Changes in intra-abdominal fat in early postmenopausal women: effects of hormone use

Objective: Intra‐abdominal fat (IAF) accumulates with age, is greater among postmenopausal vs. premenopausal women, and is linked to risk for both type 2 diabetes and cardiovascular disease. Whether hormone replacement therapy (HRT) prevents or attenuates changes in IAF and related risk factors is not clear. The objectives of this observational study were to 1) determine whether HRT attenuated the expected age‐related increase in IAF and 2) identify the independent effects of HRT and fat distribution on changes in disease risk factors. Research Methods and Procedures: Subjects were early postmenopausal white women 45 to 55 years of age. Women either used HRT at the time of enrollment (n = 33) or did not (n = 17). Subjects were evaluated at baseline and 2 years for body composition (DXA), body fat distribution (computed tomography), insulin sensitivity (Si; minimal model), and serum lipids. Results: IAF increased significantly over 2 years, and this increase was not attenuated by HRT. HRT users had less IAF throughout the study. HRT users showed an increase in Si, whereas non‐users showed a decrease. Superficial subcutaneous adipose tissue was significantly and independently related to total cholesterol, whereas IAF was related to high‐density lipoprotein cholesterol, triglycerides, and Si. Discussion: HRT users had less IAF at baseline and throughout the study. Whether HRT altered the relationship between total body fat and IAF or whether differences between groups existed before the study should be addressed through a randomized, interventional study design. HRT had a significant effect on Si; IAF and superficial subcutaneous adipose tissue were significant determinants of disease risk factors.     

Metabolic,hormonal and immunological associations with global DNA methylation among postmenopausal women

DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from 173 overweight/obese postmenopausal women. Global DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for LINE-1 repeats. We used correlations and linear regression analyses to investigate associations between continuous data and DNA methylation, while t-tests were used for categorical data. Secondary analyses stratified by serum folate levels and multivitamin use were also conducted. There was little variability in LINE-1 methylation (66.3–79.5%). Mean LINE-1 methylation was significantly higher among women with elevated glucose levels. Mean LINE-1 methylation was also higher among women with high CD4+/CD8+ ratio, and lower among women with elevated vitamin B6, but neither reached statistical significance. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations (estrone, estradiol, testosterone and sex hormone binding globulin) among women with low serum folate levels (n = 53). Conversely, among women with high serum folate levels (n = 53), DNA methylation was positively associated with several immune markers (CD4/CD8 ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that global DNA methylation is generally stable, with differential associations for sex hormones and immune markers depending on one-carbon status.     

Metabolic,hormonal and immunological associations with global DNA methylation among postmenopausal women

DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from 173 overweight/obese postmenopausal women. Global DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for LINE-1 repeats. We used correlations and linear regression analyses to investigate associations between continuous data and DNA methylation, while t-tests were used for categorical data. Secondary analyses stratified by serum folate levels and multivitamin use were also conducted. There was little variability in LINE-1 methylation (66.3–79.5%). Mean LINE-1 methylation was significantly higher among women with elevated glucose levels. Mean LINE-1 methylation was also higher among women with high CD4+/CD8+ ratio, and lower among women with elevated vitamin B6, but neither reached statistical significance. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations (estrone, estradiol, testosterone and sex hormone binding globulin) among women with low serum folate levels (n = 53). Conversely, among women with high serum folate levels (n = 53), DNA methylation was positively associated with several immune markers (CD4/CD8 ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that global DNA methylation is generally stable, with differential associations for sex hormones and immune markers depending on one-carbon status.     

