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Lack of effect of isoflavonic phytoestrogen intake on leptin concentrations in premenopausal and postmenopausal women.

OBJECTIVE: To assess the effect of soy isoflavone ingestion on plasma leptin concentrations in premenopausal and postmenopausal women. DESIGN: Randomized, crossover studies, with blinding of participants and laboratory personnel. SETTING: Procedures involving free-living individuals were carried out at the University of Minnesota General Clinical Research Center. PATIENT(S): Fourteen regularly cycling premenopausal women, and 18 postmenopausal women. INTERVENTION(S): Each premenopausal participant consumed, on a daily basis, each of three soy protein powders containing different levels of isoflavones for three menstrual cycles plus 9 days, with plasma samples collected every other day the last 6 weeks of each diet period. Similarly, each postmenopausal participant consumed each of the three powders for 93 days, with plasma samples collected daily on days 64 to 66 and 92 to 94 of each diet period. The powders, dosed on a per-kilogram body weight basis, provided mean isoflavone intakes of 8, 65, and 130 mg/day, for the control, low-isoflavone, and high-isoflavone diet periods, respectively. MAIN OUTCOME MEASURE(S): Plasma leptin concentrations. RESULT(S): Isoflavone intake had essentially no effect on leptin concentrations in either premenopausal or postmenopausal participants. Concentrations in the premenopausal women were higher during the periovulatory and midluteal phases as compared to the early follicular and midfollicular phases. CONCLUSION(S): Despite the well-documented effect of estrogens to enhance leptin production, even high levels of isoflavone consumption do not alter leptin concentrations in women. Further studies are needed to more precisely delineate the nature of estrogenic and/or antiestrogenic effects of isoflavones in humans.

Administration, Oral↗

Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries.

OBJECTIVE: To quantify nerve fibers and mast cells in human ovaries at different functional stages. DESIGN: Retrospective study. SETTING: Research laboratory of the university. SPECIMEN(S): 8 human ovaries in the follicular (cyclic) phase, 7 polycystic ovaries, and postmenopausal ovaries with (n=5) or without (n=7) hyperthecosis. MAIN OUTCOME MEASURE(S): Single- and double immunohistology for the S100 antigen in glial cells of autonomic nerve fibers, for chymase and tryptase in mast cells, and for the common leukocyte antigen on leukocytes. Histometric evaluation was also performed. INTERVENTION(S): None. RESULT(S): Polycystic ovaries contained significantly more S100-positive nerve fibers in the corticomedullary region than did cyclic ovaries (mean +/- SD per 2-mm(2) area, 476 +/- 136 and 224 +/- 133; P<.01). Postmenopausal ovaries with or without hyperthecosis had the highest density of nerve fibers. In cyclic and polycystic ovaries, more tryptase-positive mast cells than chymase-positive mast cells were found in the interstitial cortex and the medulla. In cyclic ovaries, areas with a moderate density of nerve fibers contained many mast cells. Hence, with increasing nerve fiber density in polycystic ovaries, the number of mast cells decreased strikingly compared with cyclic ovaries (p<.001). Almost no mast cells were seen in postmenopausal ovaries with and without hyperthecosis. The number of leukocyte antigen-positive leukocytes was similar in all groups. CONCLUSION(S): The high density of nerve fibers in polycystic and postmenopausal ovaries, together with a conspicuous decrease in mast cells, indicates altered neuroimmune communication.

Aged↗

Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women.

