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

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

Leptin production in pre- and postmenopausal women

OBJECTIVES: To investigate the differences in leptin production between pre- and postmenopausal women. METHODS: Subjects were 75 pre- and 75 postmenopausal women. Age, height, weight, and body mass index (BMI, wt/ht(2)) were recorded. Serum leptin levels were measured by RIA. Total body fat mass and percentage of body fat mass were measured by whole-body scanning with dual-energy X-ray absorptiometry. Serum leptin levels, the ratio of serum leptin levels to total body fat mass (leptin-fat mass ratio), baseline characteristics, and anthropometric variables were compared between the two groups. In all subjects (n=150), relationship of serum leptin levels with menopausal status (pre- and postmenopause) was investigated by univariate and multiple regression analysis. RESULTS: Serum leptin levels in premenopausal women 8.4+/-4.8 ng/ml, which did not differ from that in postmenopausal women (9.2+/-7.1 ng/ml). Total body fat mass, percentage of body fat mass, and BMI did not differ between the two groups. Leptin-fat mass ratio in premenopausal women was 0.43+/-0.17 ng/ml/kg, which did not differ from that in postmenopausal women (0.44+/-0.24 ng/ml/kg). On both univariate and multiple regression analysis, serum leptin levels were not correlated with menopausal status. CONCLUSIONS: Menopausal status does not have a significant impact on leptin production.     

Serum leptin levels in postmenopausal women: effects of transdermal hormone replacement therapy

OBJECTIVE: To evaluate serum leptin levels in postmenopausal women who are receiving hormone replacement therapy (HRT) and postmenopausal women who are not receiving HRT with similar body mass index (BMI) to determine whether estrogens exert effects on leptin secretion. DESIGN: Cross-sectional, prospective study comparing serum leptin levels in premenopausal women, postmenopausal women who were not receiving HRT (group A), and postmenopausal women who were receiving HRT (group B). RESULTS: Serum leptin levels were significantly higher in group A in comparison to group B and control women (15.82 +/- 6.6 ng/ml, 8.14 +/- 4.17 ng/ml, and 10.12 +/- 5.48 ng/ml, respectively; p < 0.05). Total fat mass (FM) was found to be significantly higher in untreated postmenopausal women in comparison to the other two groups (22.66 +/- 2.79 kg vs. 19.14 +/- 3.39 kg vs. 18.98 +/- 3.82 kg; p < 0.05). No significant difference was observed in weight, height, BMI, blood pressure, or glucose levels among the three groups. A linear correlation between BMI and serum leptin levels as well as between total FM and serum leptin levels was observed in all groups. No correlation was found between serum leptin levels and months from menopause and months of HRT. CONCLUSIONS: Our results show that serum leptin is increased in untreated postmenopausal women, possibly as a consequence of the increase in FM, and that HRT reduces serum leptin levels to premenopausal values. These data need further investigation by a broader longitudinal study.     

Association of body mass index and Trp64Arg polymorphism of the beta3-adrenoreceptor gene and leptin level in Tehran Lipid and Glucose Study

In this study the association between beta3-adrenoceptor gene polymorphism and serum concentration of leptin with body mass index (BMI) is investigated. Using subjects in the Tehran Lipid and Glucose Study, genotyping of the Trp64Arg polymorphism of the beta3-adrenoreceptor gene was performed using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used and the association with obesity was investigated. At total of 197 men and 204 women were divided into four groups (BMI<20, 20< or =BMI<25, 25< or =BMI<30, BMI< or =30) and 97, 98, 104 and 102 subjects, respectively, were placed randomly in the four groups. Leptin level was determined by an enzyme immunoassay (EIA) method and FBS, HDL-C, triglyceride and total cholesterol levels were determined by an enzyme colorimetric method. Body mass index (BMI) was also measured. The A (Arg) allele frequency was 0.08 among the population and its presence was significantly associated with increase of leptin level (AA/TA, 30.5+/-24.8 ng/mL; TT, 22.6+/-20.9 ng/mL; P=0.014) but there was no significant association with increased BMI (AA/TA, 27+/-5.6 kg/m2; TT, 25.4+/-5.5 kg/m2; P=0.072). These data show that the presence of the Arg64 allele at the beta3-adenoceptor gene locus is related to increase in leptin level in this population, but is not related to body mass index.     