Longitudinal studies on the phenomenon of postmenopausal estrogen production

Longitudinal studies on the phenomenon of postmenopausal estrogen pr oduction are presented. Cytohormonal screening was repeated after 1-4 years in 5633 women. The outcome of the 2nd smear was determined by the cytologic characteristics of the 1st smear and by body weight. A thin woman with an atrophic 1st smear had only 4.8% probability of showing an estrogenic 2nd smear, whereas a grossly obese woman with an estrogenic 1st smear had a 26.2% chance of showing an estrogenic 2nd smear. Series of 8-12 cytologic smears were studied within 2 months in 80 women. Evidence indicated that the phenomenon of postmenopausal estrogenic smears tended to be continuous. 24-hour urine specimens from 100 normal women were analyzed and the cytologic-biochemical relationships were studied. Persistent estrogenic smears predicted higher excretion of estrone and estriol and slightly lower excretion of androsterone and etiocholanolone.     

Subcutaneous fat accumulation shows a beneficial correlation with serum cholesterol in postmenopausal Japanese women

This study aimed to investigate whether accumulation of subcutaneous abdominal fat has a beneficial correlation with lipid metabolism in premenopausal and/or postmenopausal Japanese women. The study enrolled 146 premenopausal women, ranging in age from 19 to 54 years, and 82 postmeno-pausal women, ranging in age from 47 to 66 years. Fat distribution, including abdominal visceral fat area (VFA) and abdominal subcutaneous fat area (SFA), were measured in an outpatient clinic by magnetic resonance imaging. Homogeneity of the regression slopes for SFA to total cholesterol (P = 0.030), low-density lipoprotein cholesterol (P = 0.020), apolipoprotein B (apoB) (P = 0.001), and the ratio of apoB to apolipoprotein A-I (apoA-I) (P = 0.003) were not found between premenopausal and postmenopausal women, even after adjustment for both VFA and age. However, the regression slopes for VFA to all measured lipid parameters, as well as apolipoproteins, were homogeneous between the premenopausal and postmeno-pausal groups. Abdominal SFA in postmenopausal women correlated negatively with total cholesterol (P = 0.007), low-density lipoprotein cholesterol (P = 0.002), apoB (P < 0.001), and the ratio of apoB to apoA-I (P = 0.001), after adjustment for age and VFA, but this was not the case in premenopausal women. The mechanisms involved in the beneficial effects of subcutaneous fat accumulation in postmenopausal women remain obscure, but upregulated aromatase expression, derived from adipose tissue, may possibly improve lipid and apolipoprotein metabolism.     

Plant defense associations in the marine environment

In contrast to terrestrial systems, few positive plant-plant associations have been recorded in tropical reef environments. This study, conducted at Carrie Bow Cay, Belize during 28 March–10 April 1984, provides the first documentation of herbivore escapes for natural combinations of palatable and unpalatable marine plants. For example, there was a highly significant association of several macrophyte taxa (Laurencia poitei, Dictyota spp., Amphiroa fragilissima, Cladophoropsis macromeres, Galaxaura cylindrica, rhodophycean turf) within a 2.0-cm radius of the herbivore-resistant brown alga Stypopodium zonale. Almost twice as many taxa occurred within 10 cm of S. zonale as within 10 cm of an equal number of random Stypopodium-free points, and there were no algal species negatively associated with S. zonale. The association of A. tribulus, L. poitei, Digenia simplex, rhodophycean turf, and Jania adherens with S. zonale provided them a fourfold greater survivorship per 48 h in the presence of grazing activity by fishes (mainly Acanthuridae and Scaridae). Reduced herbivory by fishes on macroalgae associated with S. zonale was not solely a consequence of its structural aspect. Losses of the palatable alga Acanthophora spicifera were significantly greater for thalli spatially remote (30 and 60 cm) from either a real or simulated Stypopodium; however, losses of A. spicifera adjacent to actual Stypopodium plants were significantly less than the losses next to models. The inter-relationships studied here, where an abundant and well-defended plant provides a significant refuge habitat for at least five relatively edible macroalgae, clearly facilitates the survival of certain taxa in the reef system and concomitantly enhances the within habitat diversity. Our findings also suggest an interaction counter to the process of competitive exclusion, since the single predominant plant has a positive rather than negative net effect on the abundances of other species that utilize the same general resources (e.g., light, space, nutrients).     

