209therapy, menses resumes within 1–1.5 years, and cycles become ovulatory in
majority of girls 2 years after the onset of menses. The pattern of recovery of
HPG-axis is similar in boys, but the progression of puberty is slower as com-
pared to girls. Although testicular volume starts increasing by 1 year after dis-
continuation of GnRH agonist therapy, testicular volume remains smaller as
compared to age-matched peers for the next 2–5 years. Fertility is not impaired
in both sexes with the use of GnRH agonist.- Does GnRH agonist therapy interfere with accrual of peak bone mass?
Although there are theoretical concerns regarding decreased bone mineral den-
sity with the prolonged use of GnRH agonist, data from various studies have
shown that GnRH agonist therapy does not influence the accrual of peak bone
mass. Optimal supplementation with vitamin D and calcium should be ensured
in all patients receiving GnRH agonist.- What are the treatment options for GIPP?
Treatment for patients with GIPP depends on the underlying cause. Surgical exci-
sion is the treatment of choice for GIPP due to adrenal, ovarian, and testicular
neoplasms. Ovarian follicular cyst spontaneously regresses and does not require
surgical treatment in majority of children. However, medroxyprogesterone ace-
tate (MDPA) may be used, if required during interim period. Optimal therapy
with glucocorticoids and fludrocortisone results in regression of secondary sexual
characteristics in children with congenital adrenal hyperplasia. Girls with GIPP
associated with McCune–Albright syndrome can be treated with MDPA, keto-
conazole, and aromatase inhibitors, whereas boys with testotoxicosis can be
treated with MDPA, ketoconazole, spironolactone, and aromatase inhibitors. If
GDPP is superimposed on GIPP, therapy with GnRH agonist may be added.- How to treat precocious puberty associated with McCune–Albright syndrome?
Therapy for precocious puberty associated with McCune–Albright syndrome
(MAS) is only partially effective. Treatment options include MDPA, ketocon-
azole, and aromatase inhibitors. MDPA is the most commonly used drug and it
acts by inhibiting ovarian steroidogenesis. The recommended dose of MDPA is
100–150 mg/m^2 /month. Therapy with MDPA results in regression of secondary
sexual characteristics; however, it does not have an effect on skeletal matura-
tion. It has glucocorticoid-like activity; therefore, prolonged therapy with
MDPA results in cushingoid appearance and inhibition of HPA axis.
Ketoconazole acts by inhibiting cytochrome P450-dependent enzymes involved
in steroidogenesis. Adverse effects of ketoconazole include transaminitis and
hypocortisolemia. Aromatase inhibitors like testolactone and letrozole are par-
tially effective for GIPP associated with MAS, and efficacy of these agents
progressively decline after a period of 6 months to 1 year; however, the benefi-
cial effects on skeletal maturation and growth velocity persist despite decrease6 Precocious Puberty