estrone-sulfate and Body-Weight

Letrozole is an orally active aromatase inhibitor for the treatment of breast cancer. The objectives of this study were to examine the pharmacokinetic profile of letrozole in Japanese subjects and to identify factors that influence variability in the pharmacokinetics of letrozole using population pharmacokinetic (PPK) analysis.. Twenty-five healthy postmenopausal Japanese women were enrolled in the study and received 2.5 mg letrozole once daily for 14 or 28 days. A PPK model was developed using NONMEM software. Age, body weight (WT), AST, ALT, total bilirubin, serum creatinine (CRE), and genotype of CYP2A6 were studied as covariates. Estrone, estrone sulfate, and estradiol in plasma were measured as pharmacodynamic markers.. CYP2A6 genotype, CRE, and AST were significant covariates for apparent systemic clearance (CL/F), and WT was a significant covariate for apparent distribution volume (Vd/F). Population mean estimates of CL/F and Vd/F in subjects without CYP2A6 mutation were 1.03 × (CRE/0.70)(-1.27) × (AST/17.5)(-0.793) L/h and 94.2 × (WT/51.1)(1.12) L respectively. CL/F in subjects possessing 1 and 2 CYP2A6 mutation alleles were 84.3% and 44.8% of the value in the subjects without mutation respectively. Estrogen levels fell to below detection limits in most subjects after letrozole administration. Three mild and transient adverse events (upper respiratory tract inflammation, arthralgia, and vomiting) were reported in the study.. CYP2A6 genotype largely influences CL/F of letrozole. Genetic polymorphism of CYP2A6 and body weight will be causes of ethnic difference in PK. However, dose adjustment is not necessary, because of the wide therapeutic range.

Topics: Aged; Antineoplastic Agents; Aromatase Inhibitors; Aryl Hydrocarbon Hydroxylases; Asian People; Bilirubin; Body Weight; Creatinine; Cytochrome P-450 CYP2A6; Estradiol; Estrone; Female; Genotype; Humans; Letrozole; Nitriles; Polymorphism, Genetic; Postmenopause; Triazoles

Obesity disproportionately affects more women than men. The loss of ovarian function during the menopause transition coincides with weight gain, increases in abdominal adiposity, and impaired metabolic health. Racial differences in obesity prevalence that results from the menopause transition are not well understood.. The purpose of the study was to assess longitudinal changes in body composition and cardiometabolic risk among black and white women during the menopausal transition.. In a secondary analysis of a prospective, observational cohort study (the Healthy Transitions study), 161 women ≥43 years old with a body mass index of 20-40 kg/m. Ninety-four women (25 black, 69 white) transitioned through menopause and were included within the analyses. At menopause onset, black women weighed more (77.8±3.0 vs 70.8±1.8 kg) and had a higher systolic (125±16 vs 118±14 mm Hg) and diastolic (80±8 vs 74±7 mm Hg) blood pressure compared with white women (all P≤.05). No other differences in body composition, sex steroid hormones, or cardiometabolic risk factors were observed at menopause onset. Before menopause, white women gained significant weight (3 kg), total body adiposity (6% percent body fat, 9% fat mass, 12% trunk fat mass) and abdominal adipose tissue (19% subcutaneous fat, 15% visceral fat, 19% total adipose tissue), which coincided with significant decreases in estradiol, sex hormone-binding globulin, and estrone sulfate and increases in follicle-stimulating hormone, total cholesterol, and low-density lipoprotein cholesterol. Conversely, black women had more abdominal adipose tissue before menopause, which was maintained across the menopause transition. Black women also had significant decreases in estrone sulfate and total testosterone and increases in follicle-stimulating hormone before menopause. In the postmenopausal years, abdominal subcutaneous adipose tissue, total adipose tissue, follicle-stimulating hormone, total cholesterol, and low-density and high-density lipoprotein cholesterol increased only in white women.. White women gained more abdominal adiposity during the menopause transition compared with black women, which, in part, may be due to differences in the pattern of sex steroid hormone changes between women of different racial backgrounds. The gains in abdominal adiposity in white women were observed in tandem with increased cardiometabolic risk factors. Future studies should consider comprehensive lifestyle approaches to target these increased gains in abdominal adiposity (ie, nutrition and physical activity coaching), while taking into account the potential interactions of race, body adiposity, sex steroid hormones, and their influence on cardiometabolic risk.

