Content of review 1, reviewed on April 12, 2023

The submitted manuscript reports the effect of pubertal suppression followed by early or late T administration on body composition, bone mass, and strength in a mouse model designed to mimic therapy for trans boys. There is a paucity of literature on the effects of gender affirming hormone therapy on physiology, particular therapy including pubertal suppression, yet we are seeing increasing numbers of patients requesting GAH, thus papers such as this manuscript are important contributions. The model is well-designed and the results provide some reassurance about the ability of T to reverse adverse effects of peripubertal GnRHa on body composition and bone. The authors appropriately reflect in the conclusions that this data cannot be used directly to counsel humans. I found the manuscript to be extremely well-written and have no major concerns.
Minor Points:
1. I was curious about the decision to continue DGX throughout the study (i.e. after T was started) since the GnRHa would typically be stopped after transition to T in humans. The authors should address this in their discussion, potentially as a limitation.
2. Throughout the manuscript, the authors seem to use GAH and T almost interchangeably despite the fact that GAH refers to both T and estradiol. Since they only studied T, when reporting results and conclusions, the authors should use "T" instead of "GAH" to describe their findings to avoid potential misunderstandings. For example, the last paragraph of page 10 ("these changes could all be counteracted by GAH..." although this issue is found elsewhere throughout the results and discussion.
3. Page 9, it seems the hypothesis should be in an earlier section of the manuscript than the results

Source

    © 2023 the Reviewer.

Content of review 2, reviewed on May 08, 2023

In my opinion, the revised manuscript is an improvement over the original submission, with all of the reviewers' comments well-addressed. I have no further concerns, just one small suggested revision -- in the final sentence of the manuscript, I would recommend stating "if confirmed in humans," rather than "when confirmed in humans."

Source

    © 2023 the Reviewer.

References

    Vanessa, D., Silvia, C., Stefanie, D., Sarah, E. K., Vera, S., Ri, K. N., Karel, D., Jolien, V. D., Roger, V., Christa, M., Leen, A., Brigitte, D., Geert, C., Frank, C., Martine, C., Dirk, V. 2023. Testosterone Restores Body Composition, Bone Mass, and Bone Strength Following Early Puberty Suppression in a Mouse Model Mimicking the Clinical Strategy in Trans Boys. Journal of Bone and Mineral Research.