Thermoregulatory and endocrine effects of a low dose of danazol in postmenopausal women: interaction with the effect of naloxone

Before and on the 30th day of danazol administration (200 mg/day), in six postmenopausal women the activity of endogenous opioid peptides has been indirectly evaluated by the effect on LH secretion and body temperature (measured as rectal temperature) exerted by the infusion of the opioid antagonist naloxone (1.6 mg/h x 4 h preceded by 1.6 mg iv bolus). Before and during danazol administration a GnRH test (100 mcg iv bolus) was also performed to evaluate possible variations in pituitary responsiveness to GnRH. Danazol significantly reduced mean plasma levels of LH and FSH (p less than 0.01), and their response to GnRH stimulus (p less than 0.05). Either before or during danazol administration mean plasma LH and FSH levels did not vary during the infusion of naloxone, while body temperature significantly decreased (p less than 0.01). The decrease in body temperature was significantly greater (p less than 0.05) during danazol than before treatment. The present data suggest that in postmenopausal women a low dose of danazol exerts an antigonadotropic effect mainly reducing the pituitary responsiveness to GnRH. The enhanced hypothermic response to naloxone observed during danazol administration also seems to suggest that in postmenopausal women a low dose of danazol enhances the thermoregulatory role of endogenous opioid peptides.     

Relation between fat distributions and several plasma adipocytokines after exercise training in premenopausal and postmenopausal women

Circulating concentrations of adipocytokines, such as leptin, tumor necrosis factor-alpha (TNF-alpha), and plasminogen activator inhibitor-1 (PAI-1), vary with exercise training, menopause, or regional variations in adipose tissues. In the present study, the relationships between body fat distributions and some adipocytokines were compared in premenopausal (N = 9) and postmenopausal women (N = 9), before and after exercise training. The training for 10 weeks (that is, 3 days/week) consisted of aqua exercise plus resistance exercise. The training reduced percent fat, body mass index, total fat mass (TFM), subcutaneous fat mass (SFM), and plasma levels of leptin and PAI-1 in both women. Mean value of plasma TNF-alpha tended to increase after training in both women. Plasma leptin levels were lower in postmenopausal than in premenopausal women, independently of training. In premenopausal women, plasma leptin levels correlated well with either TFM or SFM before and after training. Regression analysis of decreases in plasma leptin with a reduced amount of SFM revealed that decreases in plasma leptin depended to a greater extent on a loss of SFM. In postmenopausal women, no significant correlation was found between leptin levels and any of the fat depots. Plasma TNF-alpha levels correlated well with visceral fat mass (VFM) in premenopausal but not in postmenopausal women. Changes in TNF-alpha levels after training correlated well with reduced amount of VFM in premenopausal but not in postmenopausal women. Plasma PAI-1 levels were not different between groups. Moreover, no significant correlation was found between PAI-1 levels and any of the fat depots in both women. Thus, in premenopausal but not in postmenopausal women, changes in plasma concentrations of leptin and TNF-alpha correlate well with specific alterations in relative amount of SFM and VFM after training, respectively. However, no significant relationship between PAI-1 and any of the fat depots was found independently of either menopause or training.     

Apoptosis in raloxifene-treated postmenopausal women

As raloxifene is a mixed estrogen receptor agonist and antagonist, it exerts different effects on apoptosis in different tissues. In this study, we aimed to evaluate apoptosis in the peripheral lymphocytes of postmenopausal women treated with raloxifene and compare it with untreated control subjects. In this way, we expected to deduce some results about the effect of raloxifene on the immune system and to serve as a guide for future studies on this newly proposed effect of a well-known agent. Twenty osteoporotic postmenopausal women treated with raloxifene for 12 months were included in this study. Another 20 osteoporotic postmenopausal women matched for age and postmenopausal years, but without any medication, were chosen as the control group. Apoptosis was evaluated using a morphological and DNA fragmentation assay, in the peripheral lymphocytes of these women. Our results revealed a decrease in the apoptosis percentages of the patients treated with raloxifene (14.6%) with respect to the control subjects (15.8%), but the difference was not statistically significant (p=0.467). This study indicated that raloxifene treatment had no apoptotic effect on peripheral human lymphocytes compared to controls.     