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

Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n=30; mean ages, 35.4±8.3 years) and postmenopausal women (n=45; mean ages, 49.5±4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m²) and as non-obese (BMI<27 kg/m²). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60±5.0; 3.67±2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60±7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50±4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05±10.53; 14.78±6.76 ng/ml, respectively, P<0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.     

Stiffness index identifies patients with osteoporotic fractures better than ultrasound velocity or attenuation alone

Objectives: To compare a composite ultrasonometry variable, the stiffness index (SI), with its two component variables of speed of sound (SOS) and broadband ultrasound attenuation (BUA), in identifying post-menopausal women with low bone mineral density (BMD) and/or osteoporotic fracture. Methods: A cross sectional sample of 1217 women (mean (S.D.) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis were assessed by detailed questionnaire and women with diseases, or those taking treatments known to affect bone metabolism were excluded. Women were allocated to one of four groups: pre-menopausal women (n=476), healthy post-menopausal women (n=583), post-menopausal women with low BMD (n=101), and post-menopausal women with osteoporotic fracture (n=57). An Achilles ultrasonometer was used to perform quantitative ultrasonometry (QUS) at the os calcis. The SI, calculated mathematically from SOS and BUA, was computed. Results: Analysis of receiver operating curves (ROC) between healthy post-menopausal women and post-menopausal women with low BMD but no fracture, showed that the area under the curve (AUC) for SI was significantly greater than that for BUA (P<0.001) or SOS (P<0.05). For healthy post-menopausal women compared to women with fracture, the area AUC for SI was significantly greater than that for BUA (P<0.05) or SOS (P<0.001). No significant difference was found for AUC between BUA and SOS. Conclusion: QUS variables discriminated women with low density or fracture from healthy postmenopausal controls. The SI was a significantly better indicator than BUA or SOS in this retrospective study.     

Obesity, estrone, and coronary artery disease in postmenopausal women

OBJECTIVES: The link between obesity and endogenous estrogen with coronary artery disease (CAD) in postmenopausal women is uncertain. In this prospective study we analyzed the association of body mass index (BMI) and blood levels of estrone in postmenopausal women with known CAD or with a high risk factor score for CAD. METHODS: Participants were 251 female clinic patients aged 50-90 years who were postmenopausal and not using estrogen therapy. Clinical and behavioral characteristics and fasting blood for estrone and heart disease risk factors were collected at baseline, and again at 1 and 2 years. Women were grouped according to their BMI (kg/m2) as normal (18.5< or =BMI<25), overweight (25< or =BMI<30) or obese (BMI > or =30), and by low and high estrone levels (<15 and > or =15pg/mL, respectively). Fatal and nonfatal events were recorded for 2 years after baseline. RESULTS: Women with a low estrone level were older, thinner, and had less hypertension, diabetes, and lower triglyceride and glucose levels. BMI was positively associated with estrone levels, hypertension, and diabetes and inversely associated with HDL cholesterol. There were 14 deaths, 8 attributed to CAD. The Kaplan-Meier survival curve showed a nonsignificant trend (p=0.074) of greater all cause mortality in women with low estrone levels (<15mL). In this model, adjusted for BMI, age [OR=1.08; p=0.03], C-reactive protein [OR=1.24; p=0.024] and hypertension [OR=6.22; p=0.003] were independent predictors of all cause mortality. CONCLUSIONS: Postmenopausal women with low estrone levels (<15pg/mL) had a trend for increased mortality over the next 2 years. Larger, longer studies are needed.     

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women

OBJECTIVE: The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor alpha [TNF-alpha]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. DESIGN: This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-alpha, estrone (E1), and estradiol (E2). RESULTS: After accounting for body mass index, TNF-alpha was significantly increased (1.5+/-0.1 vs 2.0+/-0.1 pg/mL, P<0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6+/-1.1 vs 4.0+/-1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-alpha (r=-0.23, P<0.05) and positively with leptin (r=0.35, P<0.01) and did not correlate with resistin. E2 correlated negatively with TNF-alpha (r=-0.24, P<0.05) and positively with leptin (r=0.34, P<0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. CONCLUSIONS: Estrogen deficiency resulted in increased TNF-alpha levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.     

Is there a role for leptin in the endocrine and metabolic aberrations of polycystic ovary syndrome?

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.      

Body mass index is associated with USF1 haplotype in Korean premenopausal women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m2) and BMI <25 kg/m2 groups in premenopausal females ( chi2=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.     

The effect of menopause on the relation between weight gain and mortality among women

OBJECTIVE: To examine the effect of menopause on the relation between weight gain and all-cause mortality. DESIGN: Prospective cohort study of 6,030 adults (ages 25-82 years) who never smoked cigarettes, had no history of coronary heart disease, cancer, or stroke, and were enrolled in a 29-year follow-up in which anthropometric data were given at baseline and at 17 years after baseline. RESULTS: Weight gain that occurred over a 17-year interval (baseline to 17 years after baseline) increased the mortality risk of men and middle-aged women, but decreased the mortality risk of older women. Further study of the women revealed that a strong protective effect of weight gains was only evident among the leanest (25 kg/m2) postmenopausal women [HR (95% CI) = 0.81 (0.41, 1.58)] or for premenopausal women [HR (95% CI) = 1.05 (0.49, 2.25) for 25 kg/m2]. We found that the protective effect of weight gain among the leanest postmenopausal women was primarily due to a more than threefold decrease in cardiovascular disease mortality risk. One possible explanation for these findings is that weight gain increases the level of adipose-tissue-derived estrogen among lean postmenopausal women. CONCLUSION: Moderate menopausal weight gain may be well tolerated in lean women.     

Quantitative ultrasound of the calcaneus in Arabian women: relation to anthropometric and lifestyle factors

OBJECTIVES: To determine factors influencing quantitative ultrasound (QUS) parameters of the calcaneus in a population-based sample of United Arab Emirates (UAE) women, and to compare QUS parameters of the calcaneus for healthy young UAE women with the manufacturer's reference ranges for other populations. METHODS: All subjects completed a questionnaire on reproductive and life style factors. Height and weight were measured, and body composition was determined by bioelectric impedence. Estimated bone mineral density (BMD), Speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) of the right calcaneus were determined by Sahara ultrasound. RESULTS: In premenopausal women (n=330), age, weight, body mass index (BMI), lean weight, fat weight, education, age at menarche, and number of pregnancies, correlated significantly with QUS parameters. Multiple regression analysis showed that age at menarche, number of pregnancies, and BMI, were the best predictors of QUS parameters although these factors explained only small amounts of the variance (R(2)=0.05). In postmenopausal women (n=81), age, BMI and physical activity were the best predictors of BUA (R(2)=0.35), SOS (R(2)=0.39), and QUI (R(2)=0.43). Mean estimated BMD, QUI and SOS for healthy young UAE women were significantly lower than the manufacturer's reference ranges for U.S. Caucasian, European Caucasian, and Chinese Asian healthy young women of the same age range (P<0.001 for all comparisons). Mean BUA was not significantly different, however. CONCLUSIONS: Menopausal status, age, BMI and physical activity are strong predictors of QUS parameters of the calcaneus in Arabian women. Healthy young Arabian women have lower estimated calcaneal BMD compared with the manufacturer's reference ranges for other populations.     

Body mass index (BMI) and parameters of bone formation and resorption in postmenopausal women

