Longitudinal Study of Hormonal and Physical Development in Young Twins

M. M. G. Koenis, R. M. Brouwer, G. C. M. van Baal, I. L. C. van Soelen, J. S. Peper, M. van Leeuwen, H. A. Delemarre-van de Waal, D. I. Boomsma, H. E. Hulshoff Pol
2013 Journal of Clinical Endocrinology and Metabolism  
Context and Objective: Information on the correlation of normative reproductive hormone levels with physical development (Tanner stages) during puberty and on the influences of genes and environment on variation in these hormones and Tanner stages is limited. Design, Setting, and Participants: One hundred twelve healthy 9-year-old twin pairs (n ϭ 224) took part in a longitudinal study, of which 89 pairs participated again at age 12 years (n ϭ 178). Main Outcome Measures: Morning urinary LH,
more » ... estradiol, and salivary testosterone levels, determined by competitive immunoassays, were measured. Tanner stages were determined through physical examination. Results: Over the 3-year interval, all hormone levels showed a 2-to 9-fold increase. LH and FSH at age 9 years predicted sex-specific Tanner stages at age 12 years in both boys and girls. Most of the associations between hormone levels at age 9 years and physical development at 12 years were explained by genetic influences. FSH in 9-year-old boys correlated with all hormone levels and Tanner stages at age 12 years. Moderate to high heritability estimates were found for hormone levels at both ages and in both sexes. In girls a shift from environmental (age 9 years) to genetic influences (age 12 years) was found for estradiol and pubic hair development, and for breast development a shift in the opposite direction was seen. Conclusions: During development LH and FSH (and testosterone in boys) levels predict secondary sexual characteristics in boys and girls 3 years later. These correlations are largely due to genes that are involved in both early pubertal hormone levels and subsequent physical development. (J Clin Endocrinol Metab 98: E518 -E527, 2013) A d v a n c e s i n G e n e t i c s -E n d o c r i n e C a r e E518 jcem.endojournals.org J Clin Endocrinol Metab, March 2013, 98(3):E518 -E527 E520 Koenis et al Hormonal and Physical Development J Clin Endocrinol Metab, March 2013, 98(3):E518 -E527 E522 Koenis et al Hormonal and Physical Development J Clin Endocrinol Metab, March 2013, 98(3):E518 -E527 Boys LH 9 -FSH 9 0.62 (0.48 -0.73) ADE-ADE 0.70 (0.53-0.83) 0.26 (Ϫ0.13-0.60) LH 9 -E2 12 0.24 (0.03-0.43) ADE-ACE 0.54 (0.33-1.00) 0.22 (Ϫ0.23-0.59) FSH 9 -LH 12 0.30 (0.06 -0.50) ADE-ADE 0.31 (0.05-0.53) 0.34 (Ϫ0.12-0.65) FSH 9 -FSH 12 0.51 (0.31-0.66) ADE-ADE 0.56 (0.35-0.71) 0.35 (Ϫ0.14 -0.70) FSH 9 -E2 12 0.25 (0.03-0.45) ADE-ACE 1.00 (0.07-1.00) Ϫ0.27 (Ϫ0.64 -0.25) FSH 9 -T 12 0.29 (0.06 -0.49) ADE-ADE 0.24 (Ϫ0.05-0.50) 0.35 (Ϫ0.10 -0.67) E2 9 -E2 12 a 0.32 (0.12-0.50) ACE-ACE 1.00 (0.36 -1.00) Ϫ0.40 (Ϫ0.68 -0.03) LH 12-FSH 12 0.32 (0.10 -0.52) ADE-ADE 0.32 (0.07-0.53) 0.03 (Ϫ0.39 -0.45) LH 12-E2 12 0.24 (0.02-0.44) ADE-ACE 0.41 (0.08 -1.00) Ϫ0.30 (Ϫ0.65-0.17) LH 12-T 12 0.49 (0.28 -0.65) ADE-ADE 0.55 (0.31-0.74) 0.09 (Ϫ0.35-0.50) FSH 12-E2 12 0.29 (0.08 -0.48) ADE-ACE 1.00 (0.23-1.00) Ϫ0.06 (Ϫ0.49 -0.40) LH 9 -Tanner-P 12 0.29 (0.03-0.50) ADE-ACE 1.00 (0.14 -1.00) Ϫ0.15 (Ϫ0.82-0.49) LH 9 -Tanner-PH 12 0.29 (0.02-0.52) b ADE-ACE 0.61 (Ϫ1.00 -1.00) 0.28 (Ϫ0.45-0.82) FSH 9 -Tanner-P 12 0.34 (0.09 -0.55) ADE-ACE 1.00 (0.22-1.00) Ϫ0.11 (Ϫ0.61-0.44) FSH 9 -Tanner-T 12 0.33 (0.04 -0.46) ADE-ACE 0.94 (0.59 -1.00) b 0.79 (Ϫ0.24 -0.86) FSH 9 -Tanner-PH 12 0.32 (0.06 -0.53) ADE-ACE 1.00 (0.48 -1.00) 0.01 (Ϫ0.62-0.64) T 9 -Tanner-PH 12 0.42 (0.18 -0.62) ADE-ACE 1.00 (0.31-1.00) Ϫ0.24 (Ϫ0.68 -0.37) LH 12-Tanner-P 12 0.39 (0.10 -0.61) ADE-ACE 1.00 (0.34 -1.00) Ϫ0.50 (Ϫ1.00 -0.25) LH 12-Tanner-PH 12 0.33 (0.01-0.59) ADE-ACE 0.43 (Ϫ1.00 -1.00) Ϫ0.04 (Ϫ0.71-0.66) T 12-Tanner-P 12 0.40 (0.16 -0.60) ADE-ACE 1.00 (0.45-1.00) Ϫ0.13 (Ϫ0.52-0.32) T 12-Tanner-T 12 0.44 (0.15-0.65) ADE-ACE 0.58 (0.20 -1.00) Ϫ0.05 (Ϫ0.70 -0.65) T 12-Tanner-PH 12 0.39 (0.13-0.60) ADE-ACE 1.00 (0.23-1.00) Ϫ0.15 (Ϫ0.69 -0.48) Tanner-P 12-Tanner-T 12 a 0.70 (0.51-0.83) ACE-ACE 1.00 (0.68 -1.00) 0.03 (Ϫ0.63-0.59) Tanner-P 12-Tanner-PH 12 a 0.30 (0.04 -0.53) ACE-ACE 1.00 (Ϫ1.00 -1.00) Ϫ0.45 (Ϫ0.84 -0.14) Girls LH 9 -FSH 9 0.64 (0.51-0.74) ADE-ADE 0.71 (0.38 -1.00) 0.59 (0.29 -0.79) b LH 9 -E2 9 0.31 (0.11-0.49) b ADE-ACE 1.00 (0.28 -1.00) b 0.05 (Ϫ0.25-0.38) LH 9 -LH 12 0.40 (0.19 -0.57) ADE-ADE 0.50 (0.17-1.00) b 0.15 (Ϫ0.24 -0.51) LH 9 -E2 12 0.40 (0.20 -0.57) ADE-ACE 1.00 (0.28 -1.00) Ϫ0.04 (Ϫ0.43-0.36) FSH 9 -E2 9 0.23 (0.04 -0.41) ADE-ACE 1.00 (0.23-1.00) 0.18 (Ϫ0.13-0.47) FSH 9 -FSH 12 0.23 (0.03-0.41) ADE-ADE 0.48 (Ϫ0.03-1.00) Ϫ0.00 (Ϫ0.36 -0.36) LH 12-FSH 12 0.56 (0.37-0.70) ADE-ADE 0.32 (Ϫ0.10 -0.65) c 0.48 (Ϫ0.04 -1.00) c LH 12-E2 12 0.53 (0.33-0.68) ADE-ACE 0.59 (0.17-1.00) 0.68 (0.38 -0.84) LH 12-T 12 0.40 (0.19 -0.57) ADE-ADE 0.47 (Ϫ0.04 -1.00) 0.32 (Ϫ0.10 -0.65) LH 9 -Tanner-B 12 0.56 (0.33-0.73) ADE-ACE 1.00 (0.56 -1.00) 0.27 (Ϫ0.40 -0.78) LH 9 -Tanner-PH 12 0.44 (0.19 -0.64) ADE-ACE 1.00 (0.36 -1.00) Ϫ0.42 (Ϫ0.81-0.20) FSH 9 -Tanner-B 12 0.44 (0.51-0.51) ADE-ACE 0.91 (0.13-1.00) 0.68 (0.17-0.95) LH 12-Tanner-B 12 0.55 (0.29 -0.74) ADE-ACE 0.78 (0.31-1.00) 0.28 (Ϫ0.71-1.00) LH 12-Tanner-PH 12 0.46 (0.20 -0.67) ADE-ACE 0.40 (0.22-0.85) b 0.82 (Ϫ0.19 -1.00) c E2 12-Tanner-B 12 a 0.70 (0.52-0.82) ACE-ACE 1.00 (Ϫ1.00 -1.00) Ϫ0.13 (Ϫ0.70 -0.51) E2 12-Tanner-PH 12 a 0.72 (0.54 -0.91) ACE-ACE 1.00 (0.63-1.00) 0.73 (0.18 -0.96) T 12-Tanner-B 12 0.30 (0.07-0.51) ADE-ACE 1.00 (0.19 -1.00) Ϫ0.28 (Ϫ0.83-0.47) T 12-Tanner-PH 12 0.33 (0.09 -0.53) ADE-ACE 0.35 (Ϫ1.00 -1.00) 0.57 (Ϫ0.07-0.88) Tanner-B 12-Tanner-PH 12 a 0.74 (0.59 -0.85) ACE-ACE 0.77 (Ϫ0.60 -1.00) 0.06 (Ϫ0.63-0.75) Abbreviations: CI, confidence interval; E2, estradiol; T, testosterone. Significant phenotypic correlations (Rph) between hormones at age 9 and 12 years and between hormones at age 9 and 12 years and Tanner stages at age 12 years are given. The extent of overlap in genetic (Rg) and unique environmental influences (Re) acting on both variables are given with their 95% confidence intervals. Bivariate ADE (ADE for both variables), bivariate ACE models (ACE for both variables), and mixed models were fitted, based on the twin correlations per variable. Rg is an estimate of the broad genetic correlation for bivariate ADE models and the additive genetic correlation in other cases. Bold-typed correlations are significant at P Ͻ .05. a In the bivariate ACE models, a common environmental correlation was estimated. It was only significantly explaining the correlation between estradiol at ages 9 and 12 years in boys ͓Rc ϭ 1.00 (0.30 -1.00)͔ and the correlation between breast development and estradiol at age 12 years in girls ͓Rc ϭ 1.00 (0.63-1.00)͔. b Correlation was not significant in the data set in which values below the detection limit were excluded. c Correlation was significant in the data set in which values below the detection limit were excluded. E524 Koenis et al Hormonal and Physical Development J Clin Endocrinol Metab, March 2013, 98(3):E518 -E527 E526 Koenis et al Hormonal and Physical Development J Clin Endocrinol Metab, March 2013, 98(3):E518 -E527
doi:10.1210/jc.2012-3361 pmid:23430788 fatcat:uyl63rixjffj5pa4rkcc2rzq7e