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and improve the final adult height. Therapeutic options for the medical manage-
ment of GDPP include GnRH agonists, medroxyprogesterone acetate (MDPA),
and cyproterone acetate. However, GnRH agonist is the treatment of choice as it
is highly effective, safe, and has a beneficial effect on final adult height, particu-
larly if the treatment is initiated before 6 years of age. Further, suppression of
HPG-axis is reversible after discontinuation of GnRH therapy.
- What are the commonly used GnRH agonists for the management of GDPP?
Leuprolide acetate depot and triptorelin acetate depot are the commonly used
GnRH agonist for the management of GDPP. The recommended dose of leup-
rolide acetate depot is 140–300 μg/Kg/month intramuscularly, while that of
triptorelin acetate depot is 60 μg/Kg/month intramuscularly. Three monthly
formulations of these agonists are also available and are equally effective as
compared to monthly preparations. Adverse events associated with use of
GnRH agonist include initial flare, sterile abscess at injection site (3–10 %), hot
flushes, and local rash. An initial “flare” response occurs within first 1–2 weeks
of administration of GnRH agonist and manifests clinically as vaginal bleed in
females and priapism in males. It occurs as a result of stimulation of GnRH
receptors and consequent secretion of gonadotropins and gonadal steroids. This
flare response can be prevented by the concurrent administration of MDPA.
- What are the advantages of GnRH agonist over MDPA in the management of
GDPP?
GnRH agonists are the treatment of choice for GDPP, because they effectively
inhibit HPG-axis. Treatment with GnRH agonist results in regression of sec-
ondary sexual characteristics, improvement in final adult height, and possibly
optimal psychosocial development. However, final adult height may not
improve in children aged >6 years at initiation of therapy, possibly because of
significant advancement of bone age at presentation. In this scenario, MDPA is
an alternative option to prevent the progression of secondary sexual character-
istics, especially in resource-constraint settings. Therapy with MDPA does not
have a beneficial effect on final adult height possibly because of incomplete
suppression of HPG-axis and deleterious effect of MDPA on epiphyseal growth
plate (glucocorticoid-like effect). Prolonged therapy with MDPA results in
cushingoid appearance and inhibition of HPA-axis. - What is the role of GnRH antagonist in the management of precocious puberty?
Long-acting preparations of GnRH antagonist can be used for the management
of GDPP. GnRH antagonists have the advantage of immediate inhibition of
HPG-axis, without any “flare” response. However, with prolonged therapy,
there is a progressive increase in the dose requirement, as therapeutic effects of
these drugs are offset by increased levels of GnRH. This occurs as a result of
reduced feedback inhibition at hypothalamus due to decrease in gonadal
steroids.
6 Precocious Puberty