Estrogen mini-dose replacement during GnRH agonist therapy in central precocious puberty: A pilot study

During GnRH agonist therapy of patients with central precocious puberty (CPP), growth is sometimes suppressed to subnormal velocity. The working hypotheses were that estrogen levels are suppressed by GnRH agonist therapy below normal prepubertal levels, that such suppression is responsible for the slow growth of girls with CPP during GnRH agonist therapy, and that a mini-dose of estrogen replacement will normalize growth. The present pilot study examined growth and bone maturation over 2 yr in 13 patients with CPP and compared therapy with a combination of GnRH agonist and 8 microg conjugated equine estrogen (group 1) to therapy with GnRH agonist alone (group 2). Both groups had adequate suppression of gonadotropins, and E2 levels were below detection levels of our assay throughout the study period. Group 2 patients decreased their growth velocity from 2.0 +/- 1.4 to -1.6 +/- 1.2 SD score compared with group 1, who maintained their growth velocity of 1.3 +/- 1.5 SD score and their height SD score for 2 yr (P < 0.01). In group 1 patients the ratio of the change in bone age/change in chronological age decreased from 1.2 +/- 0.7 to 0.75 +/- 0.3, and in group 2 patients it decreased to 0.6 +/- 0.3 and 0.4 +/- 0.2 (P < 0.05) during the first and second years of therapy, respectively. It is concluded on a pilot basis that estrogen suppression is responsible for the slow growth of girls with CPP during GnRH agonist therapy and that a mini-dose of estrogen replacement is safe and effective for at least 24 months in maintaining normal prepubertal growth without acceleration of bone maturation or pubertal development. The current pilot results do not suggest an indication or provide a justification for such therapy.