Biomedical subjects

Frank Z Stanczyk

Publications and source records attributed to Frank Z Stanczyk.

At least 19 recordsLinked to original sources

PubMed2007

Acute effects of metformin therapy include improvement of insulin resistance and ovarian morphology.

OBJECTIVE: To evaluate the acute effects of metformin therapy on biochemical markers and polycystic ovarian morphology among insulin-resistant (IR) and noninsulin-resistant (NIR) patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective interventional study. SETTING: Reproductive endocrinology clinic in a university hospital. PATIENT(S): Five IR and five NIR patients with PCOS. The mean age of patients was 29.5 +/- 4.8 years (range, 23-36 years). INTERVENTION: Metformin therapy, using 850 mg orally per day for 1 week. MAIN OUTCOME MEASURE(S): Serum levels of T, FSH, and LH, fasting glucose/insulin ratio, levels of anti-Müllerian hormone (AMH) and inhibin B, and antral follicle count. RESULT(S): Levels of AMH and inhibin B were statistically significantly higher in patients with PCOS compared to controls (2.81 +/- 1.79 ng/mL versus 0.95 +/- 1.17 ng/mL, and 56.24 +/- 29.39 pg/mL versus 17.89 +/- 12.87 pg/mL, respectively). Levels of AMH and inhibin B were similar among IR and NIR patients with PCOS (2.77 +/- 1.92 ng/mL versus 2.85 +/- 1.89 ng/mL, and 53.96 +/- 28.58 pg/mL versus 58.51 +/- 33.28 pg/mL, respectively). One week of metformin therapy did not alter either AMH or inhibin B levels. However, there was a statistically significant increase in glucose/insulin ratios (4.59 +/- 1.57 versus 6.35 +/- 3.6), and a significant decrease in the number of antral follicles after 1 week of metformin therapy (38.8 +/- 19.3 versus 23.1 +/- 7.4). CONCLUSION(S): Levels of AMH and inhibin B are significantly increased in patients with PCOS compared to controls, but are not associated with insulin resistance. Low-dose metformin therapy improves IR and polycystic ovary morphology, even though levels of T, AMH, and inhibin B remain unchanged.

Adult↗

PubMed2006

Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors.

Several polymorphisms have been identified in genes that code for enzymes involved with estrogen biosynthesis and metabolism. Little is known about the functional relevance of these polymorphisms on sex hormones in vivo. We examined the association between CYP17, CYP1B1, COMT or SHBG genotypes and serum concentrations of estrone, estradiol, free estradiol, sex hormone-binding globulin (SHBG), testosterone, free testosterone and dehyroepiandrosterone in 366 post-menopausal breast cancer survivors in New Mexico, California and Washington. Hormone levels were determined by high performance liquid chromatography and radioimmunoassay in blood drawn approximately 2 years post-diagnosis. We used generalized linear regression to calculate mean hormone levels by genotype, adjusting for age, race/ethnicity, stage, study site, tamoxifen use, number of remaining ovaries, hormone therapy use, marital status and BMI. No associations were observed between any of the genotypes and sex hormones when analyzing the main effects. In subgroup analyses, androgen levels of Hispanic women with the variant (A2) CYP17 genotype were 46-87% higher than those of women with the wild-type; androgen levels were 13-20% lower in non-Hispanic whites with the variant genotype; no difference by genotype was observed for African-American women. Current tamoxifen users with the variant asn(327) SHBG genotype had 81% higher serum SHBG and 39% lower free testosterone concentrations than women with the wild-type genotype. Non-tamoxifen users with the variant SHBG allele had elevated free estradiol levels. These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors.

Adolescent↗

PubMed2006

Maternal hormone levels and perinatal characteristics: implications for testicular cancer.

PURPOSE: It was hypothesized that the risk for testicular germ cell tumors (TGCTs) is associated with maternal hormone levels. To examine the hypothesis, some studies used perinatal factors as surrogates for hormone levels. To determine the validity of this assumption, hormone-perinatal factor relationships were examined in the Collaborative Perinatal Project. METHODS: Maternal estradiol, estriol, and testosterone levels in first- and third-trimester serum samples were correlated with perinatal factors in 300 mothers representative of populations at high (white Americans) or low (black Americans) risk for TGCT. RESULTS: For white participants, testosterone levels were associated negatively with maternal height (p < 0.01) and age (p = 0.02) and positively with maternal weight (p = 0.02) and body mass index (BMI; p < 0.01), whereas estradiol levels were associated negatively with height (p = 0.03) and positively with son's birth weight (p = 0.04). For black participants, estriol levels were associated negatively with maternal weight (p = 0.01), BMI (p = 0.02), and gestational age p < 0.01) and positively with son's birth weight (p < 0.01), length (p = 0.04), and head circumference (p = 0.03). CONCLUSIONS: These findings indicate that use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. For white men, previously reported associations of TGCT with maternal weight and age may be caused by lower maternal testosterone levels.

