Published online Mar 15, 2020. doi: 10.4239/wjd.v11.i3.66
Peer-review started: October 31, 2019
First decision: December 4, 2019
Revised: January 3, 2020
Accepted: January 19, 2020
Article in press: January 19, 2020
Published online: March 15, 2020
Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of heart disease and stroke. Testosterone and estradiol play important roles in regulating body fat and muscle and in the general population, males who have relatively high levels of testosterone compared with females are at higher risk for heart disease. The increased risk of heart disease may be related to the effects of testosterone or estradiol therapy on fat and muscle distribution, as well as insulin resistance, a measure of diabetes and heart disease risk. The effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined.
Studies demonstrating that transgender people on hormone therapy are at increased risk of adverse cardiovascular events highlight the importance of investigating surrogate markers while awaiting further long-term research. Both oestrogen and testosterone are capable of altering insulin resistance in both cisgender women and men, however, the impact of gender-affirming hormone therapy on insulin resistance in transgender individuals is less clear. This review was conducted to examine the relationship between insulin resistance and its relationship to the changes in body composition brought about by hormone therapy in order to enable clinicians to proactively lower risk factors which may contribute to heart disease and diabetes.
We aimed to investigate the existing evidence of the effects of gender-affirming hormone therapy on insulin resistance and body composition, as this may provide insight into the long-term risks of hormone therapy in transgender individuals.
We performed a systematic 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.
The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled 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.
Masculinising gender-affirming hormone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Feminising gender-affirming hormone therapy decreases lean mass, increases fat mass, and may worsen insulin resistance. Further research is required to further characterise the impact of gender-affirming 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 is paramount.
Clinicians need to be aware of body composition changes and potential insulin resistance changes. Proactive lowering of cardiovascular risk factors such as optimising diet and physical activity as well as managing weight, lipids, blood pressure and glucose are important. Long-term prospective controlled studies will provide further insights in the future.