Araştırma Makalesi
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Effects of cyproterone acetate treatment interruption on testicular histology: an experimental rat study relevant to transgender females with incomplete sperm cryopreservation

Yıl 2025, Cilt: 50 Sayı: 4, 955 - 963, 22.12.2025
https://doi.org/10.17826/cumj.1662549

Öz

Purpose: The aim of this study was to investigate the reversibility of the deterioration of testicles as Cyproterone acetate (CPA) treatment ceased in an experimental rat model, and possible contribution of two angiotensin converting enzyme inhibitors on the process.
Materials and Methods: In the first step, the effects of CPA treatment (14 days) on testicular histology on rats were investigated. In the second step, following the treatment period of 14 days with CPA, the effects of captopril or lisinopril application (for three days or seven days or 14 days) were investigated. Sixty-six rats in eleven groups were investigated. The testicles of the rats were planned to be examined on the following day of the last treatment schedule. Right testicular weight values were recorded. Testicles were histologically evaluated based on light microscopical findings, and also a scoring system was used.
Results: CPA treatment caused weight loss of the testicles, and caused histological scoring value changes. The second step findings revealed that the weight values of the testicles returned to control values in the third day and thereafter. Also, histological scoring values were indifferent compared to control, statistically. Histopathological findings, noted, besides scoring, showed that edema, present in all rats in the seventh day in physiological serum treatment group, was not the case for captopril groups. Also, in captopril groups, no rat with germ cell depletion was observed.
Conclusion: We conclude that the changes in testicular histology were over in the third day in our rat population, and inflammatory reactions or a delay in recovery may be prevented by use of angiotensin converting enzyme inhibitors, especially a thiol-group containing agent, captopril.

