11:28am Thursday 19 September 2019

Rethinking the age boys reach puberty

(L-R) Dr Catherine Itman and Professor Kate Loveland

The largest study of its type, enrolling 4131 healthy boys between six and 16 years of age with broad geographical representation, provides a convincing demonstration that male puberty begins in the general population around 10-11 years of age, six to 24 months earlier than is understood from studies undertaken 40-50 years ago.

This carefully managed study recorded distinct differences between African American, Hispanic and Caucasian (termed “White”) boys in the age of puberty onset, documenting that  one in five boys as young as six years of age selectively in the African American cohort have visible signs of development, such as pubic hair and testis growth.

These findings will inevitably raise questions about why this is happening and how this impacts on the health of boys and men.  Recent research has provided basic knowledge about which physiological processes control the timing of pubertal initiation however many aspects are poorly understood, such as the social impact of pubertal timing, how socio-economic conditions might influence pubertal onset and whether the measured indicators of puberty correlate with hormonal changes that are of clinical importance.

If the onset of puberty is advancing, what is causing this? 

Differences in pubertal timing between ethnic groups suggest that genetics underlie at least part of the biology of puberty. Some progress was recently made in identifying candidate genetic factors, with our report that timing of testis development is explicitly dependent on the Smad3 protein, which conveys information from outside of the cell to the genes, switching them on or off. In unraveling this complex story we discovered that testis development occurs earlier when Smad3 levels are reduced, but when it is absent, testis development is delayed.  Importantly, these differences in developmental timing occurred without measurable changes in reproductive hormones, showing that testis maturation is not solely under the control of the hormonal axis. 

How an individual’s genetic make-up, environmental factors they are exposed to and the interaction between these can influence the timing of pubertal onset and pace of puberty are important targets for future research.

Does it matter if puberty occurs earlier?  

Pubertal development in boys is driven by a sudden and sustained increase in the hormone testosterone.  Testosterone prepares the testis to produce sperm and causes development of secondary sexual characteristics, such as pubic and facial hair and vocal deepening.  Boys who develop elevated testosterone and associated features much earlier than their peers may experience significant and long-term social and educational challenges that emerge from peer group and physiological pressures.  

Should we reassess when and how children are taught about their bodies? Can this information improve the health and wellbeing of boys? 

The central outcome of this study is that the average age of pubertal onset in boys is around 10-11 years of age, earlier than the current clinical definition of normal puberty.  This has immediate relevance to the management of boys’ health; health care providers must recalibrate what is considered ‘normal’, so that children experiencing altered pubertal timing do not escape diagnosis. Early (precocious) puberty may arise from serious medical conditions, such as testicular or pituitary tumours which require treatment.  But perhaps surprising to many, redefinition of the age of pubertal onset is of much greater relevance to boys with delayed puberty.  Testosterone not only drives puberty but is also important for normal bone and muscle development. Delayed puberty results in lower bone density in adulthood, placing these men at increased risk of developing osteoporosis and resulting in reduced quality of life and significant social and health care burdens.  Timely testosterone treatment of boys with excessively delayed puberty promotes bone growth, so that these boys may achieve normal bone density and strength in adulthood. 

One immediate impact of this study relates to the diagnosis and treatment of boys with Klinefelter syndrome.  This condition, arising from the presence of an extra X chromosome, affects around 1 in 580 males and is characterized by under-development of the testes and low to absent testosterone.  While boys with Klinefelter syndrome are not remarkably distinguishable from other boys during infancy and early childhood, it is the delay or absence of puberty due to insufficient testosterone production that precipitates diagnosis.  The associated features of this condition, which can include lack of physical coordination, behavioural and learning difficulties and poor muscle and bone strength can be minimized with early diagnosis, medical intervention and educational support.  Unfortunately, because of the inert nature of Klinefelter syndrome during early years, many boys are not diagnosed until well into their teens.  The major challenge for health professionals is to identify these boys early enough to put interventions in place that will support their health, educational and social development.  Formal recognition that puberty in boys occurs between 10-11 years will increase the chance of earlier diagnosis for these boys.

Nature versus Nurture?  Key, fundamental questions that relate to the timing of pubertal onset remain: what factors influence pubertal timing (e.g. nutrition and body weight) and what genes control puberty?   Much suspicion is aimed at endocrine disrupting chemicals in our environment which disrupt normal hormone function.  Exposure to these chemicals is most commonly associated with delayed puberty, as their mode of action is to block testosterone production and/or action. However, there is an intriguing hint in this paper that socio-economic factors correlate with timing of puberty.  In this study population, 80% of White boys had medical insurance, whereas only one third of African American boys did – and it is African American boys who enter puberty one year earlier than white boys.  The question whether pubertal timing reflects socio-economic conditions, which itself affects nutrition, health status and other lifestyle factors, requires urgent inquiry.  On the other hand, disorders of male reproductive development, which are risk-factors for testicular cancer, were twice as common in White boys as African American and Hispanic boys.  These disorders, which are increasing in frequency worldwide, arise due to abnormal events during fetal life and surface during puberty or early adulthood, apparently provoked by hormonal changes.  

This observation could lead us to question whether a longer prepubertal period increases the chance of testis changes that precede cancer, or alternatively, could a shorter prepubertal period be protective?

Kate Loveland is Professor and NHMRC Senior Research Fellow in Biochemistry & Molecular Biology and Anatomy and Developmental Biology at Monash University.

Dr Catherine Itman is a Research Fellow in the Department of Biochemistry and Molecular Biology at Monash University.

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