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BACKGROUND: Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials. OBJECTIVE: We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin-like growth factor (IGF) proteins. METHODS: We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age = 60.0 y) and 537 to the placebo group (474 completed; mean age = 59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantified at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model. RESULTS: Women in the GTE group had significantly higher blood total estradiol (16%; P = 0.02) and bioavailable estradiol (21%; P = 0.03) than in the placebo group at month 12. There was a statistically significant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction = 0.001). The catechol-O-methyltransferase genotype did not influence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points. CONCLUSION: These results suggest that a 12-mo GTE supplementation significantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735.

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BACKGROUND: Obesity is a risk factor for breast cancer (BC). Some mechanisms through which obesity can lead to cancer development are insulin-like growth factors (IGFs), adipokines, and microRNAs (miRs). The objective of the study was to determine whether miR-17-5p, miR-195-5p, and miR-221-3p expressions were deregulated in serum samples of obese and nonobese postmenopausal women with BC. In addition, insulin, adiponectin, leptin and IGFs were analyzed. METHODS: Fifty postmenopausal women with newly diagnosed BC and 50 postmenopausal healthy women were evaluated. Differences in miRs between BC and healthy cases and between obese and lean participants were analyzed. Receiver operating characteristic curves for miRs for discriminating patients with or without BC were established, and relationships between the miRs, adipokines, and breast tumor characteristics were also investigated. RESULTS: miR-17-5p and miR-195-5p were higher in patients with BC in comparison to the controls, while miR-221-3p and adiponectin were significantly lower. Increased levels of miR-195-5p allowed the differentiation of BC from controls with a sensitivity of 83.3 and a specificity of 78.3%, and were associated with lobular and poorly differentiated cancer. There was no difference in miRs levels between obese and lean groups. CONCLUSIONS: Circulating miRs and adiponectin were deregulated in postmenopausal women with BC.

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En la obesidad glúteo-femoral, las consecuencias metabólicas son comparativamente escasas y los efectos endocrinos resultan directamente ligados al exceso de tejido adiposo. En la obesidad abdominal -en cambio- la actividad hormonal es muy importante: resistencia a la insulina e hiperinsulinemia, aumento de la actividad de los factores de crecimiento insulin-análogos (IGFs), aumento de la producción de testosterona (T), dihidrotestosterona (DHT) y estradiol (E2) "biodisponibles", por disminución de la proteína ligadora de andrógenos y estradiol (GLAE). Estas condiciones sugieren una posible asociación con el cáncer mamario y/o endometrial. La secreción de la hormona de crecimiento (HC) se reduce significativamente en la obesidad, junto con los factores hipotalámicos, hipofisarios y periféricos que contribuyen a la secreción anormal de la HC, jugando así un importante papel en la conformación corporal y en el balance de energía. La leptina circulante, producto que se expresa en los adipocitos con el gen ob, ejerce un efecto estimulante sobre la HC. Finalmente, una serie de pacientes seleccionados por su obesidad han sido identificados con importantes aumentos en los factores de crecimiento con valores descendidos de las proteínas portadoras de los IGFs. La obesidad abdominal se caracteriza también por la hiperinsulinemia de ayuno y una exagerada liberación de la insulina después de la carga de glucosa.

In the gluteo-femoral obesity, the metabolic consequences are comparative scarce and the endocrine effects are directly linked to the excess of adipose tissue. In abdominal obesity the endocrine effects are very important: insulin resistance and hyperinsulinemia, increase of IGF-I activity, increase of active androgen production by ovarian estroma, important reduction of sex-hormone-binding-globulin (SHBG) and increasing "bioavailable" estradiol (E2), testosterone (T) and dihidrotestosterone (DHT). In short, obesity and abnormal endocrinology appear to be associated with the development of endometrium and breast cancer in women. Growth hormone (GH) secretion is markedly reduced in obesity, and hypothalamic, pituitary and peripheral factors may contribute to the abnormal GH secretion. GH plays a critical rol in the regulation of body composition and energy balance. The circulating leptin is a product of specific adipocyte ob-gene that exerts stimulating effect on GH release. Furthermore, selected series of obese patients have shown that high free insulin like growth factor (IGF-I) and low IGF-binding proteins generally increased in overweight subjects. Obesity is also characterized by fasting hyperinsulinemia and exaggerated insulin release after a glucose load. Recently it has also demonstrated that leptine plays an important role in the reproductive system at all levels of the hypothalamus-pituitary-gonadal axis.

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