1. In this retrospective cohort study, fertility preservation proved feasible in transgender feminizing youth, both before and after the initiation of gender-affirming hormonal therapies.
2. Of the 2 patients on gender-affirming hormonal therapies prior to initiation of fertility preservation, 1 was able to complete semen cryopreservation after cessation of therapies while the other was ultimately experienced persistent azoospermia.
Evidence Rating Level: 3 (Average)
Study Rundown: In recent years, more transgender patients have presented to physicians seeking gender-affirming hormonal therapy. Despite this increase, little research has been completed examining fertility preservation in this population, particularly after the start of hormonal therapies. In this study, researchers sought to explore fertility preservation outcomes of transgender female youth, both before and after the initiation of gender-affirming hormonal therapies. Researchers discovered that patients who had not previously been started on hormonal therapies were all able to complete a semen collection. For the 2 patients who had previously been started on hormone therapy, 1 was able to provide a largely normal semen sample after cessation of hormone therapy for a period of 5 months. The other participant experienced persistent azoospermia after cessation of hormone therapy for 4 months, at which point a previously-scheduled gender-affirming surgery, including orchiectomy, was performed. Author Jason Rafferty, MD, notes in his associated commentary the urgency with which hormonal therapies may be started in the setting of gender dysphoria and the new ethical concerns implied by the results of this study. This commentary, as well as the small sample size of the study, affirm the need for further research into this previously under-explored topic.
In-Depth [retrospective cohort]: In this study, researchers retrospectively analyzed outcomes in 10 feminizing transgender youth (average age 19.5 years, all participants identified as non-Hispanic, white) who were referred for fertility preservation referred between January 1, 2015 and September 30, 2018 at the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh and Magee-Women’s Hospital. Eight of the ten (80%) participants had no history of hormonal therapy use, whether to suppress puberty or induce feminization. All of these participants were able to provide a semen sample, all of which were largely within normal limits for all parameters except morphology (median 6.0%, normal range >13.0% by modified Kruger criteria). One of the two patients with previous exposure to hormonal therapy had been receiving leuprolide acetate injections for 6 months prior to semen collection. This participant was able to provide an adequate semen sample 5 months after cessation of therapies; the sample was within normal limits for all parameters, with the exception of also demonstrating low morphology (9%). The second patient had been on spironolactone and estradiol for 26 months prior to attempted fertility preservation. She experienced azoospermia for 4 months after cessation of hormonal therapies and ultimately did not complete specimen collection prior to her previously scheduled gender-affirming surgery, which included orchiectomy.
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 Matthew Leinung, Marco Urizar, Nilem Patel, and Shannon Sood (2013) Endocrine Treatment of Transsexual Persons: Extensive Personal Experience. Endocrine Practice: July 2013, 19(4), pp. 644-650.