As far as the "science" goes, this is 40k we are talking about, it blatantly ignores science all the time with everything from space marines to titans, none of this stuff works if a scientist starts looking at it seriously. By 40k standards it's positively easy to make female custodians because the Emperor himself has both an X and Y chromosome. A woman just has two X chromosomes, no new genes that a man doesn't have, no autoimmune problems so long as the chromosomes are compatible enough for surgery in the first place. Even more important is that Custodians are each custom made by a team of scientists rather than using crude gene seed methods like Astartes. The group of scientists can simply modify the procedure to make it work on a woman.
On the note about the physical weakness of women, a custodian isn't a human anymore but a scientifically remade trans human, it's not the strength of the original man that makes a male custodian strong, the scientists could pick up the weediest little dude they could possibly find and still turn him into a custodian just as strong as any other custodian. They can do the same with a woman, and at the end she's not going to be a "woman", she's going to be a trans human custodian. Think of the super mutants from the Fallout game series, half of them were originally women and half were men, but when turned into super mutants nobody can tell the difference anymore, they are both hulking behemoths completely unrecognisable from their original sex. At best you would have to take off a super mutant's underpants to look between their legs to see if they are a boy or girl. The same would be true of Custodians, male or female you are not going to tell unless you look between their legs, the amount of testosterone alone would give female custodians deep voices and facial hair.
Could the Emperor of old find the most skilled female blade master on terra and think to himself "it's a pity one so skilled is so small and weak, with a bit of upgrading she would make a great bodyguard, I think I will order my scientists to remake her body to fit her awesome skills"?, Yes, yes the Emperor absolutely could. Not only women of extraordinary skill but also tiny men, midgets, heck anyone he deemed worthy, he's the freaking Emperor of Man, he can do anything he likes. If the Emperor himself deemed your skill sets and loyalty worthy enough then it doesn't matter who or what you are, the Emperor has the power to remake your body into a Custodian with enough effort and resources.
So there is nothing at all implausible about there having "always been female custodians", it just comes back to men in the fan base not liking it because of personal taste.
(Note I have glanced at the comments, Dustfan I do intend to get back to you in more detail with a private message, unfortunately I have been very sick all week with a throat infection and it makes it hard for me to reply as much as I would like when it's so hard to breathe. When I am in a better state of health I will get back to you.
Pillow43 and Quinlongfei I have read your comments and I agree, I've just been a bit too under the weather to reply.
That brings us to the last two comments… Yeah… Ranting about Nazis and Communists in one reply, and a "no you" in the other. I mean, thank you for sharing I guess?)