Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, USA.
Alcohol Clin Exp Res. 2010 May;34(5):915-24. doi: 10.1111/j.1530-0277.2010.01164.x. Epub 2010 Mar 10.
The long-term ingestion of alcohol diminishes hypothalamic-pituitary-adrenal (HPA) axis reactivity in alcohol-dependent men, potentially altering future relapse risk. Although sex differences in HPA axis functioning are apparent in healthy controls, disruptions in this system have received little attention in alcohol-dependent women. In this study, we assessed the basal secretory profile of adrenocorticotropic hormone (ACTH) and cortisol, adrenocortical sensitivity in both the presence and absence of endogenous corticotropic pituitary activation, and feedback pituitary glucocorticoid sensitivity to dexamethasone.
Seven women 4- to 8-week abstinent alcohol-only dependent subjects and 10 age-matched female healthy controls were studied. All subjects were between 30 and 50 years old, not taking oral contraceptives, and were studied during the early follicular phase of their menstrual cycle. Circulating concentrations of ACTH and cortisol were measured in blood samples collected at frequent intervals from 2000 to 0800 hour. A submaximal dose of cosyntropin (0.01 microg/kg), a synthetic ACTH (1-24), was administered at 0800 hour to assess adrenocortical sensitivity. In a separate session, low-dose cosyntropin was also administered following high-dose dexamethasone (8 mg intravenous) to assess adrenocortical sensitivity in the relative absence of endogenous ACTH. In addition, the ACTH response to dexamethasone was measured to determine the pituitary glucocorticoid negative feedback. Sessions were 5 days apart, and blood draws were obtained every 5 to 10 minutes.
Mean concentrations and pulsatile characteristics of ACTH and cortisol over 12 hours were not statistically different between the 2 groups. Healthy controls had a somewhat higher (p < 0.08) net peak, but not net integrated, cortisol response to cosyntropin relative to the alcohol-dependent women. There were no significant group differences in either the ACTH or cortisol response to dexamethasone nor in the net cortisol response to cosyntropin following dexamethasone.
Significant differences in pituitary-adrenal function were not apparent between alcohol-dependent women and matched controls. Despite the small n, it appears that alcohol-dependent women do not show the same disruptions in HPA activity as alcohol-dependent men. These findings may have relevance for gender-specific treatment effectiveness.
长期饮酒会降低酒精依赖男性的下丘脑-垂体-肾上腺（HPA）轴反应性，从而可能改变未来的复发风险。尽管健康对照组中存在 HPA 轴功能的性别差异，但在酒精依赖女性中，这一系统的紊乱并未受到太多关注。在这项研究中，我们评估了促肾上腺皮质激素（ACTH）和皮质醇的基础分泌谱，在存在和不存在内源性促皮质素垂体激活的情况下评估了肾上腺皮质敏感性，以及地塞米松对垂体糖皮质激素敏感性的反馈。
研究了 7 名 4 至 8 周酒精依赖且仅饮酒的女性受试者和 10 名年龄匹配的女性健康对照者。所有受试者年龄在 30 至 50 岁之间，不服用口服避孕药，并且在月经周期的早期卵泡期进行研究。从 2000 到 0800 小时，每隔一段时间采集血液样本，测量 ACTH 和皮质醇的循环浓度。在 0800 小时给予合成 ACTH（1-24）的亚最大剂量（0.01μg/kg），即促皮质素（cosyntropin），以评估肾上腺皮质敏感性。在另一个会议上，在高剂量地塞米松（8mg 静脉注射）后也给予低剂量 cosyntropin，以评估在缺乏内源性 ACTH 的情况下肾上腺皮质的敏感性。此外，还测量了地塞米松对 ACTH 的反应，以确定垂体糖皮质激素的负反馈。这些会议间隔 5 天，每隔 5 到 10 分钟采血一次。
2 组之间，12 小时内 ACTH 和皮质醇的平均浓度和脉冲特征在统计学上无差异。健康对照组对 cosyntropin 的净峰（但不是净积分）皮质醇反应略高（p <0.08），与酒精依赖的女性相比。酒精依赖的女性与匹配的对照组之间，无论是对 dexamethasone 的 ACTH 还是皮质醇反应，还是对地塞米松后的 cosyntropin 的净皮质醇反应，均无显著差异。
酒精依赖女性与匹配对照组之间，垂体-肾上腺功能的显著差异并不明显。尽管 n 很小，但似乎酒精依赖女性的 HPA 活动并没有像酒精依赖男性那样受到干扰。这些发现可能与性别特异性治疗效果有关。
