Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4427-e4437. doi: 10.1210/clinem/dgab476.
Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals that may affect sex hormones and accelerate reproductive aging in midlife women.
To examine associations between serum PFAS concentrations at baseline (1999-2000) and longitudinal serum concentrations of follicle-stimulating hormone (FSH), estradiol, testosterone, and sex hormone-binding globulin (SHBG) at baseline and through 2015-2016.
Prospective cohort.
General community.
1371 midlife women 45 to 56 years of age at baseline in the Study of Women's Health Across the Nation (SWAN).
MAIN OUTCOME MEASURE(S): FSH, estradiol, testosterone, SHBG.
In linear mixed models fitted with log-transformed hormones and log-transformed PFAS adjusting for age, site, race/ethnicity, smoking status, menopausal status, parity, and body mass index, FSH was positively associated with linear perfluorooctanoate [n-PFOA; 3.12% (95% CI 0.37%, 5.95%) increase for a doubling in serum concentration), linear perfluorooctane sulfonate [PFOS; 2.88% (0.21%, 5.63%)], branched perfluorooctane sulfonate [2.25% (0.02%, 4.54%)], total PFOS (3.03% (0.37%, 5.76%)), and 2-(N-ethyl-perfluorooctane sulfonamido) acetate [EtFOSAA; 1.70% (0.01%, 3.42%)]. Estradiol was inversely associated with perfluorononanoate [PFNA; -2.47% (-4.82%, -0.05%)) and n-PFOA (-2.43% (-4.97%, 0.18%)]. Significant linear trends were observed in the associations between PFOS and EtFOSAA with SHBG across parity (Ps trend ≤ 0.01), with generally inverse associations among nulliparous women but positive associations among women with 3+ births. No significant associations were observed between PFAS and testosterone.
This study observed positive associations of PFOA and PFOS with FSH and inverse associations of PFNA and PFOA with estradiol in midlife women during the menopausal transition, consistent with findings that PFAS affect reproductive aging.
全氟和多氟烷基物质（PFAS）是广泛存在的化学物质，可能会影响中年女性的性激素并加速生殖衰老。
研究基线（1999-2000 年）时血清 PFAS 浓度与基线和 2015-2016 年期间卵泡刺激素（FSH）、雌二醇、睾酮和性激素结合球蛋白（SHBG）的纵向血清浓度之间的关联。
前瞻性队列研究。
普通社区。
基线时年龄在 45 至 56 岁的 1371 名中年女性，参加了妇女健康跨国家研究（SWAN）。
FSH、雌二醇、睾酮、SHBG。
在调整年龄、地点、种族/民族、吸烟状况、绝经状态、产次和体重指数后，使用对数转换激素和对数转换 PFAS 的线性混合模型拟合，FSH 与线性全氟辛烷磺酸（n-PFOA；血清浓度加倍时增加 3.12%（95%CI，0.37%，5.95%））、线性全氟辛烷磺酸（PFOS；2.88%（0.21%，5.63%））、支链全氟辛烷磺酸（2.25%（0.02%，4.54%））、总 PFOS（3.03%（0.37%，5.76%））和 2-（N-乙基-全氟辛烷磺酰胺基）乙酸盐（EtFOSAA；1.70%（0.01%，3.42%））呈正相关。雌二醇与全氟壬酸（PFNA）呈负相关[2.47%（-4.82%，-0.05%）]和 n-PFOA（-2.43%（-4.97%，0.18%）]。在 SHBG 与产次之间的 PFOS 和 EtFOSAA 关联中观察到显著的线性趋势（趋势 P≤0.01），在未生育妇女中通常呈负相关，但在生育 3 次及以上的妇女中呈正相关。PFAS 与睾酮之间未见显著关联。
本研究观察到在绝经过渡期间，中年女性的 PFOA 和 PFOS 与 FSH 呈正相关，PFNA 和 PFOA 与雌二醇呈负相关，这与 PFAS 影响生殖衰老的发现一致。