Black or African American↗

PubMed2006

Comparison of methods to measure low serum estradiol levels in postmenopausal women.

CONTEXT: Accurate measurement of low serum estradiol (E(2) < 30 pg/ml or < 110 pmol/liter) is needed to study relationships between endogenous E(2) and risks of diseases in older women. OBJECTIVE: The objective of this study was to determine whether an extraction-based (indirect) assay or a non-extraction-based (direct) assay correlates better with mass spectrometry and body mass index (BMI). DESIGN/SETTING: In a pilot study of 40 postmenopausal women, endogenous E(2) measurements from three indirect and four direct assay methods and gas chromatography-tandem mass spectrometry (GC-MS/MS) were compared. A confirmatory study compared an indirect and a direct assay, selected among those in the pilot study, to GC-MS/MS; this study was conducted in 374 postmenopausal women not taking hormone therapy from the Ultra Low-dose TRansdermal estrogen Assessment (ULTRA) trial. MAIN OUTCOMES: Pearson correlation coefficients among E(2) measurements by assay methods and BMI, and their confidence intervals, by bias-corrected bootstrap method, were used. RESULTS: In the pilot study, E(2) by three indirect assays correlated better (P < 0.03) with GC-MS/MS and with BMI than measurements by four direct assays. In the confirmatory study, the indirect assay correlated better (P < 0.01) with GC-MS/MS and BMI than the direct assay. Measurements by the indirect and direct assays were overestimated, but deviations in direct assay measurements were less precise. Mean E(2) by the indirect and direct assays were higher (by 14 and 68%, respectively) and less reproducible than by GC-MS/MS. CONCLUSION: Until mass spectrometry is practical for wide use, extraction-based indirect assays may be preferable for measuring low postmenopausal serum E(2).

Aged↗

PubMed2006

Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic proteins.

OBJECTIVE: The purpose of this study was to evaluate the effects of the contraceptive patch and an oral contraceptive (OC) on serum concentrations of estrogen-sensitive hepatic proteins, ethinyl estradiol (EE) and levonorgestrel (LNG). METHODS: Twenty-four women were randomized to receive three cycles of a contraceptive patch that delivers EE 20 microg/day and norelgestromin 150 microg/day or an OC that contains EE 35 microg and norgestimate 250 microg. Blood samples were taken at baseline and at the end of Cycle 3. Serum levels of sex-hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG), corticosteroid-binding globulin (CBG) and C-reactive protein (CRP) were quantified by immunoassay methods. EE and LNG levels in patch users were measured by radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The paired t test and Student's t test were used for statistical analysis. RESULTS: Nineteen women completed the study (patch, n=10; OC, n=9). Treatment with both the patch and OC resulted in significant increases from baseline in SHBG, TBG and CBG. The increase in CRP was significant in the patch group and approached significance in the OC group. The increases in SHBG and TBG observed with the patch were significantly greater than those associated with the OC. By way of RIA and LC-MS/MS assay methods, the patch was associated with mean EE levels of 114 and 111 pg/mL, respectively. CONCLUSIONS: The serum concentrations of estrogen-sensitive hepatic proteins and EE associated with the patch suggest that this new contraceptive system may have relatively large net estrogen effects.

Administration, Cutaneous↗

PubMed2006

An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors.

Insulin receptor substrate-1 (IRS-1) is a key downstream signaling molecule common to both the insulin and IGF signaling pathways that can interact with the estrogen pathway to regulate breast cell growth. We investigated whether a putative functional variant for IRS-1 (G972R) influences circulating levels of sex hormones, sex hormone binding globulin (SHBG), C-peptide, and insulin-like growth factor 1 (IGF-1) levels among post-menopausal African-American and non-Hispanic white breast cancer patients enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones and growth factors can influence breast cancer recurrence and survival. Serum estrone, estradiol, testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at 30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In African-American patients, the IRS-1 variant was associated with increased serum levels of estrone (p = 0.02), free estradiol (p = 0.04), total testosterone (p = 0.04), free testosterone (p = 0.006) and decreased levels of sex hormone-binding globulin (p = 0.02). No association was present for white patients. Our findings provide suggestive evidence that IRS-1 G972R variant may be associated with circulating levels of sex hormones and SHBG in African American breast cancer survivors.

