In the first instance (I haven't actually decided what order these will play out in), due to an accident, the male lead ends up being turned into a girl for a while. It does eventually wear off, but until he turns back, one of his companions- a yandere type who's otherwise completely obsessed with him- actually loses all interest in his female form, only coming around once he's male again. Granted, another party member who's into other women takes an interest in the male lead while he's a girl, though she's rather very hesitant at first, and it takes some serious coaxing from another character before she makes a move on him.
In the second instance, a minor character is a woman that has been living as a male for several years- she was the squire of a famed monster slayer, and after he was fatally wounded, she assumed his identity so that his legacy would live on. When circumstances force her to reveal her real identity, one of her comrades who had a crush on the male persona is actually repulsed to find out that the person she was attracted to was another girl.