Abstract
Background
There are known sex disparities in temperature perception with lower thermal detection thresholds found in people assigned female at birth compared to people assigned male at birth. However, underlying mechanisms of these differences and the influences of sex hormones are not yet sufficiently understood.
Methods
To assess the effects of sex hormones on temperature perception, we measured in a prospective observational cohort study temperature detection and pain thresholds with quantitative sensory testing and subjective temperature sensation in transgender patients undergoing gender-affirming hormone therapy (GAHT). We included 12 trans women (male-to-female transgender) and 17 trans men (female-to-male transgender) before and 3 and 6 months after start of GAHT. As a control group, we measured 13 cis women and 10 cis men without hormone treatment at the same timepoints.
Results
Here we show that temperature detection thresholds in persons assigned female at birth at baseline are lower than in persons assigned male at birth. Accordingly, in trans women, temperature detection thresholds decrease with GAHT. Pain detection thresholds do not differ between sexes assigned at birth and do not change with time.
Conclusions
We demonstrate that in trans women undergoing GAHT with estradiol and cyproterone acetate sensitivity to temperature changes increases, consistent with the greater temperature sensitivity observed in cis women compared to cis men. Future studies need to assess at which neurobiological processing stages the relevant changes occur and what molecular mechanisms play a role.
Trial registration
NCT04838249.
Plain english summary
Previous investigations showed that cis women can detect smaller temperature differences on their skin than cis men. However, it is not yet known if hormones play a role in these variations, or if, e.g., only different genes are responsible. To learn more about the influences of hormones on temperature perception, we tested how persons with different sex hormone levels can sense temperature. We measured 12 trans women (male-to-female transgender) and 17 trans men (female-to-male transgender) before and after 3 and 6 months of their hormone therapy. In trans women, temperature perception improved. These results help to better understand sex differences and hormone levels in temperature perception.
Similar content being viewed by others
Data availability
The source data for Figs. 1 and 2 is in Supplementary Dataset 1. Other datasets generated and/or analyzed during the current study are not publicly available due to patient confidentiality. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.
References
Greenfield, A. M., Alba, B. K., Giersch, G. E. W. & Seeley, A. D. Sex differences in thermal sensitivity and perception: implications for behavioral and autonomic thermoregulation. Physiol. Behav. 263, 114126 (2023).
Golja, P., Tipton, M. J. & Mekjavic, I. B. Cutaneous thermal thresholds—the reproducibility of their measurements and the effect of gender. J. Therm. Biol. 28, 341–346 (2003).
Averbeck, B., Seitz, L., Kolb, F. P. & Kutz, D. F. Sex differences in thermal detection and thermal pain threshold and the thermal grill illusion: a psychophysical study in young volunteers. Biol. Sex Differ. 8, 29 (2017).
Kuhtz-Buschbeck, J. P., Andresen, W., Göbel, S., Gilster, R. & Stick, C. Thermoreception and nociception of the skin: a classic paper of Bessou and Perl and analyses of thermal sensitivity during a student laboratory exercise. Adv. Physiol. Educ. 34, 25–34 (2010).
Doeland, H. J. et al. The relationship of cold and warmth cutaneous sensation to age and gender. Muscle Nerve 12, 712–715 (1989).
Inoue, Y. et al. Sex differences in age-related changes on peripheral warm and cold innocuous thermal sensitivity. Physiol. Behav. 164, 86–92 (2016).
Li, X., Petrini, L., Defrin, R., Madeleine, P. & Arendt-Nielsen, L. High resolution topographical mapping of warm and cold sensitivities. Clin. Neurophysiol. 119, 2641–2646 (2008).
Matos, R. et al. Quantitative sensory testing in the trigeminal region: site and gender differences. J. Orofac. Pain 25, 161–169 (2011).
Tansey, E. A. & Johnson, C. D. Recent advances in thermoregulation. Adv. Physiol. Educ. 39, 139–148 (2015).
Nagashima, K., Tokizawa, K. & Marui, S. Thermal comfort. Handb. Clin. Neurol. 156, 249–260 (2018).
Valenza, A., Bianco, A. & Filingeri, D. Thermosensory mapping of skin wetness sensitivity across the body of young males and females at rest and following maximal incremental running. https://doi.org/10.1113/JP277928 (2019).
Gagge, A. P., Stolwijk, J. A. & Hardy, J. D. Comfort and thermal sensations and associated physiological responses at various ambient temperatures. Environ. Res. 1, 1–20 (1967).
Karjalainen, S. Thermal comfort and gender: a literature review. Indoor Air 22, 96–109 (2012).
Rupp, R. F., Vásquez, N. G. & Lamberts, R. A review of human thermal comfort in the built environment. Energy Build 105, 178–205 (2015).
Schweiker, M., Huebner, G. M., Kingma, B. R. M., Kramer, R. & Pallubinsky, H. Drivers of diversity in human thermal perception – A review for holistic comfort models. Temperature 5, 308–342 (2018).