OBJECTIVES: Aim of this study was to evaluate increased body mass index (BMI) as an anthropometric factor, predisposing to lower rates of bone turnover or changes in bone balance after menopause. MATERIAL AND METHODS: For this purpose, we calculated BMI, and measured spinal (BMD(SP)) and femoral bone mineral density (BMD(FN)) and biochemical markers of bone formation (serum osteocalcin (S-OC), serum procollagen type I C propeptide (S-PICP), serum bone-specific alkaline phosphatase (S-B-ALP)) and resorption (urine N- and C-terminal cross-linking telopeptide of type I collagen (U-NTX-I and U-CTX-I), pyridinoline (U-PYD) and deoxypyridinoline (U-DPD)) in 130 healthy postmenopausal women, aged 46-85 years. Bone balance indices were calculated by subtracting z-scores of resorption markers from z-scores of formation markers, to evaluate bone balance. RESULTS: S-PICP ( r = -0.297, P = 0.002), S-OC ( r = -0.173, P = 0.05) and bone balance indices (zPICP-zDPD) and (zPICP-zPYD) were negatively correlated with BMI (r = -0.25, P = 0.01 and r = -0.25, P = 0.01 and r = -0.21, P = 0.037) and with BMD(SP) (r = -0.196, P = 0.032 and r = -0.275 and P = 0.022). Women were grouped according to their BMI, in normals (BMI < 25 kg/m2), overweight (BMI = 25-30 kg/m2, and obese (BMI > 30 kg/m2). Overweight and obese women had approximately 30% lower levels of S-PICP compared to normals (68.11 +/- 24.85 and 66.41 ng/ml versus 97.47 +/- 23.36 ng/ml, respectively; P = 0.0001). zPICP-zDPD, zPICP-zCTX-I and zPICP-zPYD were significantly declined in obese women compared to normals (P = 0.0072, 0.02 and 0.0028). CONCLUSIONS: We conclude that in postmenopausal women, BMI is inversely associated with levels of collagen I formation marker, serum PICP. In obesity formation of collagen I was reduced, in favor of degradation, but since this finding is not followed by simultaneous decrease in bone mineral density, it seems that increased body weight may have different effects on mature estrogen-deficient bone and extraskeletal tissues containing collagen I.     

Effects of postmenopausal hormone therapy every day and every other day on lipid levels according to difference in body mass index

OBJECTIVE: The objective of this study was to determine the effects of postmenopausal estrogen and progestogen therapy (EPT) every day and every other day on lipid levels, particularly triglyceride (TG) levels, according to difference in body mass index (BMI). DESIGN: Ninety-nine postmenopausal women (mean age, 53.9 +/- 5.6 years; mean BMI, 22.8 +/- 2.8 kg/m) were randomly treated with EPT every other day or every day for 1 year. Fifty women received oral administration of 0.625 mg of conjugated equine estrogen (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) every other day, and 49 women received oral administration of 0.625 mg of CEE and 2.5 mg of MPA every day. Blood samples were collected at baseline and after 1 year of therapy for measurement of fasting TG, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and apolipoproteins. Data from 88 of the 99 postmenopausal women were used for analysis. RESULTS: In women whose BMI was 25 kg/m or higher, TG levels during EPT every day increased by 26.8%, while TG levels during EPT every other day decreased by 12.3%. There was a significant (P < 0.05) difference between percentage changes in TG during EPT every day and every other day. In women whose BMI was less than 25 kg/m, TG levels during EPT every day increased by 21.7%, while during EPT every other day TG levels did not change. The mean levels of estradiol during EPT every day in women whose BMI was less than 25 kg/m and in women whose BMI was 25 kg/m or higher were 28.5 and 38.7 pg/mL, respectively, the difference between these levels was significant (P < 0.01). On the other hand, there was no significant difference between levels of estradiol during EPT every other day in these two BMI groups. CONCLUSIONS: Triglyceride levels during EPT every day with conventional doses of CEE and MPA increased more in overweight and obese postmenopausal women in association with increased estrogen levels.     

Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients

OBJECTIVES: Because estrogens stimulate the synthesis and release of leptin in the adipocytes, the effect of antiestrogens on the circulating leptin levels were studied. METHODS: Thirty postmenopausal patients with breast cancer were randomized to start either with tamoxifen (20 mg/day, n=15) or toremifene (40 mg/day, n=15), and the patients were examined and serum leptin concentrations measured before the study and at 6 and 12 months. RESULTS: The baseline leptin concentrations ranged from 4.4 to 60.0 microg/l (15.3+/-13.1 microg/l, mean+/-S.D.), and it correlated positively with the body mass index (BMI) of the subjects (r=0.73, P=0.0001). Taking as a whole the antiestrogen regimen was associated with elevated leptin levels at 6 months (19.5+/-13.8 microg/l, P=0.0001) but no excess increase in leptin levels were seen at 12 months (20.9+/-13.5 microg/l, NS). Subgroup analysis showed no difference between the effects of tamoxifen or toremifene on leptin. BMI increased in 21 women (from 26.2+/-4.3 to 27.3+/-4.8 kg/m2, P=0.0001) at 6 months, but not after that; in nine women BMI did not change. There was no significant correlation between the change in leptin levels and the change in BMI in either group implying that antiestrogens may specifically stimulate leptin production. CONCLUSIONS: Antiestrogens may stimulate the synthesis and release of leptin in the adipocytes. This effect of antiestrogens resembles the effect of estrogen and consequently stimulation of leptin production can be added to the estrogenic effects of antiestrogens.     

Effect of body mass index on mortality of patients with lymphoma undergoing autologous hematopoietic cell transplantation.

High-dose therapy with autologous hematopoietic cell transplantation (auto-HCT) is frequently used to improve outcomes in lymphoma. However, small studies suggest a survival disadvantage among obese patients. Using a retrospective cohort analysis, we studied the outcomes of 4681 patients undergoing auto-HCT for Hodgkin or non-Hodgkin lymphoma between 1990 and 2000 according to body mass index (BMI). Four groups categorized by BMI were compared by using Cox proportional hazards regression to adjust for other prognostic factors. A total of 1909 patients were categorized as normal weight (BMI 18-25 kg/m2), 121 as underweight (BMI<18 kg/m2), 1725 as overweight (BMI>25-30 kg/m2), and 926 as obese (BMI>30 kg/m2) at the time of HCT. Outcomes evaluated included overall survival, relapse, transplantation-related mortality (TRM), and lymphoma-free survival. TRM was similar among the normal, overweight, and obese groups; the underweight group had a higher risk of TRM (relative risk [RR], 2.46; 95% confidence interval [CI], 1.59-3.82; P<0.0001) compared with the normal-BMI group. No differences in relapse were noted. Overall mortality was higher in the underweight group (RR, 1.48; 95% CI, 1.17-1.88; P=.001) and lower in the overweight (RR, 0.87; 95% CI, 0.79-0.96; P=.004) and obese (RR, 0.76; 95% CI, 0.67-0.86; P<.0001) groups compared with the normal-BMI group. In light of our inability to find differences in survival among overweight, obese, and normal-weight patients, obesity alone should not be viewed as a contraindication to proceeding with auto-HCT for lymphoma when it is otherwise indicated.     

Serum leptin correlates with serum uric acid but not serum testosterone in non-obese male adolescents

To identify the serum factors that affect circulating leptin levels, we measured the serum concentrations of leptin, testosterone (T), estradiol (E), serum alanine aminotransferase, total cholesterol and uric acid (UA) in healthy male adolescents (age, 18.3 +/- 0.1 years, n=96). We also measured body mass index (BMI), percent body fat and thickness of skin fold to assess the effect of body constitution on serum leptin level. Since serum concentration of leptin significantly correlated with BMI (r=0.820, p<0.001), we analyzed the relation-ship between leptin/BMI ratio (L/BMI) and serum parameters. Analysis of data of subjects with normal serum T level showed a significant inverse correlation between L/BMI and serum T levels (n=96, r=-0.294, p<0.005), but no such correlation was present among non-obese subjects (n=70) with BMI of +/-20% of normal (22 kg/m2). There was no correlation between L/BMI and serum E level. Serum UA level significantly correlated with L/BMI in both the test group (n=96, r=0.520, p<0.001) and non-obese subjects (r=0.369, p<0.005). Stepwise multiple regression analysis showed that UA independently and significantly influenced serum leptin levels in both the test and control groups. Our results demonstrate that T weakly influences serum leptin concentration, and that UA concentrations strongly influences serum leptin in healthy male adolescents independent of their obesity level.     

Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications

Obesity is considered the most important risk and prognostic factor for estrogen-dependent breast cancer in postmenopausal women. Adipokines, in particular leptin, are at the center of the etiopathogenetic mechanisms by which obesity and related metabolic disorders influence breast cancer risk and its prognosis. The present prospective observational study aims to investigate the relationship between body mass index (BMI), serum levels of leptin and proinflammatory cytokines, and breast cancer prognostic factors. In the study, 98 postmenopausal and 82 premenopausal patients with ER-positive breast cancer participated. During the same study period, 221 control subjects were simultaneously recruited. Women underwent baseline measurements pre-operatively, before any surgical and systemic treatments. Pathologic characteristics of tumors were abstracted from pathology reports. Leptin and proinflammatory cytokines were assayed in stored fasting blood specimens. In postmenopausal breast cancer patients, BMI, leptin, and interleukin-6 significantly correlated with pathological tumor classification (pT) and TNM stage. Multivariate regression analysis showed that BMI and leptin, but not interleukin-6, were independent predictive variables of pT and TNM stage. Our results seem to suggest a twofold role of leptin in the etiopathogenesis of postmenopausal estrogen-positive breast cancer. Indeed, leptin reflects the total amount of fat mass, which correlates to aromatase activity and subsequent estrogens levels. Further studies are warranted to clarify the role of leptin and interleukin-6 in breast carcinogenesis and identify new therapeutic options, beyond the use of aromatase inhibitors, acting selectively on adipokine-driven pathways.     

High Serum Osteopontin Levels Are Associated with Low Bone Mineral Density in Postmenopausal Women

Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the bone and kidneys. It is reportedly involved in bone resorption and formation. We examined the association between serum OPN levels and bone mineral density in postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409) participated in the study. We measured serum osteopontin levels and their relationships with bone mineral density and previous total fragility fractures. The postmenopausal women had higher mean serum OPN levels compared to the premenopausal women (43.6±25.9 vs 26.3±18.6 ng/mL; P<0.001). In the postmenopausal women, high serum OPN levels were negatively correlated with mean lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple linear regression model, serum OPN levels were associated with BMD of the spine, femoral neck, and total hip after adjustment for age, body mass index, smoking, and physical activity in postmenopausal women. However, serum OPN levels did not differ between postmenopausal women with and without fractures. Postmenopausal women exhibit higher serum OPN levels than premenopausal women and higher serum OPN levels were associated with low BMD in postmenopausal women.     

Body mass and risk of complications after hysterectomy on benign indications

BACKGROUND: This study examines BMI in relation to risk of complications after hysterectomy on benign indications, and explores whether any associations vary by route of surgery. METHODS: In this cohort study, we included data on health and lifestyle collected prospectively for all hysterectomy referrals for benign indications in Denmark from 2004 to 2009. Logistic regression was used to investigate relationship between BMI and complications reported at surgery or during the first 30 days after surgery. RESULTS; Of the 20 353 women with complete data, 6.0% had a BMI < 20 kg/m(2), 31.9% with BMI between 25 and 30 kg/m(2) (classified as overweight) and 17.5% with a BMI ≥ 30 kg/m(2) (categorized as obese). The overall rate of complications was 17.6%, with bleeding being the most common specific complication (6.8%). After adjustment for age, ethnicity, education, indication for surgery, uterus weight, use of prophylaxis, American Society of Anaesthesiologists classification, co-morbidity status and route of hysterectomy, obesity was associated with an increased risk of heavy bleeding during surgery [odds ratio (OR) = 3.64 (2.90-4.56)], all bleeding complications [OR = 1.27 (1.08-1.48)] and infection [OR = 1.47 (1.23-1.77)]. The risk of all bleeding complications [OR = 1.48 (1.28-1.82)] and re-operation [OR = 1.66 (1.26-2.17)] were also increased among women with a BMI < 20. This U-shaped relation between BMI and bleeding, and the association between high BMI and infections were only seen for the abdominal route [abdominal hysterectomy (AH)]. The risk of infections was elevated among women with BMI<20 who underwent laparoscopic surgery [laparoscopic hysterectomy (LH)]. CONCLUSIONS; Obesity increases the risks of bleeding and infections after AH. A BMI below 20 seems to increase the risks of bleeding and infection after AH and LH, respectively.