High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People

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• 作者：Georg S. Kranz^a ; Wolfgang Wadsak^b ; Ulrike Kaufmann^c ; Markus Savli^a ; Pia Baldinger^a ; Gregor Gryglewski^a ; Daniela Haeusler^b ; Marie Spies^a ; Markus Mitterhauser^b ; Siegfried Kasper^a ; Rupert Lanzenberger^a ; ^{rupert.lanzenberger@meduniwien.ac.at" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Estradiol ; Hormone treatment ; Positron emission tomography ; Serotonin transporter ; Testosterone ; Transsexual
• 刊名：Biological Psychiatry
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：78
• 期：8
• 页码：525-533
• 全文大小：591 K

文摘

Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiologic findings. Here, we used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin reuptake transporter (SERT) binding in female-to-male and male-to-female transsexuals.

Methods

Thirty-three transsexuals underwent [¹¹C]DASB positron emission tomography before start of treatment, a subset of which underwent a second scan 4 weeks and a third scan 4 months after treatment start. SERT nondisplaceable binding potential was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT nondisplaceable binding potential.

Results

One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding_, indicating a protective effect of estradiol against SERT loss.

Conclusions

Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties.