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

Halley Wasserman, Heidi J. Kalkwarf, Mekibib Altaye, Kimberly Yolton, Catherine M. Gordon
In: Journal of Pediatric and Adolescent Gynecology · 2025 · vol. 38(4) , pp. 485–491 · doi:10.1016/j.jpag.2025.03.005 · PMID:40097088 · W4408478014
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This case-control study investigated the effects of transdermal estrogen therapy on bone mineral density and neurobehavioral outcomes in young patients diagnosed with premature ovarian insufficiency.

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Abstract

Study objectiveEstrogen 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 on these outcomes in adolescents with POI.MethodsNine adolescents with idiopathic POI, naïve to ERT, and 9 controls with regular menses matched for age, race, and body mass index were recruited between 2018 and 2023 for a 24-month study. The primary bone health outcomes were changes in lumbar spine bone mineral density (BMD) Z-score and 3% distal radius trabecular volumetric BMD. The primary neurocognitive outcomes were quality of life (CHQ-87 survey) and memory (ChAMP).ResultsAdolescents with POI experienced significant increases in BMD Z-scores at all dual-energy x-ray absorptiometry skeletal sites (lumbar spine ∆ +0.68, total hip ∆ +0.37, femoral neck ∆ +0.56, total body less head ∆ +0.82, all P < .05). Control participants exhibited an increase in BMD Z-score at the total body less head (∆ 0.43, P = .034) with no significant change at other skeletal sites. There were no significant changes from baseline to 24 months in peripheral quantitative computed tomography measures. Total memory index significantly increased in both groups from baseline to 24 months (controls ∆ +17.2, cases ∆ +24.6, P = .041 and .001, respectively), but there was no difference between groups. There were no other significant differences in neurocognitive outcomes among or between groups.ConclusionCentral BMD increased in adolescents with idiopathic POI in response to transdermal estrogen replacement therapy, but peripheral BMD measures were unchanged. The impact on neurocognitive outcomes in these adolescents remains uncertain.

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