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Luteinizing hormone acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter\u2010related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins containing luteinizing hormone activity, particularly human chorionic gonadotropin, can effectively restore spermatogenesis in azoospermic males with hypogonadotropic hypogonadism, the use of these drugs to treat other forms of non\u2010obstructive azoospermia is the subject of an ongoing debate. In this review, we delve into the molecular properties and functions of human chorionic gonadotropin in spermatogenesis regulation and explore available preparations for therapeutic use. We examine the evidence regarding the effectiveness of human chorionic gonadotropin in treating infertility in men with pre\u2010testicular or testicular non\u2010obstructive azoospermia and, additionally, identify the main areas for future research. Our review highlights the critical role of luteinizing hormone activity in spermatogenesis and emphasizes the potential of human chorionic gonadotropin in treating male infertility. The variation in the characteristics of patients with non\u2010obstructive azoospermia underscores the importance of assessing hormonal profiles when contemplating hormonal treatment for these patients. A novel stratification of male infertility patients, the APHRODITE criteria, which considers clinical and laboratory indicators, may assist in identifying individuals who could benefit from human chorionic gonadotropin therapy. While accumulating evidence suggests promising venues for pharmacological treatment in male infertility, including non\u2010obstructive azoospermia, further research is required to completely elucidate the mechanisms underlying the effects of exogenous gonadotropins with luteinizing hormone activity on sperm production and to establish the most effective dosages and treatment durations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70003","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T03:37:42Z","timestamp":1738640262000},"page":"1029-1063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Human chorionic gonadotropin\u2010based clinical treatments for infertile men with non\u2010obstructive azoospermia"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-9680","authenticated-orcid":false,"given":"Sandro C.","family":"Esteves","sequence":"first","affiliation":[{"name":"ANDROFERT Andrology and Human Reproduction Clinic  Campinas Brazil"},{"name":"Department of Surgery (Division of Urology) State University of Campinas (UNICAMP)  Campinas Brazil"},{"name":"Faculty of Health Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C.","family":"Viana","sequence":"additional","affiliation":[{"name":"ANDROFERT Andrology and Human Reproduction Clinic  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold P. P.","family":"Achermann","sequence":"additional","affiliation":[{"name":"Department of Surgery (Division of Urology) State University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology Department of Medical Specialties Azienda Ospedaliero \u2013 University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2022.102310"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2013(sup01)09"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00763"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255\u2010011\u20100065\u20100"},{"issue":"16","key":"e_1_2_10_6_1","first-page":"1055","article-title":"Exogenous stimulation of corpus luteum formation in the rabbit: influence of extracts of human placenta, decidua, fetus, hydatid mole, and corpus luteum on the rabbit gonad","author":"Hirose T","year":"1920","journal-title":"J Jpn Gynecol 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