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Volume 13
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10.3390/biomedicines13030622
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Article

Testosterone Supplementation: A Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis

by
Wenzhi Yang
1,2,
Wendi Xiao
3,
Xiangyi Liu
1,2,
Hui Li
4,
Tao Huang
3,* and
Dongsheng Fan
1,2,*
1
Department of Neurology, Peking University Third Hospital, Beijing 100080, China
2
Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing 100080, China
3
School of Public Health, Peking University, Beijing 100080, China
4
Key Laboratory of Carcinogenesis and Translational Research, Peking University, Beijing 100080, China
*
Authors to whom correspondence should be addressed.
Biomedicines 2025, 13(3), 622; https://doi.org/10.3390/biomedicines13030622
Submission received: 8 January 2025 / Revised: 6 February 2025 / Accepted: 26 February 2025 / Published: 4 March 2025
(This article belongs to the Topic Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models, from Animals to Humans, from Qualitative to Quantitative Methods, 3rd Edition)
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Abstract

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by the degeneration of spinal cord and brain neurons. Proteomics combined with Mendelian randomization (MR) is an effective method for finding disease treatment targets. Methods: We aimed to seek new therapeutic targets for ALS. A large-scale GWAS on proteomics (4907 circulatory protein) with 35,559 individuals was included as the exposure data; a GWAS with 138,086 ALS patients was used as the outcome data; we found that a high level of sex hormone-binding globulin (SHBG) is a risk factor by MR analysis. Colocalization analyses were used to validate the causality between SHBG and ALS further. Functional enrichment found a high level of SHBG was associated with a low level of bioavailable testosterone. Two-sample MR confirmed the association of SHBG (400,210 samples), bioavailable testosterone (367,289 samples), and ALS. Results: A high level of SHBG, and a low level of bioavailable testosterone are risk factors for ALS. Conclusions: A low level of bioavailable testosterone is a risk factor for ALS. Although our study is relatively limited and cannot fully confirm that testosterone supplementation has a therapeutic effect on ALS, it offers a promising direction for ALS therapy.
Keywords: amyotrophic lateral sclerosis; ALS; proteomics; mendelian randomization; MR; SHBG; testosterone; bioavailable testosterone amyotrophic lateral sclerosis; ALS; proteomics; mendelian randomization; MR; SHBG; testosterone; bioavailable testosterone

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MDPI and ACS Style

Yang, W.; Xiao, W.; Liu, X.; Li, H.; Huang, T.; Fan, D. Testosterone Supplementation: A Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis. Biomedicines 2025, 13, 622. https://doi.org/10.3390/biomedicines13030622

AMA Style

Yang W, Xiao W, Liu X, Li H, Huang T, Fan D. Testosterone Supplementation: A Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis. Biomedicines. 2025; 13(3):622. https://doi.org/10.3390/biomedicines13030622

Chicago/Turabian Style

Yang, Wenzhi, Wendi Xiao, Xiangyi Liu, Hui Li, Tao Huang, and Dongsheng Fan. 2025. "Testosterone Supplementation: A Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis" Biomedicines 13, no. 3: 622. https://doi.org/10.3390/biomedicines13030622

APA Style

Yang, W., Xiao, W., Liu, X., Li, H., Huang, T., & Fan, D. (2025). Testosterone Supplementation: A Potential Therapeutic Strategy for Amyotrophic Lateral Sclerosis. Biomedicines, 13(3), 622. https://doi.org/10.3390/biomedicines13030622

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