Sheldon gets mad at Leonard for not telling him he is home, and refuses to believe anything he says, though with Howard's help they eventually reconcile.
Meanwhile, Howard experiences weight gain and mood swings; he had applied estrogen ointment to his mother without gloves, so absorbing it through his skin.
The next day, Amy is even madder at Sheldon when he embarrasses her at lunch in front of her colleagues.
At home, Penny and Leonard explain to him that Amy is right, so he goes to her apartment and apologizes, but re-offends her by saying she can be difficult to put up with.
Sheldon mentions Howard's comments to Bernadette, who then confronts Howard and gets mad after he tries to deny his statements, forcing Howard to stay at Raj's place. Howard promises to spend more time with her, but only after he and Raj finish their video game, once again enraging Bernadette.