Disclaimer: I don't own Doctor Who.
When the Doctor lost Rose it was painful. She had been the first companion after the devastation of the Time War. He had even begun developing a romantic attachment to her. But to have his pink and yellow human ripped away from him- sucked into the Void and then locked away forever in a parallel world had nearly destroyed him.
When Martha walked away, it hurt. It hurt because he'd ruined her, he'd turned her into a solider and she had walked the earth alone. He knew it was best to see Martha go, she did need to spend time and recover with her family. She did, but it hurt. He'd lost another companion.
When the Doctor lost Donna, it burned. She was his best friend, his best mate. Just him and Donna off to see the universe. But then his past came out and dragged her into the mess. The meta crisis happened and he lost Rose all over again. But then Donna, his best mate, another one of his kind (sort of.) The DoctorDonna was burning. His magnificat human was burning up from the inside. He did the only thing he could, he saved her... And in doing so he lost her, forever... It burned.
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When the Doctor met River Song the second time, she scared him. He fought falling in love for her because he was scared, he knew he was going to lose her- in fact, she might as well be already lost. Needless to say, in the end, he got married.
When the Doctor met Rory, he'd not really paid any attention to him, other than that nose. He couldn't help but feel bad for that. Rory was amazing, clever, and brave. He was also the calmer and more logical side of his marriage with Amelia. Rory the Roman, the Last Centurion, the boy who waited two thousand years.
When the Doctor met little Amelia Pond in her backyard and scared of the crack in her wall, he couldn't just let her all alone in that big empty house. Crying children were his weakness. Of course, he had flown away in his big blue box and come back twelve years later to see Amelia Pond all grown up. She had so reminded him as Donna, bright red hair and completely furious. But then he'd missed her again, by leaving and coming back two years later. Amy Pond, the girl who waited. One of his best and dearest friends.
And then, in one moment when he'd wrapped his bow tie around River's- er, Melody's hand, kissed her, and sealed the marriage, all four of them- River, Rory, Amy, and himself became a family.
One big family adventuring through time and space.
But then one by one they left.
First was Rory and Amy. The weeping angels ripping Rory away and then Amelia following him because his Ponds went Together or not at all. The Doctor had always known it wasn't going to be not at all... No one stayed forever. And then he'd said goodbye to River at the Singing Towers and all his wonderful magnificent Ponds were gone. It was like losing Gallifrey all over again. The Ponds had been family and they'd been cruelly ripped away from him by his beloved universe.
The Doctor learned a painful lesson that day...
The universe doesn't care.
Then simply in a few clicks of some buttons and the pushing of a lever, the Doctor was gone for a thousand years.
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Rose, Martha, and Donna.
A lover, a doctor, and a best mate.
River, Rory, and Amy.