Sex hormones and headache the normal female life cycle is associated with a number of hormonal milestones menarche pregnancy contraceptive use menopause and the use of replacement sex hormones menarche marks the onset of menses and cyclic changes in hormone levels. Periodic discontinuation of oral preparations of sex hormones may contribute to headaches associated with oc use and hormonal replacement therapy a possible mechanism for estrogen induced headaches is a disparity between the ovarian cycles of estrogen and progestin and the intrinsic pulse of central nervous system estrogen sensitive neurons including perhaps the serotonergic pain modulating systems. Headaches associated with oc use or menopausal hormonal replacement therapy may be related in part to periodic discontinuation of oral sex hormone preparations the treatment of migraine associated with changes in sex hormone levels is frequently difficult and the patients are often refractory to therapy. The effects of estrogen on the genesis of headache may be a result of a mismatch between the ovarian cycles of the sex hormones and the inherent rhythm of cns estrogen sensitive neurons including perhaps the sero tonergic pain modulating systems