Black or African American↗

PubMed2006

Does St. John's wort interfere with the antiandrogenic effect of oral contraceptive pills?

BACKGROUND: St. John's wort (SJW), a commonly used herbal remedy, has been shown to compromise the efficacy of drugs, including oral contraceptive pills (OCPs), by inducing cytochrome P-450. We investigated whether the simultaneous use of SJW with OCPs resulted in elevated serum androgen levels with implications of impaired OCP treatment of hirsutism and acne. MATERIALS AND METHODS: Fifteen healthy women were treated with the low-dose OC Loestrin 1/20trade mark for 2 months and then additionally with SJW for 2 months. Androgen and sex hormone-binding globulin (SHBG) levels were measured in serum by immunoassay methods; free testosterone (fT) was calculated. Results were analyzed using the Wilcoxon signed-rank test. RESULTS: There were no statistically significant differences in androgen levels after the addition of SJW in women using Loestrin 1/20trade mark. However, there were decreases in total testosterone and fT levels (10.7% and 15.8%, respectively) along with a small increase in SHBG levels (7.0%). CONCLUSIONS: In women using OCPs and SJW simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of OCPs.

Acne Vulgaris↗

PubMed2006

Phase I study of STX 64 (667 Coumate) in breast cancer patients: the first study of a steroid sulfatase inhibitor.

PURPOSE: Inhibition of steroid sulfatase (STS), the enzyme responsible for the hydrolysis of steroid sulfates, represents a potential novel treatment for postmenopausal women with hormone-dependent breast cancer. Estrone and DHEA are formed by this sulfatase pathway and can be converted to steroids (estradiol and androstenediol, respectively), which have potent estrogenic properties. EXPERIMENTAL DESIGN: STX64 (667 Coumate), a tricylic coumarin-based sulfamate that irreversibly inhibits STS activity, was selected for entry into the first phase I trial of a STS inhibitor in postmenopausal women with breast cancer. STX64 was administered orally (nine patients at 5 mg and five patients at 20 mg) as an initial dose followed 1 week later by 3 x 2 weekly cycles, with each cycle comprising daily dosing for 5 days followed by 9 days off treatment. Blood and tumor tissue samples were collected for the assessment of STS activity and serum was obtained for steroid hormone measurements before and after treatment. RESULTS: The median inhibition of STS activity by STX64 was 98% in peripheral blood lymphocytes (PBL) and 99% in breast tumor tissue at the end of the 5-day dosing period. As expected, serum concentrations of estrone, estradiol, androstenediol, and DHEA all decreased significantly from pretreatment levels. Unexpectedly, androstenedione and testosterone concentrations also decreased. Four patients, all of whom had previously progressed on aromatase inhibitors, showed evidence of stable disease for 2.75 to 7 months. The drug was well tolerated with only minor drug-related adverse events recorded. CONCLUSION: STX64 is a potent, well-tolerated STS inhibitor. It inhibits STS activity in PBLs and tumor tissues and causes significant decreases in serum concentrations of steroids with estrogenic properties.

Administration, Oral↗

PubMed2006

Effects of 60-Hz magnetic field exposure on nocturnal 6-sulfatoxymelatonin, estrogens, luteinizing hormone, and follicle-stimulating hormone in healthy reproductive-age women: results of a crossover trial.

PURPOSE: Exposure to residential magnetic fields may disrupt the normal nocturnal rise in melatonin levels, resulting in increased risk for breast cancer, possibly through increased levels of reproductive hormones. We investigated whether exposure to a 60-Hz magnetic field under controlled conditions is associated with a decrease in urinary nocturnal 6-sulfatoxymelatonin level and increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen levels in healthy premenopausal women. METHODS: Using a crossover design, half the participants were assigned to magnetic field exposure of 5 to 10 mG greater than ambient levels for 5 consecutive nights during the early to midluteal phase of the menstrual cycle. On the last night of exposure, a nocturnal urine sample was collected. The next month, participants were sham exposed. The other half of participants were assigned the reverse order of exposure. RESULTS: Magnetic field exposure was associated with decreased 6-sulfatoxymelatonin levels, but no changes in reproductive hormone levels were observed. Participants using prescription medications and anovulatory participants had more pronounced decreases in 6-sulfatoxymelatonin levels with magnetic field exposure. CONCLUSION: This study provides further evidence that exposure to magnetic fields is associated with decreased nocturnal melatonin levels, but does not support the hypothesis that such exposure results in increased urinary levels of estrogens, LH, or FSH.

