Effect of Transdermal Estrogen Therapy on Bone and Neurobehavioral Health in Youth with Premature Ovarian Insufficiency: A Case-Control Study.

Abstract

Study objective: Estrogen replacement therapy (ERT) improves bone and neurocognitive health in adult women with premature ovarian insufficiency (POI). However, the response in adolescents is largely unknown. We aimed to assess the impact of transdermal estrogen replacement therapy (TDE2) in adolescents with POI on these outcomes.

Methods: Nine adolescents with idiopathic POI, naïve to ERT, and 9 controls with regular menses matched for age, race and BMI were recruited between 2018-2023 for a 24-month study. Primary bone health outcomes were changes in lumbar spine BMD Z-score and 3% distal radius trabecular volumetric BMD. Primary neurocognitive outcomes were quality of life (CHQ-87 survey) and memory (ChAMP).

Results: Adolescents with POI experienced significant increases in BMD Z-scores at all DXA skeletal sites (lumbar spine ∆ +0.68, total hip ∆ +0.37, femoral neck ∆ +0.56, total body less head ∆ +0.82, all p<0.05). Control participants exhibited an increase in BMD Z-score at the total body less head (∆ 0.43, p=0.034) with no significant change at other skeletal sites. There were no significant changes from baseline to 24 months in pQCT measures. Total memory index significantly increased in both groups from baseline to 24 months (controls ∆ +17.2, cases ∆ +24.6, p=0.041 and 0.001 respectively), but there was no difference between groups. There were no other significant differences in neurocognitive outcomes among or between groups.

Conclusions: Central BMD increased in adolescents with idiopathic POI in response to TDE2, but peripheral BMD measures were unchanged. The impact on neurocognitive outcomes in these adolescents remains uncertain.