ORIGINAL ARTICLES

THE EFFECT OF ORAL CONTRACEPTIVES ON MIGRAINE

Migraine is prevalent in women during the fertile age. Indeed, both neuroendocrine events related to reproductive stages (menarche, pregnancy, and menopause) and menstrual cyclicity and the use of exogenous sex hormones, such as hormonal contraception and replacement therapy, may cause significant changes in the clinical pattern of migraine. Menstrual migraine may be more severe, long-lasting, and refractory to both acute and prophylactic treatment and, therefore, requires tailored strategies. The use of headache diaries, which makes it possible to record prospectively the characteristics of every attack, is of paramount importance for evaluating the time pattern of headache and for identifying a clear link with menstrual cycle-related features. Estrogen variations are highly implicated in modulating the threshold to challenges by altering neuronal excitability, cerebral vasoactivity, pain sensitivity, and neuroendocrine axes throughout the menstrual cycle and not only at the time of menstruation. On the other hand, estrogen withdrawal may really constitute a triggering factor for migraine in women with peculiar characteristics of vulnerability with menstruation or following the discontinuation of exogenous estrogen, as happens with hormonal contraception during the fertile age or with hormone therapy at menopause. In addition, exogenous estrogen may contribute to the occurrence of neurological symptoms, such as aura. When aura occurs, hormonal treatment should be discontinued.

We conducted a 2-part systematic review of published studies to examine the evidence that combination oral contraceptives can aggravate or cause headache.

We used trials with a control group to assess headache risk that was attributable to oral contraceptive use and prospective cohort trials to answer important clinical questions about the natural history and treatment response of headache that occurs with oral contraceptive use.

Because of differences in study populations, oral contraceptive formulations, trial end points and trial duration, it was not possible to pool data; but the evidence supports several conclusions. There is little indication that oral contraceptives have a clinically important effect on headache activity in most women.

Headache that occurs during early cycles of oral contraceptive use tends to improve or disappear with continued use. No evidence supports the common clinical practice of switching oral contraceptives to treat headache; however, manipulating the extent or duration of estrogen withdrawal may provide benefit.

During women's reproductive years, migraine is three times more common than in men of a similar age. Although this female preponderance is commonly assumed to be associated with the additional trigger of fluctuating sex hormones of the menstrual cycle, few studies have been done to confirm or refute this. This review is confined to the relation between oestrogen and attacks of migraine. The evidence for an association between oestrogen “withdrawal” and attacks of migraine without aura is presented, as well as evidence for an association between high oestrogen states and attacks of migraine with aura. Only clinical data are presented here.

This chapter presents a study on hormone-sensitive headache in women. The chapter states that migraine occurs more frequently in adult women (18%) than in men (6%), although its prevalence in children is equal, gender wise. The chapter discusses menstrual migraine, migraine in the menopause, migraine associated with hormonal contraceptive use, and others. The discussion also includes course of migraine during and after pregnancy, postpartum headache, and secondary headaches during pregnancy. Migraine develops most frequently in second decade, with the peak incidence occurring with adolescence. Menstrually related migraine begins at menarche in a third of affected women. Menstrually related migraine occurs mainly at the time of menses in many migrainous women and exclusively with menses. Menstrual migraine (MM) can be associated with other somatic complaints that arise before and often persist into menses, such as nausea, backache, breast tenderness, and cramps, and so on , which appears to be the result of falling sex hormone levels. Migraine often worsens during the first trimester of pregnancy and, although many women become headache-free during the last two trimesters, 25% have no change in their migraine. MM typically improves with pregnancy, perhaps because of sustained high estrogen levels. Hormonal replacement with estrogens can exacerbate migraine and oral contraceptives (OCs) can change its character and frequency.

There is a link between the female sex hormones, estrogen and progesterone, and migraine.29, 77, 83, 86 Migraine occurs more frequently in women than in men, although prevalence is equal in prepubertal children. Migraine develops most frequently in the second decade, with the peak incidence occurring at adolescence.29, 77 Menstrually related migraine (MM) begins at menarche in 33% of affected women.²⁹ MM occurs mainly at the time of menses in many migrainous women and exclusively with menses (true menstrual migraine [TMM]) in some.²⁹ MM can be associated with other somatic complaints arising before and often persisting into menses, such as nausea, backache, breast tenderness, and cramps, and, similar to them, appears to be the result of falling sex hormone levels.4, 86 Premenstrual migraine can be associated with late luteal phase dysphoric disorder (premenstrual dysphoric disorder, also called premenstrual syndrome [PMS]), which is distinct from the physical symptoms of the perimenstrual period and probably is not driven directly by declining progesterone levels.⁵⁹ Migraine occurring during (rather than before) menstruation usually is not associated with PMS.

Migraine often worsens during the first trimester of pregnancy. Although many women become headache-free during the last two trimesters, 25% have no change in their migraine.82, 86 MM typically improves with pregnancy.82, 86 Hormonal replacement with estrogens can exacerbate migraine, and oral contraceptives (OCs) can change its character and frequency.10, 46 Migraine prevalence decreases with advancing age but may regress or worsen at the menopause.⁶⁴ Changes in the headache pattern with OC use and during menarche, menstruation, pregnancy, and menopause are related to changes in estrogen levels. These phenomena suggest a relationship between migraine headaches and changes in sex hormone levels.⁵² This article discusses the endocrinology of the menstrual cycle and approaches to the therapy of hormone-related headaches, in particular headaches associated with the menstrual cycle, the menopause, and OC use.