We used the
aromatase inhibitor testolactone (40 mg/kg.day) to treat 12 girls with
precocious puberty due to the
McCune-Albright syndrome for periods of 0.5-5 yr. In the 7 girls who received
testolactone for at least 3 yr, the mean +/- SD serum
estradiol level was 618 +/- 268 pmol/L at the start of
therapy and fell to 156 +/- 84 pmol/L at 1 yr, 116 +/- 48 pmol/L at 2 yr, and 241 +/- 260 pmol/L at 3 yr (P < 0.05 compared to the start of
therapy), with recurrent
ovarian cysts at 3 yr in 2 patients. These 7 girls averaged 8 menses/yr before
therapy. The average frequency of menses decreased to 2 episodes/yr during the first year of treatment, 3/yr during the second year, and 4/yr during the third year. The mean +/- SD
testosterone levels were slightly above the normal prepubertal range (0.51 +/- 0.2 nmol/L) before treatment and did not change significantly during treatment. The mean +/- SD
androstenedione levels rose from 1.1 +/- 0.6 nmol/L before treatment to 2.1 +/- 0.1 nmol/L at 2 yr and 2.8 +/- 0.1 nmol/L after 3 yr of treatment (P < 0.05 compared to before treatment) and were consistent with normal adrenarche. The mean predicted adult stature was 143.0 +/- 7.8 cm before treatment and 147.3 +/- 11.5 cm at 3 yr (P = NS). In 3 of 12 girls, all with bone age greater than 12 yr, the
gonadotropin responses to
LHRH indicated early
central precocious puberty after 1-4 yr of treatment. The adverse effects of
testolactone were transient
abdominal pain,
headache, and
diarrhea in 3 girls and elevated hepatic
enzymes in 1 girl who had abnormal liver function before treatment. Six families acknowledged difficulty in adhering to the daily dosing schedule. We conclude that
testolactone can be effective in the treatment of
LHRH-independent
precocious puberty in girls with
McCune-Albright syndrome, but that some patients exhibit an escape from the effects of treatment after 1-3 yr.