Consider doing up to six UK to East coast of the US flights in a month (which I have done). The return flight means you lose one complete nights sleep each pattern, six times a month. Now imagine doing this for months on end and you start to get the picture.
I was rosterered 11 US East Coast Atlantic crossings over 2 consecutive 4 week periods one summer. I remember it as tiring as it is possible to be. Also going shorthaul, 6 day blocks with many earlies and truncated sleeps gets you just as tired, but in a slightly different way.
I'm absolutely astonished that the duty hours pilots produce vastly outweigh the normal 9-5 duty hours that normal people sustain- there is none of the protection for time on duty that 'normal' people have- it's absolutely incredible. The tiredness pilots (and cabin crew!) experience is 'superhuman'- long duty hours combined with massive time changes and irregular overnight working- frankly a killing combination. And so many times you see the press refer to pilots 'working' 1000 hrs/year= 20 hrs A WEEK! That's flying hours only! The outrage from laymen is loud! The present duty limitations are at the top scale of human limitations for a satisfactory life- I watch the new attempt at increasing duty limitations with disgust and horror.
Fate has grounded me now- my involuntary departure from the industry has coincided with a vastly more relaxed existence- fortunately I have a delightful small plane to play with. Once a pilot, always a pilot, but my goodness, working for it is becoming hard!