Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan.
Department of Obstetrics and Gynecology, School of Medicine, University of Michigan, Ann Arbor, Michigan.
J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3169-82. doi: 10.1210/clinem/dgaa303.
Previous epidemiologic studies of per- and polyfluoroalkyl substances (PFASs) and menopausal timing conducted in cross-sectional settings were limited by reverse causation because PFAS serum concentrations increase after menopause.
To investigate associations between perfluoroalkyl substances and incident natural menopause.
A prospective cohort of midlife women, the Study of Women's Health Across the Nation, 1999-2017.
1120 multiracial/ethnic premenopausal women aged 45-56 years.
Serum concentrations of perfluoroalkyls were quantified by high-performance liquid chromatography isotope dilution tandem mass spectrometry. Natural menopause was defined as the bleeding episode prior to at least 12 months of amenorrhea not due to surgery or hormone use. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
Participants contributed 5466 person-years of follow-up, and 578 had incident natural menopause. Compared with the lowest tertile, women at the highest tertile of baseline serum concentrations had adjusted HR for natural menopause of 1.26 (95% CI: 1.02-1.57) for n-perfluorooctane sulfonic acid (n-PFOS) (Ptrend = .03), 1.27 (95% CI: 1.01-1.59) for branched-PFOS (Ptrend = .03), and 1.31 (95% CI: 1.04-1.65) for n-perfluorooctanoic acid (Ptrend = .01). Women were classified into four clusters based on their overall PFAS concentrations as mixtures: low, low-medium, medium-high, and high. Compared with the low cluster, the high cluster had a HR of 1.63 (95% CI: 1.08-2.45), which is equivalent to 2.0 years earlier median time to natural menopause.
This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life.
以前在横断面研究中进行的有关全氟和多氟烷基物质（PFAS）与绝经时间的流行病学研究受到反向因果关系的限制，因为 PFAS 血清浓度在绝经后会增加。
研究全氟烷基物质与自然绝经发生的关联。
1999-2017 年，一项针对中年女性的妇女健康全国研究（Study of Women's Health Across the Nation）的前瞻性队列研究。
1120 名年龄在 45-56 岁的多种族/族裔的绝经前女性。
通过高效液相色谱-同位素稀释串联质谱法定量测定全氟烷基物质的血清浓度。自然绝经的定义为出血事件前至少 12 个月闭经，且非手术或激素使用所致。使用 Cox 比例风险模型计算危险比（HR）和 95%置信区间（CI）。
参与者共提供了 5466 人年的随访时间，有 578 人发生了自然绝经。与最低三分位相比，基线血清浓度最高三分位的女性发生自然绝经的调整 HR 为 n-全氟辛烷磺酸（n-PFOS）1.26（95%CI：1.02-1.57）（Ptrend =.03）、支链-PFOS 1.27（95%CI：1.01-1.59）（Ptrend =.03）和 n-全氟辛酸（n-PFOA）1.31（95%CI：1.04-1.65）（Ptrend =.01）。根据其 PFAS 总体浓度作为混合物将女性分为四个聚类：低、低-中、中-高和高。与低聚类相比，高聚类的 HR 为 1.63（95%CI：1.08-2.45），相当于自然绝经中位数提前 2.0 年。
这项研究表明，某些 PFAS 血清浓度与自然绝经提前有关，而绝经提前是晚年不良健康结局的一个危险因素。
