In Unearthed Arcana, which is still open content at this moment, there’s a section in the Sanity rules (adapted from d20 Call of Cthulhu) on Psychosexual Disorders:
Recognizable disorders of this type include transsexualism (a belief that one is actually a member of the opposite sex), impaired sexual desire or function, nymphomania and satyriasis (inordinate and uncontrollable sexual appetite in women and men, respectively), and paraphilia (requirement of an abnormal sexual stimulus, such as sadism, masochism, necrophilia, pedophilia, exhibitionism, voyeurism, fetishism, or bestiality).
Most of these disorders could make players of the afflicted characters uncomfortable and thus are not appropriate for most roleplaying groups, although they can make for striking (if unpleasant) NPCs.
So you could use WotC’s own OC to build a world where transgender characters aren’t fit to be PCs but can be unpleasantly memorable NPCs. And someone could accuse you of offensive hate speech if you declare the opposite to be true. It’s the official policy of the ruling party in the UK and of the party that’s taken the US presidency three times this century so far that it
is hateful, disruptive, and false to say trans people are normal people who deserve the same rights as anyone else.
Right now, WotC won’t frown at you for saying that Jenna Katerin Moran, creator of Nobilis, is striking but not unpleasant or disordered. All of us who know and like her and/or her work are glad that’s so. But can anyone say with certainty that Hasbro will never, in the next twenty years, have EOs allied with anti-trans forces, who tend to be exuberantly pro-corporate? Sure enough to bet the creative prospects, not to mention personal safety, of everyone like Jenna who’d want their framing to treat trans people well?
And it goes like that through issue after issue, many of which you probably never thought of. I know that I, someone who’s been marked and marginalized several ways for forty years, keep getting surprised by bigotries I never thought of since they happen not to target me or to have come up where I’d notice them. And I’m an expert pro at it! I have prestige levels in being enfeebled!
It’s just too darned too easy to assume that of course a provision I approve when used against targets I approve of targeting will always and ever be used that way. History suggests, alas, that it’s not so reliably simple, however much I used to think or wish it so.