OBJECTIVE: To evaluate the effects of dehydroepiandrosterone (DHEA) supplementation on the growth hormone-releasing hormone-growth hormone (GHRH-GH) axis in lean and obese postmenopausal women. DESIGN: Prospective study. SETTING: Postmenopausal women in a clinical research environment. PATIENT(S): Thirty-one postmenopausal women were divided in two groups by age (50 to 55 and 60 to 65 years). Within each group, lean and obese patients were considered. INTERVENTION(S): All patients underwent hormonal evaluations before and at the third and sixth month of therapy (50 mg of DHEA orally each day) and a GHRH test (1 microg/kg) before and at the sixth month of treatment. Ultrasound and bone mass density (BMD) examinations were performed before and after the sixth month of therapy. MAIN OUTCOME MEASURE(S): Plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), E1, E2, androstenedione (A), testosterone (T), osteocalcin, GH, insulin-like growth factor 1 (IGF-1) concentrations. RESULT(S): The levels of all of the steroids that derived from DHEA metabolism (E1, E2, A, T, DHEAS) and osteocalcin were increased in plasma under DHEA supplementation. The supplementation protocol also increased the levels of GH and IGF-1. However, GHRH-induced GH and IGF-1 responses were not modified by DHEA supplementation. CONCLUSION(S): Administration of DHEA significantly affects several endocrine parameters in early and late postmenopausal women independently from body mass index. Our data support the hypothesis that DHEA treatment acts similarly to estrogen-progestin replacement therapy on the GHRH-GH-IGF-1 axis. This suggests that DHEA is more than a more than a simple "diet supplement" or "antiaging product"; rather it should be considered an effective hormonal replacement treatment.

Administration, Oral↗

Mammographic density changes during different postmenopausal hormone replacement therapies.

OBJECTIVE: To determine the degree of change in mammographic breast densities during different types of postmenopausal hormone replacement therapies. DESIGN: A retrospective study. SETTING: Ege University Hospital. PATIENT(S): The mammographies of 216 women on various postmenopausal hormone replacement therapies were evaluated. INTERVENTION(S): Estrogen alone (n = 76) or estrogen in cyclic (n = 44) or continuous (n = 61) combination with progestin or tibolone-only (n = 35) replacement therapies were used. Mammographic density was quantified according to the Wolfe classification in patients with different hormone replacement regimens. MAIN OUTCOME MEASURE(S): Mammographic density changes were interpreted. RESULT(S): An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy 31.1% (19 of 61) than among those receiving estrogen-only 3.9% (3 of 76) treatment. There were no significant mammographic breast density changes among women receiving cyclic continuous combination hormone replacement therapy or tibolone-only treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. In continuous combined postmenopausal hormone replacement therapy with norethisterone acetate, the increase in mammographic density was 34.1% (15 of 44), followed by medroxyprogesterone acetate 23.5% (4 of 17). CONCLUSION(S): Our findings show that mammographic breast density changes related to postmenopausal hormone replacement therapy are dependent on the selected hormone regimen. The continuous administration of the progestin component of the combined-hormone replacement therapy seems to effect the breast density most.

Cyproterone Acetate↗

Effects of tibolone on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To determine the effects of tibolone on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled, cross-over trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Eighteen healthy women who have been in postmenopause for 1-4 years. INTERVENTION(S): Women received either tibolone 2.5 mg/day (group A) or placebo (group B) for 1 month; then the treatment was inverted for the second month. MAIN OUTCOME MEASURE(S): Plasma concentration of NO stable oxidation products and blood pressure were evaluated at baseline, month 1, and month 2. RESULT(S): Baseline concentration of NO metabolites were similar in both groups. At month 1, mean concentration of NO metabolites increased significantly in group A alone. At the end of month 2, NO metabolite levels in group A returned to baseline, whereas in group B they increased significantly. CONCLUSION(S): Tibolone induced a sustained increase in plasma levels of NO in postmenopausal women, suggesting that tibolone may exert a direct cardiovascular protective effect in postmenopausal women.

Cross-Over Studies↗

Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis.

OBJECTIVE: To determine whether leptin is involved in bone remodeling in patients with postmenopausal osteoporosis. DESIGN: Cross-sectional study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University. PATIENT(S): Ninety postmenopausal osteoporotic women (37 obese and 53 nonobese) and 30 healthy premenopausal women from the same clinic served as controls. Lumbar spine bone mineral density (LS-BMD) of osteoporotic patients was more than 2.5 SD below the normal mean of healthy premenopausal women. MAIN OUTCOME MEASURE(S): Serum levels of leptin, osteocalcin (OC), bone alkaline phosphatase (B-ALP), urinary deoxypyridinoline (DPyr), and N-telopeptide of type 1 collagen (NTX) as well as LS-BMD using dual energy X-ray absorptiometry (DEXA). RESULT(S): The serum leptin level in obese postmenopausal osteoporotic patients was significantly increased compared with nonobese osteoporotic patients. There were no significant differences of bone formation markers (B-ALP, OC), bone resorption markers (DPyr, NTX), or LS-BMD between the obese and nonobese groups. There were no significant correlations between serum leptin and any biomarkers of bone turnover and BMD. CONCLUSION(S): In postmenopausal osteoporotic patients with increased bone turnover, serum leptin concentration is not correlated with BMD or with the biomarkers of bone formation or bone resorption.

