Monash Addiction Research Centre and Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Richmond, Victoria, Australia.
Monash Alfred Psychiatry Research Centre, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University and the Alfred Hospital, Melbourne, Victoria, Australia.
Addict Biol. 2021 Nov;26(6):e13079. doi: 10.1111/adb.13079. Epub 2021 Aug 10.
Stimulant use disorder is associated with significant global health burden. Despite evidence for sex differences in the development and maintenance of stimulant use disorder, few studies have focused on mechanisms underpinning distinct trajectories in females versus males, including the effect of the ovarian sex hormones estrogen and progesterone. This review aimed to identify and synthesise the existing preclinical and clinical literature on the effect of ovarian sex hormones on stimulant consumption in females. A systematic search of peer-reviewed literature identified 1593 articles, screened using the following inclusion criteria: (1) adult female humans or animals, (2) using stimulant drugs, (3) ovarian sex hormones were administered exogenously OR were measured in a validated manner and (4) with stimulant consumption as an outcome measure. A total of 50 studies (3 clinical and 47 preclinical) met inclusion criteria. High-estrogen (low progesterone) phases of the menstrual/estrus cycle were associated with increased stimulant use in preclinical studies, while there were no clinical studies examining estrogen and stimulant consumption. Consistent preclinical evidence supported progesterone use reducing stimulant consumption, which was also identified in one clinical study. The review was limited by inconsistent data reporting across studies and different protocols across preclinical laboratory paradigms. Importantly, almost all studies examined cocaine use, with impact on methamphetamine use a significant gap in the existing evidence. Given the safety and tolerability profile of progesterone, further research is urgently needed to address this gap, to explore the potential therapeutic utility of progesterone as a treatment for stimulant use disorder.
兴奋剂使用障碍与重大的全球健康负担有关。尽管有证据表明，在兴奋剂使用障碍的发展和维持方面存在性别差异，但很少有研究关注女性与男性之间不同轨迹的潜在机制，包括卵巢性激素雌激素和孕激素的影响。本综述旨在确定和综合现有的关于卵巢性激素对女性兴奋剂消费影响的临床前和临床文献。通过同行评议文献的系统搜索，确定了 1593 篇文章，使用以下纳入标准进行筛选：（1）成年女性人类或动物，（2）使用兴奋剂药物，（3）卵巢性激素被外源性给予或以验证的方式测量，以及（4）以兴奋剂消费作为结果测量。共有 50 项研究（3 项临床研究和 47 项临床前研究）符合纳入标准。在临床前研究中，月经/发情周期的高雌激素（低孕激素）阶段与兴奋剂使用增加有关，而没有研究检查雌激素和兴奋剂消费之间的关系。一致的临床前证据支持孕激素的使用可以减少兴奋剂的消费，这在一项临床研究中也得到了证实。本综述受到以下限制：研究之间的数据报告不一致，以及临床前实验室范式之间的方案不同。重要的是，几乎所有的研究都检查了可卡因的使用，而对甲基苯丙胺使用的影响是现有证据中的一个显著空白。鉴于孕激素的安全性和耐受性特征，迫切需要进一步研究来填补这一空白，探索孕激素作为兴奋剂使用障碍治疗方法的潜在治疗效用。
