Estrone Sulfate Levels Research Articles

The relationship between bilateral oophorectomy and plasma hormone levels in postmenopausal women.

Oophorectomy prior to natural menopause reduces breast cancer risk. We evaluated whether timing of oophorectomy (during premenopause vs. postmenopause) or hysterectomy was associated with hormone levels, specifically estradiol, estrone, estrone sulfate, testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin, using data from the Nurses' Health Study. We included 2,251 postmenopausal women not using hormones who provided blood samples in 1989-1990 and/or 2000-2002, and who were controls in various nested case-control studies. We used multivariate linear mixed-effects models to assess geometric mean hormone levels by surgery status. Bilateral oophorectomy was associated with 25% lower testosterone levels versus women with natural menopause (20.8 vs. 15.5 ng/dL) (P < 0.0001) with no effect of timing of surgery (P = 0.80). SHBG levels were lower among women with a premenopausal oophorectomy (52.2 nmol/L) versus those with natural menopause (58.1 nmol/L) or a postmenopausal oophorectomy (62.0 nmol/L) (P = 0.02). There was no significant association of oophorectomy with estradiol, estrone, estrone sulfate, DHEAS, or prolactin levels (P ≥ 0.23). A simple hysterectomy was associated with a significant 8% lower testosterone (P = 0.03) and 14 % lower DHEAS (P = 0.02) levels compared with women with natural menopause but not with other hormone levels. Although limited by small numbers, our findings suggest no differential influence of timing of surgery on sex hormone levels. The reduction of testosterone levels in women with oophorectomy or hysterectomy suggests a possible role of this hormone in postmenopausal breast cancer development.

276P - Biological and Clinical Implications of Aromatase Inhibitors for Neoadjuvant Therapy in Breast Cancer

ABSTRACT Aim: Neoadjuvant aromatase inhibitors (AIs) therapy has become acceptable. Estrogens play a major role in promoting the growth of breast cancers (BCs). Androst-5-ene-3b,17b-diol (ADIOL) possesses estrogenic properties. Here we report the efficacy of AIs and the influence of letrozole (LET) on BC tissue and plasma levels of estrone (E1), estradiol (E2), estrone sulfate (E1S), ADIOL, and androstendione (AONE) in postmenopausal women undergoing neoadjuvant therapy for estrogen receptor (ER)–positive BCs. Methods: Twenty-nine postmenopausal patients with stage I (n = 3), IIA (n = 11), IIB (n = 5), IIIA (n = 2) and IIIB (n = 9) BCs were treated with anastrozole, LET or exemestane as neoadjuvant treatment. One patient had bilateral BC. Plasma and BC tissue samples were obtained from 9 patients before and after 4 months of neoadjuvant therapy with LET. Steroids concentrations were measured by liquid chromatography/ electrospray tandem mass spectrometry. Results: One of 30 tumors showed complete response (CR), 15 showed partial response (PR) and 14 showed stable disease (SD). All treatments were well tolerated. After treatment, a decrease of progesterone receptor expression was more frequent in responding tumors (93.8%) than in non-responding tumors (35.7%). Suppression of Ki67 after treatment was significantly greater in responding tumors than in non-responding tumors (P = 0.002). The mean BC tissue levels of E1, E2, E1S, ADIOL, and AONE at base line were 0.534, 0.409, 0.13, 1.65, and 6.09 pmol/g, respectively. After neoadjuvant therapy, the levels of E1, E2, E1S, ADIOL, and AONE were 0.002, 0008, 0.002, 2.22, and 5.63 pmol/g, respectively. The mean plasma levels of E1, E2, E1S, ADIOL, and AONE at base line were 621.5, 27.0, 1799.5, 1033, and 2258 pmol/l, respectively. After therapy, the levels of E1, E2, E1S, ADIOL, and AONE were 1.7, 1.6, 3.4, 1111, and 2826 pmol/l, respectively. LET significantly suppressed estrogens. Although plasma and tissue ADIOL levels were high after treatment, there was no progress disease in the 9 cases. With a median follow up of 69 months, there was no significant difference in overall survival between patients with CR or PR and those with SD. Conclusions: Neoadjuvant AIs therapy provided satisfactory efficacy and safety profiles. The activity of AIs was correlated with significantly reduced estrogens levels, but not with ADIOL levels. Disclosure: All authors have declared no conflicts of interest.

