Abstract Background The aim of this study was to evaluate the self-reported perceived quality of life (QoL) in female to male (FTM) and male to female (MTF) transgenders and compare it with a general population sample, and to find possible determinants that likely contribute to their QoL. Methods Participants were 71 trandgenders participating in the communities of Isfahan and Fars provinces, Iran, including 30 MTF and 41 FTM, and 142 gender- and age-matched controls. Persian version of the Short Form 36-Item Questionnaire was used to evaluate self-reported QoL, which measures QoL across eight domains. Results Compared to control group, the QoL of transgenders in the most dimensions of the SF-36 questionnaire was lower. MTF had a lower QoL than FTM for the subscale physical functioning (p = 0.044). There was a significant relationship between education and subscales of emotional well-being (p = 0.048) and social function (p = 0.008); economic status and physical function subscale (p = 0.003); employment status and physical function (p = 0.012) and social function subscales (p = 0.003). Compared to male controls, MTF transgenders had lower physical functioning (P < 0.001), role limitation due to physical health (P = 0.015), vitality (P = 0.023), social functioning (P < 0.001) and pain score (P = 0.044) and no significant differences between female controls and FTM transgenders were seen. Conclusion Transgenders have lower physical and mental QoL, FTM transgender has better QoL than MTF transgender. Employment, education, province of residence and economic status as well as therapeutic intervention is associated with transgender’s QoL
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