Res Ipsa - Testicular histology after feminizing hormone therapy
Pathology community is aware of the “hot seat” or unknown slide conference. For the author during his residency training the “hottest” seat was the “Res Ipsa” cases during unknown slide conference by one of the faculty members. Res Ipsa (Latin for “the thing speaks for itself”) was “all” that was provided as the clinical history / relevant information needed to diagnose the case. Thanks to A&CR for providing a platform for my Res Ipsa. Thankfully, I am not the one on the hot seat today.
Hormonal therapy followed by gender reassignment surgery is now the standard of care in people with gender dysphoria. Clinical Practice Guideline from endocrine societies in fact recommend gender-affirming surgery only after completion of at least 1 year of consistent and compliant hormone treatment.
The objective of hormonal therapy is to suppress endogenous hormone levels and replace them with exogenous hormones of the desired sex. The hormone therapy regimen for male-to-female gender transition involves the use of an antiandrogen in conjunction with an estrogen. The antiandrogens demonstrate their effect by reducing endogenous testosterone levels to those found in adult biological female. This also enables the estrogen therapy to have its maximal effect.
Orchiectomy is one of the surgeries patients seeking male-to-female physical adaptation must undergo. Depending upon institutional policy these specimens are usually subjected to histopathologic evaluation.
Histopathologic alterations are mostly hormone therapy related changes and they are present in almost all cases, albeit to variable extent. Some of the most common changes as described in the literature include reduced diameter of seminiferous tubules and peri-tubular fibrosis, aspermatogenesis with maturation arrest, and absence of Leydig cells.
Most histologic changes in the testicular parenchyma including reduced / absent spermatogenesis are secondary to alterations in the physiologic mechanisms governed by testosterone as well as estrogenization. Additionally, as the epididymal epithelium is shown to express ER,
Pathologists usually find themselves struggling to find appropriate wording for signing out such cases. The following example may be helpful in this regard.
The images depict an orchiectomy specimen from a 24-year-old adult who underwent gender reassignment surgery after hormonal therapy with estradiol, micronized progesterone, and spironolactone.
1 Hembree WC, Cohen-Kettenis PT, Gooren L, et al. T’Sjoen GG. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869-903.
2 Matoso A, Khandakar B, Yuan S, et al. Spectrum of findings in orchiectomy specimens of persons undergoing gender confirmation surgery. Hum Pathol. 2018;76:91-9.
3 Jiang DD, Swenson E, Mason M, et al. Effects of estrogen on spermatogenesis in transgender women. Urology. 2019;132:117-22.