Association Between Circulating Levels of Sex Steroid Hormones and Barrett’s Esophagus in Men: A Case–Control Analysis

Esophageal adenocarcinoma is believed to result from the progression of gastroesophageal reflux disease to erosive esophagitis and re-epithelialization of the esophagus with a columnar cell population termed Barrett's esophagus (BE). Men develop BE and esophageal adenocarcinoma more frequently than women, yet little is known about the mechanisms of this difference. We assessed whether sex steroid hormones were associated with BE in a male population. We analyzed data from the Barrett's Esophagus Early Detection Case Control Study, based at the Walter Reed National Military Medical Center. Blood samples were collected from 174 men with BE and 213 men without BE (controls, based on endoscopic analysis); 13 sex steroid hormones were measured by mass spectrometry and sex hormone binding globulin was measured by enzyme-linked immunosorbent assay. We also calculated free estradiol, free testosterone, and free dihydrotestosterone (DHT). We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, race, smoking status, alcohol consumption, body mass index, heartburn, regurgitation, and gastroesophageal symptom score (excluding heartburn and regurgitation). Levels of free testosterone and free DHT were associated positively with BE risk; patients in the highest quartile for these hormones were most likely to have BE (free testosterone: OR, 5.36; 95% CI, 2.21-13.03; P = .0002; free DHT: OR, 4.25; 95% CI, 1.87-9.66; P = .001). Level of estrone sulfate was associated inversely with BE risk (P for trend = .02). No other hormone was associated with BE risk. Relationships were not modified by age or BMI. In an analysis of men, levels of free testosterone and free DHT were significantly associated with BE.

The association of reproductive and lifestyle factors with a score of multiple endogenous hormones.

We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation = 2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p < 0.0001) and each 15g/day increase in alcohol consumption was associated with a 0.41 (95%CI: 0.18, 0.63) unit increase in the score (p = 0.0004). Family history of breast cancer, age at menarche, and physical activity were not associated with the score. Reproductive breast cancer risk factors were not associated with elevated levels of multiple endogenous hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones.

Relationship of body mass index with aromatisation and plasma and tissue oestrogen levels in postmenopausal breast cancer patients treated with aromatase inhibitors

BackgroundRecent data have raised concern about the clinical efficacy of aromatase inhibitors in overweight and/or obese breast cancer patients. We report in vivo aromatase inhibition and plasma and tissue oestrogen levels in relation to body mass index (BMI) status among breast cancer patients treated with different aromatase inhibitors. MethodsWe compared data on in vivo aromatase inhibition (64 patients) as well as plasma and tissue oestrogen levels from patients participating in our studies to BMI values. ResultsWe found a weak positive correlation between pretreatment aromatisation level and BMI (n=64; R=0.236; p=0.060) but no correlation between on-treatment aromatisation levels or percentage aromatase inhibition and BMI within patient subgroups treated with any of a panel of aromatase inhibitors. Pre-treatment levels of plasma estradiol (p<0.001), estrone (p=0.001) and estrone sulphate (p=0.002) correlated to BMI. While on-treatment levels of plasma estrane sulphate correlated to BMI in patients on letrozole (R=0.601; p=0.001; n=25 for all) or anastrozole (n=12; R=0.611; p=0.035) therapy, letrozole suppressed plasma estrone sulphate more than anastrozole independent of BMI. No correlation between on-treatment tumour oestrogen levels and BMI was recorded. ConclusionsOur unique data do not support a lack of effective aromatase inhibition in overweight patients or therefore a need for alternative therapy. The higher levels of estrogens in overweight postmenopausal breast cancer patients before and during aromatase inhibition may be due to effects of BMI on oestrogen metabolism rather than aromatisation.

