Carter R Colin, Jacobson Joseph L, Dodge Neil C, Granger Douglas A, Jacobson Sandra W
Division of Pediatric Emergency Medicine , Columbia University Medical Center, New York, New York.
Alcohol Clin Exp Res. 2014 Jun;38(6):1671-9. doi: 10.1111/acer.12395. Epub 2014 Apr 9.
Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic-pituitary-gonadal axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development.
The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/ml), self-reported Tanner stages for pubertal development, and age at menarche (females).
Prenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure, but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group × testosterone interaction term and potential confounders.
This study is the first to show a relation between prenatal alcohol exposure and increased testosterone during adolescence and evidence of decreased testosterone responsiveness in tissues related to pubertal development in humans. Further studies examining androgen receptor expression and other hormonal and cellular factors affecting pubertal development may reveal important mechanisms underlying these teratogenic effects of alcohol exposure.
动物模型已证明，胎儿酒精暴露会破坏下丘脑 - 垂体 - 性腺轴的神经内分泌功能，并对雄性和雌性的青春期发育及性行为产生下游影响，但对人类的这些影响知之甚少。本研究调查了产前酒精暴露是否与青少年时期睾酮水平的改变有关，以及是否会影响青春期发育的时间。
样本包括来自底特律纵向队列研究的265名非裔美国青少年，他们有睾酮和/或青春期发育数据。受试者是在首次产前诊所就诊时招募的女性的后代，以过度代表中度至重度饮酒情况，包括5%的低水平饮酒者/戒酒者随机样本。在每次产前检查时，通过时间线追溯法询问母亲她们的饮酒情况、吸烟和药物使用情况以及社会人口学因素。在14岁时，青少年提供唾液样本，分析其中的睾酮（pg/ml）、自我报告的青春期发育坦纳分期以及初潮年龄（女性）。
在控制混杂因素后，产前酒精暴露与男性和女性的睾酮浓度升高有关，但与坦纳分期或初潮年龄的变化无关。在按酒精暴露分层的回归模型中，轻度至无产前酒精暴露的男性中，睾酮与阴毛发育之间存在预期关系，但中度至重度产前酒精暴露的男性中则不存在。在包括酒精暴露组×睾酮交互项和潜在混杂因素的多变量模型中，证实了睾酮与产前酒精暴露之间的这种相互作用。
本研究首次表明产前酒精暴露与青少年时期睾酮增加之间的关系，以及人类青春期发育相关组织中睾酮反应性降低的证据。进一步研究雄激素受体表达以及影响青春期发育的其他激素和细胞因素，可能会揭示酒精暴露这些致畸作用的重要潜在机制。
