Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS)

Schneider, Florian; Neuhaus, Nina; Wistuba, Joachim; Zitzmann, Michael; Heß, Jochen; Mahler, Dorothee; Ahlen, H. van; Schlatt, Stefan; Kliesch, Sabine

doi:10.1111/jsm.13022

Cited by 89 publications

(74 citation statements)

References 29 publications

(38 reference statements)

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“…Ultrastructural studies showed a loss of the apico-basal differentiation in Sertoli cells and dedifferentiation of Leydig cells after estrogen treatment3940. However, detailed histomorphological and histochemical analyses of the effects of long-term treatment with estradiol, specifically linked to a patients‘ treatment plans are still lacking, as stated in the literature41.…”

mentioning

confidence: 99%

Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Leavy

Trottmann²,

Liedl

et al. 2017

Sci Rep

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Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26–52 years. Each patient had a minimum of 1–6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis.

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mentioning

confidence: 99%

Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Leavy

Trottmann²,

Liedl

et al. 2017

Sci Rep

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“…How long CHT should be provided before SRS is a matter of debate. We performed a multi‐center study revealing that some clinics advise their patients to terminate CHT several weeks prior to SRS, whereas other clinics advise continued treatment until the day of surgery (Schneider et al ., ). Reasons for discontinuation of CHT include the fear of increased bleeding during surgery or complications of wound healing in post‐operative care (Hess et al ., ).…”

Section: Cross‐sex Hormone Therapy (Cht)mentioning

confidence: 97%

“…In our study, we found a highly diverse outcome: More feminized hormonal levels (low testosterone, high estradiol levels) on the day of SRS were seen with continued CHT. In contrast, termination of CHT days or weeks prior to SRS leads to a partial or full masculine hormone profile (Schneider et al ., ). Several questions remain unanswered: Do different male or female hormone patterns on the day of SRS have any implications for the well‐being of the individual patient prior or post‐surgery?…”

Section: Cross‐sex Hormone Therapy (Cht)mentioning

confidence: 97%

“…In our own study, we analyzed testicular tissues of 108 patients. We confirmed the variability of the spermatogenic involution under CHT based on differing testicular weights and corresponding degrees of germ cell depletion (Schneider et al ., ). In 24% of the patients, we found qualitatively complete spermatogenesis on the day of SRS.…”

Section: Effect Of Cht On Testicular Morphologymentioning

confidence: 97%

“…Only those patients with a continuous CHT showed feminized blood levels and low intratesticular testosterone levels on the day of SRS. Intriguingly though, these data were independent of the degree of the histologically detectable spermatogenic involution indicating that the endocrine process can be reverted to a male pattern in just a few weeks, whereas the spermatogenic involution will persist for a longer period (Schneider et al ., ) (Table ).…”

Section: Effect Of Cht On Testicular Morphologymentioning

confidence: 99%

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Andrology of male‐to‐female transsexuals: influence of cross‐sex hormone therapy on testicular function

Schneider¹,

Kliesch²,

Schlatt³

et al. 2017

Andrology

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Patients with gender dysphoria are offered cross-sex hormone therapy and sex reassignment surgery to achieve the transition between the sex assigned at birth and gender identity. According to international guidelines, cross-sex hormone therapy in trans-women should lead to a psychologically and physiologically healthy body with feminized serum hormone levels, resulting in suppression of spermatogenesis. However, in a recently published multi-center study, we discovered a high proportion of patients with male serum hormone levels and qualitatively intact spermatogenesis on the day of sex reassignment surgery. The objective of this study was to review the content of 11 publications that focus on the influence of cross-sex hormone therapy on testicular morphology. These publications were identified based on a PubMed search for the key words transgender/transsexual/gender dysphoria in male-to-female persons, cross-sex hormone therapy, and testicular tissues. Whereas three publications described a marked reduction of the spermatogenic level in all patients examined, eight publications reported inconsistent results. Histological analyses showed highly variable outcomes from qualitatively normal spermatogenesis and undisturbed Leydig/Sertoli cell morphology to full testicular regression with severe cellular damage and hyalinization. Explanations for these heterogeneous findings include insufficient cross-sex hormone therapy regarding dosage or duration. As complete spermatogenesis is associated with virilized serum hormone levels, these patients may face challenges especially after sex reassignment surgery in adjusting to the abruptly established hypogonadal state following removal of the testes. These findings also suggest that contraception should be discussed, and fertility preservation should be offered during/prior to cross-sex hormone therapy. There is a need for more individualized and better-controlled cross-sex hormone therapy and post-treatment regimens. Evidence-based guidelines for attending clinicians need to be established in order to deliver the most appropriate care.

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Association of Surgical Risk With Exogenous Hormone Use in Transgender Patients

2019

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IMPORTANCE A growing number of transgender patients are receiving gender-affirming hormone treatments. It is unclear whether the evidence supports the current practice of routinely discontinuing these hormones prior to surgery. OBJECTIVE To determine how medications used in cross-sex hormone treatment (CSHT) affect perioperative risk.EVIDENCE REVIEW A series of searches were carried out in PubMed and Excerpta Medica Database to identify articles using each of the terms testosterone, estrogen, estradiol, oral contraceptive, spironolactone, cyproterone acetate, finasteride, dutasteride, leuprolide, goserelin, and histrelin, in combination with the terms surgery, perioperative, thrombosis, thromboembolism, and operative. The search was not restricted to perioperative outcomes in transgender populations because many surgeons routinely discontinue hormone use prior to surgery in this population, which makes it impossible to study how hormones affect outcomes. Additional sources were also identified from the texts of reviewed articles. Articles were excluded if they were animal studies or case reports, did not explicitly discuss surgical outcomes, or were restricted to removal of hormonally sensitive tissues.FINDINGS Eighteen articles addressing perioperative outcomes were identified by this systematic review, including 1 on CSHT, 12 on estrogens and progesterones, 1 on testosterone, and 4 on spironolactone and antiandrogens. Data were limited, but use of exogenous testosterone was not found to be associated with an increased risk of venous thromboembolism or other complications during surgery. Moderate evidence suggests that spironolactone is not associated with negative surgical outcomes. The data linking estrogen use and thrombosis is inconsistent in the perioperative period and does not address the types of estrogens most often used for CSHT.CONCLUSIONS AND RELEVANCE Current evidence does not support routine discontinuation of all CSHT prior to surgery, particularly given the lack of information on risks associated with resuming these medications after they have been stopped. Evidence suggests there is no need to discontinue either testosterone or spironolactone, although their association with perioperative outcome quality has not been studied in depth. Most of the evidence that supports discontinuation of estrogen prior to surgery is based on oral estrogen regimens that are not typically used in transgender patients, and even with those formulations, there are conflicting reports on perioperative risk. Further research is needed to determine the safety of continuing hormone treatment and elucidate risks of short-term discontinuation.

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Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS)

Cited by 89 publications

References 29 publications

Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Andrology of male‐to‐female transsexuals: influence of cross‐sex hormone therapy on testicular function

Association of Surgical Risk With Exogenous Hormone Use in Transgender Patients

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