I don't have massive hands and I handle a G21 fine. I also know less-than-manly women who handle G21's. I'd suggest, assuming that one doesn't have petite, "girly" hands, actually shooting a G21 before writing off the G21 as only a weapon fit for King Kong or Might Joe Young.
You'll find the G21 to be plenty accurate and one of the easiest-to-handle, softest-shooting .45's you ever shot.