Absorptiometry, Photon↗

Acute effects of transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To investigate the acute effects of transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, placebo-controlled trial. SETTING: Normal human volunteers in an academic research environment. PATIENT(S): Twenty healthy postmenopausal women. INTERVENTION(S): Transdermal administration of 100 micrograms/d E2 or placebo. MAIN OUTCOME MEASURE(S): Plasma concentrations of NO stable oxidation products and serum concentrations of E2 were assessed before and 24 hours after the administration. RESULT(S): In the group treated with E2 mean concentration of NO metabolites 24 hours after patch application (37.31 +/- 7.62 mumol/L) resulted significantly higher than baseline (21.04 +/- 5.71 mumol/L) and the control group (23.50 +/- 4.03 mumol/L). The correlation between the mean percent increase in NO metabolites and absolute E2 concentrations 24 hours after the E2 administration was statistically significant. CONCLUSION(S): Transdermal administration of E2 to healthy postmenopausal women increases the plasma levels of NO and this supports the hypothesis that a NO-related mechanisms may contribute to the cardiovascular protective effect of estrogens in postmenopause.

Administration, Cutaneous↗

The long-term effects of oral and transdermal postmenopausal hormone replacement therapy on nitric oxide, endothelin-1, prostacyclin, and thromboxane.

OBJECTIVE: Oral postmenopausal hormone replacement therapy (HRT) decreases the risk of cardiovascular disorders, but the mechanisms of this protection are largely unknown. We compared the long-term effects of sequential oral HRT and transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as vasoconstrictive endothelin- and thromboxane A2, all of which may be factors in the protective effect of HRT against cardiovascular disorders. DESIGN: Prospective, randomized study. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Fifty-two healthy postmenopausal female nonsmokers (n = 42) or smokers (n = 10) who had climacteric symptoms. INTERVENTION(S): The women received either oral HRT (2 mg of estradiol on days 1-12, 2 mg of estradiol plus 1 mg of norethisterone acetate on days 13-22, and 1 mg of estradiol on days 23-28; n = 21) or transdermal HRT (50 microg/d of estradiol on days 1-28 followed by 250 microg/d of norethisterone acetate on days 14-28; n = 21) for 1 year. Ten female smokers received transdermal HRT for 1 year. MAIN OUTCOME MEASURE(S): Plasma levels of nitrate as an index of nitric oxide production, endothelin-1, and urinary output of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha) and that of the thromboxane A2 metabolite (2,3-dinorthromboxane B2) were measured before and during the combined phases of the 2nd, 6th, and 12th treatment months. RESULT(S): Both regimens increased plasma estradiol levels and alleviated vasomotor symptoms. Neither regimen caused significant changes in nitrate, endothelin-1, prostacyclin, or thromboxane A2 in nonsmoking women. Female smokers had significantly higher levels of endothelin-1, which were significantly reduced by transdermal HRT at 6 months of treatment. CONCLUSION(S): Nitric oxide, endothelin-1, prostacyclin, and thromboxane A2 are not of primary importance in the protective effect of sequential oral HRT against cardiovascular disorders in otherwise healthy nonsmoking postmenopausal women. In this regard, transdermal HRT appears comparable to oral HRT. Postmenopausal female smokers have high levels of endothelin-1 that are reduced by transdermal HRT.

Administration, Cutaneous↗

Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels.

