Epidemiology

• Delayed puberty occurs in approximately 3% of children.^[2]
• Constitutional delay in growth and puberty (CDGP) is more common in boys than in girls.^[3]

Causes of delayed or abnormal puberty

• Central (both sexes):
  • Intact hypothalamo-pituitary axis:
    • Constitutional delay in growth and puberty (CDGP) - sporadic or familial; see also separate article Short Stature.
    • Chronic illness, eg kidney disease, Crohn's disease.
    • Malnutrition, eg anorexia nervosa, cystic fibrosis, coeliac disease.
    • Excessive physical exercise, particularly athletes or gymnasts.
    • Psychosocial deprivation.
    • Steroid therapy.
    • Hypothyroidism.
  • Impaired hypothalamo-pituitary axis:
    • Tumours adjacent to the hypothalamo-pituitary axis, eg craniopharyngioma, optic glioma, germinomas, astrocytomas, pituitary tumours (including hyperprolactinaemia).
    • Congenital anomalies, eg septo-optic dysplasia, congenital panhypopituitarism.
    • Irradiation treatment.
    • Trauma: surgery, head injury.
    • Gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH)/follicle-stimulating hormone (FSH) deficiency, eg congenital idiopathic, Prader-Willi syndrome, Bardet-Biedl syndrome, Kallmann's syndrome.^[4]
• Peripheral:
  • Boys:
    • Bilateral testicular damage: cryptorchidism, failed orchidopexy, atresia, testicular torsion, infection (mumps rarely causes prepubertal damage).
    • Syndromes associated with cryptorchidism: Noonan's syndrome, Prader-Willi syndrome.
    • Gonadal dysgenesis: Klinefelter's syndrome other XY aneuploidy syndromes, XO/XY.
    • Irradiation, total or testicular.
    • Drugs, eg cyclophosphamide.
  • Girls:
    • Gonadal dysgenesis: Turner's syndrome, pure gonadal dysgenesis.
    • Irradiation, total or abdominal.
    • Drugs, eg cyclophosphamide, busulfan.
    • Intersex disorders, eg complete androgen insensitivity syndrome (primary amenorrhoea may be the presenting symptom), congenital adrenal hyperplasia.
    • Polycystic ovarian syndrome.
    • Toxic damage: galactosaemia, iron overload (thalassaemia).

Assessment

See also separate article Puberty - Normal and Abnormal.

A diagnosis can almost always be made by taking a thorough history, a proper assessment of growth, pubertal status and skeletal maturity (bone age) and a thorough physical examination. The cause of pubertal delay may be obvious (eg ovarian failure following total body irradiation prior to bone marrow transplantation, bilateral testicular torsion).

History

• Growth pattern: adolescents with constitutional delay in growth and puberty (CDGP) have a long-standing history of short stature. Use any available growth charts.
• General health: any symptoms of chronic ill health.
• Gonadal impairment: history of cryptorchidism, orchidopexy, and gonadal irradiation. Smell (for Kallmann's syndrome).
• Family patterns: age at menarche in female members of family, delayed growth spurt.
• Social and educational aspects: any indication of psychosocial problems.

Examination

• Height, weight; any suspicion of malnutrition.
• Measured parental and sibling heights (reported heights are much less reliable). See separate Short Stature article.
• Pubertal staging.
• Dysmorphic features.
• General examination, including fundoscopy and visual fields (pituitary tumour) and any indication of chronic disease, eg finger clubbing.

Investigations

Most boys and girls with delayed puberty have CDGP and do not need detailed investigation. In selected cases:

• Investigations for chronic disease: FBC, ferritin, renal function tests and electrolytes, coeliac screening, urinalysis for blood and protein, etc.
• Investigations related to disorders of gonadal axis:
  • Chromosomes (eg for Turner's syndrome and Klinefelter's syndrome).
  • Basal FSH and LH and serum estradiol/testosterone.
  • Pelvic ultrasound in girls.
  • Bone age: a delayed bone age may occur in CDGP, growth hormone deficiency and hypothyroidism.
  • GnRH test and tests for prolactin and growth hormone (see separate article Pituitary Function Tests); some cases of central delay are difficult to assess and the GnRH test cannot distinguish between physiological delay and gonadotrophin deficiency.
  • MRI or CT scan of the pituitary and surrounding structures may be indicated.

Management

Constitutional delay in growth and puberty (CDGP):

• Medical treatment is usually not necessary and reassurance and monitoring are sufficient. However, short courses of sex hormones are an option if delayed growth and puberty are causing psychological distress.^[3]
• CDGP in boys: induction of puberty may be achieved with short courses of low-dose testosterone therapy for appropriately selected boys with delayed puberty.^[5]
• CDGP in girls: gradually increasing doses of oestrogen treatment, with cyclical progesterone therapy once adequate oestrogen levels have been achieved.

Chronic disease:

• Treat the underlying cause if possible; induction of puberty and hormone treatment may be required.

Primary testicular and ovarian failure:

• Pubertal induction followed by ongoing hormone replacement. Testosterone/oestrogen production may be adequate and ongoing hormone treatment unnecessary.
• Boys:
  • Regular testosterone injections are preferred but oral testosterone or testosterone patches, gel, and buccal pellets are alternatives.
  • There is not yet sufficient evidence for the routine use of other therapies (eg growth hormone, aromatase inhibitors) for CDGP.^[5]
• Girls:
  • Oestrogen replacement should be gradual to avoid premature fusion of the epiphyses and prevent overdevelopment of the areolae of the breast.
  • Gradually increased doses of ethinylestradiol with cyclical progesterone therapy once adequate oestrogen levels have been achieved or if breakthrough bleeding occurs.
  • A low-dose combined oral contraceptive pill can then be used.

Central delay:

• Treatment of any underlying cause, eg craniopharyngioma.
• Pubertal induction and hormone replacement.

Counselling with respect to sexual function and fertility as appropriate.