@Tulpa I don't mean to be offensive by anything I say, I'm just a bit confused as well.
You mention that these worlds are fantasy, and that in these worlds people who are transgender should not be persecuted because it is fantasy. I can understand that.
However, sense these worlds are fantasy couldn't everyone simply be born with the same sex and gender? I understand how many people play characters similar to themselves. However if you were born male but were of female gender (IRL) wouldn't the best representation be to simply play female? Sense, essentially, you are female?
Everything obviously is up to GM decision, but why as a player would you want to play transgender? Isn't the ultimate goal of transgenderism to be the other gender without a problem? (Not discussing lighter forms of transgenderism, like cross-dressing)
The only reason I can see playing as a transgender character is if you believe the transgender experience is different somehow from being cis gendered at a fundamental level. In which case, wouldn't that make it an issue?
What I was trying to get at too. At the same time, I recognise what @Strawberry425 said.