A recent article by Meharvan Singh and colleagues discusses how progesterone acts as a protective factor against neurodegenerative diseases and cognitive decline. After menopause, estrogen and progesterone production decrease and put most women in a hormone deficiency negatively affecting cognition (Singh et al, 2024) (Greene & Dixon, 2002). Hormonal treatments like birth control are often prescribed to post-menopausal women to treat the hormone deficiency and negate the symptoms such as memory issues and migraines. These hormonal deficiencies have been discussed as a potential reason for why women have higher Alzheimer’s disease rates than men (Breeze et. al, 2024) and explicitly link estrogen and progesterone levels as protective factors against neurodegeneration. Lacking sufficient estrogen and progesterone allows for higher rates of cognitive issues. While the hormonal sex differences affecting neurodegenerative disease rates and cognition are currently being studied, few research articles bridge the gap between sex hormones being neuroprotective and what that means for transgender people using HRT. An article by van Heesejewijk et al. (2021) assesses how the cognitive functioning of transgender women over the age of 55 using long-term gender affirming hormonal replacement therapy (HRT) may differ from both cisgender men and women.
Gender affirming hormonal therapy for adults who are transgender does not standardly involve inhibiting estrogen or progesterone (Unger C.A., 2016). Feminizing treatments may involve an individual taking estrogen supplements to trigger breast tissue growth and where body fat is predominantly stored. They may also take anti-androgens to limit the influence of testosterone on the body’s physical presentation. Progesterone is less commonly prescribed as a part of this treatment. During masculinizing treatment an individual may take testosterone supplements to increase its impact on their body such as increasing body hair and deepening their voice. Masculinizing and feminizing treatments are not restricted to transgender men and women, as cisgender people are also capable of gender dysphoria and may use treatments to minimize it. Other transgender people using these treatments may also not strictly align themselves as man or woman but wish to medically alter their appearance and presentation. The aforementioned treatments do not directly inhibit progesterone or estrogen and instead increase their amounts. This then creates the question of how increasing estrogen and progesterone through HRT in amounts high enough to cause physical alteration might impact cognition as a protective factor. That is not to say other treatments are detrimental. Puberty blockers do inhibit estrogen and testosterone yet are prescribed very rarely and are approved by/have guidelines created by the Endocrine Society and the American Academy of Pediatrics (Brownstein, M. 2025) for proper and safe use. It is extremely relevant to understand how gender affirming hormonal therapy is standardly conducted and differs amongst all those who participate to avoid scientific blindspots and misconceptions. Gender affirming care and hormonal therapy are not exclusive to transgender people, however full gender transition treatments are often looked at in isolation and not concurrently with ongoing research and breakthroughs in related areas.
The article “Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared with Cisgender Women and Men” by van Heesejewijk et al. (2021) tested and compared the results of 37 transgender women over the age of 55 who had used feminizing hormone therapy for at least ten years to the results of cisgender men and women between the ages of 55-65. Transgender women are women who were born with male physical sex characteristics but identify as women. In this study all participants who are transgender women had medically transitioned. Participants were matched into groups (1 transgender woman, 3 cisgender men, 3 cisgender women) based on education and age. The researchers wanted to understand how hormonal therapy may have affected specifically transgender women’s cognition in comparison to others of the same age or background. Due to the newly found neuroprotective properties of growth hormones researchers hypothesized that there would be a difference amongst the three categories of participants in cognitive areas. Participants completed several cognitive tests and the results were compared against each other. Throughout the tests, transgender women scored more consistently with cisgender men than women but had higher scores than both cisgender men and women in the MMSE test. The MMSE (Mini-Mental State Examination) is a scored test utilized as a screening tool for dementia and general memory problems. Transgender women, however, scored lower than both cisgender men and women in the delayed and immediate memory recall tests. The outcomes of this study revealed minimal yet statistically significant effects of hormonal therapy on cognition. It also raises further questions for the long-term impact of HRT. Do older transgender people who have been on HRT for an extended period of time have the same or lower rates of neurodegenerative diseases, such as Alzheimer’s, when compared to the cisgender population? For transgender men using HRT, would their cognitive test results be akin to cisgender men and women, or would they score more similarly to transgender women if included in this study? These are questions that will hopefully be considered and pursued in the future.
References
Breeze, B., Connell, E., Wileman, T., Muller, M., Vauzour, D., & Pontifex, M. G. (2024). Menopause and Alzheimer’s disease susceptibility: Exploring the potential mechanisms. Brain Research, 149170. https://doi.org/10.1016/j.brainres.2024.149170
Brownstein, M. (2025, January 6). Gender-affirming care is rare, study says— Harvard Gazette. Harvard Gazette. https://news.harvard.edu/gazette/story/2025/01/gender-affirming-care-is-rare-study-says/
Greene, R. A., & Dixon, W. (2002). The role of reproductive hormones in maintaining cognition. Obstetrics and Gynecology Clinics of North America, 3, 437–453. https://doi.org/10.1016/s0889-8545(02)00019-0
Singh, M., Krishnamoorthy, V. R., Kim, S., Khurana, S., & LaPorte, H. M. (2024). Brain-derived neuerotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotection. Frontiers in Endocrinology, 15. https://doi.org/10.3389/fendo.2024.1286066
Unger C. A. (2016). Hormone therapy for transgender patients. Translational andrology and urology, 5(6), 877–884. https://doi.org/10.21037/tau.2016.09.04
van Heesewijk, J. O., Dreijerink, K. M. A., Wiepjes, C. M., Kok, A. A. L., van Schoor, N. M., Huisman, M., den Heijer, M., & Kreukels, B. P. C. (2021). Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared with Cisgender Women and Men. The Journal of Sexual Medicine, 8, 1434–1443. https://doi.org/10.1016/j.jsxm.2021.05.013
No comments:
Post a Comment