Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The association between urinary organophosphate insecticide metabolites and erectile dysfunction in the United States


Organophosphate (OP) insecticides are the main chemicals used in agriculture for pest elimination, and they have been linked with many diseases. However, there is no literature regarding the impacts of organophosphate insecticide metabolite exposure on erectile dysfunction (ED). We aimed to evaluate the correlation between 4 urinary organophosphate insecticide metabolites and the presence of ED in a representative sample of men aged 20 and older. The dataset including a total of 555 subjects was obtained from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. ED was assessed by a question from a self-report questionnaire. Weighted proportions and multivariable logistic regression analysis were utilized to examine the relationship between organophosphate insecticide metabolite exposure and ED. In multivariable logistic regression analysis, diethylphosphate (DEP) was positively correlated with ED (OR 1.07; 95% CI 1.01–1.14; P = 0.033) after full adjustment. Men in DEP tertile 4 had a significant 33% higher risk of ED than those in tertile 1. Furthermore, in a subgroup analysis, our results showed that higher DEP levels were significantly associated with ED in the young age group (20 ≤ age ≤ 39). Our study revealed a significant association between organophosphate insecticide metabolite exposure and an increased risk of ED. Moreover, the correlations were more evident in the young age group. The evaluation of urinary organophosphate insecticide metabolite exposure should be included in the risk assessment of ED. Further study to investigate the underlying mechanism, such as how long the urinary metabolite is present, whether ED is reversible in this population by lowering DEP concentrations, and how exposure to this metabolite affects erectile tissue, is warranted.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Data availability

All data in the current study are public and available free of charge in the NHANES repository (


  1. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61.

    Article  CAS  Google Scholar 

  2. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84:50–56.

    Article  CAS  Google Scholar 

  3. Wessells H, Joyce GF, Wise M, Wilt TJ. Erectile dysfunction. J Urol. 2007;177:1675–81.

    Article  Google Scholar 

  4. Latini DM, Penson DF, Wallace KL, Lubeck DP, Lue TF. Clinical and psychosocial characteristics of men with erectile dysfunction: baseline data from ExCEED. J Sex Med. 2006;3:1059–67.

    Article  Google Scholar 

  5. Pastuszak AW, Hyman DA, Yadav N, Godoy G, Lipshultz LI, Araujo AB, et al. Erectile dysfunction as a marker for cardiovascular disease diagnosis and intervention: a cost analysis. J Sex Med. 2015;12:975–84.

    Article  Google Scholar 

  6. Aguilar-Garduño C, Lacasaña M, Blanco-Muñoz J, Rodríguez-Barranco M, Hernández AF, Bassol S, et al. Changes in male hormone profile after occupational organophosphate exposure. A longitudinal study. Toxicology. 2013;307:55–65.

    Article  Google Scholar 

  7. Barr DB, Wong LY, Bravo R, Weerasekera G, Odetokun M, Restrepo P, et al. Urinary concentrations of dialkylphosphate metabolites of organophosphorus pesticides: National Health and Nutrition Examination Survey 1999-2004. Int J Environ Res public health. 2011;8:3063–98.

    Article  CAS  Google Scholar 

  8. Atwood D, Paisley-Jones CJUEPA, Washington, DC. Pesticides industry sales and usage: 2008–2012 market estimates. 2017; 20460: 2017-2001.

  9. Wei GL, Li DQ, Zhuo MN, Liao YS, Xie ZY, Guo TL, et al. Organophosphorus flame retardants and plasticizers: sources, occurrence, toxicity and human exposure. Environ Pollut (Barking, Essex: 1987). 2015;196:29–46.

    Article  CAS  Google Scholar 

  10. Marklund A, Andersson B, Haglund P. Organophosphorus flame retardants and plasticizers in air from various indoor environments. J Environ Monit. 2005;7:814–9.

