Current Epidemiology Reports

, Volume 5, Issue 3, pp 197–204 | Cite as

Impacts of Air Pollution on Gynecologic Disease: Infertility, Menstrual Irregularity, Uterine Fibroids, and Endometriosis: a Systematic Review and Commentary

  • Shruthi MahalingaiahEmail author
  • Kevin J. Lane
  • Chanmin Kim
  • J. Jojo Cheng
  • Jaime E. Hart
Environmental Epidemiology (F Laden and J Hart, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Environmental Epidemiology


Purpose of Review

Air pollution is widely known to affect human cardiopulmonary health, but only recently has research begun to focus on understanding the association between ambient air pollution and reproductive health and gynecologic disease incidence. In this article, we conducted a systematic literature review to examine studies conducted to evaluate the association between air pollution and the heterogeneous gynecologic diseases of infertility, menstrual irregularity, uterine fibroids, and endometriosis. In this review, the authors discuss exposure assessment considerations, outcome definitions, statistical analyses, and relevant biological mechanisms, and also provide ideas for future directions of research.

Recent Findings

Emerging literature evaluated associations between gynecologic diseases of infertility, menstrual irregularity, uterine fibroids, and endometriosis with air pollution exposures, specifically fine particulate matter (particles ≤ 2.5 μm in aerodynamic diameter [PM2.5]), coarse particulate matter (particles 2.5–10 μm in aerodynamic diameter [PM2.5–10]), traffic-related pollutants (NO2, NOx), and proximity to major roadways. Suggestive associations have been observed with distance to road and traffic exposures with incident infertility, fertility rates, and menstrual cycle irregularity. However, to date, the number of studies examining similar exposures and outcomes has been quite limited.


While initial studies suggest a potential relationship between air pollution and both infertility and menstrual irregularity, more studies need to be performed to validate these findings in other datasets and populations.


Air pollution Uterine fibroids Infertility Endometriosis Menstrual irregularity Fine particulate matter 


Funding Information

SM would like to acknowledge the Building Interdisciplinary Research Careers in Womens Health (HD043444 BIRCWH K12) and the Reproductive Scientist Development Program (HD000849 RSDP K12) for funding and support of the research team to conduct the series of papers noted in this review on air pollution and gynecologic disease incidence. SM would like to acknowledge the Boston University Superfund Research Program (BU SRP) for support during post-doctoral work on this topic. JEH was supported by P30 ES000002.