Kaikaew, K. et al. Sex difference in cold perception and shivering onset upon gradual cold exposure. J. Therm. Biol. 77, 137–144 (2018).
Sarlani, E., Farooq, N. & Greenspan, J. D. Gender and laterality differences in thermosensation throughout the perceptible range. Pain 106, 9–18 (2003).
Asuthkar, S. et al. The TRPM8 protein is a testosterone receptor: II. Functional evidence for an ionotropic effect of testosterone on TRPM8. J. Biol. Chem. 290, 2670–2688 (2015).
Gkika, D. et al. Testosterone-androgen receptor: The steroid link inhibiting TRPM8-mediated cold sensitivity. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 34, 7483–7499 (2020).
Kubo, T. et al. Effects of β-estradiol on cold-sensitive receptor channel TRPM8 in ovariectomized rats. Exp. Anim. 66, 337–343 (2017).
Hiroi, H. et al. Expression and regulation of transient receptor potential cation channel, subfamily M, member 2 (TRPM2) in human endometrium. Mol. Cell. Endocrinol. 365, 146–152 (2013).
Yazğan, Y. & Nazıroğlu, M. Ovariectomy-induced mitochondrial oxidative stress, apoptosis, and calcium ion influx through TRPA1, TRPM2, and TRPV1 are prevented by 17β-estradiol, tamoxifen, and raloxifene in the hippocampus and dorsal root ganglion of rats. Mol. Neurobiol. 54, 7620–7638 (2017).
Glintborg, D. et al. Gender affirming hormonal treatment in Danish transgender persons: a nationwide register-based study. Andrology 10, 885–893 (2022).
Wiepjes, C. M. et al. The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): trends in prevalence, treatment, and regrets. J. Sex. Med. 15, 582–590 (2018).
Springer, K. W., Mager Stellman, J. & Jordan-Young, R. M. Beyond a catalogue of differences: a theoretical frame and good practice guidelines for researching sex/gender in human health. Soc. Sci. Med. 1982 74, 1817–1824 (2012).
DuBois, L. Z. & Shattuck-Heidorn, H. Challenging the binary: Gender/sex and the bio-logics of normalcy. Am. J. Hum. Biol. Off. J. Hum. Biol. Counc. 33, e23623 (2021).
Coleman, E. et al. Standards of care for the health of transgender and gender diverse people, version 8. Int. J. Transgender Health 23, S1–S259 (2022).
Coleman, E. et al. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7. Int. J. Transgend. 13, 165–232 (2012).
Mosteller, R. D. Simplified calculation of body-surface area. N. Engl. J. Med. 317, 1098 (1987).
Medi Cal Healthcare GmbH. Biacorpus RX 4004M User Manual (Version 2021-4). https://biacorpus.de/files/medi-cal/pdf/Biacorpus_RX4004M-2021-4_DE.pdf (accessed 1 February 2025).
Medoc Ltd. Neurosensory Analyzer Model TSA-II (2001) User Manual (Version 10, 8/2018). https://8c887ae7-b860-4881-b2fe-914593193686.filesusr.com/ugd/744993_a9be81123f794fc0bf7a9ce779592ff8.pdf (accessed 1 February 2025).
Palmer, S. T. & Martin, D. J. Thermal perception thresholds recorded using method of limits change over brief time intervals. Somatosens. Mot. Res. 22, 327–334 (2005).
Fruhstorfer, H., Lindblom, U. & Schmidt, W. C. Method for quantitative estimation of thermal thresholds in patients. J. Neurol. Neurosurg. Psychiatry 39, 1071–1075 (1976).
Bertelsmann, F. W., Heimans, J. J., Weber, E. J., van der Veen, E. A. & Schouten, J. A. Thermal discrimination thresholds in normal subjects and in patients with diabetic neuropathy. J. Neurol. Neurosurg. Psychiatry 48, 686–690 (1985).
Stevens, J. C. & Choo, K. K. Temperature sensitivity of the body surface over the life span. Somatosens. Mot. Res. 15, 13–28 (1998).
Van Someren, E. J. W. et al. The experienced temperature sensitivity and regulation survey. Temperature 3, 59–76 (2016).
Chatfield, M. & Mander, A. The Skillings-Mack test (Friedman test when there are missing data). Stata J 9, 299–305 (2009).
XLSTAT Help Center. Durbin, Skillings-Mack test in Excel tutorial. Help Center https://help.xlstat.com/6376-durbin-skillings-mack-test-excel-tutorial.
Uchida, Y. & Izumizaki, M. Effect of menstrual cycle and female hormones on TRP and TREK channels in modifying thermosensitivity and physiological functions in women. J. Therm. Biol. 100, 103029 (2021).