Associations between Dietary Acrylamide Intake and Plasma Sex Hormone Levels

The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiologic studies have observed positive associations between acrylamide intake and endometrial, ovarian, and breast cancer risks, which suggest that acrylamide may have sex-hormonal effects. We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and sex hormone-binding globulin (SHBG) among 687 postmenopausal and 1,300 premenopausal controls from nested case-control studies within the Nurses' Health Studies. There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin, or SHBG. Among normal-weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, whereas statistically significant positive associations for testosterone and androstenedione were observed among overweight women. Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biologic plausibility to the observed increased risks of endometrial, ovarian, and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers. The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation.

Sex Hormone Levels and Risk of Breast Cancer With Estrogen Plus Progestin

Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer. We conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided. Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P < .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04). Women with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings.

Characterization of the ovarian cycle in the two-toed sloths (Choloepus didactylus): An innovative, reliable, and noninvasive method using fecal hormone analyses

Little is known about reproductive physiology in the two-toed sloth (Choloepus didactylus). Therefore, the aim of this study was to obtain detailed information about the ovarian cycle. Measurements of reliable gonadal steroids in the feces of this species were undertaken. For this purpose, fecal samples were collected one to three times per week from nonpregnant captive females (n = 2) over a 16-month period. Before assay analysis, the fecal samples were extracted with methanol. Radioimmunoassays and enzyme immunoassays for fecal progesterone, estradiol-17β, pregnanediol-glucuronide (PdG), and estrone sulfate were tested for their ability to detect the ovarian activity. Using the lowest and highest progesterone values, the ovarian cycle length was comparatively analyzed. The ovarian cycle (n = 26) averaged between 31.4 ± 9.1 days (lowest progesterone) and 32.5 ± 7.5 days (highest progesterone) throughout the whole year. The length of the follicular phase, as indicated by low progesterone levels, was 18.1 ± 4.4 days (range 12–25 days), and the length of the luteal phase, as characterized by elevated progesterone levels, was 13.2 ± 1.8 days (range 11–16 days). In contrast, estradiol-17β and estrone sulfate were not suitable to detect the cycle due to irregular collection intervals. Fecal progesterone and PdG, as well as estradiol-17β and estrone sulfate, significantly correlated (r = 0.621, P < 0.01 and r = 0.606, P < 0.01). PdG concentrations (dilution factor (DF) 1:40) were considerably higher than progesterone concentrations (DF 1:10), PdG amounted in the range of 1326.7 ± 320.2 ng/g wet feces (animal S1) and 1373.8 ± 468.3 ng/g wet feces (animal S2) compared with progesterone concentrations in the range of 98.0 ± 17.0 ng/g (S1) and 105.9 ± 30.0 ng/g (S2). The estrone sulfate levels (DF 1:2) were similar to estradiol-17β (DF 1:22). The mean fecal estradiol-17β concentrations were 6.7 ± 0.9 ng/g for animal S1 and 7.5 ± 1.6 ng/g for animal S2. In conclusion, the ovarian activity of the two-toed sloth was studied using the noninvasive method by means of the fecal steroid monitoring. Progesterone was the most reliable fecal steroid hormone to determine the duration of the ovarian cycle independent of the weekly defecation rate. The course of progesterone concentrations resulted in a cycle length of 4–5 weeks length in the two-toed sloth. Thus, the reproductive activity of the two-toed sloth does not show any seasonality like the three-toed sloth.

