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The 35-year-old created, wrote and starred in the award-winning HBO drama which first premiered in 2012 and ran for six seasons until 2017.
Dunham, who played aspiring writer Hannah Horvath in the series, marked the milestone occasion by reflecting on the project in an essay for Vogue.
In the piece, Dunham opens up about how she struggled to make friends while growing up and how this difficulty connecting only heightened when she began creating Girls due to the long work schedule.
She wrote: “By the time I wrote Girls, I had 24 years of experience with feeling both connected to and separated from, well, girls.
“Many people saw the title of the show as a pronouncement that I was speaking for all the girls, that I fancied myself a microphone for half the population and, in the process, was grinding us down to one monolithic and unlikable soapstone.
“But this was actually my attempt to understand, perhaps even master, my relationships with girls, with women.”
The series followed aspiring writer Hannah and her three friends as they navigate their 20s in New York City.
During its run it received multiple awards including the international prize at Bafta TV Awards, two Golden Globes for best television series and best actress in a comedy or musical for Dunham.
Dunham also noted in a post on Instagram that she had gotten emotional reading some of the “really sweet messages” fans had shared about what the show meant to them.
She added: “There’s no insta wrap-up that can describe the magic and mayhem of this journey, or room enough in a caption to celebrate the people I made the show with (though a big fat thank you to my @hbo family is the place to start.)
“The audience is better equipped than I am to argue the finer points of what we did and didn’t do, so all I can say is: my life is too transformed to imagine a world without this having been my (admittedly singular) first grownup job.”
She instead directed her followers to her essay about female friendship and said “I hope you’ll recognise some of yourself in it, just as you perhaps recognised yourselves in our maddening, imperfect but always striving-for-honesty show.”
She added: “Because of Girls I am a working artist, which is all I ever wanted to be- and even on my worst days I don’t take the chance to keep writing and making things for granted.”