    Article  CAS  Google Scholar 

  11. Makinen MSE, Makinen MRA, Koistinen JTB, Pasanen AL, Pasanen PO, Kalliokoski PJ, et al. Respiratory and dermal exposure to organophosphorus flame retardants and tetrabromobisphenol A at five work environments. Environ Sci Technol. 2009;43:941–7.

    Article  CAS  Google Scholar 

  12. Wang X, Liu J, Yin Y. The pollution status and research progress on organophosphate ester flame retardants. Prog Chem. 2010;22:1983–92.

    CAS  Google Scholar 

  13. Luo K, Liu J, Wang Y, Aimuzi R, Luo F, Ao J, et al. Associations between organophosphate esters and sex hormones among 6–19-year old children and adolescents in NHANES 2013–2014. Environ Int. 2020;136:105461.

    Article  CAS  Google Scholar 

  14. Omoike OE, Lewis RC, Meeker JD. Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999-2002. Reprod Toxicol. 2015;53:99–104.

    Article  CAS  Google Scholar 

  15. Luo Y, Zhang H, Liao M, Tang Q, Huang Y, Xie J, et al. Sex hormones predict the incidence of erectile dysfunction: From a Population-Based Prospective Cohort Study (FAMHES). J Sex Med. 2015;12:1165–74.

    Article  CAS  Google Scholar 

  16. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007;120:151–7.

    Article  Google Scholar 

  17. Jaffe M Ueber den Niederschlag, welchen Pikrinsäure in normalem Harn erzeugt und über eine neue Reaction des Kreatinins. 1886; 10: 391-400.

  18. Bravo R, Caltabiano LM, Weerasekera G, Whitehead RD, Fernandez C, Needham LL, et al. Measurement of dialkyl phosphate metabolites of organophosphorus pesticides in human urine using lyophilization with gas chromatography-tandem mass spectrometry and isotope dilution quantification. J Expos Anal Environ Epidemiol. 2004;14:249–59.

    Article  CAS  Google Scholar 

  19. Cole SR, Chu H, Nie L, Schisterman EF. Estimating the odds ratio when exposure has a limit of detection. Int J Epidemiol. 2009;38:1674–80.

    Article  Google Scholar 

  20. Loprinzi PD, Edwards M. Association between objectively measured physical activity and erectile dysfunction among a nationally representative sample of American Men. J Sex Med. 2015;12:1862–4.

    Article  Google Scholar 

  21. Marumo K, Nakashima J, Murai M. Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function. Int J Urol: Off J Jpn Urol Assoc. 2001;8:53–59.

    Article  CAS  Google Scholar 

  22. Timchalk C, Busby A, Campbell JA, Needham LL, Barr DB. Comparative pharmacokinetics of the organophosphorus insecticide chlorpyrifos and its major metabolites diethylphosphate, diethylthiophosphate and 3,5,6-trichloro-2-pyridinol in the rat. Toxicology. 2007;237:145–57.

    Article  CAS  Google Scholar 

  23. Busby-Hjerpe AL, Campbell JA, Smith JN, Lee S, Poet TS, Barr DB, et al. Comparative pharmacokinetics of chlorpyrifos versus its major metabolites following oral administration in the rat. Toxicology. 2010;268:55–63.

    Article  CAS  Google Scholar 

  24. Roca M, Miralles-Marco A, Ferré J, Pérez R, Yusà V. Biomonitoring exposure assessment to contemporary pesticides in a school children population of Spain. Environ Res. 2014;131:77–85.

    Article  CAS  Google Scholar 

  25. Kavvalakis MP, Tsatsakis AM. The atlas of dialkylphosphates; assessment of cumulative human organophosphorus pesticides’ exposure. Forensic Sci Int. 2012;218:111–22.

    Article  CAS  Google Scholar 

  26. Yang F, Li J, Pang G, Ren F, Fang B. Effects of diethyl phosphate, a non-specific metabolite of organophosphorus pesticides, on serum lipid, hormones, inflammation, and gut microbiota. Molecules. 2019;24:1–12.

