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68 C H A P T E R 5 ABSTRACT Importance: Increasing numbers of transgender individuals are presenting for gender- affirmingmedical care.For transgender individuals assignedmale at birth,gender-affirming hormone therapy (GAHT) generally consists of estrogen combined with an anti-androgen and will promote feminization but also impair spermatogenesis. Clinical guidelines therefore suggest sperm cryopreservation prior to GAHT based on the dogma that GAHT causes irreversible azoospermia and infertility. However, it is unknown if spermatogenesis can recover if GAHT is stopped. Objective: To determine if the loss of spermatogenesis in transgender women using gender-affirming hormonal treatment can be reversed after hormonal treatment is ceased. Design: Case series. Setting: Sexual health clinic in Coffs Harbour, Australia, and gender identity clinic in Amsterdam, the Netherlands. Participant: Nine transgender women (mean age 26.1 years) who had been on GAHT for > 6 months (median 36 months) before interrupting treatment for reproductive purposes. Intervention: Longitudinal follow up to assess semen quality after cessation of hormonal treatment. Main outcome measure: Presence of spermatozoa in semen analysis. Results: Spermatozoa were successfully identified in all nine participants after cessation of GAHT. Six individuals already had spermatozoa present on their initial semen analyses taken 3-27 months after stopping hormones; the other three showed initial azoospermia but eventually had spermatozoa identified 8-17months after hormone cessation. Of the four individuals who attempted to conceive with their partners, three successfully did so 4-40 months after stopping treatment. Conclusion and relevance: Taken together, these findings suggest that the inhibitory effect of GAHT on spermatogenesis can be reversed, and have important implications for clinical practice.

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