How can we know whether a gender-affirming hormone dose is right? Until now, the answer has relied largely on clinical experience and on each person’s symptoms. A new study published in the journal Hormones proposes a more objective route: reading the “biochemical signature” that treatment leaves in the blood and comparing it with the hormonal profile of the sex with which the person identifies.
The study starts from a simple but powerful idea. When a transgender person receives gender-affirming hormones, their body should shift toward the hormonal pattern of the sex to which their identity belongs. If that shift is correct, the dose is adequate; if not, something is wrong. The authors frame it as a hypothesis: the biochemical shift toward the profile of the identified sex correlates with appropriate dosing.
To test it, the researchers used data from the United States National Health and Nutrition Examination Survey (NHANES), with more than 5,400 cisgender people, and built a model able to distinguish male and female hormonal profiles. They then applied that model to people on affirming treatment to see whether their blood tests matched the expected pattern.
The results were striking. The model reached 91% accuracy in the NHANES sample and 81.5% in the ENIGI validation cohort, although that figure dropped to 10.7% at 36 months of treatment. In transgender women, the model-predicted median estradiol concentration was 59.0 ng/L, significantly lower than expected, suggesting that many doses may be below target.
The authors conclude that the innate sexual dimorphism of biochemical parameters can serve as a framework for validating the targets of gender-affirming hormone therapy. In other words, a blood test could become a clinical tool to adjust doses more precisely and personally, rather than relying only on subjective response.
The finding opens the door to laboratory markers that help endocrinologists calibrate each person’s treatment, a step toward data-driven affirming medicine rather than approximation. Although the authors warn that more studies are needed, the direction is clear: biochemistry can speak, and it is worth learning to listen.
Source: Hormones (2026). DOI: 10.1007/s42000-026-00822-y