Sulfonation of Maternal Steroids is a Conserved Metabolic Pathway in Vertebrates

All vertebrate embryos develop in the presence of maternally derived steroids, and maternal steroids have been hypothesized to link phenotype of the offspring to maternal physiology. In placental vertebrates, it is known that maternally derived steroids are metabolized during development via the sulfonation pathway. We used eggs from the red-eared slider turtle (Trachemys scripta) to determine whether the same metabolic pathway is used to metabolize maternally derived steroids in an oviparous vertebrate. To examine the relationship between estradiol and estrogen sulfates during development, levels of maternally derived estradiol were compared with levels of estradiol sulfate, estrone sulfate, and estriol sulfate at oviposition and after 20 days of embryonic development. Estrone sulfate was the only detectable estrogen sulfate. At oviposition, levels of both estradiol and estrone sulfate varied seasonally with clutches from later in the nesting season having significantly higher concentrations of both steroids. Levels of estrone sulfate increased during development, demonstrating that the sulfonation of maternally derived steroids occurs in oviparous vertebrates as well as in placental vertebrates. We also found that exogenous estrone sulfate increases the production of female hatchlings, thereby demonstrating the ability of this metabolite to influence embryonic development. To examine the role of sulfonation in the metabolism of maternal progesterone and testosterone, we characterized the metabolic fate of both steroids by applying tritiated forms of each steroid at oviposition and characterizing metabolites after 20 days of incubation. Similar to what was demonstrated for estradiol, both progesterone and testosterone are converted to sulfonated metabolites during embryonic development. These data suggest that steroid sulfates, both those that are maternally derived and those resulting from the metabolism of maternal steroids, are a key component of the mechanism underlying steroid-mediated maternal effects.

Aromatase Inhibition in Obese Women: How Much Is Enough?

Aromatase Inhibition in Obese Women: How Much Is Enough?

Suppression of Plasma Estrogen Levels by Letrozole and Anastrozole Is Related to Body Mass Index in Patients With Breast Cancer

To investigate whether suppression of plasma estradiol and estrone sulfate levels by the aromatase inhibitors (AIs) anastrozole and letrozole is related to body mass index (BMI) in postmenopausal women with early estrogen receptor (ER) -positive breast cancer. Recent studies have reported that the AI anastrozole has lower effectiveness than tamoxifen in women with high BMI. This effect with high BMI might hypothetically be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels and might be overcome by the use of an increased dose of anastrozole or, alternatively, the use of a more potent AI such as letrozole. Plasma estradiol and estrone sulfate levels from a highly sensitive radioimmunoassay were available for 44 postmenopausal patients who received anastrozole (1 mg per day) for 3 months followed by letrozole (2.5 mg per day) for 3 months or the opposite sequence. Correlations between the estrogen suppression by each AI and BMI were assessed. Baseline values of estradiol and estrone sulfate were significantly correlated with BMI (r = 0.57; P < .001, and r = 0.38; P = .006, respectively). Levels of estrogen in patients receiving treatment were greater at higher levels of BMI with both AIs, but although this was significant with letrozole (r = 0.35; P = .013, and r = 0.30; P = .035 for estradiol and estrone sulfate, respectively), it was not with anastrozole. Suppression of both estrogen types was greater with letrozole across the full range of BMIs in this study. The suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer treated with the AIs anastrozole and letrozole are related to BMI.

Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes

Estrogen plus progestin therapy (EPT) in postmenopausal women increases breast cancer risk and mammographic density to a higher extent than does estrogen therapy alone. Data from the randomized placebo-controlled Postmenopausal Estrogen/Progestinv Interventions trial showed that EPT-induced increases in serum estrone and estrone sulfate levels were positively correlated with increases in mammographic density. Here, after adjusting for serum estrone and estrone sulfate levels, we investigated the roles of posttreatment serum progestogen increase and of progesterone receptor gene (PGR) genetic variations on changes in mammographic density. We measured the percent mammographic density and serum progestogen levels in 280 Postmenopausal Estrogen/Progestin Interventions trial participants randomized to EPT treatment. Analyses of genetic variations in PGR were limited to 260 white women for whom we successfully obtained PGR genotypes. We used linear regression analyses to determine how an increase in progestogen levels and PGR genetic variation influenced mammographic density change after EPT. The increase in posttreatment serum progestogen level was positively associated with greater increases in mammographic density after adjustment for covariates (P trend = 0.044). Compared with women in the lowest quartile of serum progestogen level, women in the highest quartile experienced a 3.5% greater increase in mammographic density (P = 0.046). We did not find a strong indication that genetic variation in PGR was associated with mammographic density increase or modified the association with serum progestogen; however, confidence in these null findings is constrained by our small sample size. Our results suggest that higher serum progestogen levels resulting from EPT treatment lead to greater increases in mammographic density.

Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: A pilot study

Vaginal promestriene was tested in gynecological cancer patients who suffered from severe vaginal dryness and dyspareunia. This form of estrogen has a low level of vaginal absorption and proved to be effective for vaginal atrophy. Method17 patients were treated with a 10mg soft vaginal suppository daily for one month. Plasma levels of estrone sulfate (E1S), used as the marker of overall estrogenicity, were measured by liquid chromatography in combination with mass spectrometry. ResultsMean E1S levels changed from 533 (22–2920) to 374 (81–856) pg/ml (p=0.39). ConclusionIn highly symptomatic gynecological cancer patients the level of circulating estrone sulfate was not significantly affected by vaginal promestriene treatment overall, but a wide range of levels was noted pre and post treatment in individual patients.

Nausea and vomiting after breast cancer surgery, and relationship with tumor receptor status

Breast surgery is associated with frequent post-operative nausea and vomiting (PONV). Studies have suggested that hormonal status affects PONV. Estrogen has been implicated in many emetic syndromes. Estrogen receptor (ER) and progesterone receptor (PR) status in breast tissue are hormonally affected. Kakugawa et al., in 2007, found a clear trend toward higher serum level of estrone, estradiol, and dehydroepiandrosterone sulfate in post menopausal women with PR-positive cancer. To investigate the possibility of an association between ER and/or PR status of breast tumor and incidence of PONV after breast cancer surgery. This observational study included 315 female patients undergoing major breast surgery. Relevant patient data, and intra-operative and postoperative details were noted. Incidence of PONV was noted using the PONV score. Patients were divided into two age groups: less than or equal to 50years and more than 50years of age. The ER and/or PR status of the patient was unknown to the investigator until the final analysis. Use of the chi-squared test revealed no association between ER and/or PR and total PONV. Patients below 50years had higher incidence of total PONV (p=0.023). In patients above 50years, the incidence of PONV was higher in the ER-positive group (p=0.018). The incidence of PONV is higher for patients below 50years of age. The positive association between ER positivity and PONV in patients above 50years of age could be attributed to the altered hormonal milieu in these patients and should be investigated further.

Highlights of This Issue

Visfatin, an adipocyte-secreted hormone, has been correlated with colorectal, prostatic, gastric, and esophageal cancers, but its role in breast cancer is not known. To address this question, Lee and colleagues examined the expression of visfatin in breast cancer tissues and correlated these results with patient clinicopathologic variables. High visfatin expression in breast cancer tissues was significantly correlated with tumor size, estrogen receptor (ER) negativity, and progesterone receptor (PR) negativity. In addition, worse disease-free and overall survival rates were observed when high visfatin expression was combined with ER- and PR-negative status. This study helps establish the prognostic significance of visfatin expression in breast cancer.Regular soy consumption has been associated with reduced breast cancer risk; however the mechanism of this hypothesized protection is not fully understood. To explore this possibility, Maskarinec and colleagues examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum. Women were randomly assigned to high- or low-soy diets for 6 months, and estrogens in serum and NAF were examined. Mean estradiol and estrone sulfate levels were lower during the high-soy diet compared with the low-soy diet. The trend toward lower estrogens in NAF during a high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk.Vitamin D compounds can inhibit prostate tumorigenesis in vitro, but epidemiologic data are inconsistent. In a nested case–control study, Albanes and colleagues examined the relationship between 25-hydroxyvitamin D [25(OH)D] and prostate cancer risk in Finnish men, ages 50 to 69 years. They found that men with higher vitamin D status, as determined by serum 25(OH)D concentrations, were at elevated risk of developing prostate cancer. No evidence was found for greater risk in men with low vitamin D status. These results suggest that caution is warranted with respect to recommendations for high-dose vitamin D supplementation.Allergic conditions are associated with reduced risk of several malignancies. In the Atherosclerosis Risk in Communities (ARIC) prospective cohort, Prizment and colleagues used blood eosinophil count, a marker for allergic disorders, to evaluate the association between colorectal cancer and allergy. The authors report an inverse association between blood eosinophil count and colorectal cancer risk that was not modified by age, sex, race, or smoking status. These novel findings support the hypothesis that allergies are protective for colorectal cancer.

