Suppression of puberty with long-acting goserelin (Zoladex-LA): effect on gonadotrophin response to GnRH in the first treatment cycle.

Background And Objectives: Depot GnRH analogues are widely used in the treatment of precocious puberty, or suppression of relatively early puberty where growth or psychosocial well-being may be compromised. One example is Zoladex (Z goserelin 3.6 mg), which can be given every 4 weeks. This injection frequency may not always achieve adequate suppression of pubertal signs. A long-acting form, Zoladex-LA 10.8 mg, has now been introduced with a potential duration of action of 12 weeks. In order to assess the efficacy of Zoladex-LA in gonadotrophin suppression we have measured LH and FSH responses to GnRH at diagnosis and 8 and 12 weeks after injection in a group of children treated with Zoladex-LA for central precocious or early puberty.

Methods: Forty-nine children (40 girls) with clinical evidence of central precocious puberty (CPP) or early puberty (EP) were started on Zoladex-LA, either de novo (n = 29) or on changing from Zoladex. Ages at diagnosis ranged from 1.7 to 10.6 years (median 7.8 years). Twenty-three had a structural cause with abnormality on magnetic resonance/computerized tomography (MR/CT) head scan, nine had a syndrome or nonspecific brain injury, and in 17 the cause was idiopathic.

Results: At diagnosis, in the de novo group, median peak LH was 13.6 IU/l and median peak FSH was 12.0 IU/l. By 12 weeks gonadotrophins were suppressed to 0.9 and 0.8 IU/l, respectively. In the previously treated group, median peak LH at diagnosis was 12.8 IU/l and median peak FSH was 15.0 IU/l with suppression to 0.8 and 1.1 IU/l, respectively, at 12 weeks. In the latter group peak FSH was higher than peak LH at both 8 and 12 weeks (P < 0.05) and there was a significant rise in peak LH (P < 0.05) and FSH (P = 0.01) between 8 and 12 weeks. There was no correlation between age at diagnosis and peak LH or FSH at 8 or 12 weeks. Nevertheless, individual patients in both groups showed evidence of incomplete gonadotrophin suppression at 12 weeks.

Conclusion: Zoladex-LA induces a significant reduction in gonadotrophins over 12 weeks. However, there are individuals, particularly those previously on Zoladex, in whom gonadotrophin suppression is waning by 12 weeks. As found with Zoladex, some children with precocious puberty treated with Zoladex-LA may require increased injection frequency, although correlation with clinical evidence of suppression needs to be studied further.