Delayed puberty

Puberty is described as delayed when a boy or girl has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, but delay of puberty may also occur due to undernutrition, many forms of systemic disease, or to defects of the reproductive system (hypogonadism) or the body's responsiveness to sex hormones.

Background: a brief synopsis of normal puberty
Puberty refers to the physical and hormonal changes which typically begin in early adolescence and lead to reproductive maturity and completion of growth. In girls the physical changes include growth of the breasts, development of pubic hair, change in body shape, increased body hair, slightly increased facial hair, and onset of menstrual periods (menarche). In boys the physical changes include growth of the penis and testes, pubic hair, increased muscle mass and strength, and increased body and facial hair. These changes in both sexes are referred to as secondary sex characteristics.

The body changes are triggered by rising levels of the sex steroids (androgens and estrogens). These arise from parallel hormonal processes termed "adrenarche" and "gonadarche." Adrenarche refers to maturation of the adrenal cortex with rising levels of adrenal androgens. These can produce early stages of pubic hair, underarm hair, adult body odor, and increased skin oiliness. This process is at least partly independent of gonadarche, which is an early part of central puberty, initiated by the central nervous system and resulting in mature fertility. Gonadarche is the consequence of a cascade of events beginning with increased amplitude of gonadotropin-releasing hormone from the hypothalamus, causing increased amplitude of gonadotropin pulses from the pituitary gland, which in turn activate the hormone producing cells of the testes and ovaries.

What’s the normal timing of puberty and what's delayed?
Approximate mean ages for onset of various pubertal changes are as follows. Ages in parentheses are the approximate 3rd and 97th percentiles for attainment. For example, less than 3% of girls have not yet achieved thelarche by 13 years of age.

For North American and European girls
 * Thelarche                10y5m      (8y-13y)
 * Pubarche                 11y        (8.5-13.5y)
 * Growth spurt            10-12.5y
 * Menarche                 12.5y     (10.5-14.5)
 * Adult height reached 14.5y

For North American and European boys
 * Testicular enlargement    11.5y   (9.5-13.5y)
 * Pubic hair                12y     (10-14y)
 * Growth spurt            12.5-15y
 * Completion of growth      17.5

The sources of the data, and a fuller description of normal timing and sequence of pubertal events, as well as the hormonal changes that drive them, are provided in the principal article on puberty.

How is delayed puberty evaluated?
Obviously anyone who is later than average is late in the ordinary sense. There are three indications that pubertal delay may be due to an abnormal cause. The first is simply degree of lateness: although no recommended age of evaluation cleanly separates pathologic from physiologic delay, a delay of 2-3 years or more warrants evaluation.
 * In girls, no breast development by 13 years, or no menarche by 3 years after breast development (or by 16).
 * In boys, no testicular enlargement by 14 years.

The second indicator is discordance of development. In most children, puberty proceeds as a predictable series of changes in specific order. In children with ordinary constitutional delay, all aspects of physical maturation typically remain concordant but a few years later than average. If some aspects of physical development are delayed, and others are not, there is likely something wrong. For instance, in most girls, the beginning stages of breast development precede pubic hair. If a 12 year old girl were to reach Tanner stage 3 pubic hair for a year or more without breast development, it would be unusual enough to suggest an abnormality such as defective ovaries. Similarly, if a 13 year old boy had reached stage 3 or 4 pubic hair with testes that still remained prepubertal in size, it would be unusual and suggestive of a testicular abnormality.

The third indicator is the presence of clues to specific disorders of the reproductive system. For example, malnutrition or anorexia nervosa severe enough to delay puberty will give other clues as well. Poor growth would suggest the possibility of hypopituitarism or Turner syndrome. Reduced sense of smell (hyposmia) suggests Kallmann syndrome.

Some possible causes of delayed puberty

 * Variation of normal (constitutional delay)
 * Prolonged high level of physical exertion / being an athlete
 * Systemic disease, e.g. Inflammatory bowel disease, chronic renal failure
 * Undernutrition e.g. anorexia nervosa, zinc deficiency
 * Hypothalamic defects and diseases e.g. Prader-Willi syndrome
 * Pituitary defects and diseases e.g. hypopituitarism, Kallmann syndrome
 * Gonadal defects and diseases e.g. Turner syndrome, Klinefelter syndrome
 * Absence or unresponsiveness of target organs e.g. androgen insensitivity syndrome, mullerian agenesis
 * Other hormone deficiencies and imbalances e.g. hypothyroidism, Cushing's syndrome

Medical evaluation of delayed puberty
Pediatric endocrinologists are the physicians with the most training and experience evaluating delayed puberty.

A complete medical history, review of systems, growth pattern, and physical examination will reveal most of the systemic diseases and conditions capable of arresting development or delaying puberty, as well as providing clues to some of the recognizable syndromes affecting the reproductive system.

An x-ray of the hand to assess bone age usually reveals whether overall physical maturation has reached a point at which puberty should be occurring.

The most valuable blood tests are the gonadotropins, because elevation confirms immediately a defect of the gonads or deficiency of the sex steroids. In many instances, screening tests such as a complete blood count, general chemistry screens, thyroid tests, and urinalysis may be worthwhile.

More expensive and complicated tests, such as a karyotype or magnetic resonance imaging of the head, are usually obtained only when specific evidence suggests they may be useful.

Management of delayed puberty
If a child is healthy but simply late, reassurance and prediction based on the bone age can be provided. No other intervention is usually necessary. In more extreme cases of delay, or cases where the delay is more extremely distressing to the child, a low dose of testosterone or estrogen for a few months may bring the first reassuring changes of normal puberty.

If the delay is due to systemic disease or undernutrition, the therapeutic intervention is likely to focus mainly on those conditions.

If it becomes clear that there is a permanent defect of the reproductive system, treatment usually involves replacement of the appropriate hormones (testosterone for boys, estradiol and progesterone for girls).