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Hormones, Headlines, and the Mouse Trap of Biomedical Research

Written by Gabby Vidaurre, Ph.D.
May 2025

Person holding vials of testosterone and estradiol© iStock.com/MargJohnsonVA

There is ongoing controversy and confusion over statements and reports by politicians and news outlets about NIH-funded researchers conducting experiments on “transgender mice.” Many assumed the term was a misquote of the scientific term “transgenic mice,” which refers to genetically modified mice, often using human DNA. However, this assumption is inaccurate—researchers themselves used the term “transgendered” in their publications. While this terminology has drawn significant public attention and media scrutiny, especially regarding taxpayer funding, the main point is being missed.

Beyond social media quarrels over semantics, the real issue is that mice are being used to study human reproductive biology.

NIH funds experiments on the effects of hormone therapy in mice in an attempt to determine how sex hormones impact human individuals undergoing gender-affirming care, as well as those affected by conditions such as endometriosis, infertility, breast cancer, and prostate cancer.1,2 However, mice are fundamentally poor models for studying these human-specific conditions due to profound anatomical and physiological differences.

Comparing Reproductive Biology: Humans vs. Mice

Anatomically, the reproductive systems of mice and humans are vastly different. Male mice, for example, possess a lobed prostate and additional sex glands such as the coagulating gland, structures not found in humans. The ejaculatory ducts of mice also differ in how the seminal vesicle ducts join the vas deferens compared to humans. In female mice, the differences are equally pronounced: mice have a closed reproductive system with coiled oviducts leading into a bursal space, while human females have an open system that allows for retrograde menstruation—an important anatomical feature that may contribute to the development of endometriosis.3

Beyond anatomy, mice and humans also diverge significantly in terms of endocrinology. Male mice have lower baseline levels of testosterone and estrogen, experience significant fluctuations in testosterone levels, and lack sex hormone-binding globulin expression.4,5 Female mice do not menstruate; instead, they experience an estrous cycle, which differs from the hormone fluctuation patterns seen in humans.6 They also do not undergo the estrogen decline seen in human menopause.6–8 Crucially, regulation of the hypothalamic-pituitary-gonadal axis differs markedly between the two species.9

Transgender or Transgenic?

According to Advocates for Trans Equality, the term transgender “describe people whose gender identity is different from the gender they were thought to be when they were born.”10 Gender identity is a human internal experience, a personal sense of being male, female, both, neither, etc., and there is no scientific evidence suggesting that mice or any other non-human animals experience gender-identity. Thus, the claim of “transgender mice” is scientifically inaccurate—but rather than debating semantics, we should be asking a more important question: Why are we still using mice to study human reproductive biology at all?

Not all mice used in hormone therapy experiments funded by the NIH are transgenic. Transgenic mice are genetically modified during embryogenesis to either have new DNA inserted or have sections of their genome changed or removed. The goal is to study the function of the modified gene, generally in the context of a human disease. While widely used to study numerous human diseases, transgenic mice are, in fact, extremely poor models.11

Creating transgenic mice is extremely inefficient: many die before or shortly after birth, and genetic modification often results in unintended changes, rendering the animals unsuitable for research. Even when genetic changes are successful, gene expression may be inconsistent or exaggerated, producing biologically irrelevant phenotypes that invalidate study results.11,12 These differences, compounded by species-specificities, make it impossible to accurately model human reproductive biology using mice.

Advancing Gender-Affirming and Reproductive Science Without Animals

Fortunately, there are better, human-specific, non-animal methods available. Technologies such as organoids, organ-chips, 3D bioprinting, and in silico modeling are increasingly used to study human reproductive biology. These methods rely on human cells, tissues, and data, offering a far more accurate representation of human biology than animal models ever could. For example, organoids are being used to study sex differences in neurodevelopment.13 PET imaging is providing insights into sex hormone expression in the brain and its effect on behavior.14 Using human endometrial organoids consisting of epithelial and stromal cells, researchers uncovered mechanisms of endometrial neoplasia due to increased androgen expression in women with polycystic ovarian syndrome (PCOS).15 Scientists have combined a multi-omic approach with human endometrial biopsies and organoids to explore how estrogen regulates the endometrium.16 Additionally, a genome-wide study of twins identified novel genetic variants associated with sex hormone regulation.17

Science or Clickbait? The ‘Transgender Mice’ Debate

Given the fundamental anatomical, endocrinological, and genetic differences between mice and humans, it is irresponsible to rely on data from experiments on mice to inform human health care. If mice don’t produce the same hormones, don’t have comparable hormone cycles, and lack the same reproductive anatomy, how can their data be meaningfully translated to humans?

With NIH and the U.S. biomedical research currently under increased public scrutiny, this is an opportunity for the scientific community to confront a long-overdue question: Is the current system truly serving human health? In this case, the answer is no.

