SAT-LB92 Sex Hormones Therapy Differentially Modulates HDL Function in Transgender Individuals

Background/aim: The main proposed atheroprotective function of high-density lipoproteins (HDL) lays on their role to promote macrophage cholesterol efflux. An insightful way to learn more about the effects of sex hormones on HDL function is to study changes during hormone therapy. The present study was aimed at evaluating the effects of exogenous sex hormones administration on HDL cholesterol efflux capacity (CEC) within transgender individuals. CEC estimates the ability of HDL to remove cholesterol from cells, i.e. the initial step in reverse cholesterol transport. Subjects/Methods: Transmen were treated with testosterone gel, a mix of testosterone esters once every three weeks) or testosterone undecanoate once every twelve weeks, whereas transwomen were treated with either oral estradiol valerate or a transdermal application of estradiol (patches). Cyproterone acetate was prescribed as a testosterone-blocking agent to all transwomen. HDL function was evaluated by a radioisotopic technique. Hormone levels, lipids and HDL function were evaluated after one year of follow-up. Results: In transmen (n= 15), testosterone markedly increased (+ 97%; p < 0.0001), whereas luteinizing hormone (LH) decreased significantly (- 64%; p = 0.049). Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not affected by testosterone treatment, whilst triglycerides (TG) were raised (+ 11.76%; p = 0.0078) and HDL-C reduced (- 19.6%, p=0.0103). Concerning HDL CEC, only the aqueous diffusion process was lowered (- 9.8%; p = 0.0032), an effect directly correlated with HDL-C changes (r = 0.6242, p = 0.0002). Total-, ATP-binding cassette transporter (ABCA1)-, and ABCG1-mediated CEC were not affected by testosterone treatment. In transwomen (n= 15), estradiol levels were raised (+200%, p=0.013) whereas LH and testosterone significantly reduced, i.e. - 97% for both. Relative to lipids, estradiol supplementation reduced total cholesterol (- 10.7%, p=0.0017), HDL-C (- 14.3%, p = 0.0024) and LDL-C (- 10.9%, p = 0.0058). Total HDL CEC decreased (- 11%, p=0.0001) with a specific decrement in CEC mediated by the ATP-binding cassette transporter (ABCA1) (-24%, p = 0.0003) and aqueous diffusion (-4.7%, p = 0.0014). This last was associated to a reduction in HDL-C (r = 0.4084, p = 0.0251). Conversely, the drop in ABCA1 and total CEC did not associate to reductions in HDL-C levels. Conclusions: In transmen, testosterone supplementation was associated with a reduction in aqueous diffusion-mediated CEC, an effect potentially dependent to HDL-C changes. In transwomen, estrogen significantly decreased HDL function (CEC), independent of HDL-C levels changes.