OBJECTIVE: To investigate the effects of oral 17beta-estradiol administration continuously combined with dydrogesterone on fasting serum total homocysteine levels in postmenopausal women. DESIGN: Randomized, double-blind study. SETTING: Gynecologic outpatient department of a university hospital. PATIENT(S): One hundred thirty-five healthy, nonhysterectomized postmenopausal women. INTERVENTION(S): Oral micronized 17beta-estradiol (2 mg/d) continuously combined with one of four dosages of dydrogesterone (2.5 mg [n = 41], 5 mg [n = 38], 10 mg [n = 37], or 15 mg [n = 19]) was given for 6 months. MAIN OUTCOME MEASURE(S): Fasting serum total homocysteine concentrations. RESULT(S): The mean fasting serum total homocysteine concentrations in the overall study population decreased significantly (by 13.5%) after the first 3 months of treatment and remained unchanged thereafter. No influence of dydrogesterone dosage was found. The greatest reduction in total homocysteine concentration was obtained in women with the highest baseline levels. CONCLUSION(S): Continuously combined hormone replacement therapy lowers fasting serum total homocysteine levels significantly in postmenopausal women. This decrease may be one of the mechanisms that underlie the cardioprotective effects of postmenopausal hormone replacement therapy.

Administration, Oral↗

Expression of P450c17 messenger ribonucleic acid in postmenopausal human ovary tissues.

OBJECTIVE: To investigate the expression of the P450c17 gene in postmenopausal human ovaries compared with normal cycling ovaries. DESIGN: Prospective nonrandomized clinical research study. SETTING: Servei de Medicina Reproductiva and Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospitals Vall d'Hebron, Barcelona, Spain. PATIENT(S): Six premenopausal women and four postmenopausal women undergoing bilateral oophorectomy for nonovarian gynecologic disease. INTERVENTION(S): Extraction of 10 mL of peripheral venous blood for hormone measurements. Extraction of RNA from surgically removed ovaries for Northern blot, ribonuclease protection, and reverse transcriptase polymerase chain reaction Southern blot assays. MAIN OUTCOME MEASURE(S): Definition of the reproductive cycle state of each patient and determination of the level of P450c17 gene expression in all samples with the use of the semiquantitative reverse transcriptase polymerase chain reaction Southern blot assay. RESULT(S): P450c17 messenger RNA levels in postmenopausal ovaries varied considerably between samples. Although the levels were similar to those detected in the early follicular phase, one of the samples had levels as high as those observed in the late follicular phase. CONCLUSION(S): Although the degree varied from one sample to another, all the postmenopausal ovaries studied expressed the P450c17 gene at the messenger RNA level. In a sample from a patient with endometrial adenocarcinoma, the level was as high as the levels observed in the late follicular phase.

Blotting, Northern↗

Relation of regional fat distribution to insulin sensitivity in postmenopausal women.

OBJECTIVE: To examine the relation between insulin sensitivity and total and regional body fat in nonobese postmenopausal women. DESIGN: Cross-sectional study. SETTING: A clinical research center. PATIENT(S): Twenty-seven women in the early postmenopausal period, with a mean (+/-SD) age of 50.8 +/- 4.1 years, who had had their last menstrual period 6 months to 3 years before the study. None were taking hormone replacement therapy, and all had an FSH level of >35 mIU/mL, a body mass index of <30 kg/m2, and a waist circumference of <94 cm. INTERVENTION(S): Computed tomography scans at the L4-5 vertebral disk space, dual-photon x-ray absorptiometry scans, and euglycemic hyperinsulinemic clamps were performed. MAIN OUTCOME MEASURE(S): Intraabdominal fat, subcutaneous abdominal fat, sagittal diameter, total body fat, percent body fat, and insulin sensitivity. RESULT(S): The natural log of insulin sensitivity correlated significantly with intraabdominal fat (r = -.39), subcutaneous fat (r = -.43), and sagittal diameter (r = -.48). After adjusting for total fat, sagittal diameter remained significantly related to insulin sensitivity. CONCLUSION(S): Central abdominal fat is inversely and independently related to insulin sensitivity after adjusting for total fat in women in the early postmenopausal period. Efforts to reduce either subcutaneous abdominal fat or intraabdominal fat should be helpful in reducing the risk of noninsulin-dependent diabetes mellitus in postmenopausal women.

Abdomen↗

Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women.

BACKGROUND: Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objectives. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. METHODS: One hundred and five healthy postmenopausal women aged 52-67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Flow mediated dilatation was inversely related to the plasma logLp(a) level. Mean change per unit logLp(a) increase:-2.83% (95% CI: -5.22--0.43). Elevated Lp(a) (>239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4%+/-1. 2) compared to Lp(a) < or =239 mg/l (5.2%+/-0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (< or =239 mg/l) (8.0+/-1.2 vs. 11.4%+/-0.8). CONCLUSION: Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.

