# The differences in sex ratio between sporadic and familial amyotrophic lateral sclerosis: a systematic review

## TL;DR

This study finds that men are more likely than women to develop sporadic amyotrophic lateral sclerosis, but not the familial form.

## Contribution

The study reveals a significant sex ratio difference in sporadic versus familial ALS, emphasizing the need for sex-specific research.

## Key findings

- ALS is more prevalent in males than females with a sex ratio of 1.25.
- Sporadic ALS shows a male-to-female ratio of 1.29, while familial ALS has a ratio of 1.05.
- Males have a 7% higher likelihood of being diagnosed with sporadic rather than familial ALS.

## Abstract

Amyotrophic lateral sclerosis (ALS) is more prevalent in males than in females. However, it is unclear whether the difference in sex ratio is observed similarly in sporadic compared to familial ALS. Here, we conducted a systematic review to investigate the differences in sex ratio between familial and sporadic ALS. Following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines, this study searched Ovid MEDLINE, Embase, Emcare, SCOPUS and Cochrane databases. We used a random-effects meta-analysis to estimate sex ratios in a total of 9269 ALS patients (4135 female, 5134 male) across 20 included studies. We confirmed that ALS is more prevalent in males than in females (sex ratio: 1.25 (95%CI 1.14–1.37). However, when we stratified the analyses, the sex ratio was only different in sporadic ALS. Male-to-female ratios were 1.29 (95% CI 1.16–1.42) for sporadic ALS and 1.05 (95% CI 0.93–1.18) for familial ALS. A further analysis showed a pooled risk ratio of 1.07 (95% CI 1.00–1.15), indicating a 7% higher likelihood of males being diagnosed with sporadic rather than familial ALS. These findings highlight the importance of considering sex-specific factors in ALS research and clinical practice.

The online version contains supplementary material available at 10.1007/s00415-026-13627-1.