Kaynakça

  • Nahata L, Chelvakumar G, Leibowitz S. Gender-affirming pharmacological interventions for youth with gender dysphoria: When treatment guidelines are not enough. Ann Pharmacother. 2017;51:1023–32.
  • Kuijpers SME, Wiepjes CM, Conemans EB, Fisher AD, Guy T, Martin den Heijer. Toward a lowest effective dose of cyproterone acetate in trans women: Results from the ENIGI Study. J Clin Endocrinol Metab. 2021;106:e3936–45.
  • Warzywoda S, Fowler JA, Wood P, Bisshop F, Russell D, Luu H et al. How low can you go? Titrating the lowest effective dose of cyproterone acetate for transgender and gender diverse people who request feminizing hormones. Int J Transgend Health. 2024;2317395.
  • Angus L, Leemaqz S, Ooi O, Cundill P, Silberstein N, Locke P et al. Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy. Endocr Connect. 2019;8:935–40.
  • Muir CA, Guttman-Jones M, Man EJ. Effects of gender affirming hormone treatment in transgender individuals – a retrospective cohort study. Endocrine. 2024;85:370-9.
  • Rosenthal SM. Approach to the patient: Transgender youth: Endocrine considerations. J Clin Endocrinol Metab. 2014;99:4379–89.
  • Telfer MM, Tollit MA, Pace CC, Pang KC. Australian standards of care and treatment guidelines for transgender and gender diverse children and adolescents. Med J Aust. 2018;209:132–6.
  • Jindarak S, Nilprapha K, Atikankul T, Angspatt A, Pungrasmi P, Iamphongsai S et al. Spermatogenesis abnormalities following hormonal therapy in transwomen. Biomed Res Int. 2018;7919481.
  • Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:3869–903.
  • O’Connell MA, Nguyen TP, Ahler A, Skinner SR, Pang KC. Approach to the patient: Pharmacological management of trans and gender-diverse adolescents. J Clin Endocrinol Metab. 2021;107:241–57.
  • Mehringer JE, Dowshen NL. Sexual and reproductive health considerations among transgender and gender-expansive youth. Curr Probl Pediatr Adolesc Health Care. 2019;49:100684.
  • Kyriakou A, Nicolaides NC, Skordis N. Current approach to the clinical care of adolescents with gender dysphoria. Acta Biomed. 2020;91:165–75.
  • Karalexi MA, Georgakis MK, Dimitriou NG, Vichos T, Katsimpris A, Petridou ET et al. Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis. Psychoneuroendocrinology. 2020;119:104721.
  • Santi D, G. Spaggiari, Marinelli L, M. Cacciani, Scipio S, A. Bichiri et al. Gender-affirming hormone treatment: Friend or foe? Long-term follow-up of 755 transgender people. J Endocrinol Invest. 2023;47:1091–100.
  • Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals with cross-sex hormones: Extensive personal experience. J Clin Endocrinol Metab. 2008;93:19–25.
  • Gur M, Dil E, Akdeniz E, Cobanoğlu U, Kalyoncu NI, Topbas M et al. The toxic effects on the testis of flutamide vs. bicalutamide vs. cyproterone acetate: An experimental rat study. New Trends in Medicine Sciences. 2024;5:84–90.
  • Gianzo M, Muñoa-Hoyos I, Urizar-Arenaza I, Larreategui Z, Quintana F, Garrido N et al. Angiotensin II type 2 receptor is expressed in human sperm cells and is involved in sperm motility. Fertil Steril. 2016;105:608–16.
  • Fouad AA, Jresat I. Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats. Fundam Clinic Pharmacol. 2011;27:152–60.
  • Ilieva I, Ohgami K, Jin XH, Suzuki Y, Shiratori K, Yoshida K et al. Captopril suppresses inflammation in endotoxin-induced uveitis in rats. Exp Eye Res. 2006;83:651–7.
  • Nandhini Elango, Jeyasooriya Ramdoss, Jayanthi Udayakumar, Bavaskar SH, Ranganathan P, Rajesh BS et al. Diagnostic efficacy of elevated serum angiotensin-converting enzyme and lymphopenia between presumed sarcoid uveitis and presumed tubercular uveitis. Int Ophthalmol. 2023;43:3651–7.
  • Yusof M, Kamada K, Gaskin FS, Korthuis RJ. Angiotensin II mediates postischemic leukocyte-endothelial interactions: role of calcitonin gene-related peptide. Am J Physiol Heart Circ Physiol. 2007;292:H3032–7.
  • Lazar HL, Bao Y, Rivers S, Bernard SA. Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury. Ann Thorac Surg. 2002;73:1522–7.
  • Wang LF, Sun YY, Pan Q, Yin YQ, Tian XM, Liu Y et al. Diminazen aceturate protects pulmonary ischemia-reperfusion injury via inhibition of ADAM17-mediated angiotensin-converting enzyme 2 shedding. Front Pharmacol. 2021;713632.
  • Al-Maghrebi M, Renno WM. The tACE/Angiotensin (1–7)/Mas axis protects against testicular ischemia reperfusion injury. Urology. 2016;94:312.e1–8.
  • Leung PS, Sernia C. The renin-angiotensin system and male reproduction: new functions for old hormones. J Mol Endocrinol. 2003;30:263–70.
  • Arena S, Iacona R, Antonuccio P, Russo T, Salvo V, Gitto E et al. Medical perspective in testicular ischemia-reperfusion injury. Exp Ther Med. 2017;13:2115–22.
  • Creasy DM. Evaluation of testicular toxicology: A synopsis and discussion of the recommendations proposed by the Society of Toxicologic Pathology. Birth Defects Res B Dev Reprod Toxicol. 2003;68:408–15.
  • Turban JL, Loo SS, Almazan AN, Keuroghlian AS. FactorslLeading to “detransition” among transgender and gender diverse people in the United States: A mixed-methods analysis. LGBT Health. 2021;8:273-80.

Siproteron asetat tedavisinin kesilmesinin testiküler histoloji üzerindeki etkileri: sperm kriyoprezervasyonu tamamlanmamış transseksüel kadınlarla ilişkili deneysel bir sıçan çalışması

Yıl 2025, Cilt: 50 Sayı: 4, 955 - 963, 22.12.2025
https://doi.org/10.17826/cumj.1662549

