Luteinizing hormone response to clomiphene citrate in central precocious puberty

The aim of the present study was to determine the LH response to clomiphene citrate administration in children with central precocious puberty and different bone ages to gain insight into the hypothalamic maturation mechanism.

Twelve children with untreated central precocious puberty were studied. Five had central nervous system lesions and seven had idiopathic central precocious puberty. Their chronological and bone ages ranged from 1.7 to 8.8 years and 3.5 to 13.5 years, respectively. Clomiphene citrate (3 mg/kg/day) was administered orally for 7 days. Blood samples were collected on days 0, 6 and 8. LH and FSH were determined by RIA. The results were compared with GnRH responses or with bone age.

No increase over basal LH levels was detected in four patients, but increased LH levels were detected in the remaining eight during clomiphene administration. The shift from negative to positive responses was around 8-9 years bone age. The sum of LH responses (days 6 and 8) to clomiphene citrate, and particularly the 8th-day LH levels, were significantly correlated with their respective bone age (r = 0.83). However, the LH responses to GnRH were not significantly correlated with bone age or with LH responses to clomiphene.

This study shows that the LH responsiveness to clomiphene citrate in central precocious puberty increases with skeletal maturation, indicating that the activation of the hypothalamic pubertal mechanism in central precocious puberty may progress in a gradual sequence. These changes in LH response to clomiphene in central precocious puberty mimic those observed with the development of normal puberty, but occur at a much earlier age.