The combined oral contraceptives (COCs) are combinations of exogenous estrogen and progestin. The primary mode of action for COCs is thought to be suppression of the pituitary-ovarian axis by higher than physiological levels of estrogen and progestin, secondarily leading to suppression of endogenous gonadotropin and gonadal hormone secretion and ovarian function. During the hormone-free interval (HFI), COCs users experience activation of their pituitary–ovarian axis. The level of hormones and follicular development are associated with the doses of estrogen, progestin formulations and the changes of HFI.