New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 66, New York, NY 10032, USA.
Horm Behav. 2010 Jun;58(1):13-21. doi: 10.1016/j.yhbeh.2009.08.010. Epub 2009 Sep 4.
Stimulant abuse continues to be a growing problem among women. Over the last 10-15 years, an increasing number of studies have focused on factors that may be implicated in stimulant abuse in women as compared to men, including the role of hormonal fluctuations across the menstrual cycle. Numerous preclinical studies have documented that female rodents are more sensitive than male rodents to the behavioral effects of stimulant administration and the hormone estradiol is involved in the enhanced response to stimulants observed in females. In contrast, fewer studies have been conducted in humans and non-human primates addressing the role of sex and gonadal hormones on the effects of cocaine. This review paper presents a recent update on data collected in our Human Cocaine Challenge Laboratory and our Non-human Primate Laboratory, including analysis of cocaine pharmacokinetics, sex differences, the menstrual cycle, and the role of progesterone in modulating the response to cocaine. Our studies indicate that there is minimal evidence that the response to intranasal cocaine varies across the menstrual cycle or between men and women. In contrast, the response to smoked cocaine is greater in the follicular phase than the luteal phase and differences between men and women generally only emerge when men are compared to women in the luteal phase. In terms of potential hormonal mechanisms for these differences, the hormone progesterone attenuates the subjective response to cocaine. With respect to cocaine self-administration, there are minimal changes across the menstrual cycle in both humans and non-human primates. Thus, there is converging evidence across a range of species that the behavioral effects of cocaine (1) differ between males and females, (2) differ in relation to hormonal fluctuations, (3) can be attenuated by progesterone (at least in females), and (4) do not appear to be related to differences in cocaine pharmacokinetics.
兴奋剂滥用在女性中仍是一个日益严重的问题。在过去的 10-15 年中，越来越多的研究集中在女性兴奋剂滥用的相关因素上，与男性相比，包括月经周期中激素波动的作用。大量的临床前研究已经证明，雌性啮齿动物比雄性啮齿动物对兴奋剂给药的行为影响更为敏感，而雌激素在女性中观察到的对兴奋剂反应增强中起作用。相比之下，在人类和非人类灵长类动物中进行的研究较少，涉及性别和性腺激素对可卡因作用的影响。这篇综述文章介绍了我们在人类可卡因挑战实验室和非人类灵长类动物实验室收集的数据的最新更新，包括可卡因药代动力学、性别差异、月经周期以及孕激素在调节可卡因反应中的作用的分析。我们的研究表明，几乎没有证据表明对鼻内可卡因的反应在月经周期或男性和女性之间有所不同。相比之下，吸烟可卡因在卵泡期的反应大于黄体期，并且只有当男性与黄体期的女性进行比较时，男女之间的差异通常才会出现。就这些差异的潜在激素机制而言，激素孕酮可减弱对可卡因的主观反应。就可卡因自我给药而言，在人类和非人类灵长类动物中，月经周期内几乎没有变化。因此，在一系列物种中存在趋同证据表明，可卡因的行为影响 (1) 男女之间存在差异，(2) 与激素波动有关，(3) 可被孕酮减弱（至少在女性中），并且 (4) 似乎与可卡因药代动力学的差异无关。