Effects of Aerobic Exercise on Premenopausal Sex Hormone Levels: Results of the WISER Study, a Randomized Clinical Trial in Healthy, Sedentary, Eumenorrheic Women

It is hypothesized that exercise can lead to a decrease in breast cancer risk through several hormonal and nonhormonal mechanisms. The WISER (Women In Steady Exercise Research) study investigated the effects of aerobic exercise on premenopausal sex hormone levels. Three hundred ninety-one sedentary, healthy, young eumenorrheic women were randomized either into an exercise intervention of 30 minutes of aerobic exercise 5 times a week for approximately 16 weeks (n = 212) or into a control group (n = 179). Serum levels of estradiol, estrone sulfate, testosterone, and sex hormone-binding globulin (SHBG), all in the midfollicular phase, and of progesterone, in the midluteal phase, were measured at baseline and at the end of the 16-week period. Compared with the controls (n = 153), exercisers (n = 166) experienced significant increases in aerobic fitness, lean body mass, and decreases in percent body fat. There were no significant changes in body weight and menstrual cycle length between or within groups. Progesterone decreased significantly in exercisers; however, this reduction was similar to that of the control group. No significant changes between or within groups were found for any of the other sex hormones or SHBG. In premenopausal women, 16 weeks of 150 minutes per week of moderate aerobic exercise in young women did not significantly alter sex hormone or SHBG levels. Any favorable effects that moderate aerobic exercise without an associated weight change may have on breast cancer risk in premenopausal women are unlikely to be a consequence of changes in levels of sex hormones or SHBG.

Effects of body mass index (BMI) on plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment.

515 Background: BMI is associated with an increased risk of BC in postmenopausal women. Moreover, BC overweight women have poorer prognosis compared to women with normal weight. Data from ATAC (the anastrozole, tamoxifen alone or in combination study) trial reported that obesity reduce the efficacy of the aromatase inhibitor (AI) anastrozole in early BC. One possible explanation is that higher estrogens levels resulting from high BMI may lead to lower efficacy of the AI treatment. No clear data are available about the effects of BMI on estrogen circulating levels during AI treatment, and if the increase of AI dosage may result in more complete estrogen suppression in overweight women. Methods: We evaluated the correlation between BMI and plasma concentration of ES in postmenopausal women with early BC during adjuvant treatment with L (2.5 mg/die). Patients were participating in two prospective Italian clinical trials (GIM4 and GIM5) evaluating L treatments after adjuvant tamoxifen. Plasma samples were obtainedafter at least six weeks of L therapy. After a non-chromatographic cleaning procedure of samples, plasma ES levels were evaluated by RIA. Ln values for plasma ES were used for statistics. Geometricmeans and 95% confidence interval (CI) were used as summary measures. Results: ES plasma concentration and BMI were evaluated in 370 women. Median treatment duration was 49wks (range 6-201wks). Median age of patients was 60 yrs (range 34-84 yrs). Table shows data regarding ES concentrations and BMI of patients. Conclusions: Circulating ES levels during L (2.5 mg/die) treatment were super imposable in all BMI groups. Our data indicate that whether BMI influences AI efficacy, this is not due to an insufficient suppression of aromatase activity in women with higher BMI. Increasing the dose of AI to further reduce ES levels in high BMI patients is a questionable way to increase AI efficacy. BMI, kg/m2 No. of pts % ES geom mean (pg/mL) 95% CI <23.0 85 23 21.7 21.2-22.5 23.0-24.9 65 18 20.2 19.6-20.9 25.0-27.9 111 30 24.2 23.8-24.6 28.0-29.9 43 12 22.5 21.5-23.6 >30.0 66 17 19.8 19.2-20.4

Profiling of Endogenous Estrogens, Their Precursors, and Metabolites in Endometrial Cancer Patients: Association with Risk and Relationship to Clinical Characteristics

