Adiposity and estrogen receptor-positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol.

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case-cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case-control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5-25 kg/m2 , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05-2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43-2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11-2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68-1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity-breast cancer relationship but does not explain all of the association.

Dramatic acceleration of reproductive aging, contraction of biochemical fecundity and healthspan-lifespan implications of opioid-induced endocrinopathy-FSH/LH ratio and other interrelationships.

Whilst disturbances of female reproductive hormones and function are commonplace in opioid dependence, their pathophysiological interrelationships are not well understood. Hormonal levels in females were compared in 77 opioid dependent patients (ODP) and 148 medical controls (MC) including 205 and 364 repeat studies. Significant changes in FSH, LH, oestradiol, testosterone and SBG were noted including power functions with age. The FSH/LH was lower in ODP (P=0.0150) and the ratio inversion point occurred at 28.06±9.36v. 46.26±4.76years, implying a 58% reduction in fertility duration. FSH has been shown to induce ovarian failure and GnRH (controlling LH and FSH) has been shown to regulate longevity systemically. This implies that, far from being benign, these findings explicate the adverse experience of female compared to male ODP, exacerbate opioid-dependent aging amongst females, and informs the care of opioid dependent women, particularly relating to the choice, dose and duration of agonist or antagonist therapy.

Direct Measurement of Free Estradiol in Human Serum and Plasma by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry.

We describe a direct method of measurement of free estradiol using equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum aliquots and internal standards are extracted by liquid-liquid extraction using methyl-tert-butyl ether (MTBE) followed by derivatization with dansyl chloride. An API 5500 mass spectrometer operated in positive electrospray mode is used for detection.

Free estradiol and sex hormone-binding globulin.

SHBG is a plasma protein that participates in the regulation of free estradiol and free testosterone in plasma. We discuss the concept of the nature of a free estradiol and how best to ascertain its value. It can be measured or calculated; the ways in which this can be done are explored along with the advantages and disadvantages of each.

Quantitative analysis of conjugated and free estrogens in swine manure: solutions to overcome analytical problems due to matrix effects.

Although animal manure is an important source for environmental estrogens, quantitative analysis of estrogens in manure is complicated due to matrix interference. In the present study, chromatographic methods have been developed for quantification of conjugated and free estrogens in manure samples collected from pig farms. The whole manure samples, immediately after collection, were stored at 4°C, acidified (pH≈2.0) and spiked with (i) (13)C-labeled internal standards to account for possible storage related degradation and (ii) deuterium labeled internal standards for calibration and quantitative analysis. The liquid samples were extracted with ethyl acetate for separating conjugated and free estrogens. The solid samples were eluted with water for desorbing conjugated hormones followed by methanol for desorbing free hormones. The water and extracts were further purified using hydrophilic-lipophilic balance and/or aminopropyl cartridges. The conjugated estrogens were analyzed using high-performance liquid chromatograph-mass spectrometer, while the free estrogens were analyzed using gas chromatograph-mass spectrometer. The extraction and calibration methods used in the present study yielded excellent sensitivity, reproducibility and >85% recovery of both free and conjugated estrogens that was independent of the manure matrix. In general, the total estrogen loads in liquid and solid samples were 5.1mg/l and 4.93mg/kg, respectively. This may represent the hormonal load of approximately 2.3tons estrogen per day.

Total estradiol, rather than testosterone levels, predicts osteoporosis in aging men / Estradiol prediz melhor osteoporose que testosterona total em homens idosos

OBJECTIVE: To study and establish sex hormone cutoff levels for osteoporosis risk in men over 50 years old. METHODS: Case-control study of 216 men > 50 years, 110 with osteoporosis (O) and 106 with normal bone density (C). We measured estradiol (E2), sex hormone binding globulin (SHBG), total testosterone (TT) and albumin. Free testosterone (FT) and bioavailable testosterone (BT) were calculated through Vermeulen's formula. RESULTS: There was no difference in TT between groups. Relative risks of osteoporosis were 1.89 for E2 < 37 pg/mL (p = 0.02); 1.91 for SHBG > 55 nmol/L (p = 0.019); 2.5 for FT < 7 ng/dL (p = 0.015); 2.7 for BT < 180 ng/dL (p = 0.0003). CONCLUSIONS: In men over 50 years old, TT was not indicative of osteoporosis risk while E2 < 37 ng/mL was. SHBG > 55 nmol/L, FT < 7 ng/dL and BT < 180 ng/dL can represent additional indications for osteoporosis screening in men over 50 years old.

OBJETIVO: Estudar e estabelecer pontos de corte dos hormônios sexuais para risco de osteoporose em homens após os 50 anos de idade. MÉTODOS: Estudo caso-controle de 216 homens > 50 anos, 110 com osteoporose e 106 com densidade óssea normal. Foram dosados: estradiol (E2), globulina ligadora de hormônios sexuais (SHBG), testosterona total (TT) e albumina. Foram calculadas: testosterona livre (TLC) e testosterona biodisponível (TB) pela fórmula de Vermeulen. RESULTADOS: Não houve diferença na TT entre os grupos. Os riscos relativos de osteoporose foram de 1,89 para E2 < 37 pg/mL (p = 0,02); 1,91 para SHBG > 55 nmol/L (p = 0,019); 2,5 para TLC < 7 ng/dL (p = 0,015) e 2,7 para TB < 180 ng/dL (p = 0,0003). CONCLUSÕES: Em homens acima de 50 anos, TT não indicou risco de osteoporose, mas E2 < 37 pg/mL sim. SHBG > 55 nmol/L, TLC < 7 ng/dL e TB < 180 ng/dL podem representar indicações adicionais para pesquisa de osteoporose em homens acima de 50 anos.

Bone mineral density and sex steroids in middle aged men

BACKGROUND: Osteoporosis is a skeletal condition that is characterized by reduction in bone volume and an increased vulnerability to fracture, practically of the proximal femur and vertebrae. But the etiology of osteoporosis in most men without history of alcohol abuse, or glucocorticoid excess is unknown. Several studies revealed that bone density in aged men was associated with serum sex steroids or sex hormone binding globulin (SHBG). METHODS: We have analyzed bone density and sex steroids, and SHBG of healthy 100 middle aged men who visited one university hospital located in Taejon city from Jan. 1997 to Nov. 1997. Aim of this study was to determine whether bone density in middle aged men was associated with serum sex steroids or SHBG. RESULTS AND CONCLUSION: Body mass index was significantly associated with serum FEI. BMI also associated negatively with SHBG. Bone density at lumbar spine was significantly positively associated with FEI (Free Estradiol Index) (r=0.359, P<0.001). SHBG was negatively associated (r=-0.273, P<0.01) with lumbar bone mineral density. After controlling for age, FEI and SHBG were still associated with BMD of lumbar spine. Because of these associations, multiple stepwise regression models were constructed, and accounted for 12-17% of the variability in bone density. Also, these results showed consistent, significant positive associations between bone density and FEI, BMI in middle aged men. Therefore, our data suggest that FEI and BMI may play an important role in the maintenance of the male skeleton.