44. Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Turner Syndrome: Experience from a Large Turner Syndrome Center

Abstract

<h3>Background</h3> More than 80% of girls with Turner syndrome (TS) experience primary ovarian failure prior to the onset of menarche. Hormone replacement therapy (HRT) is recommended to start between 11-12 years of age, followed by titration to adult dosing over 18-24 months. Current guidelines recommend that HRT starts with transdermal estradiol, followed by the addition of oral progesterone once breakthrough bleeding occurs or after 18-24 months of unopposed estrogen therapy, whichever occurs first. In our TS population, several individuals have experienced abnormal uterine bleeding (AUB) while undergoing pubertal induction with transdermal estradiol. The objective of this study was to identify risk factors associated with and evaluate the management practices of AUB during pubertal induction among females with TS. <h3>Methods</h3> A retrospective case series of 45 TS females seen between January 2007 and June 2019 . Among these, 64% (n=29) served as controls and 55% (n=16) experienced AUB. <h3>Results</h3> Several risk factors for the development of AUB were identified: frequency of progestin cycling less than monthly (56.5% for cases vs. 0% for control), prolonged duration of unopposed estrogen (median of 21 months for cases vs. 17 months for controls), low dose (<200 mg) of progestin (50% of cases vs. 13.5% of control), and noncompliance with HRT (18.8%). Of the patients who experienced AUB, 3 received an additional 10 day course of progestins, 7 were treated by increasing their progestin dose, 6 were switched to another method of HRT (e.g. IUD or OCP), 6 increased cycling frequency to monthly, 4 required hospitalization, 2 required iron supplementation, and 2 required a transfusion with blood products. <h3>Conclusions</h3> Based on our experience, we recommend the following to prevent AUB during pubertal induction with transdermal estrogen in TS girls: 1) Cycle with progestins monthly, 2) Introduce progestins at the onset of breakthrough bleeding or at 18 months, whichever occurs first, 3) Use progestin dosing at the upper end of the recommended range (e.g. 200 mg for micronized progesterone) 4) Counsel all patients regarding the risk of AUB, 5) Monitor all patients regularly during pubertal induction, 6) Monitor with heightened surveillance those patients who show rapid development of secondary sex characteristics on low dose estrogen.