We have demonstrated that the PvuII polymorphism in the ORalpha gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels.

Adolescent↗

PubMed1999

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history.

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c-erbB-2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c-erbB-2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.

Body Mass Index↗

PubMed1995

Endometrial evaluation in postmenopausal breast cancer patients receiving tamoxifen: an ultrasound, color flow Doppler, hysteroscopic and histological study.

The purpose of this study was to evaluate the effect of tamoxifen therapy on the endometrium by transvaginal color Doppler sonography, hysteroscopy and endometrial sampling. The study group (tamoxifen group) was composed of 38 asymptomatic postmenopausal women. All had been treated with tamoxifen (20-30 mg/day) for breast cancer for at least 1 year. The patients of the tamoxifen group underwent transvaginal color Doppler sonography, hysteroscopy and, if necessary, endometrial biopsy. Thirty asymptomatic postmenopausal women (control group) and 25 asymptomatic postmenopausal breast cancer patients not on tamoxifen therapy (no-tamoxifen group) served as the control groups. The endometrium was scanned by transvaginal ultrasound to evaluate thickness, echotexture, border and intraluminal fluid. Color and pulsed Doppler were used to evaluate the pulsatility (PI) and resistance (RI) indices of the uterine and endometrial arteries when possible. The patients receiving tamoxifen had a significantly thicker endometrium compared to the control groups. Endometrial pathology was observed in 61% (23/38) of cases and an endometrial thickness of "> or =" 10 mm was always associated with an endometrial lesion. Nineteen benign endometrial polyps were found, most of them having a typical sonographic endometrial pattern with regular borders and small hypoechoic cystic areas which we define as polypoid. Four endometrial hyperplasias, one of these atypical were observed. There were no endometrial cancers. The mean PI and RI of the uterine arteries in the tamoxifen group were 2.04 +/- 0.77 and 0.82 +/- 0.1, respectively and were significantly lower than those of the control group (2.93 +/- 0.9 and 0.93 +/- 0.06) and the no-tamoxifen group (2.53 +/- 0.7 and 0.89 +/- 0.1). The blood velocity changes were very similar to those described in postmenopausal women receiving estrogen replacement therapy. A correlation between the time of beginning tamoxifen therapy after menopause and development of endometrial pathology was observed: in patients who started therapy many years after the onset of menopause, the risk of developing endometrial pathology was higher than in those who began therapy a few years after the onset of menopause. Patients receiving tamoxifen, particularly those who start therapy many years after the onset of menopause, should be closely monitored by transvaginal ultrasound and color Doppler imaging to detect endometrial lesions.

Aged↗