{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:40:45Z","timestamp":1792471245290,"version":"4.5.0"},"reference-count":76,"publisher":"The Endocrine Society","issue":"10","funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD090071"],"award-info":[{"award-number":["R01 HD090071"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Variation in pubertal timing is associated with a wide range of adult risks and outcomes, but it is unclear whether these associations are causal, and it is largely unknown whether these associations can be modified by treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evidence Acquisition<\/jats:title><jats:p>We conducted PubMed searches to identify Mendelian randomization (MR) studies on the influence of pubertal timing on adult health and studies on sex-steroid treatment of the following conditions associated with reduced reproductive endocrine function in adolescence: constitutional delay, Turner syndrome, and Klinefelter syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evidence Synthesis<\/jats:title><jats:p>Results of MR studies suggest that earlier pubertal timing increases body mass index; increases risk for breast, ovarian, endometrial, and prostate cancers; elevates fasting glucose levels and blood pressure; impairs lung capacity and increases risk for asthma; leads to earlier sexual intercourse and first birth; decreases time spent in education; and increases depressive symptoms in adolescence. Later pubertal timing appears to lower bone mineral density (BMD). Although studies of constitutional delay have not shown that sex-steroid treatment alters adult height or BMD, studies of girls with Turner syndrome and boys with Klinefelter syndrome suggest that earlier initiation of sex-steroid treatment improves physical and neurocognitive outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite having some limitations, MR studies suggest that pubertal timing causally influences many adult conditions and disease risks. Studies of Turner syndrome and Klinefelter syndrome suggest that earlier sex-steroid exposure may have short- and long-term benefits. The mechanisms underlying these findings and the effects of trends and treatments affecting pubertal timing remain to be determined.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2019-00569","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T13:16:29Z","timestamp":1560431789000},"page":"4578-4586","source":"Crossref","is-referenced-by-count":30,"title":["Effects of the Timing of Sex-Steroid Exposure in Adolescence on Adult Health Outcomes"],"prefix":"10.1210","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-8502","authenticated-orcid":false,"given":"Yee-Ming","family":"Chan","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, Boston Children\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Feld","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, Boston Children\u2019s 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