It's a gender-bending story, but it doesn't feel like one. Hazumu changes from boy to girl... but it's irreversible and the whole world's knows about it, so he thinks that's that. He's a girl now and he's completely okay with it. He doesn't brood about what he's gained/lost and he doesn't even want to change back. This genre's standard jokes and tropes are being ignored, after Hazumu's girl-training in ep.2.
To be honest, the plot would hardly change if Hazumu had always been female. It's a love story. The central triangle involves Hazumu's childhood friend Tomari (a tomboy whose hobbies include weight training, athletics and kicking their mutual friend in the head, while disliking activities like cooking) and Yasuna (a girly girl who can't handle men to a degree that needs professional help and medical research).
The original manga's author is Satoru Akahori and here he wanted to explore a message of steady true love. He was better known for ecchi fanservice and he thought that the unspoken target of love stories tends to be sex (at least in the audience's minds), so his first thought for counteracting this was an all-female main cast. That's been done a million times, though, so he added the gender-bending and a main character who could never turn back and wouldn't even want to. (Then, in addition, the scriptwriter is Jukki Hanada. I know that name. Princess Jellyfish, K-On!, Nichijou, Natsume's Book of Friends, Accel World, The Pet Girl of Sakurasou, Tamako Market, Love, Chunibyo & Other Delusions, No Game No Life, all the good versions of Love Live!, A Place Further than the Universe, Steins;Gate, Hitori Bocchi no Marumaru Seikatsu... I need to watch more Jukki Hanada anime.)
It's quite an interesting show, albeit a relatively low-key one. What I think of as "the real show" is emotionally sensitive, occasionally brutal and mature enough that I had no idea how it would end. All I knew was that someone would get hurt.
The show also, though, has a split personality. It's basically serious and intelligent, but sometimes it's stupid or goofy. Examples include:
(a) the aliens that change Hazumu's gender. We're watching a show that's in most respects 100% real-world... and then a space battleship flies overhead. It then does a whoopsie with Hazumu and broadcasts the fact to the entire world. Two aliens later arrive in the main cast as wacky and occasionally invisible magical observers.
(b) Namiko-sensei, who's tooth-grindingly unfunny. Even her voice actress can be annoying. (She gets slightly better when she falls in love with one of the aliens, though.) Her appearances usually go as follows. 1. announce that she's 35 years old and has never had a boyfriend. 2. say and do stupid things. 3. fall off, into or out of something, e.g. a cliff, a window.
(c) Hazumu's parents. They're amusing when they're being airheads, but I was creeped out by Hazumu's father trying to see her naked. (We're expected to find this funny, because he always fails due to the Wrath Of Mum.)
(d) Asuta Soro, another childhood friend of Hazumu and Tomari. He's the only male member of the core cast and he actually gets some good material. I liked him. Unfortunately, he also turns into an idiot who keeps wondering if his friends are in love with him (SPOILER: no). I never thought for even a millisecond that Asuta had any chance whatsoever, although I was surprised for a while by what Hazumu said to him in ep.7.
To be honest, I wouldn't even call Hazuna the protagonist. Everything revolves around her, but she's a bit opaque (e.g. the exact nature of her sexuality) and it's Tomari who's the viewpoint character. We explore her feelings. We experience her emotional journey, torn between "selflessly supportive" and "selfishly wanting Hazuna for herself". It's interesting to see this aggressively mannish girl struggling with her love for her best friend who'd previously been a boy but had always been girl-like anyway. (The only thing undercutting Tomari's masculine qualities is that she's the shortest character. I laughed in ep.9 when her family freaks when she says something feminine. Mum phones Dad in a panic. "Leave work and come home right now! Tomari's saying girly things!")
I like the title, by the way, which is fun to say. "Kashy Mashy".
It has some distracting elements, but this is basically a good story. It avoids fanservice and the usual jokes and story devices of gender-bending stories. To my surprise and delight, it also criticises an anime protagonist who can't choose between girls and declares that his indecisiveness will wreck everything. (It nearly does.) It ends with aliens conducting a lesbian marriage. (Gay marriage still isn't legal yet in Japan today, incidentally, let alone nearly twenty years ago in 2006.) I can't really imagine myself rewatching this series, but it's quite interesting.