Adult↗

PubMed2006

Sex steroid hormones in young manhood and the risk of subsequent prostate cancer: a longitudinal study in African-Americans and Caucasians (United States).

OBJECTIVE: To investigate the relation of sex hormone levels in young adults to subsequent prostate cancer risk. METHODS: From 1959 to 1967, the Child Health and Development Studies collected sera from 10,442 men (median age: 34 years) and followed them for a median of 32 years. In this analysis, we selected 119 African-Americans and 206 Caucasians diagnosed with prostate cancer during the follow-up period. Two prostate cancer-free men were chosen to match each prostate cancer case on race and birth year. We compared the levels of testosterone, estradiol, and sex hormone-binding globulin in cases to those of their matched controls using conditional logistic regression. RESULTS: There was no significant association between absolute levels of sex hormones in youth and prostate cancer risk in either race. However, among Caucasians, but not African-Americans, prostate cancer risk was positively associated with the ratio of total testosterone to total estradiol (odds ratio relating the fourth to the first quartile: 3.01; 95% confidence interval: 1.42-6.39). CONCLUSIONS: The association between testosterone to estradiol ratio and prostate cancer risk in young Caucasians is consistent with similar findings in older Caucasians. The absence of this association in African-Americans needs confirmation in other data involving larger numbers of African-Americans.

Adult↗

PubMed2006

Diagnosis of hyperandrogenism: biochemical criteria.

Biochemical derangements in ovarian, adrenal, and peripheral androgen production and metabolism play an important role in underlying causes of hyperandrogenism. Specific diagnostic serum markers such as testosterone (total) and dehydroepiandrosterone sulfate (DHEAS), respectively, may be helpful in the diagnosis of ovarian and adrenal hyperandrogenism, respectively. Validated immunoassays or mass spectrometry assays should be used to quantify testosterone, DHEAS and other principal androgens. Free testosterone measurements, determined by equilibrium dialysis or the calculated method, are advocated for routine evaluation of more subtle forms of hyperandrogenism. The skin, with its pilosebaceous units (PSUs), is an important site of active androgen production. A key regulator in PSUs is 5alpha-reductase, which transforms testosterone or androstenedione to dihydrotestosterone (DHT). DHT in blood is not effective in indicating the presence of hyperandrogenism. However, distal metabolites of DHT have been shown to be good markers of clinical manifestations of hirsutism, acne and alopecia. Assays for these peripheral markers need improvement for routine clinical testing.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2006

Alcohol and dietary fibre intakes affect circulating sex hormones among premenopausal women.

BACKGROUND: The association of alcohol and fibre intake with breast cancer may be mediated by circulating sex hormone levels, which are predictors of breast cancer risk. OBJECTIVE: To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women. METHODS: A total of 205 premenopausal women completed a validated food-frequency questionnaire at baseline and after 2 years; blood samples taken at the same time were analysed for circulating sex hormone concentrations, including oestrone (E1), oestradiol (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by radioimmunoassay. We used mixed models to estimate least-square means of sex hormone concentrations for alcohol intake categories and quartiles of dietary intake. RESULTS: After adjustment for covariates, alcohol consumption was moderately associated with higher circulating oestrogen levels; those who consumed more than one drink per day had 20% higher E2 (Ptrend=0.07) levels than non-drinkers. In contrast, higher dietary fibre intake was associated with lower serum levels of androstenedione (-8% between the lowest and highest quartiles of intake, Ptrend=0.06), but not oestrogens. Similarly, consumption of fruits (-12%, Ptrend=0.03), vegetables (-9%, Ptrend=0.15) and whole grains (-7%, Ptrend=0.07) showed inverse associations with androstenedione levels. CONCLUSIONS: The consistency of the observed differences in sex hormone levels associated with alcohol and fibre-rich foods indicates that these nutritional factors may affect sex hormone concentrations and play a role in breast cancer aetiology and prevention.

