Education Resource from the Society for Endocrinology
Endocrine Nurses Training Course 2005, John MacIntyre Centre, The University
of Edinburgh, 18 Holyrood Park Road, Edinburgh EH16 5AY, UK
30 August - 1 September 2005
Although, for at least the last 100 years, children have been becoming taller, this is largely the result of earlier maturation. Current 10 year-olds (for example) are more mature than their parents (and their parents) were at the same age, and hence taller. It means, too, that adults are not as relatively taller but have reached maturity earlier. In the middle of the 19th century, the age of menarche in European girls was ~16-17 years. Currently, the mean age of menarche is 13 years of even less. During the Industrial Revolution in Britain, mean menarcheal ages became earlier among the then more privileged female children. However, the modern secular trend to earlier pubertal maturation and increased adult height has not simply been the continuation of a unidirectional trend over prolonged historical periods. Studies of the fossil remains of our hominid ancestors demonstrate that the stature of individuals living during the last hundred millennia reaches the range of heights seen today. Probably phenomena responsible for positive and negative secular trends have affected height throughout history. Thus it cannot simply be assumed that the ‘recent’ trend towards earlier puberty and taller adult stature will simply continue. Indeed, recent indications are that the secular trend is now stopping gradually. Recent US data on the timing of puberty need to be looked at critically in that context.
There is no absolute age at which puberty is precocious but 3% of UK boys and girls will have started puberty by 9 & 8 yr respectively. Children with precocious puberty may simply have early onset of normal (central) mechanisms which may be idiopathic or secondary to underlying pathology, or they may have an abnormal mechanism causing development (pseudopuberty). Investigations, treatments and potential outcomes vary depending on the presence or absence of underlying pathology but also on psychosocial factors.
Oestrogen is responsible both for the pubertal growth spurt and epiphyseal fusion at the end of growth in both sexes. The growth-stimulatory effect of oestrogen is likely to be via the hypothalamo-pituitary-growth hormone axis whilst the growth-inhibiting action seems to be from a direct effect of oestrogen on growth cartilage. At low concentration, oestrogens stimulate the growth rate in childhood and adolescence but, in higher concentrations, they accelerate bone maturation so that the net effect on final height is, in most cases, negative. Any contribution of environmental oestrogen to the trend to earlier puberty remains speculative.
There is a strong association between childhood obesity (which is reaching epidemic proportions in some developed countries) and earlier puberty. Obesity is also associated with adverse cardiovascular risk and metabolic profiles as well as potential psychological distress.
Two decades ago, when gonadotrophin releasing hormone analogue (GnRHa) treatment was being introduced for the treatment of central precocious puberty, it was thought that there were only two distinct conditions resulting in premature sexual maturation from a gonadal aetiology; central precocious puberty and isolated premature thelarche, of which the latter is a benign condition and not requiring treatment. However, there is no pathognomonic endocrinological distinction between these two conditions; LH and FSH secretion represent a complete spectrum in girls with isolated premature thelarche having predominant FSH secretion, and those with central precocious puberty predominant LH secretion.
In recent years, we have realised that this variation in gonadotrophin secretion represents a spectrum of disorders of gonadal maturation which have received different names depending on the countries in which they were reported: “unsustained central sexual precocity”, “slowly progressive precocious puberty”, “thelarche variant” and “exaggerated thelarche”. It is probable that all four conditions are identical.
In previous publications, many of these patients have probably been included with those with “true” central precocious puberty, thus making the effect of GnRH therapy in improving final height appear better than it actually is. In addition, most studies fail to recognise that in comparing adult height achieved with predicted adult height (PAH) at the start of treatment, skeletal maturational (bone age) estimations on the same individual repeated through puberty do not show increments of 1 ‘year’ bone age (BA) per year chronological age (CA) because BA accelerates and deviates from a cross-sectional-based centile in a way similar to that for height. BA standards are based on those with puberty at an average age, thus in those entering puberty at an age younger than average, a rapid acceleration and progressive advancement of BA occurs – at peak height velocity BA velocity can be up to 2.5 ‘years’ per year. As a result, PAH at the start of treatment is misleadingly low and any treatment effect on adult height (eg from GnRHa treatment) will be overestimated.
Claims are being widely made for treatments improving final height in the context of precocious puberty which, in my view, cannot be sustained. This, in turn, leads to the inappropriate treatment of many children with medication which is both expensive and uncomfortable to administer. In the absence of underlying pathology, there is no prima facie reason why those who, for genetic or constitutional reasons, are destined to reach adult height earlier than average should fail to reach their genetically determined adult height.
A critical review of the evidence suggests that any improvement in height prognosis in children with central precocious puberty treated with GnRHa therapy is, at best, marginal. In my view, the indication for suppressing puberty with gonadotrophin releasing hormone analogues is for psychological or psychosocial reasons and not to achieve an improvement in final stature.
Revised:
16-Sep-2005