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Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic\u2013pituitary\u2010testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90\u2013106\u2009years. We found that 94% of men exhibited preserved hypothalamic\u2013pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging\u2010related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic\u2013pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.<\/jats:p>","DOI":"10.1111\/acel.13656","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T06:44:38Z","timestamp":1656571478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Integrity of <scp>hypothalamic\u2013pituitary\u2010testicular<\/scp> axis in exceptional longevity"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-1392","authenticated-orcid":false,"given":"Sandra","family":"Aleksic","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimpi","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health (Biostatistics) Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Department of Systems &amp; Computational Biology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Duran","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Crandall","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Atzmon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Department of Genetics Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Department of Natural Science University of Haifa  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Barzilai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Department of Genetics Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiya","family":"Milman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Institute for Aging Research Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Department of Genetics Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2004.52068.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22324"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018\u201000229"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008\u20101902"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem\u201056\u20106\u20101278"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13014"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800612R"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab216"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u20101649"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2000.tb03278.x"},{"key":"e_1_2_6_12_1","volume-title":"Endotext [Internet]","author":"Handelsman D. 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