Background: Endometrial cancer (EC) predominantly occurs after menopause and is strongly related to steroid hormones, particularly estrogens. However, the relationship between these hormones and clinical characteristics remains unaddressed. Experimental Design: We analyzed the circulating levels of 18 steroids including adrenal precursors, androgens, estrogens, and their glucuronide metabolites, using specific and validated methods based on tandem mass spectrometry. Our goals were to compare circulating levels in postmenopausal women with EC (n = 126) with those of healthy postmenopausal women (n = 110) and to investigate how these hormonal levels relate to clinical characteristics. Results: After adjustment for potential confounders, most hormones were significantly elevated in EC patients compared with healthy controls. In women with type I cancer, estrogen levels were up to 3-fold those of healthy women (P &amp;lt; 0.05). These higher levels were associated with an increased risk of cancer, particularly estrogens and their direct precursors, testosterone and androstenedione (odds ratios ranging from 4.4 to 13.3; P ≤ 0.0003). Elevated circulating levels of estrogens and their metabolites were found in cancer cases with type I endometrioid cancer and low-grade and noninvasive tumor, suggesting an association between these hormones and the tumoral estrogenic activity. In addition, levels of estrone sulfate in EC patients with relapse were 2-fold over levels of EC patients without relapse (P &amp;lt; 0.05), and 4.5-fold over those of healthy women (P &amp;lt; 0.001). Conclusions: Circulating levels of steroids were associated with increased risk of EC. Estrogens may represent novel biomarkers predictive of clinical characteristics, including evidence for an increased risk of relapse.

Associations of Body Composition Measures and Endogenous Sex-Steroid Hormones among Postmenopausal Women

Several studies have shown a positive association between body mass index (BMI) and endogenous levels of female sex-steroid hormones, but relationship with the body fat mass and the fat free mass components of BMI has rarely been investigated. In this cross-sectional study, we included 265 women from the Danish Diet, Cancer and Health cohort who were postmenopausal and never users of hormone replacement therapy and who previously were included in a nested case-control study on breast cancer. Multiple log-linear regression analyses of the association between anthropometric measurements and serum levels of estrone, estrone sulfate and sex hormone binding globulin (SHBG) were performed. We found positive associations between all the anthropometric measurements included and estrone and estrone sulfate, whereas negative associations were found for SHBG. We confirmed previous findings of associations between BMI and serum levels of estrogen and SHBG among postmenopausal women. Associations were in the same direction for the two components of BMI, body fat mass index (BFMI) and fat free mass index (FFMI), and use of these more detailed measures did not give a better prediction of the hormone levels than use of BMI alone.

Efficacy of non-nutritive sorbent materials as intestinal-binding agents for the control of boar taint

In many countries, male pigs are castrated to prevent boar taint, but this practice raises concerns about animal welfare and reduces the production efficiency of pork. The objective of this study was to develop dietary manipulations to prevent boar taint. We evaluated the effectiveness of adding activated carbon (AC) or Tween-60 (Tween; polyoxyethylene sorbitan monostearate) to pig finishing diets to reduce levels of androstenone (AND) and skatole in plasma and fat of entire male pigs. Boars (159 ± 2 days of age at the start of the experiment) were fed diets supplemented with either 5% AC or 5% Tween for 28 days followed by either 14 or 28 days of recovery. Plasma samples were collected at experimental days 0, 7, 14, 21, 28, 42 and 56, and backfat biopsies were taken at experimental days 0, 28, 42 and 56. Feeding AC significantly (P < 0.05) reduced the levels of AND in plasma by day 28 compared to day 0 and by day 42 in fat compared to day 0. AC treatment also decreased levels of oestrone sulphate (E1S) in plasma by day 7 compared to day 0. Treatment with Tween significantly decreased (P < 0.05) the levels of plasma AND by day 28 from levels at day 0. Tween treatment did not significantly affect levels of fat AND or plasma E1S compared to day 0; however, fat AND levels decreased between days 28 and 42 following treatment with Tween (P < 0.05). Levels of plasma E1S, plasma AND and fat AND for control boars remained constant throughout the experiment. Skatole plasma concentrations were very low and did not vary significantly (P > 0.05) from day 0 for any treatment, but fat skatole levels decreased by day 42 in the Tween treatment group. Importantly, there was no difference in growth rate between the control and experimental groups. We conclude that adding AC or Tween to finishing diets for boars can reduce the levels of plasma and fat AND, but further work is needed to confirm the effects of these treatments on reducing fat skatole levels.