Precocious Puberty

Dr. Mrs. Meena P. Desai
Precocious Puberty - Treatment
Q. What are the goals of management in these children ?
A. The management is directed towards reversing and preventing further progression of puberty, arrest of skeletal maturation which compromises height potential and dealing with the emotional and psychologic problems which are frequently encountered. These children should be guarded against sexual abuse.

Q. What are the indications for the use of GnRH agonist? How it should be given ?
A. The use of drugs in the idiopathic form of TPP is influenced by the age of onset of symptoms and rapidity of progression. When CPP is rapidly progressive and occurs in a young child with the possibility of compromising height potential, the best form of medical therapy available today is with GnRH agonist. Chronic administration of these compounds down regulates and desensitizes GnRH receptors on pituitary gonadotropes. This leads to inhibition of gonadotropin release followed by decreased secretion of sex steroids. Depending on the nature of the preparation, GnRH can be administered by the SC route or intranasally daily or in a long acting repository form every 4 weeks. Within 2-4 weeks of adequate treatment with these agonists, the mean LH response to GnRH is within the prepubertal range and the sex steroid levels are suppressed by 4-12 weeks. The secondary sex characters regress and the accelerated growth velocity and bone age advance are slowed during the first year of therapy.

Leuprolide Acetate (Lupron depot ped) is the only depot preparation approved in USA and is given as 0.25 to 0.3 mg/kg, minimum 7.5 mg IM once in 4 weeks. Triptorelin available here as (Decapeptyl) is used in doses of 60 to 75 mcg/kg IM once in 3 to 4 weeks. Aqueous daily S.C. injection of Leuprolide 50 mcg/kg twice a day or intranasal Nafarelin (Synarel) 800 mcg bid are other preparations.

Therapy should be monitored in these children at regular intervals, with gonadotropin and sex steroid levels maintained in prepubertal range in both the sexes. Skeletal maturation is retarded to a greater degree than linear growth with resultant increase in prediction for adult stature. Occasional allergic reaction may occur otherwise no toxic reactions are reported. Medical therapy is advisable for nonprogressive neurogenic lesions causing CPP including postmeningitic forms or hamartomas.

Q. What treatment modalities are available ?
A. Treatment varies with the underlying cause.GnRH agonists, Medroxyprogesterone Acetate (MPA) and Cyproterone Acetate (CPA) are used for gonadotropin dependent CPP.

GnRH independent sexual precocity in the females (e.g. ovarian cysts) is usually treated with MPA, or occasionally with testolactone. In boys CAH is the usual cause of peripheral sexual precocity and is treated with corticosteroids. Testotoxicosis is a rare condition treated with ketoconazole, Spironolactone and flutamide.

The normal variation of pubertal development such as a premature thelarche, premature isolated menarche and premature adrenarche are benign and self limited conditions requiring careful follow up without institution of therapy. Surgery, radiation, or chemotherapy are required for CNS tumor. Occasionally pedunculated hamartomas have been extirpated.

The unusual syndrome of sexual precocity associated with juvenile hypothyroidism is reversible with the institution of the thyroid therapy.

In peripheral incomplete forms of sexual precocity, GnRH-A is ineffective. Testolactone a competitive inhibitor of the enzyme aromatase which converts androgens to estrogens has been used in gonadotropin- independent McCune Albright Syndrome. MPA has been useful in the treatment of recurrent ovarian cysts, McCune Albright Syndrome and familial testotoxicosis. If TPP supervenes before/after treatment of PPP, GnRH-(A) therapy may be added.

Q. How effective are other forms of treatment in CPP ?
A. Medroxy progesterone acetate (MPA) has been administered I.M. in doses varying from 50 to 400mg per month (initially 100mg/m2 ) or daily orally as 5mg twice to four times a day. It is available freely, is more economical and is effective in controlling menses and secondary sex characters. Cyproterone acetate(CA) has been used in doses varying from 100 to 150 mg/m2 /day in 2-3 divided doses. Both MPA and CA can suppress gonadotropin secretion in addition CA has an antiandrogenic effect. Both these drugs have very little effect on linear growth or skeletal maturation, which continues to progress.

Q. Can normal pubertal development resume when GnRH treatment is discontinued? Any other problems related to treatment ?
A. Within 6 to 18 months of discontinuation of treatment, normal pubertal development is resumed. Long term use may decrease the bone mass density as skeletal calcification may be affected to some extent. Occasionally polycystic Ovarian Syndrome (PCOS) is described.

Precocious Puberty Precocious Puberty 02/25/2001
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