Administration, Sublingual↗

Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan.

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.

Adult↗

[Comparative study of the type of obesity in pre- and postmenopausal women: Relationship with fat cell data, fatty acid composition and endocrine, metabolic, nutritional and psychological variables].

BACKGROUND: The weight increase that many women experience during menopause may be the result of ageing. However, the precise factors inducing obesity during this period remain to be identified. The object of this study was to determine the type of obesity in a group of women along with its distinctive features, if any, as a function of the menopause stage. PATIENTS AND METHOD: The sample consisted of 55 women (22 premenopausal and 33 postmenopausal) with grade I and II obesity. Distribution of body fat, composition of the adipose tissue, size and number of adipocytes, lipidic and hormonal profile as well as nutritional and psychological aspects were all taken into account. RESULTS: Postmenopausal women had an android distribution of fat, whereas it was gynoid in premenopausal women. The adipose tissue showed different cell characteristics, the number of fat cells and content of saturated fatty acids (myristic and palmitic) being significantly lower in the postmenopausal group. Menopause was associated with an increase in plasmatic lipids and a decrease in the levels of certain hormones (dehydroepiandrosterone-sulphate and insulin). Postmenopausal women tended to have healthier eating habits than premenopausal women, with a significantly lower fat intake but higher carbohydrate and fibre intakes. However, the degree of physical activity was lower than in premenopausal women. CONCLUSIONS: The type of obesity differs as a function of the menopausal status, a finding that should be taken into account when establishing a dietetic treatment.

Adipose Tissue↗

Influence of body fatness on the coronary risk profile of physically active postmenopausal women.

We have shown previously that endurance-trained postmenopausal runners demonstrate more favorable coronary heart disease (CHD) risk factors compared with age-matched sedentary women. However, the runners exhibited higher levels of physical activity and lower levels of body fatness, both of which can influence CHD risk factors. To gain insight into the influence of body fatness per se, we studied 38 postmenopausal healthy women: 10 swimmers, 10 runners, and nine obese and nine leaner sedentary subjects matched for age, hormone replacement use, and years postmenopause. Swimmers and runners were further matched for exercise training volume (4.5+/-0.2 v 4.6+/-0.6 h/wk) and relative competitive performance (79%+/-5% v 77+/-3% of age-adjusted world record). Maximal oxygen consumption (VO2max) on the treadmill was lower (P < .01) in swimmers versus runners. Body mass (65.0+/-2.0 v 59.0+/-1.3 kg), percent body fat (29%+/-2% v 23%+/-2%), and waist circumference (79+/-3 v 71+/-1 cm) were greater (P < .01) in swimmers than in runners. There were no significant differences in total caloric intake or dietary composition between swimmers and runners. Insulin sensitivity (via Bergman's minimal model) and fasting plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), glucose, and plasminogen activator inhibitor-1 (PAI-1) activity were not different between the groups. However, plasma high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL-C/TC, insulin, fibrinogen, fibrin D-dimer, PAI antigen, tissue plasminogen activator (t-PA) activity, and t-PA antigen levels all were less favorable (P < .05) in swimmers versus runners. Daytime, nighttime, and 24-hour systolic blood pressure (SBP) was 6 to 10 mm Hg higher in swimmers compared with runners, but resting blood pressure, 24-hour blood pressure load, and blood pressure variability were not significantly different. Stepwise regression showed that measures of body fatness were the primary independent determinants of most of the metabolic CHD risk factors. When analysis of covariance (ANCOVA) was performed with body fatness as a covariate, differences in CHD risk factors between swimmers and runners were abolished (P=.18 to .90). We conclude that among endurance-trained postmenopausal women matched for training volume and competitive eliteness, higher total and abdominal body fatness is, in general, associated with a less favorable metabolic CHD risk profile. Thus, high levels of habitual aerobic exercise do not appear to negate the deleterious effects of adiposity on the coronary risk profile of healthy middle-aged and older women.

Adipose Tissue↗

Transdermal hormone replacement therapy in postmenopausal women with uterine leiomyomas.

