Well, the appearance of strong states (England, Russia, Sweden in the later part) for one part, as the Hansa didn't had the possibility to fight back at the same scale, being composed of too many divergent interests (even if they actually tried to choose sort of a podestat-equivalent).
No real possibility to impose itself on the Atlantic trade, against the said states mainly grieved them.
The Reformation and the subsequent wars caused many big turmoil, and unrest is never good for business.
Actually, it's less one factor than many ones happening in the same time.