Silberstein S D
Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Rev Neurol (Paris). 2000;156 Suppl 4:4S30-41.
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. Pregnancy is associated with rising noncyclic levels of sex hormones, and menopause with declining noncyclic levels. Hormonal contraceptive use during the reproductive years and hormone replacement in menopause are therapeutic hormonal interventions that alter the levels and cycling of sex hormones. These events and interventions may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions between the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Estrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of Menstrually-related migraine (MM) appears to be the withdrawal of estrogen rather than the maintenance of sustained high or low estrogen levels. However, changes in the sustained estrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. 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. Based on what is known of the pathophysiology of migraine, we have attempted to provide a logical approach to the treatment of headaches that are associated with menses, menopause, and OCs using abortive and preventive medications and hormonal manipulations. Considerable evidence suggests a link between estrogen and progesterone, the female sex hormones, and migraine. (Silberstein and Merriam, 1997; Lipton and Stewart, 1993; Epstein et al., 1975; Goldstein and Chen, 1982; Selby and Lance, 1960) Although no gender difference is apparent in prepubertal children, with migraine occurring equally in 4p. 100 of boys and girls, (Goldstein and Chen, 1982, Waters and O'Connor, 1971) migraine occurs more frequently in adult women (18p. 100) than in men (6p. 100). (Lipton and Stewart, 1993) Migraine develops most frequently in the second decade, with the peak incidence occurring with adolescence. (Selby and Lance, 1960; Epstein et al., 1975) Menstrually-related migraine (MM) begins at menarche in 33p. 100 of affected women (Epstein et al. , 1975). MM occurs mainly at the time of menses in many migrainous women, and exclusively with menses (true menstrual migraine [TMM]) in some (Epstein et al., 1975). Menstrual migraine can be associated with other somatic complaints arising before and often persisting into menses, such as nausea, backache, breast tenderness, and cramps and like them appears to be the result of falling sex hormone levels (Silberstein and Merriam, 1997; American Psychiatric Association, 1994). In addition, premenstrual migraine can be associated with premenstrual dysphoric disorder (PDD), also called "premenstrual syndrome" (PMS), which is distinct from the physical symptoms of the perimenstrual period and is probably not directly driven by declining progesterone levels (Mortola, 1998). Migraine occurring during (rather than prior to) menstruation is usually not associated with PMS (Silberstein and Merriam, 1997). Migraine may worsen during the first trimester of pregnancy and, although many women become headache-free during the last two trimesters, 25p. 100 have no change in their migraine (Silberstein, 1997). MM typically improves with pregnancy, perhaps due to sustained high estrogen levels (Silberstein, 1997). Hormonal replacement with estrogens can exacerbate migraine and oral contraceptives (OCs) can change its character and frequency
初潮、怀孕、使用避孕药、绝经以及使用替代性性激素。初潮标志着月经开始以及激素水平的周期性变化。怀孕与非周期性升高的性激素水平相关，绝经则与非周期性下降的性激素水平相关。生育期使用激素避孕以及绝经后进行激素替代是改变性激素水平和周期的治疗性激素干预措施。这些事件和干预可能会导致头痛患病率或严重程度的变化。月经周期是下丘脑、垂体、卵巢和子宫内膜之间精心编排的一系列相互作用的结果，性激素在每个层面都充当调节因子和效应器。雌激素和孕激素对中枢5-羟色胺能和阿片样物质神经元有强大作用，可调节神经元活动和受体密度。与月经相关的偏头痛（MM）的主要触发因素似乎是雌激素撤退，而非持续的高雌激素水平或低雌激素水平。然而，怀孕（升高）和绝经（降低）时持续雌激素水平的变化似乎会影响头痛。与口服避孕药（OC）使用或绝经后激素替代疗法相关的头痛可能部分与周期性停用口服性激素制剂有关。与性激素水平变化相关的偏头痛治疗通常很困难，患者往往对治疗有抵抗性。基于对偏头痛病理生理学的了解，我们试图提供一种合理的方法，使用中止发作和预防性药物以及激素操作来治疗与月经、绝经和口服避孕药相关的头痛。大量证据表明女性性激素雌激素和孕激素与偏头痛之间存在联系。（西尔伯斯坦和梅里亚姆，1997年；利普顿和斯图尔特，1993年；爱泼斯坦等人，1975年；戈尔茨坦和陈，1982年；塞尔比和兰斯，1960年）虽然青春期前儿童中没有明显的性别差异，男孩和女孩中偏头痛的发生率均为4%，（戈尔茨坦和陈，1982年；沃特斯和奥康纳，1971年）但成年女性中偏头痛的发生率（每100人中有18人）高于男性（每100人中有6人）。（利普顿和斯图尔特，1993年）偏头痛最常发生在第二个十年，发病率高峰出现在青春期。（塞尔比和兰斯，1960年；爱泼斯坦等人，1975年）33%的受影响女性的与月经相关的偏头痛（MM）始于初潮（爱泼斯坦等人，1975年）。在许多偏头痛女性中，MM主要发生在月经期间，在一些女性中则仅在月经时发生（真正的月经性偏头痛[TMM]）（爱泼斯坦等人，1975年）。月经性偏头痛可能与月经前出现且常常持续到月经期间的其他躯体不适有关，如恶心、背痛、乳房触痛和痉挛，并且与它们一样似乎是性激素水平下降的结果（西尔伯斯坦和梅里亚姆，1997年；美国精神病学协会，1994年）。此外，经前偏头痛可能与经前烦躁障碍（PDD）相关，也称为“经前综合征”（PMS），它与月经周期周围的身体症状不同，可能并非直接由孕激素水平下降驱动（莫托拉，1998年）。在月经期间（而非月经前）发生的偏头痛通常与经前综合征无关（西尔伯斯坦和梅里亚姆，1997年）。偏头痛在怀孕的前三个月可能会加重，尽管许多女性在怀孕的后两个三个月没有头痛，但25%的女性偏头痛没有变化（西尔伯斯坦，1997年）。MM通常在怀孕期间有所改善，这可能是由于持续的高雌激素水平（西尔伯斯坦，1997年）。用雌激素进行激素替代会加重偏头痛，口服避孕药（OCs）会改变其特征和频率
