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Pyrethroid Pesticide Exposure and Risk of Primary Ovarian Insufficiency in Chinese Women Chunming Li, Miaofeng Cao, Linjuan Ma, Xiaoqing Ye, Yang Song, Wuye Pan, Zhengfen Xu, Xiaochen Ma, Yibing Lan, Peiqiong Chen, Weiping Liu, Jing Liu, and Jianhong Zhou Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.7b06689 • Publication Date (Web): 15 Feb 2018 Downloaded from http://pubs.acs.org on February 20, 2018
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Pyrethroid Pesticide Exposure and Risk of Primary Ovarian Insufficiency in Chinese Women Chunming Li,†, a Miaofeng Cao,‡, a Linjuan Ma,† Xiaoqing Ye,‡ Yang Song,† Wuye Pan,‡ Zhengfen Xu,† Xiaochen Ma,‡ Yibing Lan,† Peiqiong Chen,† Weiping Liu,‡,§ Jing Liu,*,‡,§ and Jianhong Zhou*,† †
Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s
Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China ‡
MOE Key Laboratory of Environmental Remediation and Ecosystem Health,
College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China §
Research Center for Air Pollution and Health, Zhejiang University, Hangzhou
310058, China a
These authors contributed equally to this work
*Correspondence and requests for materials should be addressed to J.L. (
[email protected]) or J. Z. (
[email protected])
Short Title: Pyrethroids and Primary Ovarian Insufficiency
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Table of Contents
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Abstract
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Pyrethroids are a class of widely used insecticides. Female animal studies suggested
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that pyrethroid exposure impaired ovarian function, which resulted in similar
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symptoms of primary ovarian insufficiency (POI). However, it is still unknown
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whether this association applies to women. In this case-control study, a total of 172
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POI patients and 247 control women were recruited in Zhejiang, China. The urinary
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concentrations of metabolites of pyrethroids, 3-phenoxybenzoic acid (3-PBA) and
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4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), as well as the serum concentrations of
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follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Mullerian
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hormone (AMH) were determined. The associations of pyrethroid metabolites with
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POI and POI-related hormones were accessed using unconditional logistic regression.
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Higher urinary levels of 3-PBA were significantly associated with increased risk of
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POI [adjusted odds ratio (OR) =2.344, 95% CI: 1.193-4.607 for the highest vs. lowest
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quartile of 3-PBA, p=0.013]. Stratified analyses showed that each log increase in
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urinary 3-PBA concentration was significantly associated with an 51.0% induction in
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odds of being in the highest quartile of FSH and 28.6% being in the highest quartile of
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LH levels, while a 25.9 % reduction in odds of being in the highest quartile of AMH
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levels (All p for trend 25
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IU/L on two occasions > 4 weeks apart. Patients who have known cause of POI (such
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as karyotypic abnormalities, previous chemotherapy and/or radiotherapy, ovarian
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surgery or autoimmune diseases, etc.) were excluded. Healthy women with long-term
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regular menstrual cycles and without any hormonal therapy in the previous 6 months
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and endocrine system diseases (such as thyroid, hyperprolactinemia, polycystic ovary
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syndrome, etc.) were recruited as controls. Controls were collected from routine
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physical checkups and matched to the POI patients based on age and body mass index
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(BMI). All of participants were Zhejiang Province residents. The study was conducted
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in accordance with the Declaration of Helsinki and was approved by the Ethics
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Committee of Women’s Hospital of Zhejiang University. Written informed consents
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were obtained from all participating women. A face to face interview was undertaken
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by trained interviewers to obtain women’s detailed socio-demographic characteristics,
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gynecological history, lifestyle factors, reproductive history, and medical histories. A 6
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total of 216 cases and 254 controls met the eligibility criteria. Among these
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participants, 25 cases and 4 controls were excluded because of lack of important
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questionnaire data, 19 cases and 3 controls were excluded due to lack of urine
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samples or samples with creatinine
