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

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. ### Competing Interest Statement Financial disclosures: This work was supported by the NWO, Netherlands [Veni grant, grant number 91619085, 2018] supplied to BB. The NWO had no involvement in the study design, data collection, analysis or interpretation of the data, or writing of the report. All other authors have no financial conflicts of interest to declare. Non-financial disclosures: none to declare. ### Funding Statement This work was supported by the NWO, Netherlands [Veni grant, grant number 91619085, 2018] supplied to BB. The NWO had no involvement in the study design, data collection, analysis or interpretation of the data, or writing of the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The RESTED study was classified as a non-WMO study by the Medical Ethical Committee of the Amsterdam University Medical Centers (location VUmc) and the local committee at the University Medical Center Groningen, meaning that the Medical Research Involving Human Subjects Act (WHO) did not apply to the data collection of this study (study id. 2019.353). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are available upon reasonable request. All data are available upon reasonable request.