Influence of sex hormone use on sleep architecture in a transgender cohort: findings from the prospective RESTED study

Abstract Sex differences in sleep architecture are well-documented, with females experiencing longer total sleep time (TST), more slow wave sleep (SWS) and shorter Rapid Eye Movement (REM) sleep duration than males. Although studies imply that sex hormones could affect sleep, effects of exogenous sex hormones on sleep architecture remain unclear. This study examined sleep architecture changes in transgender individuals after 3 months of gender-affirming hormone therapy (GAHT). We assessed sleep architecture in 73 transgender individuals: 38 transmasculine participants who started using testosterone and 35 transfeminine participants who started using estrogens and anti-androgens. Sleep architecture was measured before GAHT and after 3 months of GAHT for 7 nights using an ambulatory single-electrode sleep EEG device. Changes in sleep architecture were analyzed using linear mixed models, and non-normally distributed outcomes were log-transformed and reported as percentages. In transmasculine participants, SWS decreased by 7 minutes (95% CI: −12; −3) and 1.7% (95% CI: −3%; - 0.5%), REM sleep latency decreased by 39% (95% CI: −52%; −22%) and REM sleep duration increased by 17 minutes (95% CI: 7; 26) after 3 months of GAHT. In transfeminine participants, sleep architecture showed no significant changes after 3 months of GAHT. Sleep architecture changes after three months of masculinizing GAHT in line with sleep in cisgender males, while it shows no changes after feminizing GAHT. The sex-specific nature of these changes raises new questions on sex hormones and sleep. Future research should focus on studying possible underlying neural mechanisms and clinical consequences of these changes. Statement of significance Sleep architecture shows differences between men and women, with women showing longer sleep, longer slow wave sleep and shorter REM sleep than men. Rodent research indicates that sex hormones can alter sleep architecture, but research on sex hormones and sleep architecture in humans is still lacking. This study examined effects of three months of gender-affirming hormone use in transgender individuals. Results show that testosterone use in persons assigned female at birth resulted in sleep architecture changes similar to cisgender males, whereas estradiol- and anti-androgen use by persons assigned male at birth did not change sleep architecture. These novel findings indicate that sex hormones could change sleep architecture in a sex-specific manner, warranting further studies into causal mechanisms underlying these changes.