Hi Sam,
Sorry for the delayed response. This is a great question and requires some thinking.
At the moment, designSampleSize is set up to reflect the sample size estimation for direct pairwise comparisons (e.g. disease male vs disease female; disease male vs control female; etc.). However, it doesn't handle sample size estimation with covariates at the moment. With covariates, the estimated number of samples should decrease. I'd need to investigate further to understand the extent of this decrease; I can say confidently it depends on your comparison of interest.
We can look to add a feature to account for your comparison for sample size calculation if you think that'd be useful.
Thanks,
Tony