Whether All Patients with Central Precocious Puberty Should Be Treated?

Precocious puberty is the appearance of secondary sexual characteristics before 8 years old in girls and 9 years old in boys. Precocious puberty is divided into 3 groups of central, peripheral and normal variants. Central precocious puberty is accompanied by activation of hypothalamic-pituitary-gonadal axis which causes increase in secretion of Gonadotropin Releasing Hormone(GnRH) and in turn increase in secretion of gonadotropins (LH and FSH) from pituitary and consequently increase in secretion of sexual steroids (estrogen or testosterone) from gonads. This results in premature closure of growth plates and shorter final height.   GnRH agonists via suppression of hypothalamic-pituitary-gonadal axis, causes decrease sex steroid production, prevention of bone age advancement and ultimately result in increasing final height  in patients. Central Precocious puberty is the most common type of precocious puberty, which has a higher prevalence in girls.  Use of GnRH agonists is the best treatment for central precocious puberty. This article reviews important factors affecting selection of patients with central precocious puberty, to be treated by GnRH agonists. Purposes of treatment with GnRH agonist: - The main objective of treating patients with central precocious puberty is to prevent  premature closure of growth plates and providing enough time for height growth to ensure normal final height.  -The other purpose of treatment of these patients is to lower their psycho-social stress, emanating from precocious beginning of pubertal signs in these children and their families. - Stoppage of menarche in patients with mental retardation or cerebral paralysis that are not able to manage their menarche. The level of increase in final height after treatment with GnRH agonists on patients with precocious puberty varies. Factors affecting final height of patients with central precocious puberty after treatment with GnRH agonists: - Pubertal beginning age: the sooner commencement of pubertal age happens, the shorter final height will be. - Advancement of bone age: this factor, at the commencement phase of treatment and its termination, is accompanied by shorter final height. This indicates that if treatment is delayed to after a specific bone age (advanced), then reviving the entire potential of final height is not feasible. Kauli and his colleagues indicated that if treatment starts prior to advancement of bone age to 12 years old, it would be more useful. - Height Standard Deviation Score (SDS): Higher SDS of patients height at the beginning or end of treatment, results in higher final height. - Target height: if target age is taller, then final height increases. Main factors for selecting patients with central precocious puberty, for their treatment with GnRH agonists: Age of patients at the beginning of pubertal signs: in patients with central precocious puberty, the lower is their age, the faster progresses their pubertal signs and bone age. This causes premature closure of growth plates and shorter final height. Rate of sexual maturation: patients with central precocious puberty, in terms of advancement of their pubertal signs, are divided into two groups of rapidly progressive and slowly progressive. In the latter group, pubertal signs and bone age progresses rapidly and this leads to shorter final height. Predicted adult height: the most common way of calculating predicted adult height is bayley-pinneau. In this method, final height is calculated on the basis of percentage of current height, bone age and relation between bone age and calendar age. Patients with precocious puberty, with lower predicted adult height, will have shorter final height. - Other factors that are needed to be taken into account in treatment of central precocious puberty are: family background of precocious puberty; small for gestational age and adapted child. Familial forms of precocious puberty are more advanced than sporadic cases. Small for gestational age children, early puberty (not precocious puberty) are turned to rapid progress in bone age and shorter final height. In summary, groups of patients with central precocious puberty benefit from treatment with GnRH agonists are: 1- Girls with central precocious puberty under the age of 6 years old and all boys with central precocious puberty under 9 years old; 2- Girl patients with rapidly progressive central precocious puberty, the one tanner stage of whom progresses in less than 3-6 month; their velocity of height growth is more than 6 centimeters in a year; and their bon age is 1.5-2 years earlier than their calendar age; 3- Girls with central precocious puberty, predicted adult height of whom is more than 150 cm, and boys with central precocious puberty, with their predicted adult height more than 160 cm, do not require treatment and will achieve their final height. GnRH agonists available for treatment of central Precocious puberty: Leuprolide: dose of 3.75 mg for monthly IM injection and dose of 11.25 mg for 3month IM  injection; Triptorelin: dose of 3.75 mg for monthly IM injection and dose of 11.25 mg for 3month IM injection. Also doses of 22.5 mg for 6 months IM injection; Histrelin: dose of 50 mg, subcutaneous implant for one year. Common side effects of treatment with GnRH agonists :  hot flashes, headache, pain at the place of injection, local skin reaction at the place of injection, an in an uncommon manner sterile abscess at the place of injection. After termination of treatment, hypothalamic-pituitary-gonadal axis, will revive again and pubertal signs appear.    Conclusion Nowadays, GnRH agonists are widely used for treatment of central precarious puberty. This happens while age of puberty has decreased in normal population. The lower, age of patients with Precocious puberty is, rate of progress in pubertal signs is faster, final predicted adult height is lower; these patients benefit more from treatment by GnRH agonists.