The physiology is clear: the fluctuation and drop of estradiol after reaching luteal phase nadir precipitates instability in estrogen receptors in the carotid node. Estradiol pellets stabilizing elevated estradiol levels (Greenblatt) or suppressing estradiol levels (Lichten) offer two effective preventative therapies with unequalled 75% or greater success rates and profound reduction of pain and migraines.Treating physicians should review gender specific medicine models of disease, observing the incidence of migraine during reproductive years favors women 6:1; yet, before and afterwards, gender ratios are fairly equivalent. As the cause is hormonal, effective preventive treatment is establishing a stable hormonal milieu. In today's practice, two concurrent estradiol patches may replace pellets and a combination of two anti-estrogenic, non-testosterone anabolics in a weekly injection may replace danazol, proving the effectiveness of similar physiological stable estradiol states. Bilateral oophorectomy has proven effective for some resistant cases.Women with migraine report the onset coincided with hormonal events: menarche, pregnancy, delivery, hormonal contraception, and/or menopausal hormonal replacement. Treatment of hormonal migraine with abortive medications (caffeine, ergot, sumatriptan) converts the episodic migraine into refractory rebound tensiontype headaches that may respond well to interrupting the muscle spasm with trigger point injections, BOTOX TM , topical muscle relaxers, and physical therapy. Lichten and Lichten 8 confirmed that menstrual migraine is an example of an epigenetic disease. Of 28 menopausal women on no hormonal therapy, an injection of depo-estradiol precipitated migraine in the 16 with a history of menstrual migraine but not in one of the controls. The "epi" factor was the drop induced at day 21 in serum estradiol levels below the 50 pg/mL threshold, yet, migraine occurred only in those with a positive (genetic) history of hormonal-induced migraine.Address all correspondence to E.M.