I used the fit calculator above to set up my Litespeed. Then, I bought an IRO with .5cm shorter top tube & some additional rise on the stem. As a result, it is very comfortable. I'm sitting slightly more upright, but still very aero when I'm in the drops. I did a 6hr ride on it this past Sunday. I was very comfortable & fresh when I finished. No saddle soreness. No arm, hand, wrist, or back discomfort. Finding the right saddle & setting the correct angle (for you) is important. I use a more padded heavier saddle on my IRO (a cheap WTB) & set it up level to slightly nose up.

If your wrists are uncomfortable, you are probably too stretched out. Either the top tube is too long, stem too long, or you need more rise on the stem (bar is too low). For a quick fix, you can move the seat forward on the rails (if it is not already all the way forward) & that may help some.