Topics: Adiposity; Black or African American; Blood Glucose; Blood Pressure; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Estradiol; Estrone; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Middle Aged; Postmenopause; Premenopause; Prospective Studies; Sex Hormone-Binding Globulin; Subcutaneous Fat, Abdominal; White People

Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study for 10 women. Serum assays for estrone (E1), estradiol (E2), estrone-3-sulfate (E1S), dehydroepiandrosterone sulfate, and sex hormone-binding globulin were conducted. Whole grapefruit intake had significant effects on endogenous E1S. Peak effects were seen at 8 hr, increasing by 26% from baseline. No changes in mean E1 or E2 with whole fruit intake were observed. In contrast, fresh juice, bottled juice, and soda intake all had significant lowering effects on E2. The findings suggest an important interaction between grapefruit intake and endogenous estrogen levels. Because endogenous estrogen levels are associated with breast cancer risk, further research is warranted.

Topics: Aged; Beverages; Body Mass Index; Body Weight; Breast Neoplasms; Citrus paradisi; Dehydroepiandrosterone Sulfate; Estradiol; Estrogens; Estrone; Female; Humans; Middle Aged; Pilot Projects; Postmenopause; Risk Factors; Sex Hormone-Binding Globulin; Surveys and Questionnaires

This study presents serum concentrations of pregnancy-associated glycoprotein (PAG), oestrone sulphate (E1-S) and progesterone (P4), and the effects of some dam and foetus-related factors on these profiles during gestation in Borana and crossbred cattle. The PAG concentrations at 4th week post-conception ranged from 1.5-5.5 and 2.1-4.7 ng/ml in Borana (n = 6) and crossbred (n = 8) cattle, respectively. The mean PAG concentrations increased progressively from 4th to 33rd week of gestation (from 3.3-173 ng/ml for Borana and 4.2-240 ng/ml for crossbred cattle) and reached peak around calving. Breed, parity status, dam body weight, foetal sex and foetal birth weight significantly influenced the PAG concentrations. After delivery, the PAG concentrations declined steadily to 5.7 ng/ml in Borana (n = 7) and 3.9 ng/ml in crossbred (n = 6) cattle 10 weeks post-partum. The serum E1-S concentrations at 17th week of pregnancy ranged from 0.3-2.6 and 0.9-5.7 ng/ml in Borana (n = 8) and crossbred (n = 9) cattle, respectively. The mean E1-S concentrations increased progressively from 17th to 33rd week of gestation (from 1.1-4.6 ng/ml for Borana and 2.7-10.8 ng/ml for crossbred). Breed, parity status, dam body weight and foetal sex significantly influenced E1-S concentrations. The P4 concentrations at 4th week of pregnancy ranged from 3.2-5.1 and 1.7-8.9 ng/ml in Borana (n = 6) and crossbred (n = 8) cattle, respectively. The P4 level remained elevated throughout pregnancy. This study indicated that the serum PAG and P4 concentrations at 4th and E1-S approximately 17th week of pregnancy were above the cut-off value for pregnancy test and the hormonal profiles observed were comparable to the previous reports. Furthermore, the PAG and E1-S profiles were considerably influenced by factors such as breed, weight and parity status of the dam, and foetal sex and foetal birth weight (only PAG).