Öz

Amaç: Bu çalışmada, deneysel bir sıçan modelinde Siproteron asetat (SA) tedavisinin kesilmesiyle testislerdeki bozulmanın tersine dönebilirliğinin ve iki anjiyotensin dönüştürücü enzim inhibitörünün bu sürece olası katkılarının araştırılması amaçlanmıştır..
Gereç ve Yöntem: İlk aşamada, sıçanlarda SA tedavisinin (14 gün) testis histolojisi üzerindeki etkileri araştırılmıştır. İkinci aşamada, SA ile 14 günlük tedavi süresini takiben, kaptopril veya lisinopril uygulamasının (üç gün veya yedi gün veya 14 gün boyunca) etkileri araştırıldı. On bir grupta altmış altı sıçan incelenmiştir. Sıçanların testisleri son tedavi uygulamasının ertesi günü incelendi. Sağ testis ağırlık değerleri kaydedildi. Testisler ışık mikroskopik bulgulara dayanarak histolojik olarak değerlendirildi ve ayrıca bir skorlama sistemi kullanıldı.
Bulgular: SA tedavisi testislerde ağırlık kaybına ve histolojik skorlama değerlerinde değişikliklere neden olmuştur. İkinci aşama bulguları, testislerin ağırlık değerlerinin üçüncü gün ve sonrasında kontrol değerlerine döndüğünü ortaya koymuştur. Aynı zamanda, histolojik skorlama değerleri istatistiksel olarak kontrole kıyasla farksızdı. Skorlamanın yanı sıra kaydedilen histopatolojik bulgular, fizyolojik serum tedavi grubunda yedinci günde tüm sıçanlarda mevcut olan ödemin kaptopril grupları için söz konusu olmadığını gösterdi. Ayrıca, kaptopril gruplarında germ hücresi azalması hiçbir sıçanda gözlenmemiştir.
Sonuç: Testis histolojisindeki değişikliklerin sıçan popülasyonumuzda üçüncü günde sona erdiği ve enflamatuar reaksiyonların veya iyileşmede gecikmenin anjiyotensin dönüştürücü enzim inhibitörlerinin, özellikle de tiyol grubu içeren bir ajan olan kaptoprilin kullanılmasıyla önlenebileceği sonucuna vardık.

