Sex hormones and ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting from a combination of genetic and environmental factors.  The disease differs by sex, with males more often diagnosed with ALS than females.  However, this gap narrows around menopause, raising the possibility that sex hormones may influence ALS. 

Researchers led by Stephen Goutman, M.D., M.S., Harriet Hiller Research Professor, investigated whether certain male and female hormones in the blood are associated with the risk of developing ALS and with survival after diagnosis.  To do so, they measured these hormones in males and females with ALS and compared them with those without ALS. 

Their research, published in Annals of Clinical and Translational Neurology, found that higher levels of certain hormones, including 11-ketotestosterone, were linked to an increased likelihood of developing ALS. In females, higher levels of specific hormones (estrone, androstenedione, and 11-hydroxyandrostenedione) were also associated with shorter survival. 

“These important findings highlight the potential significance of sex hormones in ALS,” explained Dr. Goutman. “This understanding provides an important new therapeutic target for this fatal disease, which currently has no effective treatments.” 

Other authors: David G. Stouffer, Dae-Gyu Jang, Ph.D., Jihyun Park, Ph.D., Benjamin Murdock, Ph.D., and Richard J. Auchus, M.D., Ph.D., all from the University of Michigan. 

Funding for this research includes the CDC/ADSTR, U.S. Department of Defense, Erik and Linda Novak, James and Margaret Hiller, Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Fund, Stanford Morris ALS Research Fund, and National Institutes of Health. 

Paper cited: Goutman SA, Stouffer DG, Jang DG, Park J, Murdock BJ, Auchus RJ. Sex Hormones Associate With Amyotrophic Lateral Sclerosis Risk and Survival. Ann Clin Transl Neurol. 2025 Dec 18. doi: 10.1002/acn3.70281. Epub ahead of print. PMID: 41412960.