SAT-307 Sudden Unexpected Vaginal Bleeding Caused by Temporal Reactivation of Hypothalamic-Hypophyseal-Gonadal Axis during Gonadotropin Releasing Hormone Agonist Treatment for Central Precocious Puberty

Abstract

The Gonadotropin-releasing hormone(GnRH) agonist has been the treatment of choice for central precocious puberty. These drugs suppress gonadotropin secretion through desensitization and downregulation of GnRH receptors, leading to reduced secretion of gonadal steroids to prepubertal levels. The regression of secondary sexual characteristics, delayed menarche, and maximization of linear growth can be achieved through this treatment. Due to initial agonistic action of this drug, withdrawal vaginal bleeding can occur after the first or second dose of the treatment. This phenomenon could occur after 6 months in rare cases. In this report, we would like to introduce a rare case of unexpected vaginal bleeding with rapid breast engorgement during the treatment course without any evidence of insufficient suppression of hypothalamic-hypophyseal-gonadal(HPG) axis. The condition was normalized with increased dosage of drug for 2 months, and suppression of HPG axis was maintained with same initial dosage untill completion of treatment. Therefore, we believed that idiopathic reactivation of HPG axis was likely a cause of this unusual condition. A 7 year-old girl visited our clinic with breast buds which was examined as Tanner stage 2-3, with pigmentation of areola. Her bone age was advanced as 10 years of age. LHRH stimulation test showed a pubertal response(LH>5.0 IU/L). Pelvic ultrasonography showed a pubertal uterus shape. Brain MRI showed no specific abnormalities. Leuprolide acetate 3.75mg was administered to the patient every 4 weeks, and until the 4th injection, she exhibited no progression of secondary sexual characteristics and changes in hormonal levels, indicating that the HPG axis was properly suppressed. However, after 5th injection, the patient complained of rapid breast engorgement and abrupt vaginal bleeding 2 weeks later. LH and estradiol was measured 0.3 IU/L(normal < 0.2 IU/L) and 38.7pg/ml(normal < 10pg/ml), respectively. Pelvic ultrasonography revealed enlarged uterus without any other pathologic findings. Leuprolide acetate 3.75mg was boosted and administered every 2 weeks for 2 months. After confirming the HPG axis suppression on studies, the injection interval was rescheduled to 4 weeks. The status of patient was stabilized without any other clinical or hormonal deterioration until completion of treatment. In conclusion, GnRH agonist can suppress HPG axis successfully in most cases, however, temporal reactivation of HPG axis can occur during the treatment course although HPG axis suppression has been maintained in serial check up. Therefore, clinician should be aware of possibility of unexpected vaginal bleeding and reevaluation should be performed to check up the status of the patient, including pelvic ultrasonography and hormonal assessment. Finally, careful advice should be given in an attempt to avoid unnecessary anxiety and achieve better compliance.