{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:06:51Z","timestamp":1779512811548,"version":"3.53.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007343","name":"Universit\u00e0 degli Studi di Brescia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007343","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Testosterone replacement therapy (TRT) with transdermal gel is widely used in men with hypogonadism. Guidelines recommend once-daily application with monitoring of serum testosterone at peak levels. However, real-world clinical experience suggests that peak\u2013trough fluctuations in some patients, potentially affecting hormonal stability and treatment tolerability. The impact of dose fractionation remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare hormonal profiles and biochemical safety parameters between once-daily and twice-daily (fractionated) testosterone gel administration in hypogonadal men receivingh the same total daily dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively identified hypogonadal men treated with 2% testosterone gel who transitioned from once-daily to twice-daily dosing, maintaining the same total daily dose. Eligible patients had serum total testosterone (TT) measurements available at both peak (3\u00a0h post-application) and nadir (pre-dose). Hormonal and laboratory parameters under the two regimens were compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve patients met inclusion criteria. Fractionated dosing was associated with lower peak TT levels [9.0 (5.3\u201313.0) vs. 5.7 (3.6\u20137.1) ng\/mL, paired difference\u2009\u2212\u20093.6 ng\/mL (95% CI: \u22124.9 to \u2212\u20091.8)] and higher nadir TT levels [1.4 (1.1\u20131.8) vs. 3.2 (2.6\u20135.4) ng\/mL, paired difference 2.6 ng\/mL (95% CI: 1.2 to 5.1)], resulting in a reduced difference between peak-to-pre-dose difference within the observed sampling window. The proportion of patients achieving target TT levels at peak increased (33% vs. 83%). Calculated free testosterone showed a similar pattern. No clinically relevant differences were observed in luteinizing hormone, prostate-specific antigen, haematocrit, or haemoglobin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this real-world cohort, fractionated testosterone gel administration was associated with a higher proportion of patients achieving biochemical targets and with a reduced peak-to-pre-dose difference within the observed sampling window, without short-term biochemical safety signals. These findings should be considered hypothesis-generating.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12020-026-04659-8","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T04:35:14Z","timestamp":1779510914000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fractionated testosterone gel replacement therapy in clinical practice: A real-world exploratory clinical experience"],"prefix":"10.1007","volume":"91","author":[{"given":"Virginia","family":"Maltese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Delbarba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Gatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Vetrugno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sansone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4317-1232","authenticated-orcid":false,"given":"Carlo","family":"Cappelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"issue":"5","key":"4659_CR1","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1210\/jc.2018-00229","volume":"103","author":"S Bhasin","year":"2018","unstructured":"S. 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