The subject of interest, a 17.2 year white female with intrinsic growth retardation and clinical features of RSD, developed POF following histrelin therapy for CPP. At 7 years growth acceleration, breast and public hair development and advancement of skeletal maturation were noted, followed by menarche at 9 years. An ovarian cyst was identified and excised at 9.3 years. Menses persisted after resection of the cyst; pulsatile gonadotropin secretion with a pubertal response to GnRH was demonstrated several months later. Subcutaneous histrelin was used on a compassionate basis for a period of 35 months (9.8-12.8 years) because of poor final height prediction. Consistent suppression of serum sex steroids and gonadotropins were maintained during the treatment period. Following discontinuation of histrelin, 3 menses occurred over the next three years (12.8-16 years). Laboratory investigation revealed POF, with elevated FSH (45.1 IU/L) and undetectable estradiol (<5 pg/mL;<18 pmol/L); anti-ovarian antibodies were negative and galactosemia evaluation normal. Peripheral blood karyotype was 46,XX. Review of ovarian histology from tissue obtained at 9.3 years revealed normal primordial follicles. FSH bioactivity was elevated concurrent with serum FSH elevation, suggesting appropriate gonadotropin bioactivity.

To the best of our knowledge, this young woman represents the first documented case of ovarian failure following GnRH analog therapy. Because the cause of POF has not been identified, and because an association between POF and RSD has not been reported, we believe careful observation of ovarian function following GnRH agonist therapy remains essential. Continued surveillance of ovarian function will ultimately confirm whether this case represents an isolated, serendipitous finding.