In many ways, the core issues of the three main characters are similar to the problems of the lion, scarecrow and tin man in The Wonderful Wizard of Oz, though of course with an adult twist. In fact, each of them confuses the sex-oriented symptoms (Gary - virginity, DiDi - anorgasmia, Zii - getting DiDi in her bed) for their real and much deeper personal problems and don't change much even after getting what they chase.
Gary has a heart and a brain, but he doesn't have the courage to stand up to people and tell them "no". The result is that people keep taking advantage of him, even after he loses his virginity. As a matter of fact, he seems to become more and more spineless after his first sexual encounter, until Peggy's advice gets to him and he decides to tell Tracy and James "No".
DiDi has courage and a heart, but lacks the brain to realize how her insensitivity hurts other people and she constantly misinterprets people's advice. It's not that she doesn't care about people, she just doesn't understand why what she does is wrong. She ends up calling Kiley the love of her life, while basically just using her as a glorified vibrator. The same thing happens when she starts dating Zii, who gives her even more explosive orgasms, but it doesn't really change her.
Zii has courage and brains, but even though she knows better, she allows her heartless impulsivity (and libido) to cause one disaster after another. She knows what she does is wrong, but she can't be bothered to be better. It's not so much that she is actively malicious, but if she has to choose between her own pleasure or doing what's right, she pretty much always ends up choosing the former. Zii knew that Sonya still had deep feelings for her, yet decided to have casual sex with her anyway, even though Zii had no feelings for Sonya. She ends up establishing a sexual relationship with DiDi (who she's been chasing since the first volume) and she's still basically the same impulsive person. Things change soon afterwards when Zii realizes that her libido has ruined too many good parts of her life and she resolves to be better.
If you pay attention to Gary's shirts they often reflect his moods or what's going on in the comic, or provide a humorous punchline. For example, in early comics he often wears an X-Men logo, marking him as the only virgin in the cast; when Dillon moves back in he usually wears a Fantastic Four shirt, reflecting the four people who then live in the apartment; when he finally loses his virginity he's wearing a shirt that says WWWYKI; when Yuki forces him to touch DiDi's breasts in an effort to help improve his art he's wearing an Adventure Time one; when Yuki explains to him why she decided to move in he has Decepticon logo, because she's lying to him; and he wears a Kirby one when he visits Amber, referring to him continuously eating Yuki out.
Gary is almost never shown standing up straight, but is usually hunched over. This reflects how extremely meek and beaten-down by life he is. His big character development at the start of volume 10 is reflected by him starting to, literally, walk tall; Zii barely recognises him.
Given that DiDi's orgasm is apparently strong enough to sprain fingers, what do you think would happen if it was a man's penis that was inside her vagina at the time? (Though it's more probable that it was her thighs that hurt Kiley's hand, rather than her vagina per se.)
A minor case, but a moment’s thought suggests that DiDi and Zii's relationship is probably destined to go down in flames. Both characters now have long term travelling careers, and both have been shown to remember life lessons like a goldfish. DiDi is known to be intensely hungry for orgasms; a quick pep-talk will not fix over a decade of issues resulting in her overpowering need to get what she wants (and she was super-ruthless in trying to achieve it just once), so months away from her constant supply is like taking a water bottle away from a man who was dying of thirst not five minutes beforehand. Zii, on the other hand, will either somehow stick to the lesson and be okay-ish with her girlfriend being away for long stretches of time, as she has been shown to at least be able to masturbate to vent her frustrations, or, worst case, will default back into borderline sexual predator territory, partly because, as shown, she like DiDi is incapable of maintaining a functional long term relationship, but mostly due to her being a Womanchild, unable to stick to her guns for longer than a strip or two.
