Hormones, Depression, and Trans Biology
I have long held that when someone describes their own personal experiences, you should take them at face value, barring very strong evidence to the contrary. This is not a popular position. With regard to transgender issues, there are some who situate the primary cause of gender dysphoria within the individual body, with a brain-sex that does not match their body. On the other hand, there are some who say the supreme cause of gender dysphoria is a transphobic society. I don’t wish to equivocate and pretend that I see both of these positions as equal; anyone familiar with my views knows I tend towards the social construction-y side of things. Nevertheless, I can’t side with vulgar constructivism either. The fact of the matter is that there are transgender people who report intense, deeply-felt dysphoria because they have a sense that their sexual characteristics should be quite different. That is not a sense that a transphobic society is likely to implant in people. The cause is likely to be found elsewhere.
It is very plausible that there is a segment of transgender people—how large, we cannot say with confidence at this time—whose gender identity is significantly based in their biology. This has been suggested by various studies. For example, several studies have found that the parts of the brain which seem responsible for self-perception of one’s own body are different in transgender people than cisgender people of the same sex.1 2 3 Other studies have found differences between transgender and cisgender people of the same sex with regard to the hypothalamus.4 5
The connection between transgender identity and the hypothalamus is interesting because of the relation to the hypothalamus to depression. The hypothalamus is the part of the brain most closely related to endocrine system, and we know that the levels of sex hormones (such as testosterone and estradiol) can influence the hypothalamus and potentially cause or diminish depression, even if limited in effect and unclear in causal pathways.6 7 8 9 10 We aren't even sure how the brain relates to depression, even though we know it does,11 so it’s no surprise that the causal mechanism is unclear, even though the connection is well-established. Additionally, it is well-known that dopamine is tied to depression,12 and dopamine levels are influenced by estradiol and testosterone, although again it’s not entirely clear how.13 14
Traditionally, hormone replacement therapy (HRT) for transgender people has been thought to help by making them feel better about their own body and experience less stigma by blending in with the general population more. However, given a connection between sex hormones and depression, it seems like there may be a biological basis for the mental health benefits of HRT. To my knowledge, no studies have been conducted on precisely this topic. (The closest is a study showing that testosterone influencing serotonin in transgender men, but it’s doubtful how much a role serotonin really plays in depression.15 16) This would explain why some transgender people report both intense psychological issues related to their gender dysphoria and distinct from social influence; and the alleviation of these issues with hormone replacement therapy.
The biological perspective certainly does not explain the phenomena of gender identity entirely. There are certainly many who feel their gender to be entirely social in nature. However, if at least some transgender people are transgender due to their biology, it is highly plausible that HRT is effective in part because of its neurological effects.
Credit to @Impossible_PhD on Twitter for a thread proposing this idea, and thanks to @akiva_malamet for asking me if there were any relevant studies that I knew of.
Burke, S.M., Manzouri, A.H. & Savic, I. Structural connections in the brain in relation to gender identity and sexual orientation. Sci Rep 7, 17954 (2017). https://doi.org/10.1038/s41598-017-17352-8
Savic, I. & Arver, S. Sex dimorphism of the brain in male-to-female transsexuals. Cereb Cortex 21, 2525–2533, https://doi. org/10.1093/cercor/bhr032 (2011).
Simon, L. et al. Regional grey matter structure diferences between transsexuals and healthy controls–a voxel based morphometry study. PLoS One 8, e83947, https://doi.org/10.1371/journal.pone.0083947 (2013).
Burke SM, Cohen-Kettenis PT, Veltman DJ, Klink DT, Bakker J. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents. Front Endocrinol (Lausanne). 2014;5:60. Published 2014 May 28. doi:10.3389/fendo.2014.00060
Berglund H, Lindström P, Dhejne-Helmy C, Savic I. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex. 2008 Aug;18(8):1900-8. doi: 10.1093/cercor/bhm216. Epub 2007 Dec 3. PMID: 18056697.
Rubinow, D. R., Roca, C. A., Schmidt, P. J., Danaceau, M. A., Putnam, K., Cizza, G., ... & Nieman, L. (2005). Testosterone suppression of CRH-stimulated cortisol in men. Neuropsychopharmacology, 30(10), 1906-1912.
Amiaz, R., & Seidman, S. N. (2008). Testosterone and depression in men. Current Opinion in Endocrinology, Diabetes and Obesity, 15(3), 278-283.
Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009 Jul;15(4):289-305. doi: 10.1097/01.pra.0000358315.88931.fc. PMID: 19625884.
Walf, A. A., & Frye, C. A. (2006). A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior. Neuropsychopharmacology, 31(6), 1097-1111.
Newhouse, P., & Albert, K. (2015). Estrogen, stress, and depression: a neurocognitive model. JAMA psychiatry, 72(7), 727-729.
Pandya, M., Altinay, M., Malone, D. A., & Anand, A. (2012). Where in the brain is depression?. Current psychiatry reports, 14(6), 634-642.
Dunlop, B. W., & Nemeroff, C. B. (2007). The role of dopamine in the pathophysiology of depression. Archives of general psychiatry, 64(3), 327-337.
Pasqualini, C., Olivier, V., Guibert, B., Frain, O., & Leviel, V. (1995). Acute stimulatory effect of estradiol on striatal dopamine synthesis. Journal of neurochemistry, 65(4), 1651-1657.
Purves-Tyson, T. D., Handelsman, D. J., Double, K. L., Owens, S. J., Bustamante, S., & Weickert, C. S. (2012). Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. BMC neuroscience, 13(1), 1-12.
Kranz, G. S., Wadsak, W., Kaufmann, U., Savli, M., Baldinger, P., Gryglewski, G., ... & Lanzenberger, R. (2015). High-dose testosterone treatment increases serotonin transporter binding in transgender people. Biological psychiatry, 78(8), 525-533.
Cowen, P. J., & Browning, M. (2015). What has serotonin to do with depression?. World Psychiatry, 14(2), 158.