Adolescent↗

PubMed2006

Relation of BMI and physical activity to sex hormones in postmenopausal women.

OBJECTIVE: Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones. RESEARCH METHODS AND PROCEDURES: Associations among adiposity, physical activity, and diet and concentrations of estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone-binding globulin (SHBG), androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin were evaluated in 267 postmenopausal women randomly selected from the Women's Health Initiative Dietary Modification Trial. RESULTS: In multiple regression analyses on log-transformed hormones, BMI was positively associated with estrone (beta = 0.031, p < 0.001), estradiol (beta = 0.048, p < 0.001), free estradiol (beta = 0.062, p < 0.001), free testosterone (beta = 0.017, p = 0.02), and prolactin (beta = 0.012, p = 0.02) and negatively associated with SHBG (beta = -0.02, p = 0.001). Total physical activity (metabolic equivalent tasks per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione (beta = -0.006, -0.007, and -0.005, respectively, all p < or = 0.05). Using a composite variable of BMI and physical activity dichotomized by median values, women with high BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL, compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical activity, low BMI/low physical activity, and low BMI/high physical activity, respectively (p trend < 0.001). Similar trends were observed for estradiol and free estradiol and, in inverse, for SHBG. DISCUSSION: These associations may, in part, explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk.

Aged↗

PubMed2006

Measurement of androgens in women.

Much of our knowledge about the physiologic role of androgens in women is based on measurements, primarily in serum, using radioimmunoassay (RIA) methodology that involves purification of the analyte by organic solvent extraction and column chromatography. Although the extraction/chromatographic RIA is highly reliable when properly validated, it is time consuming and costly. For this reason, direct RIA methods were developed. Subsequently, the radioactive marker was replaced by other labels that have been used in direct chemiluminescent, fluorescent, and enzyme immunoassays on autoanalyzers. Although direct immunoassays are simple and rapid, they are seldom thoroughly validated, and generally lack the sensitivity and specificity for reliable measurements of testosterone levels found in postmenopausal serum. In recent years there has been increased use of mass spectrometry assay methods to quantify steroid hormones. These methods are touted to become the gold standard for all steroid hormone measurements. Because urine contains predominantly glucuronidated androgens, multistep procedures are required for the measurement, which is not practical for diagnostic testing. Androgens also can be measured in saliva, but major methodologic problems are associated with the measurements. In addition, there is a misconception that salivary testosterone levels reflect free testosterone levels in serum.

Androgens↗

PubMed2006

Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells.

Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA synthesis relative to levels of AR occupancy of the prostate-specific antigen (PSA) gene. The locus also displayed up to 10-fold-higher levels of histone H3-K9/K14 acetylation and H3-K4 methylation across the entire body of the gene. Although similar increased mRNA expression and locus-wide histone acetylation were also observed at another kallikrein locus (KLK2), at a third AR target locus (TMPRSS2) increased gene expression and locus-wide histone acetylation were not seen in the absence of ligand. Androgen-independent PCa cells have thus evolved three distinctive alterations in AR-mediated transcription. First, increased RNA polymerase initiation and processivity contributed to increased gene expression. Second, AR signaling was more sensitive to ligand. Third, locus-wide chromatin remodeling conducive to the increased gene expression in the absence of ligand was apparent and depended on sustained AR activity. Therefore, increased AR ligand sensitivity as well as locus-specific chromatin alterations contribute to basal gene expression of a subpopulation of specific AR target genes in androgen-independent PCa cells. These features contribute to the androgen-independent phenotype of these cells.

Acetylation↗

PubMed2006

Racial/ethnic differences in postmenopausal endogenous hormones: the multiethnic cohort study.

Postmenopausal women with increased estrogens and lowered sex hormone-binding globulin (SHBG) concentrations are at increased risk of breast cancer. In the Multiethnic Cohort Study, the highest incidence rates of postmenopausal breast cancer were observed among Native Hawaiians followed by Japanese Americans, Whites, African Americans, and Latinas. Ethnic differences in endogenous sex hormone profiles may contribute to some of the variation in breast cancer incidence. Plasma concentrations of androstenedione, testosterone, estrone (E(1)), estradiol (E(2)), and SHBG were measured in 739 postmenopausal women from the Multiethnic Cohort Study (240 African Americans, 81 Native Hawaiians, 96 Japanese Americans, 231 Latinas, and 91 Whites). After adjusting for age, known breast cancer risk factors and lifestyle factors, the mean levels of testosterone, estrogen, and SHBG varied across populations (Ps < or = 0.004). Across racial/ethnic groups, Native Hawaiians had the highest mean levels of androstenedione, testosterone, and estrogens and the lowest mean levels of SHBG. Compared with Whites, Native Hawaiians had higher androstenedione (+22%, P = 0.017), total testosterone (+26%, P = 0.013), bioavailable testosterone (+33%, P = 0.002), E(1) (> or =21%; P = 0.009), total E(2) (+26%, P = 0.001), bioavailable E(2) (+31%, P < 0.001), and lower SHBG (-12% P = 0.07) levels. Compared with Whites, Japanese Americans had higher E(2) (+15%, P = 0.036) and bioavailable E(2) (+18%, P = 0.024) levels. African Americans also had higher E(1) (+21%, P = 0.004), E(2) (+20%, P = 0.007), and bioavailable E(2) (+20%, P = 0.015) levels compared with Whites, whereas mean levels in Latinas were similar to those of Whites. Many of the differences in endogenous postmenopausal hormonal milieu across these five racial/ethnic groups are consistent with the known differences in breast cancer incidence across these populations.

Black or African American↗

PubMed2006

Effect of exercise on bone mineral density and lean mass in postmenopausal women.

PURPOSE: To evaluate the effects of physical activity on bone mineral density, bone mineral content, and lean mass in postmenopausal, overweight/obese women. METHODS: We conducted a 12-month randomized controlled aerobic exercise intervention versus control in 173 sedentary, overweight/obese, postmenopausal women, aged 50-75 yr. The exercise prescription consisted of >or=45 min of moderate-intensity aerobic exercise (60-75% of maximal heart rate), 5 d.wk for 12 months. Control participants attended 45-min stretching sessions once a week. Ninety-eight percent (N=170) completed the trial. Exercisers averaged 172 min.wk (SD=89) of exercise and expended 3828 kJ.wk (SD=2053). We assessed body fat, total lean mass, and total body bone mineral density and content using dual-energy x-ray absortiometry (DXA). We compared baseline with 12-month changes in exercisers versus controls. RESULTS: Exercisers lost significantly more weight than stretchers (1.3-kg loss vs 0.1-kg gain, P=0.01). However, no differences between exercisers and controls in the change from baseline to 12 months were detected: exercisers' average bone mineral density increased by 0.005 g.cm and controls' by 0.003 g.cm (P=0.61). Similarly, no significant differences were detected for bone mineral content. Lean mass increased by 0.2 kg in both groups (P=0.84). CONCLUSION: Overall, the results from this randomized controlled study suggest that a yearlong moderate-intensity aerobic exercise intervention does not affect total body bone mineral density, bone mineral content, or lean mass in overweight/obese postmenopausal women.

Aged↗

PubMed2005

Metabolite ligands of estrogen receptor-beta reduce primate coronary hyperreactivity.

Previous reports showed that 17beta-estradiol implants attenuate in vivo coronary hyperreactivity (CH), characterized by long-duration vasoconstrictions (in coronary angiographic experiments), in menopausal rhesus monkeys. Prolonged Ca2+ contraction signals that correspond with CH in coronary vascular muscle cells (VMC) to the same dual-constrictor stimulus, serotonin + the thromboxane analog U-46619, in estrogen-deprived VMC were suppressed by >72 h in 17beta-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-beta (ER-beta) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E3 treatment in vivo for 4 wk significantly attenuated the angiographically evaluated vasoconstrictor response to intracoronary serotonin + U-46619 challenge. In vitro treatment of rhesus coronary VMC for >72 h with nanomolar E3 attenuated late Ca2+ signals. This reduction of late Ca2+ signals also appeared after >72 h of treatment with subnanomolar 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), an endogenous dihydrotestosterone metabolite with ER-beta binding activity. R,R-tetrahydrochrysene, a selective ER-beta antagonist, significantly blocked the E3- and 3beta-Adiol-mediated attenuation of late Ca2+ signal increases. ER-beta and thromboxane-prostanoid receptor (TPR) were coexpressed in coronary arteries and aorta. In vivo E3 treatment attenuated aortic TPR expression. Furthermore, in vitro treatment with E3 or 3beta-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E3- and 3beta-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-beta-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