Topics: Animals; Birth Weight; Body Weight; Cattle; Estrone; Female; Gestational Age; Glycoproteins; Hybridization, Genetic; Male; Parity; Pregnancy; Pregnancy Proteins; Progesterone; Sex Factors; Species Specificity

This study aimed to describe the association between incidence of boar taint and pubertal changes in gonadal hormones, size of reproductive organs and aggressive behaviour in entire male pigs. In total, 111 entire male pigs were included in the study. Sampling was performed first at 90 kg live weight (LW) and, then, at 115 kg LW. Variables measured were skatole and androstenone levels in plasma and fat, testosterone and oestrone sulphate in plasma, free oestrone in fat, weight of testes and length of bulbourethral glands. Aggressive interactions between pigs were registered when a limited amount of feed was provided to the pigs prior to routine feeding. The number of initiated interactions (attacks) and the difference between number of initiated and received interactions (relative attacks) were calculated for each pig. Multivariate analysis revealed that gonadal hormones and reproductive organ size influenced prevalence of boar taint, accounting for 30% of the variation in skatole levels in fat and for 37% of the variation in androstenone levels in fat. These relations were independent of aggression levels in entire male pigs. Skatole levels were influenced by the levels of oestrone sulphate in plasma and free oestrone in fat, but not levels of plasma testosterone. Pigs with testes weight below 565 g and a bulbourethral gland length <90 mm did not produce high amounts of skatole; therefore, these values can be used as a threshold level to detect pig carcasses with low skatole levels. High androstenone levels could not be predicted by measuring reproductive organ sizes. More research is required to develop a rapid and accurate method for the analysis of carcasses of entire male pigs.

Topics: Adipose Tissue; Aggression; Androsterone; Animals; Behavior, Animal; Body Weight; Estrone; Genitalia, Male; Male; Organ Size; Sexual Maturation; Skatole; Swine; Testosterone

Oleoyl-estrone is a powerful, slimming adipose tissue-derived signal that has biological effects widely opposed to those of its estrone moiety. The present experiment was designed to determine whether oleoyl-estrone effects on body energy are mediated by the estrogen receptor, blocked with the antagonist tamoxifen. Male Wistar rats were given daily oral doses of 10 micromol/kg d of oleoyl-estrone in oil containing 0 or 0.40 mg/kg d of tamoxifen. The data were compared with controls receiving only oil or 50 nmol/kg d of free estrone. After 10 days, the rats were killed, and their body composition and plasma metabolites and hormones were analyzed. Rats receiving estrone increased their body energy and lipid content compared with controls. Both groups of oleoyl-estrone-treated rats lost body weight, energy, and lipid; the losses in the rats receiving tamoxifen alone were less marked than in those receiving oleoyl-estrone. No significant changes in plasma glucose or triacylglycerols were observed. The patterns of change of estrone sulphate, estradiol, and oleoyl-estrone were consistent with a noticeable hydrolysis of oleoyl-estrone. The lack of differences in the fat mass in oleoyl-estrone-treated rats irrespective of the presence of tamoxifen suggested that the estrogenic pathway was not responsible for the slimming effects observed. Thus, it can be concluded that oleoyl-estrone effects are not mediated through its conversion to estrone or estradiol acting through the estrogen receptor. Tamoxifen partly mimicked the slimming effects of oleoyl-estrone; this could be speculatively explained by tamoxifen acting through the oleoyl-estrone signalling pathway.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Body Composition; Body Weight; Energy Intake; Energy Metabolism; Estradiol; Estrogen Antagonists; Estrone; Lipid Mobilization; Male; Oleic Acids; Rats; Rats, Wistar; Receptors, Estrogen; Tamoxifen; Triglycerides

To investigate whether bone loss occurs in the premenopause, we measured the bone mineral content (BMC), bone mineral density (BMD), and bone area in the spine (L2-L4), femoral neck, and total hip, as well as the sex hormone levels of 130 healthy premenopausal white women (age, 31-50 yr) at least three times over 1-9 yr. We found an increase in all three bone measurements at the spine but no change in volumetric density. Neither could we detect any age-related changes in any of the three measurements in the total hip. In contrast, we detected a significant decrease in femoral neck BMD over time, due to a decrease in BMC and increase in bone area. Greater loss in femoral neck BMD was associated independently with weight loss and lower levels of estrone sulfate or E2. Separating the women into those with FSH spikes (>20 IU/liter) and women with consistently low FSH, we found the latter group had smaller decrease in BMD and that the decrease was due less to a decline in BMC and more to an increase in bone area. In summary, femoral neck BMD decreases in premenopausal women, particularly those with lower levels of estrogens resulting from slowing ovarian function despite regular menses. This decrease can be offset by more rapid weight gain.