Kenshalo, D. R. Changes in the cool threshold associated with phases of the menstrual cycle. https://journals.physiology.org/doi/epdf/10.1152/jappl.1966.21.3.1031; https://doi.org/10.1152/jappl.1966.21.3.1031 (1966).
Söderberg, K., Sundström Poromaa, I., Nyberg, S., Bäckström, T. & Nordh, E. Psychophysically determined thresholds for thermal perception and pain perception in healthy women across the menstrual cycle. Clin. J. Pain 22, 610–616 (2006).
Zhang, Z., DiVittorio, J. R., Joseph, A. M. & Correa, S. M. The effects of estrogens on neural circuits that control temperature. Endocrinology 162, bqab087 (2021).
Zhang, Z. et al. Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice. Nat. Commun. 11, 6378 (2020).
Szeliga, A. et al. The role of kisspeptin/neurokinin B/dynorphin neurons in pathomechanism of vasomotor symptoms in postmenopausal women: from physiology to potential therapeutic applications. Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol. 34, 913–919 (2018).
Crandall, C. J., Mehta, J. M. & Manson, J. E. Management of menopausal symptoms: a review. JAMA 329, 405–420 (2023).
Yang, J. L., Hodara, E., Sriprasert, I., Shoupe, D. & Stanczyk, F. Z. Estrogen deficiency in the menopause and the role of hormone therapy: integrating the findings of basic science research with clinical trials. Menopause 31, 926–939 (2024).
Van Mulder, T. J. S. et al. High frequency ultrasound to assess skin thickness in healthy adults. Vaccine 35, 1810–1815 (2017).
Hembree, W. C. et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society* clinical practice guideline. J. Clin. Endocrinol. Metab. 102, 3869–3903 (2017).
Chen, C. & Ding, S. How the skin thickness and thermal contact resistance influence thermal tactile perception. Micromachines 10, 87 (2019).
Lundström, R., Dahlqvist, H., Hagberg, M. & Nilsson, T. Vibrotactile and thermal perception and its relation to finger skin thickness. Clin. Neurophysiol. Pract. 3, 33–39 (2018).
Park, S., Roh, S.-H. & Lee, J.-Y. Body regional heat pain thresholds using the method of limit and level: a comparative study. Eur. J. Appl. Physiol. 119, 771–780 (2019).
Lue, Y.-J., Wang, H.-H., Cheng, K.-I., Chen, C.-H. & Lu, Y.-M. Thermal pain tolerance and pain rating in normal subjects: gender and age effects. Eur. J. Pain 22, 1035–1042 (2018).
Ravn, P., Frederiksen, R., Skovsen, A. P., Christrup, L. L. & Werner, M. U. Prediction of pain sensitivity in healthy volunteers. J. Pain Res. 5, 313–326 (2012).
Acknowledgements
We thank all participants for their participation in the study. We thank Jens Przybilla and Paul Czechowski for statistical advice. We thank Natalia Schischkarjow, Björn Drechsler-Kryst, Lotte Oldenburg and Antonia Stengler for helping to conduct the study. Pauline Zimmermann and Franziska Labinski received a 6-month scholarship from the German Diabetes Society (Deutsche Diabetes Gesellschaft e.V.) during their medical studies. The study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy—EXC-3105/1— 533765739 (to M.S.) and a research grant from Besins Healthcare (to H.S.). The funders had no role in the study design, data collection, data analysis, interpretation of results, or the writing of the manuscript. Coverage of the publication fee was supported by the Open Access Publishing Fund of Leipzig University.
Funding
Open Access funding enabled and organized by Projekt DEAL.
Author information
Authors and Affiliations
Contributions
P.Z.: data analysis, conduction of the study, writing, reviewing and editing of the manuscript; M.K.: conduction of the study, reviewing and editing of the manuscript; T.B.: conduction of the study, reviewing and editing of the manuscript; L.M.: conduction of the study, reviewing and editing of the manuscript; F.L.: conduction of the study, reviewing and editing of the manuscript; F.E.: reviewing and editing of the manuscript; M.B.: funding acquisition, resources, reviewing and editing of the manuscript; M.S.: funding acquisition, resources, reviewing and editing of the manuscript; S.H.: conceptualization, conduction of the study, reviewing and editing of the manuscript; H.S.: conceptualization, funding acquisition, data analysis, conduction of the study, project administration, writing, reviewing and editing of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
H.S. received financial support for this study from Besins Healthcare. The funder had no role in the study design, data collection, data analysis, interpretation of results, or the writing of the manuscript. M.B. received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, and Sanofi. All other authors have no competing interests.
Peer review
Peer review information
Communications Medicine thanks the anonymous reviewers for their contribution to the peer review of this work. A peer review file is available.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Zimmermann, P., Kaar, M., Bokeloh, T. et al. Changes in temperature perception in transgender persons undergoing gender-affirming hormone therapy. Commun Med (2026). https://doi.org/10.1038/s43856-026-01420-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s43856-026-01420-0


