Adult Height, Insulin Levels and 17β-Estradiol in Young Women

Background: Adult height and insulin levels have independently been associated with breast cancer risk. However, little is known about whether these factors influence estradiol levels. Thus, we hypothesize that adult height in combination with insulin levels may influence premenopausal 17β-estradiol throughout the entire menstrual cycle of possible importance of breast cancer risk. Methods: Among 204 healthy women, aged 25-35 years who participated in the Norwegian EBBA I study, birth weight and age at menarche were assessed by questionnaire, personal health record and interview. 17β-estradiol concentrations were estimated by daily saliva samples throughout one entire menstrual cycle using radioimmunoassay (RIA). Measures of height (cm) were taken as well as waist circumference (cm), body mass index (BMI kg/m2) and total fat percentage (DEXA % fat). Fasting blood samples were drawn, and serum concentrations of insulin were determined. Results: The women reported a mean height of 166.5 cm, birth weight of 3389 g and age at menarche 13.1 years. Mean BMI was 24.4 kg/m2, mean waist circumference 79.5 cm and mean total fat percentage 34.1%. Women with an adult height of more than 170 cm and insulin levels higher than 90 pmol/L experienced on average an 37.2 % increase in 17β- estradiol during an entire menstrual cycle compared to those with the same height, and insulin levels below 90 pmol/L. Moreover, this was also observed throughout the entire menstrual cycle. Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, suggesting that women who become taller are put at risk for higher estradiol levels when their insulin levels rise of possible importance for breast cancer risk.Anthropolog

17β-Estradiol Levels During An Entire Menstrual Cycle In Response To Adult Stature and Insulin, Of Possible Importance For Breast Cancer Risk: The EBBA-I study.

Background: The normal breast cells develop into malignant cells as a result of a complex interplay between genetic, environmental, nutritional and hormonal factors. Attained adult stature and insulin levels, risk factors for breast cancer, may also vary in response to the same factors. Thus, we hypothesize that 17β-estradiol, a key factor in the carcinogenesis of the breast, may vary in response to adult height in combination with insulin levels of possible importance of breast cancer risk. Methods: Among 204 healthy women, aged 25-35 years who participated in the Norwegian EBBA-I study, 17β-estradiol concentrations were measured in daily saliva samples throughout one entire menstrual cycle using radioimmunoassay (RIA). Attained height (cm) was measured, and serum concentrations of insulin were determined in fasting blood samples. The associations between adult height, insulin and 17β-estradiol levels throughout a menstrual cycle were studied using multivariate linear regression analyses and linear mixed models for repeated measures. Adjustments for potential confounding factors were performed. Results: A 37.2 % increase in 17β-estradiol levels was observed during the entire menstrual cycle among women with an adult height ≥170 cm (upper tertile) and insulin levels ≥ 90 pmol/L (upper tertile) compared to women with the same attained adult height, and insulin levels < 90pmol/L. The association was even more pronounced when we looked into those women with attained adult height ≥170 cm (upper tertile) and serum insulin ≥ 101 pmol/L (upper quartile) (Fig. 1). Adjustments for potential confounding factors were performed. Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, suggesting that women who become taller are put at risk for higher estradiol levels throughout the entire menstrual cycle when their insulin levels rise, of possible importance for breast cancer risk.AnthropologyHuman Evolutionary Biolog

State injury profile for Georgia

Estrogen and progesterone are key factors in the development of breast cancer, but it remains unclear whether these hormones are associated with mammographic density phenotypes in premenopausal women. We measured percent mammographic density, nondense area, and absolute mammographic density using computer-assisted breast density readings (Madena) from digitized mammograms taken on a scheduled day of the menstrual cycle (day 7–12) among 202 healthy, premenopausal women (Energy Balance and Breast cancer Aspects Study-I). Daily salivary concentrations of 17β-estradiol and progesterone throughout an entire menstrual cycle and fasting morning serum concentrations of hormones on 3 specific days of the menstrual cycle were assessed. Salivary and serum 17β-estradiol and progesterone were positively associated with percent mammographic density, we observed by 1 SD increase in overall salivary estradiol (β-value equal to 2.07, P=0.044), luteal salivary progesterone (β-value equal to 2.40, P=0.020). Women with above-median percent mammographic density had a 20% higher mean salivary 17β-estradiol level throughout the menstrual cycle. The odds ratio for having above-median percent mammographic density (>28.5%) per 1 SD increase in overall salivary 17β-estradiol was 1.66 (95% confidence interval 1.13–2.45). Women in the top tertile of the overall average daily 17β-estradiol concentrations had an odds ratio of 2.54 (confidence interval 1.05–6.16) of above-median percent mammographic density compared with women in the bottom tertile. Our finding of a relationship between estrogen, progesterone, and percent mammographic density and not with other mammographic density phenotypes in premenopausal women is biologically plausible, but needs to be replicated in larger studies

Physical Activity, Heart Rate, Metabolic Profile, and Estradiol in Premenopausal Women

Purpose: To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17[beta]-estradiol (E2) of importance for breast cancer risk. Methods: Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical activity (LPA), resting heart rate (HR), blood pressure (BP), anthropometry, and serum glucose, lipids, and insulin [Norwegian Energy Balance and Breast Cancer Aspect (EBBA) study]. E2 was measured in daily saliva samples throughout an entire menstrual cycle. A clustered metabolic risk score [z metabolic syndrome (zMS); total cholesterol-high-density lipoprotein-cholesterol (HDL-C) ratio, insulin resistance, total fat tissue, BP, and triglycerides] was defined. Linear regression and linear mixed models were used, and confounding factors were tested. Results: Physically active women had lower fat percentage (Ptrend = 0.003) and HRs (Ptrend = 0.003) than sedentary women. We estimated an increase in E2 of 1.27 pmol[middle dot]L-1 [95% confidence interval (CI), 0.06-2.47] for each 11.7 beats[middle dot]min-1 (1 SD) increase in HR, and this corresponds to the 7% change in mean concentration of E2 for the total group. Associations with E2 were also found for fat tissue, total cholesterol-HDL-C ratio, insulin resistance, and triglycerides. A dose-response relationship was observed among the three levels of LPA and HR and zMS (Ptrend = 0.03 for LPA; Ptrend = 0.004 for HR). Women in the highest tertile of the clustered metabolic risk score had average salivary E2profiles that were markedly higher, throughout the cycle, than those of the other groups, with a cycle peak-day difference in E2 of 22-28%. Conclusion: LPA and HR were associated with metabolic risk score, and this score was associated with daily level of E2, pointing to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk.AnthropologyHuman Evolutionary Biolog

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

Background: High-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear. Methods: Among 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35–75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics. Results: The breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m2; total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5 %. Most (93 %) of the patients had estrogen receptor (ER) positive tumors (≥1 % ER+), and 82 % had progesterone receptor (PgR) positive tumors (≥10 % PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22–0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51–1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28–4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36–1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1’s contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression. Conclusion: Our findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studies

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

Background: High-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear. Methods: Among 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35–75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics. Results: The breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m2 ; total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5 %. Most (93 %) of the patients had estrogen receptor (ER) positive tumors (≥1 % ER+), and 82 % had progesterone receptor (PgR) positive tumors (≥10 % PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22–0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51–1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28–4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36–1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1’s contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression. Conclusion: Our findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studie