To make a hormone ineffective, the most relevant option would be receptors on the outside of the target cell. If the receptors are absent, blocked, or malfunctioning, the hormone will not be able to bind and exert its effects on the target cell, rendering it ineffective.
The other options about frequency of production, travel time, and distance may influence how often or how quickly hormones act, but they do not determine the effectiveness of the hormone at the receptor site.