Gender identity in Klinefelter Syndrome: a patient-centered approach to treatment

There is increasing evidence that gender dysphoria (GD) is more prevalent in the Klinefelter Syndrome (KS) population than in males in the general population; however, the exact incidence is uncertain. The aim of this study was to further explore the prevalence of gender-related issues, the role that physical characteristics play in gender identity, and the issues surrounding Hormone Replacement Therapy (HRT) in KS.

As part of a registered Quality Improvement Project (QIP), one online 23-point questionnaire on KS patient attitudes toward gender identity was shared with members of the Klinefelter Syndrome Association (KSA). In total, 139 anonymous responses were collected between December 2021 and January 2023. The questionnaire was developed with the guidance of multiple clinicians (including gender psychiatrists, urologists, psychosexual medicine specialists, and endocrinologists) and patient Delphi rounds. Data was reviewed and analyzed by 4 independent researchers within the QIP team.

Only 53% of KS patients responding to this survey fully identified as male and 19% stated that they did not enjoy living as the sex on their birth certificate, with 43% considering changing aspects of their physical appearance to better match their gender. Regarding HRT, 67% of respondents were receiving Testosterone Replacement Therapy (TRT). 63% wanted TRT and 17% wanted estrogen, including 6% of TRT users who would prefer estrogen instead. 36% that were currently receiving TRT did not identify as male, and 3 participants stated that they have GD.

These results indicate that a significant proportion of KS patients do not fully identify with the male gender and are unhappy living as the sex on their birth certificate. Although TRT worked for most, its use should be discussed carefully with those with gender identity concerns.