Topics: Adult; Body Weight; Bone Density; Cohort Studies; Estradiol; Estrone; Female; Femur Neck; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Longitudinal Studies; Middle Aged; Osteoporosis; Premenopause

Whether use of hormone-replacement therapy (HRT) influences menopause-related changes in body weight is unclear. HRT may affect energy balance by influencing synthesis of the adipocyte-derived hormone leptin. The objectives of this study were to: 1) identify factors influencing circulating leptin in postmenopausal women; 2) determine whether HRT influences serum leptin after adjusting for confounding factors; and, 3) identify potential independent effects of HRT or leptin on resting energy expenditure (REE). Subjects were 54 postmenopausal women, 45-55 yr old, 35 of whom used HRT (estrogen plus progestin). Total and regional body composition and fat distribution were determined by dual-energy x-ray absorptiometry and computed tomography; fasting serum leptin and insulin, by RIA; and REE, by indirect calorimetry. Stepwise multiple linear regression analysis indicated that serum leptin could best be predicted from total fat mass, fasting serum insulin, and total lean mass [log leptin = 1.08 x log fat mass) + (0.46 x log insulin) + (-1.25 x log lean mass) + 1.88; model R2 = 0.78, P < 0.001]. Multiple linear regression analysis indicated that visceral fat was independently related to leptin (parameter estimate = 0.23, P < 0.05), after adjusting for s.c. abdominal fat and leg fat, as well as lean mass and insulin. After adjusting for total fat mass, total lean mass, and fasting insulin, serum leptin did not differ between users and nonusers of HRT (21.7 +/- 1.0 vs. 20.2 +/- 1.3 ng/mL, P = 0.369, adjusted mean +/- SE, respectively). Serum estradiol was inversely correlated with (adjusted) leptin in non-HRT users (r = -0.50), suggesting that ovarian senescence may lead to an increase in leptin. Multiple linear regression analysis indicated that REE (adjusted for fat mass, fat-free mass, and ethnicity) was not associated with leptin (P = 0.298) or hormone use status (P = 0.999; 1323 +/- 31 vs. 1316 +/- 42 kcal/day, adjusted mean +/- SE for users and nonusers, respectively). These results indicate that, in postmenopausal women: 1) total fat mass, lean mass, and fasting insulin, but not HRT, are significant determinants of serum leptin; 2) visceral and s.c. fat contribute to serum leptin; and, 3) neither HRT nor leptin is independently related to REE.

Topics: Absorptiometry, Photon; Adipose Tissue; Basal Metabolism; Blood Glucose; Body Composition; Body Weight; Calorimetry, Indirect; Estradiol; Estrogen Replacement Therapy; Estrone; Female; Humans; Insulin; Leptin; Middle Aged; Postmenopause

Plasma concentrations of progesterone, oestradiol-17beta, oestrone, oestrone sulphate and PGFM have been measured daily during the first peri-partum period of 45 Hereford x Friesian heifers bred at 11 months of age. Anatomical measurements of dam and calf were also recorded. Twelve of the calvings were scored easy, 33 difficult. Each of five models (fitted by linear logistic regression) relating difficulty of calving to the hormonal and anatomical measurements, predicts with at least 94% accuracy the calving score (easy or difficult) among the calvings. The models predict that increases of progesterone concentration on the day before calving, of oestrone sulphate concentration on the day after calving and of heifer heart girth decrease the odds of difficult calving, whereas increases of heifer body length and of calf head circumference increase the odds of difficult calving.

