Among the fears that come with starting feminising hormone therapy is the one about what changes inside the body: whether estradiol redistributes fat, whether the liver notices, whether cardiometabolic risk goes up. Data on gender-affirming hormone therapy (GAHT) as it is prescribed today are still limited, and that leaves many questions open in the clinic.
A team at an academic medical centre in the greater Boston area (Massachusetts, United States) has now published in The Journal of Clinical Endocrinology & Metabolism a prospective 12-month follow-up using the contemporary regimen — 17β-estradiol plus an anti-androgen — in 26 transgender women and nonbinary individuals.
What did not move
The primary outcome was visceral fat, the fat surrounding the abdominal organs and the one most closely linked to cardiovascular disease. After a year, neither its mass nor its volume had changed. Nor had insulin sensitivity, which remained stable — relevant because insulin resistance is the step before type 2 diabetes. The authors conclude that the key indices of metabolic health did not shift in this group or over this period.
What did change
- Fat stored in the liver fell modestly but significantly (median change: −0.2%; interval −1.3 to 0.1; p = 0.03). It was the parameter that improved the most.
- Bone mineral density increased at the lumbar spine, total hip and femur: bone gained ground during the first year.
- Total lean mass and height-adjusted appendicular lean mass — a marker used to estimate sarcopenia risk — decreased (mean change: −0.31 ± 0.38 kg/m²; p = 0.0003). Muscle is the part of the body that comes out on the losing side in this first year.
- Blood triglycerides rose. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol did not change.
All participants were between 20 and 30 years old (median: 26) and none had a history of cardiovascular disease or diabetes when they entered the study. Free testosterone at the end of follow-up independently predicted the change in liver fat, even after adjusting for estradiol levels, body mass index and waist-to-hip ratio: the less circulating androgen, the less liver fat.
Why it matters
The numbers here are small — 26 people, a single medical centre, no comparison group — and follow-up lasts one year, so they say nothing about long-term cardiovascular events. What they do is clear up the most frequent question in the consultation room: in the first year, feminising hormone therapy does not put on internal fat and does not worsen sugar control. The signal that deserves attention is the loss of muscle mass, which the authors themselves link to sarcopenia risk and to the need for strategies that offset it, such as strength training and sufficient protein intake.
The study does not address the biological basis of gender identity: it measures the metabolic impact of a medical treatment already under way in thousands of people. It does, however, add a clinical piece of data that was missing, with the regimen prescribed today and at the stage of treatment when the body changes fastest.
Source: Visceral adipose tissue and liver fat on 17-beta estradiol-dominant gender-affirming hormone therapy: A US-based cohort. Talathi R, Juhasz V, Delgado M, et al. The Journal of Clinical Endocrinology & Metabolism 2026;111(6):1713-1726. DOI: 10.1210/clinem/dgaf665.
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