{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:59:16Z","timestamp":1792007956060,"version":"4.4.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>How does gender-affirming hormone therapy (GAHT) regimen impact testicular spermatogenesis in transgender and gender diverse (TGD) individuals?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Cyproterone acetate (CPA) and progesterone significantly impair spermatogenesis, whereas spironolactone does not, compared to no use of anti-androgen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>GAHT is known to suppress spermatogenesis in TGD individuals assigned male at birth, but the extent of impairment varies across hormone regimens. Prior studies suggest that anti-androgens and progestogens may exert distinct effects on testicular function, but direct comparisons between regimens are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This was a retrospective single-center cohort study including 287 TGD patients who underwent gender-affirming orchiectomy between November 2017 and January 2024. A total of 573 testis specimens were histologically reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>All included patients had received GAHT prior to surgery, with exposure categorized based on the type and duration of hormone therapy. The primary exposure variables were estrogen use (N\u2009=\u2009287, 100%), anti-androgen type (CPA: N\u2009=\u2009127, 44.3%; spironolactone: N\u2009=\u2009110, 38.3%), and progesterone use (N\u2009=\u200973, 25.4%). Testicular histology was evaluated to determine spermatogenesis stage, and multivariable regression was performed to identify independent predictors of impaired sperm maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>In total, 287 patients were included in the study period, and 573 testis specimens were reviewed. Mean age at surgery was 33.9\u2009years (SD\u2009=\u200911.7, range\u2009=\u200918.4\u201380.6), and duration of GAHT was 3.8\u2009years (SD\u2009=\u20093.0, range\u2009=\u20091\u201328). Older age was associated with impairment in spermatogenesis, with a mean age of 41.4 (SD\u2009=\u200912.8, range\u2009=\u200923.0\u201366.5) for end-stage testis failure and a mean age of 33.4 (SD\u2009=\u200911.2, range\u2009=\u200920.2\u201380.6) for complete maturation (P\u2009=\u20090.002). Hormone therapy duration did not show a significant difference between groups (P\u2009=\u20090.22). GAHT included estrogen (n\u2009=\u2009287, 100%), progesterone (n\u2009=\u200973, 25.4%), and an anti-androgen (n\u2009=\u2009259, 90.2%). CPA (n\u2009=\u2009127, 44.3%) and spironolactone (N\u2009=\u2009110, 38.3%) were the most common anti-androgens used. Spermatogenesis was most significantly impaired with the use of CPA, with only 8.7% of patients having active spermatogenesis versus 53.3% of patients taking spironolactone (P\u2009&amp;lt;\u20090.001). Progesterone use had an independent negative effect on spermatogenesis (P\u2009=\u20090.005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>The retrospective design and absence of a control group of untreated individuals limit direct causal inferences. Variability in GAHT duration, adherence, and regimen composition may introduce confounding effects due to self-reporting. Additionally, histological assessment alone does not confirm functional fertility potential, and future studies should explore this aspect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>These findings provide clinically relevant insights for fertility counseling in TGD individuals, emphasizing that CPA and progesterone significantly impair spermatogenesis, whereas spironolactone may allow for greater preservation of sperm maturation. This has implications for fertility preservation discussions prior to GAHT initiation and may inform individualized hormone regimen selection based on reproductive goals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This research received no specific grant or funding. The authors have no competing interests to declare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>n\/a<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deaf216","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T19:52:59Z","timestamp":1762717979000},"page":"78-85","source":"Crossref","is-referenced-by-count":3,"title":["Impact of gender-affirming hormone therapy on spermatogenesis: analysis of testicular histological specimens"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-1899","authenticated-orcid":false,"given":"Yulia","family":"Wilk Goldsher","sequence":"first","affiliation":[{"name":"Transition Related Surgery Program, Women\u2019s College Hospital , Toronto, ON,","place":["Canada"]},{"name":"Division of Urology, Department of Surgery, University of Toronto , Toronto, ON,","place":["Canada"]},{"name":"Faculty of Medical and Health Sciences, Tel Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Al-Hadi","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine, University of Toronto , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Mullen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital , Toronto, ON,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emery","family":"Potter","sequence":"additional","affiliation":[{"name":"Transition Related Surgery Program, Women\u2019s College Hospital , Toronto, ON,","place":["Canada"]},{"name":"Lawrence S. 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