Ding Ning, Zheutlin Emily, Harlow Siobán D, Randolph John F, Mukherjee Bhramar, Park Sung Kyun
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA.
Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA.
J Endocr Soc. 2023 Feb 3;7(4):bvad024. doi: 10.1210/jendso/bvad024. eCollection 2023 Feb 9.
Phthalates, ubiquitous endocrine-disrupting chemicals, may affect ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1189 multiracial/multiethnic women aged 45 to 56 years without hormone therapy from the Study of Women's Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999 to 2000 and 2002 to 2003, resulting in a total of 2111 observations. Linear mixed-effect models were used to calculate percentage differences (%D) and 95% CIs in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed statistically significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%; 95% CI, -3.66 to -0.47) and MnBP with testosterone (%D: -1.99%; 95% CI, -3.82 to -0.13), after adjusting for multiple comparisons with false discovery rates less than 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%; 95% CI, -24.10 to -3.14), MEHHP (%D: -15.58%; 95% CI, -24.59 to -5.50), and MEOHP (%D: -13.50%; 95% CI, -22.93 to -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.
邻苯二甲酸盐是普遍存在的内分泌干扰化学物质，可能会影响卵巢卵泡生成和类固醇生成。我们研究了中年女性尿中邻苯二甲酸酯代谢物与包括雌二醇、睾酮、促卵泡激素（FSH）、性激素结合球蛋白（SHBG）和抗苗勒管激素（AMH）在内的激素之间的关联，以及自然绝经的时间。数据来自全国女性健康研究（SWAN）中1189名年龄在45至56岁且未接受激素治疗的多种族/多民族女性。在1999年至2000年以及2002年至2003年期间重复测量了12种邻苯二甲酸酯代谢物和激素的尿浓度，总共得到2111次观察结果。使用线性混合效应模型计算雌二醇、睾酮、FSH、SHBG和AMH血清浓度的百分比差异（%D）和95%置信区间（CI）。使用Cox比例风险模型计算自然绝经的风险比（HR）和95%CI。在调整错误发现率小于5%的多重比较后，我们观察到邻苯二甲酸酯代谢物与较低的睾酮浓度之间存在统计学显著关联：MCOP与睾酮（%D：-2.08%；95%CI，-3.66至-0.47）以及MnBP与睾酮（%D：-1.99%；95%CI，-3.82至-0.13）。还发现较高的MECPP（%D：-14.26%；95%CI，-24.10至-3.14）、MEHHP（%D：-15.58%；95%CI，-24.59至-5.50）和MEOHP（%D：-13.50%；95%CI，-22.93至-2.90）与较低的AMH浓度相关。未观察到与其他激素或自然绝经时间的关联。这些结果表明，接触邻苯二甲酸盐可能会影响中年女性的循环睾酮水平并减少卵巢储备。鉴于广泛的接触，减少邻苯二甲酸盐的接触可能是预防邻苯二甲酸盐生殖影响的关键一步。
