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Previous guidelines have discussed hormone replacement therapy (HRT) in children with TS. However, some practical issues related to puberty induction in TS require clarification, such as how to implement HRT to achieve adequate bone health. It is generally assumed that earlier initiation of HRT will result in better bone health in young adults with TS and estrogen deficiency. The present study reviews pubertal development, bone health, and current pubertal induction therapies in TS, with a particular focus on patients without endogenous estrogen production. Current guidelines recommend using transdermal estradiol patches starting at the age of 11\u201312\u2009years if necessary to mimic the gradual increase in circulating, physiological estradiol. Theoretically, earlier therapy combined with forecasting estrogen deficiency on the basis of increased FSH may allow a closer approximation to endogenous estradiol secretion in patients with TS without spontaneous puberty. This approach may lead to better long\u2010term outcomes, such as the acquisition of normal bone mineral density. Further research is needed to assess how the achievement of normal bone density and bone quality relates to the timing of HRT in children and young adults with TS. The resulting improvements in transdermal estradiol therapy may help patients with TS achieve optimal bone health.<\/jats:p>","DOI":"10.1002\/ajmg.c.32155","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:37:47Z","timestamp":1761107867000},"page":"107-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bone Health and Pubertal Induction in Turner Syndrome: The Possibility of Earlier Transdermal Lower\u2010Dose Estradiol Therapy for Healthy Bone Density and Quality"],"prefix":"10.1002","volume":"199","author":[{"given":"Yukihiro","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism Tokyo Metropolitan Children's Medical Center  Tokyo Japan"},{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo 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