'antiestrogen' originates from Greek elements: the prefix 'anti-' (from Greek 'antí') and the root of 'oestrogen' (from Greek 'oistros' plus suffix '-gen'), where 'anti-' meant 'against', 'oistros' referred to 'gadfly' or 'sexual passion' (leading to 'estrus'), and '-gen' meant 'producer'.

'antiestrogen' was formed in English in the mid-20th century by combining 'anti-' with 'oestrogen' (often written 'anti-oestrogen' or with the British spelling 'oestrogen'); over time the spelling standardized in many contexts to 'antiestrogen' (with the US spelling 'estrogen') and the hyphen often dropped.

Initially it denoted a substance acting against oestrogenic or estrous-producing effects; its meaning has remained essentially the same and now refers broadly to drugs or agents that block estrogen action.