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69 SUCCESSFUL RESTORATION OF SPERMATOGENESIS FOLLOWING GENDER-AFFIRMING HORMONE THERAPY 5 INTRODUCTION Increasing numbers of transgender, gender diverse, and non-binary (henceforth, trans) people are seeking hormonal intervention as part of gender-affirming medical care. For trans individuals assigned male at birth, gender-affirming hormone therapy (GAHT) typically consists of estrogen combined with an anti-androgen. Such treatment promotes feminization, but can also cause unwanted effects, including impaired spermatogenesis. 3 Specifically, multiple studies have observed that most trans women who have received GAHT do not produce mature sperm at the time of gender-affirming surgery. 27,28,103-107 Some of these studies reported relatively normal spermatogenesis in a variable minority of trans women (e.g. 11-40%), but Vereecke et al. found that none of the 97 individuals they studied had complete spermatogenesis at gonadectomy. 103,106,107 Current international clinical guidelines therefore recommend that trans women “should be informed about sperm preservation options and encouraged to consider banking their sperm prior to hormone therapy”. 93 Such advice would appear sensible, especially in light of prominent claims from leaders in the transgender health field that GAHT “eventually results in irreversible infertility”. 3 However, to know if GAHT actually causes “irreversible infertility” requires the longitudinal study of patients and a determination whether loss of spermatogenesis can be reversed after GAHT is ceased . To our knowledge, no such studies have been previously reported. To address this important gap, we therefore identified trans individuals assigned male at birth, each of whom stopped GAHT for reproductive purposes, and assessed their subsequent ability to produce sperm. PARTICIPANTS AND METHODS Trans women attending either a sexual health clinic in Coffs Harbour, Australia, or the Center of Expertise on Gender Dysphoria at the Amsterdam UMC, Netherlands, who wished to temporarily stop GAHT for reproductive purposes were identified, and informed consent to participate in this study was obtained. Relevant clinical data were extracted from the medical records and included: confirmed gender incongruence, age at commencement of GAHT, type of estrogen and anti-androgen therapy, duration and dose, reasons for stopping GAHT, subsequent semen analysis results, and reproductive outcomes. Any patients on GAHT for < 6 months were excluded from the study. RESULTS In total, nine trans women were included who met our study criteria (Table 1). Four individuals stopped GAHT to conceive with their current partners; the remaining five wished to bank sperm to conceive in the future. Their mean age was 26.1 years, and median duration on GAHT was 36 months (range 6-216 months). Seven individuals had been on oral estradiol (median dose 4mg, range 2-4mg), while the other two had been on topical estradiol, and all had used estrogen in combination with an anti-androgen (spironolactone or cyproterone acetate).

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