I was actually thinking about it the other day and I can buy that it only worked on male subjects because the genetic technology was rushed and shitty.
The text is of course inconsistent, but I get the impression that Big E gets way too much credit for being a super genius mad scientist and is instead just cribbing from dark age tech that he doesn't fully understand. The Space Marine and Primarch program in particular gets a lot of pushback from other characters who are in positions of trust and power, with Malcador going so far as to asking "yo, why are they all dudes" and not getting a really satisfactory answer. The writers mostly play it straight, but the setting is ridiculous and reflective of sexism IRL.