Background Women report more work-related pain and neck/shoulder musculoskeletal disorders than men. For the same absolute workload, due to lower strength, females generally work at a higher relative intensity, which could induce more fatigue. However, the arm’s anthropometric load (AL) of men is higher. Therefore, simply lifting their arm could be more fatiguing. Sex as a variable is formed of many constructs, and analyses can become muddied by their differing responses to fatigue. No studies have considered AL, when comparing how fatigue affects men and women. The purpose was to determine if including the arm’s AL in the statistical analysis would impact findings of sex-specific effects of shoulder fatigue on muscle EMG. Methods Fifty-five (29m/26f) participants completed a repetitive pointing task (RPT) at shoulder height until they reported fatigue of 8+ on the BORG CR-10 scale. Muscle activities were measured using surface electrodes placed over the anterior deltoid (AD) and upper trapezius (UT) muscles. Muscle activity amplitude was quantified using root mean square (RMS). First- and last-minute data were used to assess change from no-fatigue (NF) to fatigue-terminal (FT) conditions. AL was calculated using sex-specific body parameter equations. General estimating equations (GEE) were used to determine the effects of sex and fatigue on RMS values, while including AL in the GEE. Results There was no sex difference in time to reach fatigue. A significant main effect of sex on RMS was observed (χ2(1) = 4.17, p = 0.04) when including AL as a covariate. Females displayed a significantly higher percentage change in AD RMS from NF to FT, compared to males (p = 0.03), when AL was included in the GEE. No sex differences in UT were observed. Conclusions This sex difference emerged when AL was included as a covariate, suggesting that sex-associated anthropometric differences may contribute to sex differences in the fatigue response. Differences in the impact of AL on AD compared to UT could be explained by differences in their respective mechanical roles or muscle fiber content. Anthropometrics may be useful to include as covariates in future research to separate individual anthropometric differences from sex differences.

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