Validation of five simple models estimating body fat in white postmenopausal women: use in clinical practice and research

The aim of this study was to validate noninvasive models, retrieved from the literature, estimating body fat in white women. The cohort used for the validation consisted of 277 postmenopausal women, and the reference method was dual-energy X-ray absorptiometry (DXA). Five models were retrieved containing anthropometric measurements such as bicep and tricep skinfolds, waist circumference (WC), height, and body weight. Models including only BMI were found to be less biased and more valid than others including skinfolds and circumferences. The model by Visser et al., estimating body density (BD = 0.0226 × sex - 0.0022 × BMI + 1.0605) with the subsequent use of Brozek's (and not Siri's) equation to estimate body fat percentage (%BF), was found to be more valid than the other models for this cohort. In conclusion, it seems that Visser's et al. model, including only BMI, with Brozek's equation, is a fast, noninvasive, and valid method to assess body composition in white postmenopausal women in clinical practice and research.     

Effects of estrogen replacement therapy on abdominal fat compartments as related to glucose and lipid metabolism in early postmenopausal women.

The effects of estrogen replacement therapy on lipid and glucose metabolism as related to abdominal fat distribution were investigated in fifty-one healthy postmenopausal women aged 52-53 years. They were randomized to treatment with either estradiol 2 mg or placebo daily for three months in a double-blind design. Forty-six women continued with estradiol for another nine months in an open design with the addition of medroxyprogesterone for ten days every three months. Intra-abdominal and subcutaneous abdominal fat, and intrapelvic and subcutaneous pelvic fat was estimated by computed tomography before and after one year of estrogen treatment. Euglycemic hyperinsulinemic clamp, oral glucose tolerance test and analyses of blood lipids were performed after 3 and 12 months of treatment. Estrogen replacement therapy decreased body fat mass as well as intra-abdominal and intrapelvic fat, but not the subcutaneous fat compartments. LDL cholesterol decreased and HDL cholesterol increased, whereas triglycerides were not changed by one year of estrogen treatment. Insulin sensitivity and glucose tolerance were not affected by estrogen treatment. In postmenopausal women estrogen treatment for one year decreased intra-abdominal and intrapelvic fat compartments, but this was not related to changes in plasma lipid levels. Insulin sensitivity and plasma triglycerides were not affected by estrogen treatment.     

Iron deficiency in obese postmenopausal women

Objective: This study evaluates whether the iron deficiency suggested in children and adolescents with overweight is also present with increasing age. Research Methods and Procedures: We examined 50 consecutive postmenopausal nondiabetic white women with a BMI ≥30 kg/m² and 50 non‐obese seemingly healthy women as a control group. In addition to the traditional indices of iron status, we measured the soluble transferrin receptor (sTfR) levels, a sensitive and highly quantitative indicator of early iron deficiency not influenced by the acute phase response. Results: Obese women have higher serum sTfR levels than control subjects [1.38 (range, 0.89 to 2.39) vs. 1.16 mg/dL (range, 0.69 to 2.03 mg/dL); p < 0.001]. However, no difference in ferritin concentration was observed between the groups [70.50 (range, 18 to 219) vs. 69.50 ng/mL (range, 24 to 270 ng/mL); p = not significant]. A positive correlation between BMI and sTfR concentration was detected. On multiple regression analyses, BMI (positively) and ferritin (inversely) were independent predictors accounting for sTfR. Discussion: These results suggest that a moderate degree of iron deficiency is also present among adult women with obesity. The determination of sTfR is useful in the evaluation of iron status in this condition. Further studies with a greater number of patients are required to investigate the relationship between tissue iron concentrations and obesity.