The role of estradiol and progesterone in modulating the subjective effects of stimulants in humans
The role of estradiol and progesterone in modulating the subjective effects of stimulants in humans
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DOI：
10.1037/1064-1297.15.5.418
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发表时间：
2007-10-01
影响因子：
2.3
通讯作者：
Evans, Suzette M.
中科院分区：
文献类型：
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作者：
Evans, Suzette M.
尽管兴奋剂滥用在女性中是一个日益严重的问题，但很少有研究关注可能涉及潜在性别差异的因素。大量的临床前研究表明，雌性啮齿动物比雄性啮齿动物对兴奋剂的行为影响更敏感，而雌二醇激素与这些性别差异有关。在人类中，对兴奋剂的主观反应在卵泡期（以雌二醇水平适中和孕酮水平最低为特征）比在黄体期（以雌二醇水平升高和孕酮水平升高为特征）更强烈。只有将处于黄体期的男性与女性进行比较时，男女之间的差异才会显现出来；在卵泡期，男性和女性对兴奋剂的主观反应是相似的。与啮齿类动物相比，很少有证据表明雌二醇能增强人类对兴奋剂的主观反应。相反，孕激素已被证明可以减弱对兴奋剂的主观反应，尤其是对女性。最近的临床前数据证实，黄体酮可以减少对兴奋剂的行为反应。总之，从人类研究中得到的证据越来越一致：(a)男性和女性对兴奋剂的主观反应确实不同；(b)这些性别差异在女性处于黄体期时表现明显，此时黄体酮水平升高；(c)黄体酮的使用减弱了对兴奋剂的主观反应。因此，月经周期应该在混合性别研究中得到解决。此外，黄体酮对减少可卡因的积极作用的调节作用可能在治疗兴奋剂滥用者方面具有一定的临床应用价值。
Although stimulant abuse is a growing problem among women, few studies have focused on factors that may be implicated in potential sex differences. Numerous preclinical studies have indicated that female rodents are more sensitive than male rodents to the behavioral effects of stimulants and that the hormone estradiol is involved in these sex differences. In humans, the subjective response to stimulants is greater in the follicular phase (characterized by moderate estradiol levels and minimal progesterone levels) than in the luteal phase (characterized by elevated estradiol levels and elevated progesterone levels). Differences between men and women emerge only when men are compared with women in the luteal phase; the subjective response to stimulants is similar in men and women in the follicular phase. In contrast to rodents, there is minimal evidence that estradiol enhances the subjective response to stimulants in humans. Rather, the hormone progesterone has been shown to attenuate the subjective response to stimulants, particularly in women. Recent preclinical data confirm that progesterone reduces the behavioral response to stimulants. In summary, there is converging evidence from studies in humans that (a) men and women do differ in their subjective response to stimulants; (b) these sex differences are evident when women are in the luteal phase, when progesterone levels are elevated; and (c) progesterone administration attenuates the subjective response to stimulants. Therefore, the menstrual cycle should be addressed in mixed-gender studies. Moreover, the modulatory effects of progesterone on reducing the positive effects of cocaine may have some clinical utility in treating stimulant abusers.