Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark.
Environ Health Perspect. 2012 Oct;120(10):1397-403. doi: 10.1289/ehp.1205113. Epub 2012 Jul 24.
In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.
We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men.
A total of 881 men gave urine, serum, and semen samples. Serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B; semen quality; and urinary concentrations of 14 phthalate metabolites, including metabolites of di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), were assessed. The proportions of DEHP and DiNP excreted as their respective primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-isononyl phthalate (MiNP)] were calculated and expressed as percentages (%MEHP and %MiNP, respectively).
The free androgen index was 15% lower [95% confidence interval (CI): -23, -8%] for men in the highest %MiNP quartile compared to the lowest quartile (p < 0.001) after adjusting for confounders, and 9% lower (95% CI: -16, -1%) in the highest %MEHP quartile (p = 0.02). %MEHP and %MiNP were negatively associated with the ratio of testosterone/LH and testosterone/FSH. %MEHP was negatively associated with total testosterone, free testosterone, and ratio of testosterone/E(2). %MiNP was positively associated with SHBG. There was little evidence of associations between urinary phthalate metabolites or sums of phthalates with reproductive hormones or semen quality.
Our data suggest that both testosterone production and pituitary-hypothalamic feedback may be compromised in individuals excreting a high proportion of primary metabolites of long-chained phthalates relative to the proportion of secondary metabolites.
在动物中,一些邻苯二甲酸酯会损害雄性生殖发育和功能。流行病学研究报告了邻苯二甲酸酯与人类睾丸功能标志物之间关联的不一致证据。
我们旨在提供邻苯二甲酸酯暴露对健康男性生殖激素水平和精液质量影响的估计值。
共有 881 名男性提供了尿液、血清和精液样本。评估了血清睾酮、雌二醇(E2)、性激素结合球蛋白(SHBG)、黄体生成素(LH)、卵泡刺激素(FSH)和抑制素-B 的水平;精液质量;以及 14 种邻苯二甲酸酯代谢物(包括邻苯二甲酸二(2-乙基己基)酯(DEHP)和邻苯二甲酸二异壬酯(DiNP)的代谢物)的尿浓度。计算并分别表示为百分比(%MEHP 和%MiNP),以表示 DEHP 和 DiNP 分别排泄为其各自的初级代谢物(单(2-乙基己基)邻苯二甲酸酯(MEHP)和单异壬基邻苯二甲酸酯(MiNP))的比例。
在调整混杂因素后,最高%MiNP 四分位组男性的游离雄激素指数比最低四分位组低 15%(95%置信区间:-23,-8%)(p < 0.001),最高%MEHP 四分位组低 9%(95%置信区间:-16,-1%)(p = 0.02)。%MEHP 和%MiNP 与睾酮/LH 和睾酮/FSH 的比值呈负相关。%MEHP 与总睾酮、游离睾酮和睾酮/E(2)的比值呈负相关。%MiNP 与 SHBG 呈正相关。尿液邻苯二甲酸酯代谢物或邻苯二甲酸酯总和与生殖激素或精液质量之间几乎没有关联的证据。
我们的数据表明,与次级代谢物的比例相比,长链邻苯二甲酸酯的初级代谢物排泄比例较高的个体,其睾丸酮的产生和垂体-下丘脑反馈可能受到损害。