A variety of evidence suggests a link between migraine and the female sex hormones. Women with migraine outnumber men by at least a 2:1 ratio and definite patterns of development and attacks are noted at menarche and throughout the period of menses, related to trimester of pregnancy, and again at menopause, although it may also regress. Hormonal replacement with estrogen can exacerbate migraine; oral contraceptives can change the character and frequency of migraine headache. This article will cover approaches to the therapy of hormone-related headaches associated with the menstrual cycle, menopause, and oral contraceptives.
PIP: Stages of the reproductive cycle--menarche, menstruation, pregnancy, and menopause--are linked to changes in estrogen and progestin levels. Menarche begins menses and cyclic fluctuations in hormone levels. Sex hormone levels rise with pregnancy and fall with menopause. Use of oral contraceptives (OCs) during the childbearing years and hormone replacement during menopause modifies the levels and cycling of sex hormones. Reproductive events and therapeutic intervention may alter the frequency or severity of headaches. Sex hormones modulate and affect the hypothalamus, pituitary, ovary, and endometrium, resulting in a sequence of interactions which comprise the menstrual cycle. For example, estrogen and progestin have strong effects on central serotonergic and opioid neurons, regulating neuronal activity and receptor density. They also alter the endometrium and stimulate production of prostaglandins and other peptides. Research indicates that withdrawal of estrogen, not the maintenance of sustained high or low estrogen levels, primarily triggers menstrual migraine. Changes in the sustained estrogen levels with pregnancy and menopause also cause changes in headaches. 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. This mechanisms may explain the rise in headaches in some women who use OCs or are pregnant while other women, e.g., those with menstrually related headache, will have fewer headaches under the same conditions. Migraine headaches linked to sex hormone level fluctuations often do not respond to treatment. Based on the mechanism theory, treatment for such migraines should include both estrogen supplements and inhibition of estrogen synthesis, e.g., ergotamine and derivatives.