Estrogens exert a wide range of biological effects through complex mechanisms of action that extend beyond reproductive regulation. Their influence spans the cardiovascular, skeletal, dermal, immune, and central nervous systems (Table 1), mediated by both genomic pathways (through direct or indirect modulation of gene transcription) and non-genomic pathways (through rapid, membrane-initiated signalling).

Estrogen responses are influenced by the distribution and function of the two receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), which can act in either a complementary or opposing manner, depending on the cellular context. In addition to receptor binding, pharmacokinetic factors such as half-life, metabolism, SHBG binding, and hepatic effects also play a crucial role in shaping estrogen activity (see Section 4). Moreover, variability in estrogen action has been observed both among individuals and across populations, reflecting differences in receptor distribution and tissue responsiveness. These variations influence not only the efficacy but also the safety of estrogen-containing therapies, underscoring the potential value of tailoring hormonal contraception to individual profiles.

This section outlines the modes of action of estrogens, including receptor-mediated signalling pathways, and their physiological roles across different tissues. Special attention is given to key estrogens used in contraception: ethinylestradiol (EE),17β-estradiol (E2), and estetrol (E4) (Table 2), each with distinct pharmacological and safety profiles.