{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:50:20Z","timestamp":1789091420057,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Androgen abuse, which is increasingly prevalent, inevitably leads to suppression of the hypothalamic-pituitary-gonadal axis (HPGA). While most individuals recover HPGA function following androgen cessation, a subset experiences prolonged hypogonadism, with symptoms persisting for months or even years. Currently, this condition lacks a standardized definition, complicating both diagnosis and treatment. In this article, we explore the potential mechanisms underlying prolonged hypogonadism after androgen abuse, including the role of prolonged androgen activity, hypothalamic-pituitary alterations, testicular changes, suppression of sex hormone-binding globulin (SHBG), genetic predisposition, and undisclosed ongoing androgen abuse. We propose the term \u2018Prolonged Post-Androgen Abuse Hypogonadism\u2019(PPAAH) to standardize diagnosis and guide future research. PPAAH is provisionally defined as persistent hypogonadism six months after cessation of androgen abuse, in individuals with a cumulative androgen exposure of at least 150 mg per week for a minimum of six months. Diagnosing PPAAH requires excluding other causes of hypogonadism. This preliminary framework is intended to support further research into the pathophysiology and management of this condition, and may require refinement as further evidence emerges.<\/jats:p>","DOI":"10.3389\/fendo.2025.1621558","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:10:52Z","timestamp":1751515852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Prolonged post-androgen abuse hypogonadism: potential mechanisms and a proposed standardized diagnosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Jo\u00ebl","family":"van Os","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederik Laurens","family":"Smit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"de Ronde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ANNEPIDEM.2014.01.009","article-title":"The global epidemiology of anabolic-androgenic steroid use: a meta-analysis and meta-regression analysis","volume":"24","author":"Sagoe","year":"2014","journal-title":"Ann Epidemiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/HSR2.1032","article-title":"Androgenic-anabolic steroid abuse trend and management: A prospective, cross-sectional, questionnaire-based survey","volume":"6","author":"Al Hashimi","year":"2023","journal-title":"Health Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1210\/JC.2018-01882","article-title":"Diagnosis and management of anabolic androgenic steroid use","volume":"104","author":"Anawalt","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1056\/NEJM199607043350101\/ASSET\/C12E6A75-37D3-40BF-ADBF-D68237145055\/ASSETS\/IMAGES\/LARGE\/NEJM199607043350101_F1.JPG","article-title":"The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men","volume":"335","author":"Bhasin","year":"1996","journal-title":"New Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"R102","DOI":"10.1530\/EC-19-0557","article-title":"Anabolic androgenic steroid abuse in young males","volume":"9","author":"de Ronde","year":"2020","journal-title":"Endocr Connect"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1159\/000528256","article-title":"Anabolic androgenic steroid use patterns and steroid use disorders in a sample of male gym visitors","volume":"29","author":"Idger De Zeeuw","year":"2023","journal-title":"European Addiction Research"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/SMS.13592","article-title":"Baseline characteristics of the HAARLEM study: 100 male amateur athletes using anabolic androgenic steroids","volume":"30","author":"Smit","year":"2020","journal-title":"Scand J Med Sci Sports"},{"key":"B8","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1210\/JC.2007-2156","article-title":"Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men","volume":"93","author":"Pitteloud","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/JC.2006-0462","article-title":"In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion","volume":"91","author":"Raven","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/JCEM-73-3-621","article-title":"Sex steroid control of gonadotropin secretion in the human male. 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