Exogenous Estrogen Therapy, Testicular Cancer, and the Male to Female Transgender Population

A Case Report

Gursimran Chandhoke; Bobby Shayegan; Sebastien J. Hotte


J Med Case Reports. 2019;12(373) 

In This Article

Estrogens and TC

Over the course of the last few decades, the overall incidence of TC has increased and has doubled over the last 40 years in many regions in the world.[5] One theory that looks to explain this phenomenon is TDS, which suggests that the increased incidence of impaired spermatogenesis, reproductive tract abnormalities (for example, cryptorchidism), and TC, all share a common etiology related to errors in gonocyte development.[6] The earliest signs of TC can be found during embryogenesis, in which excessive levels of estrogen during early pregnancy can lead to a disturbance in the development of primordial germ cells destined to form spermatogonia. This results in premalignant cells which may become carcinoma in situ after birth. These cells remain dormant until there is a change in their local microenvironment, attributable to changes in (1) androgen levels, (2) excessive estrogens, or (3) exogenous hormonal imbalance.[7] These can be manifested as the hormonal changes of puberty, through exogenous hormonal administration, and from exposure to occupational and environmental estrogenic chemicals.

With this in mind, a 1987 study that assessed the histology of testicles in male to female transgendered patients following exposure to exogenous estrogens found atrophy of the seminiferous tubules, cellular hypertrophy, and hyperplasia of the rete testis, and to a lesser extent of the ductuli efferentes, and of the epididymal ductal epithelium.[8]

Furthermore, a recent study has demonstrated a pro-growth impact of estrogens on human testicular germ cells, mediated through the activation of an extracellular regulated kinase and protein kinase A.[9]

Our review of the literature reveals one other case of a male to female transgendered patient who, after being on estrogen therapy for 22 years, developed TC that required surgery and four cycles of BEP chemotherapy.[10]

Continued reporting of similar cases is imperative to understand any potential putative link between exogenous estrogen exposure and the development of TC. While there is a paucity of data to support or refute this suggestion, completing a screening scrotal ultrasound in male to female transgendered patients prior to being placed on estrogen therapy may be useful and is non-invasive and inexpensive. If a patient is planned to undergo prolonged hormonal therapy, regular interval ultrasounds (for example, every 6 to 12 months) could be considered.