Topics: Animal Feed; Animals; Animals, Newborn; Body Weight; Cattle; Cattle Diseases; Dinoprost; Dystocia; Estradiol; Estrogens; Estrogens, Conjugated (USP); Estrone; Female; Insemination, Artificial; Labor, Obstetric; Logistic Models; Male; Multivariate Analysis; Numerical Analysis, Computer-Assisted; Pregnancy; Progesterone; Radioimmunoassay

There is both epidemiologic and experimental support for the hypothesis that a high-fiber diet can reduce breast cancer risk; this may be due, at least in part, to a reduction in circulating estrogens. This study examined the effects of three levels of wheat bran supplementation (5, 10, and 20 g/d for 2 mo) on the major serum estrogens during both the luteal and follicular phases of the menstrual cycle. The 10- and 20-g supplements, which increased the total dietary fiber intakes to approximately 20 and 32 g/d, respectively, resulted in significant decreases in the luteal serum estrone (P < 0.05 and < 0.02, respectively). The serum estradiol was significantly reduced in the 10-g wheat bran group after 2 mo (P < 0.05); the 20-g supplemented group showed a significant decrease in estradiol at 1 mo (P < 0.02), but not at 2 mo. No changes occurred in the estrone sulfate concentrations. During the follicular phase, the 10-g wheat bran group exhibited a significant reduction in the serum estrone (P < 0.02). Only the serum estrone sulfate showed any reduction with the 20-g supplement, and this just failed to achieve significance (P = 0.07). Serum sex hormone-binding globulin levels were unaffected by wheat bran. When of long duration, these effects may be sufficient to favorably influence breast cancer risk in Western women.

Topics: Adult; Body Weight; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Dietary Supplements; Energy Intake; Estradiol; Estrogens; Estrone; Female; Follicular Phase; Humans; Luteal Phase; Middle Aged; Nutrition Assessment; Progesterone; Sex Hormone-Binding Globulin; Triticum

At 50 d prior to predicted calving, 37 multiparous Angus cows were grouped by sire of mating, age and weight of cow and placed on either a high energy (HE, n = 19) diet or a moderate energy (ME, n = 18) diet. Objectives were to determine the effect of prepartum nutrition on: prepartum serum concentrations of estrone (E1), estrone sulfate (E1SO4) and progesterone (P4); pre- and postpartum cow body weight changes; calf birth weight and cow and calf postpartum performance. The ME cows were group-fed Coastal bermudagrass hay ad libitum and dormant pasture; HE cows were group-fed 2.7 kg ground corn X head-1 X d-1 in addition to the ME treatment. Both groups were combined and fed identically after calving. Cows fed HE were heavier (P less than .01) than cows fed ME at d 10 prepartum and their calves were heavier (P less than .05) at birth and weaning than calves from cows fed ME. Serum E1 concentrations were not significantly different between groups, but serum E1SO4 was higher (P less than .01) at d 10 prepartum in ME cows compared with HE cows. Serum P4 concentrations of ME cows were higher (P less than .05) than those of HE cows. Cow body weights were greater (P less than .01) for the HE group than for the ME group during the first 6 mo postpartum. Cow rebreeding performance was identical for both groups.

Topics: Animals; Birth Weight; Body Weight; Cattle; Energy Metabolism; Estrone; Female; Pregnancy; Pregnancy, Animal; Progesterone

The purpose of this study was to evaluate, without using radioisotopes, the peripheral contribution of dehydroepiandrosterone (D) to estrogens and to androstenedione (A) in patients with hypogonadotropic hypogonadism associated with weight loss (HH) and in normal menstruating women (N). Unlabelled D was infused for 48 h in 12 normal women and in 12 women affected by HH. Plasma levels of D, dehydroepiandrosterone sulfate (DS), A, estrone (E1), estrone sulfate (E1s) and estradiol (E2) were measured before and after 48 h of infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of DS, A, E1, E1s and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of all steroids studied were found to be significantly lower in the patient group than in the control. The MCRD in the normal and the HH groups were similar (1420 +/- 340 l/day versus 1670 +/- 569 l/day, P greater than 0.05). No significant difference was found in PRD between the 2 groups (mean +/- SD 10.3 +/- 5 versus 13.3 +/- 5.5 mg/day, P greater than 0.05). Administration of D increased the levels of estrogen in the normal group but not in the HH group. The relative increase in plasma levels of DS resulting from infusion of D (delta cDS/delta cD) was found to be larger in the HH group than in the normal group (40.4 +/- 17 versus 26.3 +/- 11.8, P less than 0.05). Furthermore, relative increases in plasma levels of A derived from infusion of D were larger in the HH group than in the normal group (0.0495 +/- 0.0021 versus 0.192 +/- 0.0071, P less than 0.001). We conclude from these results that in the HH patients there is a blockage of the peripheral conversion of D to E1 and E1s and an enhancement of the peripheral conversions of D to DS and to A. These metabolic changes may account for the androgenization of the patients under study.

