The Link between Estradiol and Neuroplasticity in Transgender Women after Gender-Affirming Surgery: A Bimodal Hypothesis

Abstract

For transgender individuals, gender-affirming surgery (GAS) and cross-sex hormone therapy (CSHT) are part of the gender transition process. Scientific evidence supporting the maintenance of CSHT after GAS-related gonadectomy is accumulating. However, few data are available on the impact of CSHT on the brain structure following hypogonadism. Thus, we aimed to investigate links between estradiol and brain cortical thickness (CTh) and cognition in 18 post-gonadectomy transgender women using a longitudinal de-sign. For this purpose, the participants underwent a voluntary period of CSHT washout of at least 30 days, followed by estradiol re-institution for 60 days. High-resolution T1weighted brain images, hormonal measures, working and verbal memory were collected at 2 time points: on the last day of the washout (t1) and on the last day of the 2-month CSHT period (t2). Between these 2 time points, CTh increased within the left precentral gyrus and right precuneus but decreased within the right lateral occipital cortex. However, these findings did not survive corrections of multiple comparisons. Nevertheless, there was a significant negative correlation between changes in estradiol levels and changes in CTh. This effect was evident in the left superior frontal gyrus, the left middle temporal gyrus, the right precuneus, the right superior temporal gyrus, and the right pars opercularis. Al-Schneider et al.though there was an improvement in verbal memory following hypogonadism correction, we did not observe a significant relationship between changes in memory scores and CTh. Altogether, these findings suggest that there is a link between estradiol and CTh.

A Multi-Modal MRI Analysis of Cortical Structure in Relation to Gender Dysphoria, Sexual Orientation, and Age in Adolescents

“…Furthermore, our results cannot generalize to ages beyond 12-to 17-years-old. Studies on adults have examined cortical structure related to GD [9,26,[102][103][104][105][106][107][108], but we know of no studies examining cortical structure of GD children. Lastly, we examined three cortical structural brain features; other aspects of adolescent GD brain structure (e.g., white matter microstructure) await investigation.…”

Estradiol Replacement as a Potential Enhancer of Working Memory and Neuroplasticity in Hypogonadal Trans Women

“…As previously reported in the methodology section in Schneider et al [53], venous samples were collected between 8 a.m. and 10 a.m. at each of the time points. E 2 was measured using an electro-chemiluminescence immunoassay (ECLIA; Roche Diagnostics, Mnaheim, Germany) with assay sensitivity of 5.0 pg.mL and intra- and inter-assay CV of 5.7% and 6.8%, respectively.…”

“…Combining nuclear magnetic resonance spectroscopy with clinical and neurocognitive data may provide a more comprehensive understanding of the role of sex hormones in the brain, particularly for their protective or deleterious effects [52]. Recently, our group showed that E 2 replacement in hypogonadal trans women strengthens the functional connectivity between the thalamus and primary sensorimotor cortex and affects cortical thickness in E 2 -receptive brain regions [17, 53]. However, the underlying biochemistry of sex hormones that translates into neuroimaging and its relationship with a neurobiological basis of neurocognition is still unclear.…”