However, calls for indiscriminate cuts to federal funding to LGBTQ health research or NIH’s workforce will not improve gender-affirming care or reproductive health research. Instead, we need strategic redirection. The recent change in priorities at NIH is a great first step, but more needs to be done. NIH should now take steps toward ending animal use in research areas in which animal models have impeded scientific progress, conducting systematic reviews of other research areas in which animals are used, and implementing a harm-benefit analysis that factors in an ethical perspective for proposed experiments on animals. There is a growing arsenal of innovative, human-specific methods available. These tools offer the potential for more accurate insights, fewer translational failures, and better outcomes related to the health of transgender people.

  1. Clarifying misinformation about “transgender mice” in research. Americans for Medical Progress. March 12, 2025. Accessed April 25, 2025. https://www.amprogress.org/research-news/2025/03/clarifying-misinformation-about-transgender-mice-in-research/
  2. McCoy C. The ‘transgender mice’ lie: How Trump’s war on science is harming real people. Wisconsin Examiner. March 13, 2025. Accessed April 25, 2025. https://wisconsinexaminer.com/2025/03/13/the-transgender-mice-lie-how-trumps-war-on-science-is-harming-real-people/
  3. Cunha GR, Sinclair A, Ricke WA, Robboy SJ, Cao M, Baskin LS. Reproductive tract biology: Of mice and men. Differentiation. 2019;110:49-63. doi:10.1016/j.diff.2019.07.004
  4. Kim NR, David K, Corbeels K, et al. Testosterone reduces body fat in male mice by stimulation of physical activity via extrahypothalamic ERα signaling. Endocrinology. 2021;162(6):bqab045. doi:10.1210/endocr/bqab045
  5. Sedelaar JPM, Dalrymple SS, Isaacs JT. Of mice and men‐warning: Intact versus castrated adult male mice as xenograft hosts are equivalent to hypogonadal versus abiraterone treated aging human males, respectively. The Prostate. 2013;73(12):1316-1325. doi:10.1002/pros.22677
  6. Koebele SV, Bimonte-Nelson HA. Modeling menopause: The utility of rodents in translational behavioral endocrinology research. Maturitas. 2016;87:5-17. doi:10.1016/j.maturitas.2016.01.015
  7. Blenck CL, Harvey PA, Reckelhoff JF, Leinwand LA. The importance of biological sex and estrogen in rodent models of cardiovascular health and disease. Circ Res. 2016;118(8):1294-1312. doi:10.1161/CIRCRESAHA.116.307509
  8. Zhang Z, He C, Gao Y, et al. α‐ketoglutarate delays age‐related fertility decline in mammals. Aging Cell. 2021;20(2):e13291. doi:10.1111/acel.13291
  9. Acevedo‐Rodriguez A, Kauffman AS, Cherrington BD, Borges CS, Roepke TA, Laconi M. Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling. J Neuroendocrinol. 2018;30(10):e12590. doi:10.1111/jne.12590
  10. Understanding transgender people: The basics. A4TE. Accessed May 9, 2025. https://transequality.org/issues/resources/understanding-transgender-people-the-basics
  11. Transgenic mice are poor models for human disease. Physicians Committee for Responsible Medicine. March 10, 2025. Accessed April 25, 2025. https://www.pcrm.org/news/good-science-digest/transgenic-mice-are-poor-models-human-disease
  12. Elefteriou F, Yang X. Genetic mouse models for bone studies—Strengths and limitations. Bone. 2011;49(6):1242-1254. doi:10.1016/j.bone.2011.08.021
  13. Pavlinek A, Adhya D, Tsompanidis A, et al. Using organoids to model sex differences in the human brain. Biol Psychiatry Glob Open Sci. 2024;4(5):100343. doi:10.1016/j.bpsgos.2024.100343
  14. Moraga‐Amaro R, Van Waarde A, Doorduin J, De Vries EFJ. Sex steroid hormones and brain function: PET imaging as a tool for research. J Neuroendocrinol. 2018;30(2):e12565. doi:10.1111/jne.12565
  15. Wiwatpanit T, Murphy AR, Lu Z, et al. Scaffold-free endometrial organoids respond to excess androgens associated with Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2020;105(3):769-780. doi:10.1210/clinem/dgz100
  16. Hewitt SC, Wu S pin, Wang T, et al. The estrogen receptor α cistrome in human endometrium and epithelial organoids. Endocrinology. 2022;163(9):bqac116. doi:10.1210/endocr/bqac116
  17. Ruth KS, Campbell PJ, Chew S, et al. Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes. Eur J Hum Genet. 2016;24(2):284-290. doi:10.1038/ejhg.2015.102
  18. NIH to prioritize human-based research technologies. NIH. April 29, 2025. Accessed May 2, 2025. https://www.nih.gov/news-events/news-releases/nih-prioritize-human-based-research-technologies

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