Endogenous Hormones

Bio: Endogenous Hormones is an academic researcher from University of Oxford. The author has contributed to research in topics: Prospective cohort study & Sex hormone-binding globulin. The author has an hindex of 5, co-authored 5 publications receiving 3017 citations.

Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies.

Abstract: Background: Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women Methods: We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case–control sets matched within each study Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate Results: The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 142 (95% confidence interval [CI] = 104 to 195), 121 (95% CI = 089 to 166), 180 (95% CI = 133 to 243), and 200 (95% CI = 147 to 271; Ptrend<001); the RRs for women with increasing quintiles of free estradiol were 138 (95% CI = 094 to 203), 184 (95% CI = 124 to 274), 224 (95% CI = 153 to 327), and 258 (95% CI = 176 to 378; Ptrend<001) The magnitudes of risk associated with the other estrogens and with the androgens were similar SHBG was associated with a decrease in breast cancer risk (P trend = 041) The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis Conclusion: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women [J Natl Cancer Inst 2002;94:606–16]

Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies

Abstract: incident prostate cancer and 6438 control subjects were pooled by the Endogenous Hormones and Prostate Cancer Collaborative Group. Relative risks (RRs) of prostate cancer by fifths of serum hormone concentration were estimated by use of conditional logistic regression with stratification by study, age at recruitment, and year of recruitment. All statistical tests were two-sided. Results No associations were found between the risk of prostate cancer and serum concentrations of testosterone, calculated free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated free estradiol. The serum concentration of sex hormone – binding globulin was modestly inversely associated with prostate cancer risk (RR in the highest vs lowest fifth = 0.86, 95% confidence interval = 0.75 to 0.98; P trend = .01). There was no statistical evidence of heterogeneity among studies, and adjustment for potential confounders made little difference to the risk estimates. Conclusions In this collaborative analysis of the worldwide data on endogenous hormones and prostate cancer risk, serum concentrations of sex hormones were not associated with the risk of prostate cancer. J Natl Cancer Inst 2008;100: 170 – 183

Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies.

Abstract: Summary Background Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk. Methods Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0·05 was considered significant. Findings IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1·28 (95% CI 1·14–1·44; p<0·0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1·38 (95% CI 1·14–1·68) for oestrogen-receptor-positive tumours and 0·80 (0·57–1·13) for oestrogen-receptor-negative tumours (p for heterogeneity=0·007). Interpretation Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours. Funding Cancer Research UK.

Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies.

Abstract: Background Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood We aimed to characterise these associations with a pooled analysis of data from seven studies Methods Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI) All statistical tests were two-sided Findings We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 119, 95% CI 106-135), calculated free oestradiol (117, 103-133), oestrone (127, 105-154), androstenedione (130, 110-155), dehydroepiandrosterone sulphate (117, 104-132), testosterone (118, 103-135), and calculated free testosterone (108, 097-121) Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 100, 95% CI 092-109), and adjustment for other factors had little effect on any of these ORs Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women

Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

Abstract: The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

Diabetes and Cancer: A consensus report

Abstract: Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.

Estrogen carcinogenesis in breast cancer.

Abstract: n this article, we review recent findings related to estrogen exposure and the risk of breast cancer, the mechanisms that may be involved, and the clinical implications of these findings. The weight of evidence indicates that exposure to estrogen is an important determinant of the risk of breast cancer. The mechanisms of carcinogenesis in the breast caused by estrogen include the metabolism of estrogen to genotoxic, mutagenic metabolites and the stimulation of tissue growth. Together, these processes cause initiation, promotion, and progression of carcinogenesis. Insight into the mechanisms of the causation of cancer by estrogen will identify determinants of susceptibility to breast cancer and new targets for prevention and therapeutic intervention.

The relation between different dimensions of alcohol consumption and burden of disease - an overview

Abstract: Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. Methods Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose-response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol-disease relationships.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

Abstract: Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case- control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two- sided. Results: Breast cancer risk increased with increasing BMI (P-trend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m(2) increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin- bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.