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Resumen de Estudio de la respuesta histopatológica testicular al tratamiento con estrógenos y antiandrógenos a largo plazo y su relación con la disgenesia testicular

Cristina Peña Barreno

  • Estrogens are involved in the regulation of multiple processes and alteration of the androgen to estrogen ratio might be implicated in several diseases, such as cancer, neuropsychiatric and immunological disorders, cardiovascular diseases and testicular dysgenesis syndrome. Some reports relate the increase in hormonal diseases to ubiquitous chemicals with estrogenic properties.

    Furthermore, estrogen and anti-androgen therapy is part of the transition process from male to female and more and more people are seeking it, despite potential side effects. Orchiectomy specimens from these patients have been previously analyzed. However, earlier research has been mainly focused on effects on testicular parenchyma and series used small sample sizes.

    A morphological and immunohistochemical analysis has been performed on 42 bilateral orchiectomy specimens from adult individuals who underwent gender reassignment surgery after receiving long-term hormone therapy with estrogen and antiandrogens. The current PhD thesis aims to increase the understanding of the effects of cross-sex hormonal treatment on testicular parenchyma and to analyze less well-known effects on epididymis, vascular structures and inflammatory cells, in order to raise awareness of possible pathological implications. A detailed morphological and immunohistochemical analysis has been conducted on the different types of cells and structures of testicular parenchyma as well as on extratesticular spermatic pathway at multiple levels with hematoxylin and eosin. Moreover, the expression of multiple immunohistochemical markers has been assessed on these structures and both morphological and functional alterations have been identified.

    The morphology and immunohistochemistry have confirmed previously reported findings, such as the identification of three histological patterns according to progressive tubular atrophy in relation to Sertoli cell dedifferentiation, leading to a severe decrease in spermatogenesis. In the interstitium, Leydig cells also show morphological alterations that suggest a process of dedifferentiation. The most common lesion in the extratesticular spermatic pathway has been atrophy. Vascular (atherosclerosis and vasculitis) and inflammatory lesions have been reported for the first time both in the testicular interstitium and the spermatic pathway with a significantly higher frequency than in non-treated subjects in the same age range. Lesions were more severe at higher doses and in patients starting hormone therapy at age 40 or later. Taken together and bearing in mind the existence of limitations such as self-medication in some patients, the present findings suggest that cross-sex hormone therapy should be provided in specialized units in order to systematize treatments and ensure adequate follow-up.


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