Liver function in transgender persons:Challenges in the COVID-19 era

Transgender persons constitute a non-negligible percentage of the general population.Physical gender-transitioning in trans persons is mainly achieved with hormonal cross-sex therapy and sex reassignment surgeries that aim to align bodily appearance with gender identity.Hormonal treatment acts via suppressing the secretion of the endogenous sex hormones and replacing them with the hormones of the desired sex.The administration of testosterone is the typical masculinizing treatment in trans men,whilst trans women are routinely treated with estradiol agents in combination with anti-androgens or gonadotrophinreleasing hormone agonists if testes are present.Exogenous androgenic steroids,estradiol agents,and anti-androgens have been implicated in a series of hepatotoxic effects.Thus,liver integrity is a major concern with the long-term administration of cross-sex therapy.Hepatic tissue is susceptible to coronavirus disease 19(COVID-19)through various pathophysiological mechanisms.Special consideration should be paid to minimize the risk of hepatic damage from the potential cumulative effect of COVID-19 and gender-affirming treatment in transgender patients.Appropriate care is significant,with continuous laboratory monitoring,clinical observation and,if needed,specific treatment,especially in severe cases of infection and in persons with additional liver pathologies.The pandemic can be an opportunity to provide equal access to care for all and increase the resilience of the transgender population.

Effects of gender-affirming hormone therapy on insulin resistance and body composition in transgender individuals: A systematic review

BACKGROUND Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively,are at increased risk of adverse cardiovascular outcomes,including myocardial infarction and stroke.This may be related to the effects of testosterone or estradiol therapy on body composition,fat distribution,and insulin resistance but the effect of genderaffirming hormone therapy on these cardiovascular risk factors has not been extensively examined.AIM To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals,to guide clinicians in minimising cardiovascular risk.METHODS We performed a review of the literature based on PRISMA guidelines.MEDLINE,Embase and PsycINFO databases were searched for studies examining body composition,insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy.Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass,fat mass or insulin resistance.RESULTS The search strategy identified 221 studies.After exclusion of studies that did not meet inclusion criteria,26 were included(2 cross-sectional,21 prospectiveuncontrolled and 3 prospective-controlled).Evidence in transgender men suggests that testosterone therapy increases lean mass,decreases fat mass and has no impact on insulin resistance.Evidence in transgender women suggests that feminising hormone therapy(estradiol,with or without anti-androgen agents)decreases lean mass,increases fat mass,and may worsen insulin resistance.Changes to body composition were consistent across almost all studies:Transgender men on testosterone gained lean mass and lost fat mass,and transgender women on oestrogen experienced the reverse.No study directly contradicted these trends,though several small studies of short duration reported no changes.Results for insulin resistance are less consistent and uncertain.There is a paucity of prospective controlled research,and existing prospective evidence is limited by small sample sizes,short follow up periods,and young cohorts of participants.CONCLUSION Further research is required to further characterise the impact of genderaffirming hormone therapy on body composition and insulin resistance in the medium-long term.Until further evidence is available,clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.

Progesterone in gender-affirming therapy of trans women

Progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland.It has additional significant actions in other tissues,such as the cardiovascular system,the central nervous system,and bones.The present article explores potential clinical implications from the addition of bioidentical progesterone to genderaffirming treatment of trans women.For this purpose,it provides an overview of the physiological action of progesterone in target tissues and speculates on possible benefits for gender transitioning.Progesterone is expected to exert moderate anti-androgen action through suppression of the hypothalamicpituitary-gonadal axis and inhibition of the conversion of testosterone to dihydrotestosterone.It may also contribute to breast maturation.In the long-term,progesterone could prevent bone loss and protect cardiovascular health.The potential benefits are mainly inferred by extrapolating evidence from biological actions in cisgender women and medical assumptions and hence,clinicians need to be cautious when applying these data into practice.Further research is needed to ascertain the efficacy and safety of progesterone in current hormonal regimens.