Environmental Health Program, Research Centre, King Faisal Specialist Hospital and Research Centre, PO Box: 3354, Riyadh, 11211, Saudi Arabia.
Chemosphere. 2022 Jan;286(Pt 1):131495. doi: 10.1016/j.chemosphere.2021.131495. Epub 2021 Jul 14.
Certain endocrine disruptor chemicals are involved in the pathogenesis of polycystic ovary syndrome (PCOS), a hormonal disease related to infertility in women. Phthalates are the most common plasticizers found in several consumer products. Experimental and epidemiologic evidence suggests that some phthalates disrupt endocrine functions in reproductive mechanisms and development. We previously measured the levels of eight phthalate metabolites in the urine of 599 Saudi women who underwent in vitro fertilization (IVF) treatment and were enrolled in a prospective study (2015-2017). The current nested case-control study aimed to determine the association between urinary levels of phthalate metabolites and PCOS. Overall, 441 women from the IVF study were identified as eligible for this study. Women in the case group included those diagnosed with PCOS (N = 82). The control group comprised those unable to conceive due to male azoospermia or who underwent preimplantation genetic diagnosis (N = 359). Most urinary phthalate metabolite levels were several-fold higher than those reported in national surveys from other countries. The ratio of luteinizing hormone to follicle-stimulating hormone, an index of PCOS, was significantly higher in the case than in the control group, with no indication of its association with phthalate metabolites. The logistic regression model was applied after adjusting for confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each metabolite modeled as a natural logarithm (ln). For each ln-unit increase in the sum of the four di (2-ethylhexyl) phthalate (∑DEHP) metabolites as well as two individual metabolites, mono-(2-ethyl-5-oxohexyl) phthalate and mono-(2-ethyl-5-carboxypentyl) phthalate, the odds of PCOS increased by 40.5% [OR = 1.405 (95% CI: 1.025, 1.925)], 41.1% [OR = 1.055 (95% CI: 1.055, 1.885)], and 38.6% [OR = 1.386 (95% CI: 1.033, 1.86)], respectively. In contrast, the % odds of PCOS decreased marginally significantly by 44% [OR = 0.560 (95% CI: 0.313, 1.002)] with an ln-unit increase of %MEHP, the ratio of mono-(2-ethylhexyl) phthalate to ∑DEHP. These findings suggest that DEHP may contribute to PCOS, and further investigation is required to understand the underlying mechanisms.
某些内分泌干扰化学物质参与多囊卵巢综合征（PCOS）的发病机制，PCOS 是一种与女性不孕有关的激素疾病。邻苯二甲酸酯是几种消费产品中最常见的增塑剂。实验和流行病学证据表明，某些邻苯二甲酸酯会破坏生殖机制和发育中的内分泌功能。我们之前测量了 599 名接受体外受精（IVF）治疗的沙特女性尿液中的 8 种邻苯二甲酸酯代谢物水平，并对她们进行了前瞻性研究（2015-2017 年）。目前的嵌套病例对照研究旨在确定尿液中邻苯二甲酸酯代谢物水平与 PCOS 之间的关联。总体而言，从 IVF 研究中确定了 441 名符合条件的女性参与了这项研究。病例组中包括被诊断患有 PCOS 的女性（N=82）。对照组包括由于男性无精子症而无法受孕或接受植入前遗传诊断的女性（N=359）。大多数尿液邻苯二甲酸酯代谢物水平比其他国家的全国性调查报告的水平高出数倍。病例组的黄体生成素与卵泡刺激素的比值（PCOS 的指标）明显高于对照组，并且没有迹象表明其与邻苯二甲酸酯代谢物有关。在调整混杂因素后，应用逻辑回归模型估计每种代谢物作为自然对数（ln）建模的比值比（OR）和 95%置信区间（CI）。对于四（2-乙基己基）邻苯二甲酸（∑DEHP）代谢物总和以及两种单独的代谢物，即单-（2-乙基-5-氧己基）邻苯二甲酸和单-（2-乙基-5-羧基戊基）邻苯二甲酸的每一个 ln 单位增加，患 PCOS 的几率分别增加了 40.5%[OR=1.405（95%CI：1.025，1.925）]、41.1%[OR=1.055（95%CI：1.055，1.885）]和 38.6%[OR=1.386（95%CI：1.033，1.86）]。相比之下，ln 单位增加 %MEHP（即单-（2-乙基己基）邻苯二甲酸与∑DEHP 的比值），患 PCOS 的几率略有显著降低 44%[OR=0.560（95%CI：0.313，1.002）]。这些发现表明 DEHP 可能导致 PCOS，需要进一步研究以了解潜在机制。