Kaynakça

  • Nahata L, Chelvakumar G, Leibowitz S. Gender-affirming pharmacological interventions for youth with gender dysphoria: When treatment guidelines are not enough. Ann Pharmacother. 2017;51:1023–32.
  • Kuijpers SME, Wiepjes CM, Conemans EB, Fisher AD, Guy T, Martin den Heijer. Toward a lowest effective dose of cyproterone acetate in trans women: Results from the ENIGI Study. J Clin Endocrinol Metab. 2021;106:e3936–45.
  • Warzywoda S, Fowler JA, Wood P, Bisshop F, Russell D, Luu H et al. How low can you go? Titrating the lowest effective dose of cyproterone acetate for transgender and gender diverse people who request feminizing hormones. Int J Transgend Health. 2024;2317395.
  • Angus L, Leemaqz S, Ooi O, Cundill P, Silberstein N, Locke P et al. Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy. Endocr Connect. 2019;8:935–40.
  • Muir CA, Guttman-Jones M, Man EJ. Effects of gender affirming hormone treatment in transgender individuals – a retrospective cohort study. Endocrine. 2024;85:370-9.
  • Rosenthal SM. Approach to the patient: Transgender youth: Endocrine considerations. J Clin Endocrinol Metab. 2014;99:4379–89.
  • Telfer MM, Tollit MA, Pace CC, Pang KC. Australian standards of care and treatment guidelines for transgender and gender diverse children and adolescents. Med J Aust. 2018;209:132–6.
  • Jindarak S, Nilprapha K, Atikankul T, Angspatt A, Pungrasmi P, Iamphongsai S et al. Spermatogenesis abnormalities following hormonal therapy in transwomen. Biomed Res Int. 2018;7919481.
  • Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:3869–903.
  • O’Connell MA, Nguyen TP, Ahler A, Skinner SR, Pang KC. Approach to the patient: Pharmacological management of trans and gender-diverse adolescents. J Clin Endocrinol Metab. 2021;107:241–57.
  • Mehringer JE, Dowshen NL. Sexual and reproductive health considerations among transgender and gender-expansive youth. Curr Probl Pediatr Adolesc Health Care. 2019;49:100684.
  • Kyriakou A, Nicolaides NC, Skordis N. Current approach to the clinical care of adolescents with gender dysphoria. Acta Biomed. 2020;91:165–75.
  • Karalexi MA, Georgakis MK, Dimitriou NG, Vichos T, Katsimpris A, Petridou ET et al. Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis. Psychoneuroendocrinology. 2020;119:104721.
  • Santi D, G. Spaggiari, Marinelli L, M. Cacciani, Scipio S, A. Bichiri et al. Gender-affirming hormone treatment: Friend or foe? Long-term follow-up of 755 transgender people. J Endocrinol Invest. 2023;47:1091–100.
  • Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals with cross-sex hormones: Extensive personal experience. J Clin Endocrinol Metab. 2008;93:19–25.
  • Gur M, Dil E, Akdeniz E, Cobanoğlu U, Kalyoncu NI, Topbas M et al. The toxic effects on the testis of flutamide vs. bicalutamide vs. cyproterone acetate: An experimental rat study. New Trends in Medicine Sciences. 2024;5:84–90.
  • Gianzo M, Muñoa-Hoyos I, Urizar-Arenaza I, Larreategui Z, Quintana F, Garrido N et al. Angiotensin II type 2 receptor is expressed in human sperm cells and is involved in sperm motility. Fertil Steril. 2016;105:608–16.
  • Fouad AA, Jresat I. Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats. Fundam Clinic Pharmacol. 2011;27:152–60.
  • Ilieva I, Ohgami K, Jin XH, Suzuki Y, Shiratori K, Yoshida K et al. Captopril suppresses inflammation in endotoxin-induced uveitis in rats. Exp Eye Res. 2006;83:651–7.
  • Nandhini Elango, Jeyasooriya Ramdoss, Jayanthi Udayakumar, Bavaskar SH, Ranganathan P, Rajesh BS et al. Diagnostic efficacy of elevated serum angiotensin-converting enzyme and lymphopenia between presumed sarcoid uveitis and presumed tubercular uveitis. Int Ophthalmol. 2023;43:3651–7.
  • Yusof M, Kamada K, Gaskin FS, Korthuis RJ. Angiotensin II mediates postischemic leukocyte-endothelial interactions: role of calcitonin gene-related peptide. Am J Physiol Heart Circ Physiol. 2007;292:H3032–7.
  • Lazar HL, Bao Y, Rivers S, Bernard SA. Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury. Ann Thorac Surg. 2002;73:1522–7.
  • Wang LF, Sun YY, Pan Q, Yin YQ, Tian XM, Liu Y et al. Diminazen aceturate protects pulmonary ischemia-reperfusion injury via inhibition of ADAM17-mediated angiotensin-converting enzyme 2 shedding. Front Pharmacol. 2021;713632.
  • Al-Maghrebi M, Renno WM. The tACE/Angiotensin (1–7)/Mas axis protects against testicular ischemia reperfusion injury. Urology. 2016;94:312.e1–8.
  • Leung PS, Sernia C. The renin-angiotensin system and male reproduction: new functions for old hormones. J Mol Endocrinol. 2003;30:263–70.
  • Arena S, Iacona R, Antonuccio P, Russo T, Salvo V, Gitto E et al. Medical perspective in testicular ischemia-reperfusion injury. Exp Ther Med. 2017;13:2115–22.
  • Creasy DM. Evaluation of testicular toxicology: A synopsis and discussion of the recommendations proposed by the Society of Toxicologic Pathology. Birth Defects Res B Dev Reprod Toxicol. 2003;68:408–15.
  • Turban JL, Loo SS, Almazan AN, Keuroghlian AS. FactorslLeading to “detransition” among transgender and gender diverse people in the United States: A mixed-methods analysis. LGBT Health. 2021;8:273-80.
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Üroloji, Üreme
Bölüm Araştırma Makalesi
Yazarlar

Fatih Çolak 0000-0001-7083-6135

Rasin Özyavuz 0000-0002-7362-6560

Nuri İhsan Kalyoncu 0000-0002-4484-8623

Ümit Çobanoğlu 0000-0001-6429-427X

Murat Topbaş 0000-0003-4047-4027

Ömer Kutlu 0000-0003-3730-6452

Cemil Bayraktar 0000-0003-4339-1147

İlke Onur Kazaz 0000-0002-2106-0016

Gönderilme Tarihi 21 Mart 2025
Kabul Tarihi 6 Ekim 2025
Yayımlanma Tarihi 22 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 50 Sayı: 4

Kaynak Göster

MLA Çolak, Fatih vd. “Effects of cyproterone acetate treatment interruption on testicular histology: an experimental rat study relevant to transgender females with incomplete sperm cryopreservation”. Cukurova Medical Journal, c. 50, sy. 4, 2025, ss. 955-63, doi:10.17826/cumj.1662549.