Aetiological role of early lifestyle exposures in puberty timing
Amidst the global secular trends towards earlier timing of pubertal development, there are abundant evidence from various populations that early puberty timing is associated with higher risks for a wide range of subsequent adverse physical and mental health outcomes. Despite the increasing recognition that rapid growth and obesity during prepubertal childhood may promote earlier puberty, it is unclear whether lifestyle behaviours are determinants of puberty timing. This thesis aimed to explore whether diet and physical activity in childhood are associated with puberty timing, using a combination of robust analytical approaches.
First, to understand the disease relevance of puberty timing independent of adiposity, published findings on the associations between puberty timing and risks for type 2 diabetes and/or impaired glucose tolerance (T2D/IGT) were systematically reviewed and pooled by inverse-variance-weighted random-effects models. Based on 28 studies in Western and Asian settings, earlier timing of puberty in females, indicated by age at menarche, was consistently associated with higher T2D/IGT risk in women (n=1,228,306). Similarly, in the only one identified study in males (n=197,714 British men), relatively younger (versus ‘about average’) voice breaking was associated with higher risk of T2D. These associations were only partially mediated by adiposity, thus warranting examination of the determinants of puberty timing that act through or are independent of changes in adiposity.
I then investigated the associations of total energy and macronutrient intakes with timings of several puberty traits in boys (n=3811) and girls (n=3919) in the Avon Longitudinal Study of Parents and Children in the United Kingdom (UK). Integrating comprehensive data on dietary intakes and puberty development from early childhood until young adulthood, higher prepubertal childhood intakes of total energy in both sexes, and protein (including animal and plant-based proteins) in girls were associated with earlier timings of puberty onset and progression and peak height velocity, independent of adiposity during puberty. Further, in the same cohort, I examined the associations of dietary and plasma phospholipid fatty acids with puberty timing in boys (n=3654) and girls (n=3872). Based on repeatedly assessed dietary intakes and objective measures of fatty acids during prepuberty, higher dietary intake of polyunsaturated fatty acids, and higher plasma concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier puberty timing in girls, but not in boys. In Mendelian Randomization (MR) analyses, higher genetically predicted circulating dihomo-γ-linolenic acid but not palmitoleic acid was associated with earlier menarche in girls. Finally, I tested the associations between accelerometer-measured physical activity prior to puberty and subsequent puberty timing in boys (n=2531) and girls (n=3079) in the UK Millennium Cohort Study. Lower total daily movement, regardless of physical activity intensity, was consistently associated with higher risk for earlier puberty timing in both sexes, independent of body mass index. Using a MR model approach, higher genetically predicted sedentary activities were associated with earlier puberty timing.
This thesis uses a variety of data types and analytical triangulation approaches to demonstrate specific lifestyle behaviours, namely dietary intakes and physical activity, during prepubertal childhood, as potential determinants of the timing of pubertal development in both boys and girls. These findings may inform future interventions to avoid early puberty timing as part of a life course approach to prevention of non-communicable diseases.