We administered the
aromatase inhibitor fadrozole to 16 girls with
gonadotropin-independent
precocious puberty due to the
McCune-Albright syndrome. The girls' ages ranged from 3.2-9.7 yr, and their bone ages ranged from 5.75-14.25 yr. After baseline evaluations,
fadrozole was started at a dose of 240 microg/kg.d (equivalent to the dose recommended for
therapy of
estrogen-dependent
breast cancer) for 12-21 months and increased to 480 microg/kg.d for an additional 12 months in 10 girls. During treatment, seven girls had evidence of
central precocious puberty; hence, the
GnRH agonist
deslorelin (4 microg/kg.d sc) was added to their regimen. One girl was on a long-acting
GnRH agonist from the start of treatment. Patients were evaluated at 2-6-month intervals throughout treatment. After the first 6-12 months of treatment,
fadrozole showed some benefits in 10 girls, including decrease in frequency of menses and/or rates of linear growth and bone maturation; however,
fadrozole had no significant benefit in the group as a whole. The seven girls with evidence of
central precocious puberty had no slowing in the progression of their puberty during the combined
fadrozole and
GnRH analog treatment. Adverse effects of
fadrozole included inhibition of
cortisol and
aldosterone biosynthesis at the dose of 480 microg/kg.d, without clinical evidence of
adrenal insufficiency. In addition, three patients complained of nonspecific
abdominal pain during
fadrozole treatment. In one patient, this resolved with a reduction in dose from 480 to 240 microg/kg.d; in two patients, it resolved spontaneously. One girl had
muscle weakness and
constipation on the 480 microg/kg.d. This resolved after discontinuation of the drug. We conclude that
fadrozole is not sufficiently potent to block
estrogen synthesis in most girls with
gonadotropin-independent
precocious puberty due to the
McCune-Albright syndrome and may impair the adrenocortical stress response.