Loyalty: In addition to Male and Female, American includes “Unspecified (X)” and “Undisclosed (U)” as gender options on an AAdvantage profile.
American also includes “Mx.” as a title option.
Changing an existing gender on an AAdvantage account requires you to upload supporting documentation, which is then reviewed by someone at American. (I uploaded a scan of the picture page of my passport.) My change was processed in 23 calendar days.
Booking: The same Unspecified (X) and Undisclosed (U) options are included in the gender field when booking a flight.
Check-in: I haven’t attempted check-in with a gender X passport on American yet.