Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study
Open accessAbstract
Background and purpose: Parkinson disease (PD) presents relevant sex‐related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human‐based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical–pathological features in male PD patients. Methods: A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α‐synuclein, amyloid‐β‐42, amyloid‐β‐40, total tau, and phosphorylated‐181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3‐T magnetic resonance imaging for further correlations. A control group of 56 age‐matched individuals was enrolled for comparative analyses. Results: Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society–Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α‐synuclein and right globus pallidus volume. FSH and LH had age‐dependent correlations with cognitive impairment and CSF amyloid‐β‐42/amyloid‐β‐40 ratio. Conclusions: The study suggested that sex hormones could differentially contribute to clinical–pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age‐dependent phenomena of amyloidopathy and cognitive decline.
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Dysregulation of microglial functions is associated with several health concerns that often show sex prevalences, including Alzheimer's disease (more prevalent among females), Parkinson's disease (more male-prevalent), and various other neurodevelopmental, neuropsychiatric and neurodegenerative disorders.
“Dysregulation of microglial functions is associated with several health concerns that often show sex prevalences, not only affecting Alzheimer’s disease, which shows more prevalence among females, and Parkinson’s disease, more male-prevalent, but also including various other neurodevelopmental, neuropsychiatric and neurodegenerative disorders [38–43].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [41]
The Introduction states that Parkinson disease is more prevalent in males, supporting the sex-prevalence portion relevant to this paper. The passages on neuroinflammation do not establish the sentence’s association between microglial dysfunction and Parkinson disease; the paper’s focus is sex hormones and PD biomarkers. (LLM, conf=0.84)
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Ragini, R., Choudhury, S., Krithika, N. C., Bharath, M. M. S., Rathod, B. L. S., Yadav, R., & Alladi, P. A. (2026) · Annals of Neurosciences · doi:10.1177/09727531261442666
When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases
Hunt, J. N., & Kortagere, S. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06163-6
- Authors
- Bovenzi, R., Sancesario, G. M., Conti, M., Grillo, P., Cerroni, R., Bissacco, J., Forti, P., Giannella, E., Pieri, M., Minosse, S., Ferrazzoli, V., Pucci, N., Laudazi, M., Floris, R., Garaci, F., Pierantozzi, M., Stefani, A., Mercuri, N. B., Picchi, E., Di Giuliano, F., & Schirinzi, T.
- Affiliations
- University of Rome Tor Vergata (IT)
- Fondazione Santa Lucia (IT)
- Neuroradiology Unit, Department of Biomedicine and Prevention University of Rome “Tor Vergata” Rome Italy
- Corresponding author
- Schirinzi, Tommaso
- ORCID
- Bovenzi, Roberta
- Sancesario, Giulia Maria
- Conti, Matteo
- Grillo, Piergiorgio
- Cerroni, Rocco
- Bissacco, Jacopo
- Giannella, Emilia
- Pieri, Massimo
- Minosse, Silvia
- Ferrazzoli, Valentina
- Pucci, Noemi
- Laudazi, Mario
- Floris, Roberto
- Pierantozzi, Mariangela
- Stefani, Alessandro
- Mercuri, Nicola Biagio
- Picchi, Eliseo
- Schirinzi, Tommaso
- Venue
- European Journal of Neurology
- Publisher
- Wiley
- Published
- 2023-04-09
- Volume
- 30
- Issue
- 7
- Pages
- 1983-1990
- ISSN
- 1351-5101 (ISSN-L)
- 1468-1331
- OpenAlex
- W4361000419
- Cited by
- 41
- References
- 45
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 14 · 2023: 4
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, sex hormones, male vulnerability, estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone, gonadotropins, alpha-synuclein, amyloid-beta, tau protein, cognitive impairment, motor impairment, brain volumetry, biomarkers
- MeSH terms
- Estradiol, Humans, Male, Parkinson Disease, Peptide Fragments, Gonadal Steroid Hormones, Testosterone, Biomarkers, Amyloid beta-Peptides, tau Proteins, alpha-Synuclein
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