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The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>Endogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13108","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T18:40:14Z","timestamp":1631472014000},"page":"209-222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age"],"prefix":"10.1111","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6740-8348","authenticated-orcid":false,"given":"Alexander W.","family":"Pastuszak","sequence":"first","affiliation":[{"name":"University of Utah School of Medicine  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Gittelman","sequence":"additional","affiliation":[{"name":"21st Century Oncology Uro\u2010Medix\/GenesisCare  Aventura Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Tursi","sequence":"additional","affiliation":[{"name":"Antares Pharma, Inc.  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