I gave this some thought, about as much as Dragon Ball Super's writer per arc (2-3 secs), and I mapped out the effect of a punch to the pills. I think that the most dangerous swing would be an uppercut, as a straight could divide with less impact and a hook could be rolled:
An uppercut has gravity working against you, so at that point it seemed better to relax and let the sack fly. I have not tested any other attacks, including variants for angles, objects, other limbs or even assault from other testicles. So far uppercuts are the deadliest mapped.
In theory could also spin in the event of an uppercut angle, even if it was a kick. There is more padding round the back and if you briefly relax your anus before clamping, then you've got them locked in an awkward position to counter attack: