Sex Hormone Replacement Therapy and Bleeding Patterns among Adolescents and Young Adult Females with Prader-Willi Syndrome.

Introduction: Prader-Willi Syndrome (PWS) is associated with hypogonadism. Limited data exist on guidelines for sex hormone replacement therapy (HRT) in females with PWS. We aimed to characterize pubertal timing, vaginal bleeding patterns, and HRT practices in adolescent and young adult females with PWS.

Methods: We conducted a retrospective review of females ages 5 to 25 years, diagnosed with PWS, at a single institution (01/2013-09/2023). Demographic and clinical data were abstracted from electronic medical records and analyzed with descriptive statistics. Patients were classified as having complete hypogonadotropic hypogonadism (HH) (luteinizing hormone [LH] <0.3 mIU/mL or lack of thelarche by 13 years) or partial hypogonadism (PH) (LH >0.3 mIU/mL and estradiol <20 pg/mL or amenorrhea by 15 years).

Results: Fifty-one patients met inclusion criteria; 21 (41%) were diagnosed with hypogonadism and were included in the final analysis. Of these, 8 (38.1%) had HH and 13 (61.9%) PH. Delayed puberty was diagnosed at a median of 13.5 years (range: 10-15) in the HH cohort and at 14.5 years (range: 13-18) in the PH cohort. Six patients (28.6%) reported spontaneous vaginal bleeding, median age of 14.0 (range: 10-16) years. Eighteen patients (85.7%) were prescribed HRT at a median of 14.0 (range: 12-21) years, of which 8 (44.4%) discontinued HRT, with half reporting breakthrough bleeding.

Discussion: Hypogonadism is common among adolescent and young adult females with PWS. We found high rates of HRT discontinuation primarily due to breakthrough bleeding. These findings highlight the need to tailor HRT regimens and identify strategies to encourage HRT adherence to optimize long-term outcomes.