Female full of trouble as one in direct confrontation (4-2)
I believe the answer is:
head-on
'one in direct confrontation' is the definition.
(I've seen this before)
'female full of trouble' is the subsidiary indication.
'female' becomes 'hen' (hen is a kind of female).
'full of' means one lot of letters goes inside another.
'trouble' becomes 'ado' (I've seen this before).
'hen' enclosing 'ado' is 'headon'.
'as' is the link.
(Other definitions for head-on that I've seen before include "(Of crash) involving the front of vehicle)" , "In direct confrontation" , "One had (anag.)" , "This collision is full frontal" , "Collision happening in full-frontal way" .)