Starting estrogen seriously kicked off a reaction in my brain of "Oh my God, what have I been missing my whole life?" (I started anti-androgens 3 days earlier, but they didn't really do much but make me feel a bit calmer.)
But seriously, estrogen was like a shot of dynamite to my brain. I don't know if anyone else gets this kind of reaction, but that first day, it was as significant as a switch being turned from "off" to "on" in my mind. After an entire adult life of feeling like my brain was stuck in this constant state of "dull grey drear" as I called it, suddenly I could feel pleasure again! Food tasted better, music "hit" me emotionally, I actually started having real emotions again, true happiness and true sadness and elation and depression instead of just a constant state of "meh" where I felt emotionally brain-dead. That might or might not have been the placebo effect, but whatever.
Over time, my sex-drive dropped, I started feeling calmer (but also more emotional, so I had both elation and freakouts,) and most importantly, I stopped feeling angry and tense and defensive all the time. It felt like my brain was taking one giant sigh and going "ahhhhh....." I just knew that it was right, that this was how I'd always wanted my mind to work.
The real test is when the physical changes start happening, though. When my skin first started softening a bit 2 weeks in, I was rubbing the back of my hand across my face all day because it just felt so good. The day that I finally saw a girl looking back at me in the mirror was seriously one of the happiest days of my life. Every single one of the changes, every single bit of feminization, just made me smile so much, and love myself for having that body feature so much.
Again... you'll be able to tell. If the physical changes and emotional changes make you feel more like your mind and body are "working" right, then yeah.
I still have some troubles with the public side of transition. Dealing with the perceived judgments of other people and dealing with clocking paranoia is a real pain in the rear end. But I knew pretty much within the first week of being on HRT that I was never going to be able to go back. Because even though I was able to tolerate testosterone for many years, my brain just never felt "right" on it. Where E made it finally feel like I was myself again. Everything just "clicked."