Learn Italian: Ci sono ottanta domande. - There are eighty questions.

No, in Italian, cardinal numbers from two upwards are invariable. This means ottanta stays exactly the same whether you are counting masculine or feminine items. Only the number one (uno or una) changes to match gender.

Does the word ottanta change if I want to say 81 or 88 instead?

Yes! When combining tens like ottanta with uno (one) or otto (eight), you drop the final vowel of the ten. So 81 becomes ottantuno and 88 becomes ottantotto. For other numbers, you just add them normally without dropping the vowel, like ottantadue (82).

Could I just say Sono ottanta domande to mean 'There are eighty questions'?

No, sono by itself just means 'they are'. To say 'there are' (stating that multiple things exist or are present), you must use ci sono. This is the plural equivalent of c'è (there is).

Why does domande end in an -e?

It is the plural form of the feminine noun domanda (question). In Italian, feminine nouns that end in -a in the singular change their ending to -e in the plural. Since we have eighty of them, we must use the plural form.