Paediatrics: Delayed puberty: management

Delayed puberty: management

·  Children with CDGP may be treated with a short course of sex steroid therapy to promote physical development and growth (see Constitutional delay of growth and puberty).

·  Children with permanent gonadotrophin deficiency or gonadal failure requiring complete induction of puberty and thus long-term treatment can have puberty induced with gradually increasing doses of sex steroids over a period of 2–3yrs.

·  Boys: testosterone esters by IM injection. Incremental increases in dose, starting from 50mg every 4–6wks to 250mg every 3–4wks.

·  Girls: ethinylestradiol, oral. Increasing doses every 6mths, starting from 2micrograms/day increasing to 5–20micrograms/day. A progesterone (e.g. norethisterone or levonorgestrel given on days 14 to 21 of the cycle only) should be added when the dose of ethinylestradiol is 10–15micrograms/day or when vaginal bleeding or spotting is first observed.

·  The aim of long-term sex steroid therapy is the maintenance of secondary sexual features, libido, and menstruation in females. There are also positive benefits in terms of bone mineralization and cardiovascular health.

Note. In males, testosterone therapy does not promote testicular growth and testicular size remains prepubertal unless spontaneous puberty occurs.

Constitutional delay of growth and puberty

This is the most common cause of delayed puberty. Usually observed in boys, this condition reflects a delay in the timing mechanisms that regulate the onset of puberty. There is often a family history of delayed puberty in parents or siblings.

·  Children presenting with CDGP are invariably healthy.

·  Onset and progress through puberty will occur normally with time.

·  Children achieve a final adult height in keeping with their predicted familial target range.

It is likely that most children with CDGP are not referred for medical attention, as they and their parents will not perceive that there is a prob-lem. However, for many others, concerns about the lack of physical devel-opment and the lack of anticipated adolescent growth spurt would be a source of much anxiety and psychological stress.

There is often evidence of delayed or slow growth in childhood, which is most pronounced in the peripubertal years due to lack of anticipated growth spurt. Children will also have evidence of delayed skeletal matura-tion on bone age assessment.

No specific therapy is required. For many children and families, explana-tion of the benign nature of the condition and reassurance that puberty will occur normally is sufficient. However, children who are experienc-ing signifi cant social or psychological diffi culties may request treatment. In this situation, low dose sex steroids may be used (e.g. boys: testosterone, 50mg IM monthly for 4–6mths). This approach will:

·induce sexual development;

·promote an increase in growth rate;

·stimulate activation of the hypothalamic–pituitary–gonadal axis.

Thus puberty may continue once the administration of sex steroids has been stopped.

Any decision regarding whether therapy is required or not must include the views of the child and their parents, who should be part of the deci-sion process.

Hypogonadotrophic hypogonadism

This indicates impaired gonadotrophin release from the pituitary gland. Congenital and acquired causes are recognized. The condition is characterized by low or undetectable gonadotrophin lev-els either under basal or stimulated (GnRH test) conditions.

Congenital causes of HH may be characterized by micropenis and unde-scended testis at birth in boys, whereas in girls physical signs are absent.

Kallmann syndrome (KS)

A genetic disorder characterized by the association of HH and anosmia (absent sense of smell). This arises due to a defect in the co-migration of GnRH releasing neurons and olfactory neurons that occurs during early foetal development. X-linked, autosomal dominant, and autosomal reces-sive modes of inheritance are recognized. The X-linked form of KS results from a mutation in the KAL gene (encoding the glycoprotein, anosmin-1). It is also characterized by a range of clinical features including synkinesia (mirror-image movements), renal agensis, and visual problems as well as craniofacial anomalies, although their expression is highly variable.