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15 days, while the suppression of gonadal steroids to prepubertal levels occurs
by 2–4 weeks in girls and 6 weeks in boys.- What are the hormonal parameters to be monitored in a child with precocious
puberty on GnRH agonist therapy?
Basal LH and estradiol/ testosterone (prior to the next dose) and stimulated LH
(after 3h of GnRH agonist depot administration) are used for the assessment of
response to GnRH agonist. However, the cutoffs for defining the adequacy of ther-
apy are not well validated, as different studies have used different GnRH agonist
preparations and variable assays to estimate LH and gonadal steroids. Further, it is
not clear whether to monitor basal LH and gonadal steroids/stimulated LH and
gonadal steroids or both during therapy with GnRH agonist. Nevertheless, a basal
LH in prepubertal range (<0.3 IU/L), testosterone (<0.7 nmol/L), estradiol (<5 pg/
ml), and a stimulated LH at 3h <3.3 IU/L following GnRH agonist depot is con-
sidered as optimal response to therapy. If these criteria are not fulfilled, either dose
or frequency of GnRH agonist administration should be increased. - What is the rationale of estimation of stimulated LH after administration of
depot preparation of GnRH agonist?
Short-acting preparations of GnRH agonist (aqueous formulations) are used to
assess LH response for the diagnosis of GDPP and to monitor the efficacy of
therapy. Long-acting preparations of GnRH agonist (depot formulations) are
used in the management of GDPP. However, these long-acting preparations can
also be used to assess the efficacy of therapy by estimation of LH levels after 3h
of administration. This is possible because of the presence of small quantity of
free form of GnRH agonist in these depot preparations. - When to discontinue therapy with GnRH agonist?
The exact time to discontinue therapy with GnRH agonist is not well defined in
children with GDPP. Retrospective analyses suggest that GnRH agonist can be
stopped at chronological age of 11 years, as there is no further significant height
gain despite continuation of GnRH agonist. Rather, continuation of GnRH ago-
nist beyond 11 years of age has been shown to result in loss of 2.5 cm of final
adult height, as growth after 11 years of age is dependent on gonadal steroids.
In children with precocity who are treated for psychosocial concerns, therapy
can be stopped at an age appropriate for the pubertal development for that par-
ticular race (e.g., 10–12 years).- What is the pattern of recovery of HPG-axis after discontinuation of GnRH
agonist therapy for precocious puberty?
Use of GnRH agonist is associated with reversible suppression of HPG-axis
and the axis recovers within a year of discontinuation of therapy. In girls, pro-
gression of pubertal signs starts within 3–6 months after discontinuation of
6 Precocious Puberty