Elsevier

Urology

Volume 132, October 2019, Pages 117-122
Urology

Infertility
Effects of Estrogen on Spermatogenesis in Transgender Women

https://doi.org/10.1016/j.urology.2019.06.034Get rights and content

Abstract

Objective

To characterize spermatogenesis in the estrogenized transgender patient.

Materials and Methods

This is a retrospective, single-center, cross-sectional study. Seventy-two transgender women underwent gender-affirming orchiectomy between May 2015 and January 2017. All were on long-term (>1 year) cross-sex hormonal therapy prior to orchiectomy. Patient data were obtained via chart review. Histologic analysis was performed by a pathology resident under the supervision of a genitourinary pathologist. The main outcome is histologic presence of germ cells and presence of spermatids (a proxy for preserved spermatogenesis) in orchiectomy specimens.

Results

There were 141 pathologic specimens available for analysis. Germ cells were present in 114 out of 141 (81%) testicles. Spermatids were present in 57 (40%) testicles. Presence of germ cells was associated with older age (43 vs 35 years, P = .007) and increased testicular weight (28.6 g vs 19.3 g, P <.001). Presence of spermatids was associated with increased weight (31.5 g vs 23.3 g, P <.001) and volume (20.3 mL vs 12.6 mL, P <.001). There was a linear correlation between testis volume and preserved spermatogenesis (Pearson's r = 0.448, P <.001).

Conclusion

Despite long-term hormone therapy, the majority (80%) of transgender women have germ cells present in the testicle. Spermatogenesis is preserved in approximately 40% of these individuals. Duration of hormonal therapy did not affect the degree of preservation of germ cells or spermatogenesis but starting hormonal treatment at a younger age may be associated with decreased germ cells in the testicle. Volume of testicles predict presence of preserved spermatogenesis.

Section snippets

MATERIALS AND METHODS

This is an IRB-approved retrospective cross-sectional study. Subjects included all transgender patients undergoing gender-affirming orchiectomy, either alone or as a part of vaginoplasty at Oregon Health and Science University from May 2015 to January 2017. All subjects (n = 72) were taking cross-sex hormones for at least 1 year prior to orchiectomy. Subjects undergoing orchiectomy alone (n = 50) did not stop estrogen prior to surgery but those who had orchiectomy with vaginoplasty (n = 22)

RESULTS

There were 141 pathologic specimens from 72 patients for histologic analysis (Table 1). Median age was 39 [IQR 30-53], most patients were white (88%), median BMI was 26.6 [IQR 23.2-31.4], the median duration of hormone use was just over 3 years (39 months [IQR 24-65]). The median weight and volume of the gonads were 26.4 grams [IQR 23.3-33.0] and 14.2 mL [IQR 10.2-20.2], respectively. Germ cells were present in 114 (80%) of the specimens. Spermatids were identified in 57 (40%) of the gonads.

The

DISCUSSION

Our study finds that despite long-term cross-sex hormone therapy, germ cells persist in the vast majority of transgender women and over one third of these women have preserved spermatogenesis. This is in contrast to early research suggesting that estrogenization invariably leads to testicular atrophy and sterility, but is consistent with more recent studies showing that some patients do maintain spermatogenesis. In 1992, Lubbert et al investigated the effects of estrogen on hormonal and semen

CONCLUSION

Despite being on long-term hormone therapy, the majority (80%) of transgender women have persistent germ cells in their testicles, and over one third have preserved spermatogenesis. Larger testicular size reliably predicts preservation of spermatogenesis, and this may be used for preoperative fertility counseling. While these findings should lend optimism to the pursuit of fertility preservation in transgender women, future study is needed to characterize factors predictive of preserved

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    Even in transfeminine people who did not start GAHT yet, sperm quality is often lower compared with the World Health Organization (WHO) data for the general population [44], which could be attributed to wearing tight undergarments and a tucking (hiding the penis by pulling it back between the legs) frequency of more than eight times per month. Normal spermatogenesis has been reported in 0–48% of all orchiectomy specimens [45–50]. For example, in people using GAHT with spironolactone, testosterone levels are not completely suppressed.

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    Bilateral orchiectomy is often performed at an early stage of their transition as it reduces the production of endogenous androgens, allows for the discontinuation of anti-androgen therapy, and reduces the dosage of estrogen [3]. Previous studies have focused on the histologic changes related to hormone therapy, particularly estrogen, on spermatogenesis in the testis [4–11]. Therefore, we aimed to provide a clinicopathologic overview of the features identified within gender-affirming orchiectomies performed at our institution to summarize our experience, confirm previous findings, and devise a proposed grossing protocol to adequately assess these increasingly encountered specimens.

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Funding: None.

Conflicts of interest: None.

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