Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Socioeconomic conditions across life related to multiple measures of the endocrine system in older adults: Longitudinal findings from a British birth cohort study.

BACKGROUND: Little is known about how socioeconomic position (SEP) across life impacts on different axes of the endocrine system which are thought to underlie the ageing process and its adverse consequences. We examined how indicators of SEP across life related to multiple markers of the endocrine system in late midlife, and hypothesized that lower SEP across life would be associated with an adverse hormone profile across multiple axes. METHODS: Data were from a British cohort study of 875 men and 905 women followed since their birth in March 1946 with circulating free testosterone and insulin-like growth factor-I (IGF-I) measured at both 53 and 60-64 years, and evening cortisol at 60-64 years. Indicators of SEP were ascertained prospectively across life-paternal occupational class at 4, highest educational attainment at 26, household occupational class at 53, and household income at 60-64 years. Associations between SEP and hormones were investigated using multiple regression and logistic regression models. RESULTS: Lower SEP was associated with lower free testosterone among men, higher free testosterone among women, and lower IGF-I and higher evening cortisol in both sexes. For example, the mean standardised difference in IGF-I comparing the lowest with the highest educational attainment at 26 years (slope index of inequality) was -0.4 in men (95% CI -0.7 to -0.2) and -0.4 in women (-0.6 to -0.2). Associations with each hormone differed by SEP indicator used and sex, and were particularly pronounced when using a composite adverse hormone score. For example, the odds of having 1 additional adverse hormone concentration in the lowest compared with highest education level were 3.7 (95% CI: 2.1, 6.3) among men, and 1.6 (1.0, 2.7) among women (P (sex interaction) = 0.02). We found no evidence that SEP was related to apparent age-related declines in free testosterone or IGF-I. CONCLUSIONS: Lower SEP was associated with an adverse hormone profile across multiple endocrine axes. SEP differences in endocrine function may partly underlie inequalities in health and function in later life, and may reflect variations in biological rates of ageing. Further studies are required to assess the likely functional relevance of these associations.

Associations of childhood and adulthood height and the components of height with insulin-like growth factor levels in adulthood: a 65-year follow-up of the Boyd Orr cohort.

CONTEXT: Taller individuals with longer legs have a higher risk of cancer but a lower risk of coronary heart disease. OBJECTIVE: We investigated whether childhood height and its components are associated with the IGF system in adulthood. DESIGN AND PARTICIPANTS: We analyzed data from 429 participants of the Boyd Orr cohort, for whom height measured in childhood (mean age, 7.4 yr) in 1937-1939 could be related to levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood (mean age, 71.1 yr). In 385 participants, measured height in adulthood could be related to IGF levels. RESULTS: In fully adjusted models (controlling for age, sex, socioeconomic factors, lifestyle, and body mass index), childhood height and its components were not associated with adult circulating IGF-I, IGF-II, or IGFBP-2 levels. IGFBP-3 was 85.5 ng/ml higher (95% confidence interval, -11.6 to 182.5; P = 0.08) per sd increase in childhood trunk length and 83.6 ng/ml lower (95% confidence interval, -10.3 to 177.5; P = 0.08) per sd increase in childhood leg/trunk ratio. Height in adulthood was not associated with IGF-I, IGF-II, or IGFBP-3 and was inversely associated with IGFBP-2 (P = 0.05) after additionally controlling for childhood height. CONCLUSION: There was no evidence that associations of childhood height with cancer and coronary heart disease risk are mediated by IGF-I in adulthood. The anthropometric associations with IGFBP-2 and IGFBP-3 could be chance findings but warrant additional investigation. IGF levels in childhood may be more important determinants of long-term disease risk than adult levels.

Association of insulin-like growth factor I and insulin-like growth factor-binding protein-3 with intelligence quotient among 8- to 9-year-old children in the Avon Longitudinal Study of Parents and Children.

BACKGROUND: Insulin-like growth factor I (IGF-I) is a hormone that mediates the effects of growth hormone and plays a critical role in somatic growth regulation and organ development. It is hypothesized that it also plays a key role in human brain development. Previous studies have investigated the association of low IGF-I levels attributable to growth hormone receptor deficiency with intelligence but produced mixed results. We are aware of no studies that investigated the association of IGF-I levels with IQ in population samples of normal children. OBJECTIVES: To investigate the association of circulating levels of IGF-I and its principle binding protein, IGF-binding protein-3 (IGFBP-3), in childhood with subsequent measures of IQ. METHODS: The cohort study was based on data for 547 white singleton boys and girls, members of the Avon Longitudinal Study of Parents and Children, with IGF-I and IGFBP-3 measurements (obtained at a mean age of 8.0 years) and IQ measured with the Wechsler Intelligence Scale for Children (at a mean age of 8.7 years). We also investigated associations with measures of speech and language based on the Wechsler Objective Reading Dimensions test (measured at an age of 7.5 years) and the Wechsler Objective Language Dimensions test (listening comprehension subtest only, measured at an age of 8.7 years). For some children (n = 407), IGF-I (but not IGFBP-3) levels had been measured at approximately 5 years of age in a previous study. Linear regression models were used to investigate associations of the IGF-I system with the measures of cognitive function. RESULTS: Three hundred one boys and 246 girls were included in the sample. IGF-I levels (mean +/- SD) were 142.6 +/- 53.9 ng/mL for boys and 154.4 +/- 51.6 ng/mL for girls. IQ scores (mean +/- SD) were 106.05 +/- 16.6 and 105.27 +/- 15.6 for boys and girls, respectively. IGF-I levels were associated positively with intelligence. For every 100 ng/mL increase in IGF-I, IQ increased by 3.18 points (95% confidence interval [CI]: 0.52 to 5.84 points). These positive associations were seen in relation to the verbal component (coefficient: 4.27; 95% CI: 1.62 to 6.92), rather than the performance component (coefficient: 1.06; 95% CI: -1.67 to 3.78), of IQ. There was no evidence that associations with overall IQ differed between boys and girls. In a data set with complete information on confounders (n = 484), controlling for birth weight (adjusted for gestation), breastfeeding, and BMI slightly strengthened the associations of IGF-I levels with IQ. Additionally controlling for maternal education and IGFBP-3 levels attenuated the associations (change in IQ for every 100 ng/mL increase in IGF-I levels: 2.51 points; 95% CI: -0.42 to 5.44 points). The weakening of associations in models controlling for markers of parental socioeconomic position and education could reflect shared influences of parental IGF levels on parents' own educational attainment and their offspring's IGF-I levels. In unadjusted models examining associations of Wechsler Objective Reading Dimensions and Wechsler Objective Language Dimensions test scores with IGF-I levels, there was no strong evidence that performance on either of these tests was associated with circulating IGF-I levels, although positive associations were seen with both measures. Associations between IGF-I levels measured at age 5 and Wechsler Intelligence Scale for Children scores (n = 407) were similar to those for IGF-I levels measured at age 7 to 8. For every 100 ng/mL increase in IGF-I levels at 5 years of age, IQ increased by 2.3 points (95% CI: -0.21 to 4.89 points). CONCLUSIONS: This study provides some preliminary evidence that IGF-I is associated with brain development in childhood. Additional longitudinal research is required to clarify the role of IGF-I in neurodevelopment. Because IGF-I levels are modifiable through diet and other environmental exposures, this may be one pathway through which the childhood environment may influence neurodevelopment.