  27. Yang FW, Zhao GP, Ren FZ, Pang GF, Li YX. Assessment of the endocrine-disrupting effects of diethyl phosphate, a nonspecific metabolite of organophosphorus pesticides, by in vivo and in silico approaches. Environ Int. 2020;135:105383.

    Article  CAS  Google Scholar 

  28. Buvat J, Maggi M, Gooren L, Guay AT, Kaufman J, Morgentaler A, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med. 2010;7:1627–56.

    Article  Google Scholar 

  29. Sette KN, Alugubelly N, Glenn LB, Guo-Ross SX, Parkes MK, Wilson JR, et al. The mechanistic basis for the toxicity difference between juvenile rats and mice following exposure to the agricultural insecticide chlorpyrifos. Toxicology. 2022;480:153317.

    Article  CAS  Google Scholar 

  30. Rush T, Liu XQ, Hjelmhaug J, Lobner D. Mechanisms of chlorpyrifos and diazinon induced neurotoxicity in cortical culture. Neuroscience. 2010;166:899–906.

    Article  CAS  Google Scholar 

  31. Maeda N, Matsuoka N, Yamaguchi I. Possible involvement of the septo-hippocampal cholinergic and raphe-hippocampal serotonergic activations in the penile erection induced by fenfluramine in rats. Brain Res. 1994;652:181–9.

    Article  CAS  Google Scholar 

  32. Kumar A. Editorial (Thematic selection: mitochondrial dysfunction & neurological disorders). Curr Neuropharmacol. 2016;14:565–6.

    Article  CAS  Google Scholar 

  33. Imam A, Ogunniyi A, Ibrahim A, Abdulmajeed WI, Aboyeji LO, Lawan AH, et al. Dichlorvos induced oxidative and neuronal responses in rats: mitigative efficacy of Nigella sativa (Black Cumin). Niger J Physiol Sci: Off Publ Physiol Soc Niger. 2018;33:83–88.

    CAS  Google Scholar 

  34. Karumuri SB, Singh H, Naqvi S, Mishra A, Flora SJS. Impact of chronic low dose exposure of monocrotophos in rat brain: Oxidative/ nitrosative stress, neuronal changes and cholinesterase activity. Toxicol Rep. 2019;6:1295–303.

    Article  CAS  Google Scholar 

  35. Belba A, Cortelazzo A, Andrea G, Durante J, Nigi L, Dotta F, et al. Erectile dysfunction and diabetes: Association with the impairment of lipid metabolism and oxidative stress. Clin Biochem. 2016;49:70–78.

    Article  CAS  Google Scholar 

  36. Chew KK, Bremner A, Stuckey B, Earle C, Jamrozik K. Is the relationship between cigarette smoking and male erectile dysfunction independent of cardiovascular disease? Findings from a population-based cross-sectional study. J Sex Med. 2009;6:222–31.

    Article  Google Scholar 

  37. O’Donnell AB, Araujo AB, Goldstein I, McKinlay JB. The validity of a single-question self-report of erectile dysfunction. Results from the Massachusetts Male Aging Study. J Gen Intern Med. 2005;20:515–9.

    Article  Google Scholar 

Download references


Thank you to the NHANES participants and staff members for their contribution to data collection and for making the data publicly available.


This study was supported by the National Natural Science Foundation of China (Grant nos. 81800667, 82270811), and the Project of Science and Technology Department of Sichuan Province (Grant nos. 22NSFSC1426).

Author information

Authors and Affiliations



Protocol/project development: ZRY and WW. Data collection or management: ZRY, WW, LDL, and KWX. Data analysis: ZRY, WW, LP, and XSG. Manuscript writing/editing: ZRY, WW, LDL, and XSG. Funding: LZ. Supervision: LZ.

Corresponding author

Correspondence to Liang Zhou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, Z., Wang, W., Lin, L. et al. The association between urinary organophosphate insecticide metabolites and erectile dysfunction in the United States. Int J Impot Res (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI:


Quick links