Topics: Adult; Amenorrhea; Androstenedione; Body Weight; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Estrogens; Estrone; Female; Humans; Hypogonadism; Luteinizing Hormone; Metabolic Clearance Rate

Plasma estrone sulphate ( E1S ) and estrone (E1) concentrations were determined in healthy postmenopausal women and in postmenopausal women with endometrial cancer, matched for body weight, age, and years since menopause. E1S levels (mean +/- SD) were significantly higher (P less than 0.05) in cancer patients with normal weight (511 +/- 200 pg/ml) than in control subjects (303 +/- 99 pg/ml). E1S levels were also higher in obese cancer patients (691 +/- 328 pg/ml) than in obese control subjects (610 +/- 139 pg/ml). Both cancer groups showed similar plasma E1 levels as compared with their respective controls. The E1S /E1 ratio was higher in both groups of cancer patients than in control subjects. These data suggest that estrogen conjugates should be taken into account during studies on estrogen balance and endometrial cancer.

Topics: Aged; Body Weight; Estrone; Female; Humans; Menopause; Middle Aged; Radioimmunoassay; Time Factors; Uterine Neoplasms

To investigate the possibility of increased tissue exposure to estrogen in breast cancer patients, plasma levels of estrogens and the percentage of unbound estradiol were measured in postmenopausal women with benign or malignant breast disease and compared with levels in normal postmenopausal women. The percentage of unbound estradiol in breast cancer patients [1.85 +/- 0.35% (S.D.)] was significantly higher (p less than 0.001) than in normal postmenopausal women [1.52 +/- 0.33%] and was still significantly higher when patients were matched with control subjects for weight (p less than 0.001) or ideal body weight (p less than 0.001). The binding capacity of sex hormone binding globulin was similar in both groups of women. No significant differences in the plasma levels of estrone, estradiol, or estrone sulfate were detected between breast cancer and normal subjects. It is concluded that, given similar concentrations of estradiol in plasma of normal and breast cancer subjects, the significant increase found in the unbound estradiol fraction may result in a very small increment in tissue exposure to estrogens in breast cancer subjects. However, even such a small increase in tissue exposure to estradiol may be significant, given the length of time required for breast tumor development.

Topics: Aged; Body Weight; Breast Diseases; Estradiol; Estrone; Female; Humans; Menopause; Middle Aged; Sex Hormone-Binding Globulin

The effect of estrogens (Es) on piglet viability was determined as measured by birth to suckling intervals. Starting on d 109 postbreeding daily blood samples were obtained from 15 Yorkshire sows, Immediately after birth, blood samples were taken from the umbilical cord (UC) and the vena cava (VC) of piglets, followed by injections via the VC of either estradiol benzoate (EB) or a saline solution. The interval from birth to suckling (BTS), and body weight gain until 96 h was recorded. Total estrone concentration in the sows' serum rose until the day before parturition and declined sharply by d 2 postpartum. Piglets given EB injections had a shorter interval from BTS (P less than .05) and females suckled sooner than males in both the control and treated groups. No significant differences in weight gain were detected between control and treated groups at 2, 24 or 96 h. Higher (P less than .001) levels of estrone and estrone sulphate were found in the UC than in VC samples, but no correlation existed between levels of Es in the UC and VC (P greater than .05). We concluded that Es or other hydroxylated compounds could be acting upon a high control center of the newborn piglet to cause hyperactivity with a consequent reduction in BTS interval.

Topics: Animals; Animals, Newborn; Birth Weight; Body Weight; Estradiol; Estrogens; Estrone; Female; Injections, Intravenous; Male; Swine