OBJECTIVE: To evaluate the effects of transdermal hormone replacement therapy (HRT) on uterine and leiomyoma size and on uterine bleeding patterns in postmenopausal women with uterine leiomyomas. METHODS: The required sample size was calculated to be 30 subjects per group to detect an effect on the size of one standard deviation (SD) with an alpha value of 0.05 (two-sided) and a power 1 - delta = 0.8. At the end of the study, the power analysis showed a value of beta = 0.826. Seventy postmenopausal women with uterine leiomyomas were enrolled and treated for 12 cycles of 28 days each with transdermal 17 beta-estradiol (E(2)) patches plus oral medroxyprogesterone acetate continuously added (group A) or with calcium carbonate (group B). At entry and every three cycles, uterine and leiomyoma dimensions were measured by transvaginal ultrasonography. To evaluate the effect of transdermal HRT on the characteristics of uterine bleeding, 35 healthy postmenopausal women without uterine leiomyomas (group C) were enrolled and treated with the same regimen as group A. A daily diary was used to record the abnormal uterine bleeding episodes, and a rank scale was used to assess the severity of bleeding. RESULTS: There were no significant changes in mean uterine or leiomyoma size between groups A and B, or in each group compared with basal values. No significant difference was detected between groups A and C in uterine bleeding patterns. CONCLUSION: Transdermal HRT did not increase the size of uterine leiomyomas or affect uterine bleeding patterns in postmenopausal women.

Administration, Cutaneous↗

Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk.

OBJECTIVE: To examine the life expectancy and cost-effectiveness of hormone replacement therapy (HRT) and raloxifene therapy in healthy 50-year-old postmenopausal women. METHODS: We performed a cost-effectiveness analysis using a Markov model, discounting the value of future costs and benefits to account for their time of occurrence. RESULTS: Both HRT and raloxifene therapy increase life expectancy and are cost-effective relative to no therapy for 50-year-old postmenopausal women. For women at average breast cancer and coronary heart disease risk, lifetime HRT increases quality-adjusted life expectancy more (1.75 versus 1.32 quality-adjusted life years) and costs less ($3802 versus $12,968) than lifetime raloxifene therapy. However, raloxifene is more cost-effective than HRT for women at average coronary risk who have a lifetime breast cancer risk of 15% or higher or who receive 10 years or less of postmenopausal therapy. Raloxifene is also the more cost-effective alternative if HRT reduces coronary heart disease risk by less than 20%. CONCLUSIONS: Assuming the benefit of HRT in coronary heart disease prevention from observational studies, long-term HRT is the most cost-effective alternative for women at average breast cancer and coronary heart disease risk seeking to extend their quality-adjusted life expectancy after menopause. However, raloxifene is the more cost-effective alternative for women at average coronary risk with one or more major breast cancer risk factors (first-degree relative, prior breast biopsy, atypical hyperplasia or BRCA1/2 mutation). These results can help inform decisions about postmenopausal therapy until the results of large scale randomized trials of these therapies become available.

Breast Neoplasms↗

Measurements of urinary prostaglandins in young ovulatory women during the menstrual cycle and in postmenopausal women.

The purpose of the present work was to study the prostaglandin excretion in young nonpregnant ovulatory women during the menstrual cycle on the one hand and in postmenopausal women on the other hand and to investigate the influence of female sex hormones (estradiol, progesterone) on urinary prostanoid excretion. Urinary excretion rates of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and their metabolites PGE-M (11 alpha-hydroxy-9, 15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid), 2,3-dinor-6-keto-PGF1 alpha, 2,3-dinor-TxB2 and 11-dehydro-TxB2 were determined by gas chromatography-triple stage quadrupole mass spectrometry (GC/MS/MS) in 41 young non-pregnant women during the follicular phase and during the luteal phase and in 23 postmenopausal women. Excretion rates of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. In contrast to the young ovulatory women, PGE2 and TxB2 were significantly higher in postmenopausal women. Concerning the other prostaglandins significant differences between these groups of women did not exist. Although serum levels of estradiol and progesterone were different in young and postmenopausal women, sex hormones have not been shown to correlate with prostaglandins. Our data do not suggest sex hormones to be responsible for the difference in the prostaglandin excretion in women of reproductive age and in women in the menopause. Further systematic investigations into age dependency of prostaglandin excretion in women are necessary.

6-Ketoprostaglandin F1 alpha↗