{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:28:36Z","timestamp":1780414116992,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T00:00:00Z","timestamp":1507161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1UO1AG14369"],"award-info":[{"award-number":["1UO1AG14369"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>There is substantial inter\u2010individual variability in serum testosterone levels in hypogonadal men treated with testosterone gels. We aimed to elucidate participant\u2010level factors that contribute to inter\u2010individual variability in testosterone levels during testosterone therapy. An exploratory aim was to determine whether polymorphisms in genes encoding testosterone\u2010metabolizing enzymes could explain the variation in on\u2010treatment testosterone concentrations in men who were randomized to testosterone arm in <jats:styled-content style=\"fixed-case\">TOM<\/jats:styled-content> Trial. We used data from three randomized trials that used 1% transdermal testosterone gels and had testosterone levels measured 2\u20134\u00a0weeks after randomization for dose adjustment: Testosterone in Older Men with Mobility Limitation (<jats:styled-content style=\"fixed-case\">TOM<\/jats:styled-content>), Effects of Testosterone on Pain Perception (<jats:styled-content style=\"fixed-case\">TAP<\/jats:styled-content>), and Effects of Testosterone on Atherosclerosis Progression (<jats:styled-content style=\"fixed-case\">TEAAM<\/jats:styled-content>). Forty\u2010seven percent, 38%, and 9% of participants in <jats:styled-content style=\"fixed-case\">TAP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TEAAM<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">TOM<\/jats:styled-content> trials, respectively, failed to raise testosterone levels &gt;400\u00a0ng\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>; 6, 8, and 30% of participants had on\u2010treatment testosterone levels &gt;1000\u00a0ng\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>. Even after dose adjustment, there was substantial variation in on\u2010treatment levels at subsequent study visits. Baseline characteristics (age, height, weight, baseline testosterone, <jats:styled-content style=\"fixed-case\">SHBG<\/jats:styled-content>, hematocrit, and creatinine) accounted for only a small fraction of the variance (&lt;8%). Polymorphisms in <jats:styled-content style=\"fixed-case\">SHBG<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AKR<\/jats:styled-content>1C3 genes were suggestively associated with on\u2010treatment testosterone levels. To conclude, baseline participant characteristics account for only a small fraction of the variance in on\u2010treatment testosterone levels investigated. Multiple dose titrations are needed to maintain on\u2010treatment testosterone levels in the target range. The role of <jats:styled-content style=\"fixed-case\">SHBG<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AKR<\/jats:styled-content>3C1 polymorphisms as contributors to variations in on\u2010treatment testosterone levels should be investigated.<\/jats:p>","DOI":"10.1111\/andr.12428","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T16:26:38Z","timestamp":1507220798000},"page":"151-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Contributors to the substantial variation in on\u2010treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials"],"prefix":"10.1111","volume":"6","author":[{"given":"S.","family":"Bhasin","sequence":"first","affiliation":[{"name":"Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. G.","family":"Travison","sequence":"additional","affiliation":[{"name":"Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"MacKrell","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Pencina","sequence":"additional","affiliation":[{"name":"Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1749-8549","authenticated-orcid":false,"given":"S.","family":"Basaria","sequence":"additional","affiliation":[{"name":"Research Program in Men's Health: Aging and Metabolism Boston Claude D. 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