Compliance with Ethical Standards

Conflict of Interest

Shruthi Mahalingaiah, Kevin J. Lane, Chanmin Kim, J. Jojo Cheng, and Jaime E. Hart declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Wolf K, Stafoggia M, Cesaroni G, Andersen ZJ, Beelen R, Galassi C, et al. Long-term exposure to particulate matter constituents and the incidence of coronary events in 11 European cohorts. Epidemiology. 2015;26(4):565–74. Scholar
  2. 2.
    Wang M, Beelen R, Stafoggia M, Raaschou-Nielsen O, Andersen ZJ, Hoffmann B, et al. Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: results from the ESCAPE and TRANSPHORM projects. Environ Int. 2014;66:97–106. Scholar
  3. 3.
    Vizcaino MAC, Gonzalez-Comadran M, Jacquemin B. Outdoor air pollution and human infertility: a systematic review. Fertil Steril. 2016;106(4):897–904.e1. Scholar
  4. 4.
    Morello-Frosch R, Jesdale BM, Sadd JL, Pastor M. Ambient air pollution exposure and full-term birth weight in California. Environ Health. 2010;9(44)
  5. 5.
    Gray SC, Edwards SE, Schultz BD, Miranda ML. Assessing the impact of race, social factors and air pollution on birth outcomes: a population-based study. Environ Health. 2014;13(1):4. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Stieb DM, Chen L, Eshoul M, Judek S. Ambient air pollution, birth weight and preterm birth: a systematic review and meta-analysis. Environ Res. 2012;117(0):100–11. Scholar
  7. 7.
    • Martens DS, Cox B, Janssen BG, Clemente DBP, Gasparrini A, Vanpoucke C, et al. Prenatal air pollution and Newborns' predisposition to accelerated biological aging. JAMA Pediatr. 2017;171(12):1160–7. First study to assess the association of prenatal exposure to particulate matter (PM) with newborn telomere length as reflected by cord blood and placental telomere length. In 641 newborns, this study found that mothers who were exposed to higher levels of PM 2.5 gave birth to newborns with shorter telomere length. CrossRefPubMedGoogle Scholar
  8. 8.
    Gouveia N, Mascolli MA. Air pollution: an important threat to infant health. BJOG. 2018;
  9. 9.
    Wilson WE, Suh HH. Fine particles and coarse particles: concentration relationships relevant to epidemiologic studies. J Air Waste Manag Assoc. 1997;47(12):1238–49.CrossRefPubMedGoogle Scholar
  10. 10.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12. Scholar
  11. 11.
    Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology. 2009 Fertil Steril. 2009;92(5):1520–4. CrossRefPubMedGoogle Scholar
  12. 12.
    •• Mahalingaiah S, Hart JE, Laden F, Farland LV, Hewlett MM, Chavarro J, et al. Adult air pollution exposure and risk of infertility in the Nurses' Health Study II. Hum Reprod. 2016;31(3):638–47. First prospective study to assess exposures to ambient air pollution and distance to major road with incidence of infertility. A small increased risk for those living closer to compared to farther from a major road, multivariable-adjusted HR = 1.11 (CI 1.02–1.20) was noted. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Yanosky JD, Paciorek CJ, Suh HH. Predicting chronic fine and coarse particulate exposures using spatiotemporal models for the Northeastern and Midwestern United States. Environ Health Perspect. 2009;117(4):522–9. Scholar
  14. 14.
    Yanosky JD, Paciorek CJ, Schwartz J, Laden F, Puett R, Suh HH. Spatio-temporal modeling of chronic PM10 exposure for the Nurses' Health Study. Atmos Environ (1994). 2008;42(18):4047–62. CrossRefGoogle Scholar
  15. 15.
    Yanosky JD, Paciorek CJ, Laden F, Hart JE, Puett RC, Liao D, et al. Spatio-temporal modeling of particulate air pollution in the conterminous United States using geographic and meteorological predictors. Environ Health. 2014;13:63. Scholar
  16. 16.
    •• Nieuwenhuijsen MJ, Basagana X, Dadvand P, Martinez D, Cirach M, Beelen R, et al. Air pollution and human fertility rates. Environ Int. 2014;70:9–14. This study evaluated the association between traffic-related air pollution and fertility rates at the Census-tract level in humans in Barcelona, Spain (2011–2012). A reduction of fertility rates with an increase in traffic-related air pollution levels was noted. (IRR = 0.87 95% CI 0.82, 0.94 per IQR) CrossRefPubMedGoogle Scholar
  17. 17.
    Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9. Scholar
  18. 18.
    Franks S. Medical progress—polycystic-ovary-syndrome. N Engl J Med. 1995;333(13):853–61. Scholar
  19. 19.
    Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456–88. Scholar
  20. 20.
    •• Mahalingaiah S, Missmer SE, Cheng JJ, Chavarro J, Laden F, Hart JE. Perimenarchal air pollution exposure and menstrual disorders. Hum Reprod. 2018;2018 Cross-sectional study of 34,832 of the original 116,430 women enrolled in 1989 from the NHSII of menstrual cycle irregularity in three categories and total suspended particulate matter. In multivariable-adjusted models, for every 45 μg/m 3 increase in average high school TSP, there were increased odds (95%CI) of 1.08 (1.03–1.14), 1.08 (1.02–1.15), and 1.10 (0.98–1.25) for moderate, persistent, and persistent with androgen excess irregularity phenotypes, respectively.
  21. 21.
    Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188(1):100–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Mehine M, Kaasinen E, Heinonen HR, Makinen N, Kampjarvi K, Sarvilinna N, et al. Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers. P Natl Acad Sci USA. 2016;113(5):1315–20. Scholar
  23. 23.
    •• Mahalingaiah S, Hart JE, Laden F, Terry KL, Boynton-Jarrett R, Aschengrau A, et al. Air pollution and risk of uterine leiomyomata. Epidemiology. 2014;25(5):682–8. First study to evaluate ambient air pollution exposures and uterine leiomyomata incidence. Results suggest that chronic exposure to PM 2.5 may be associated with a modest increased risk of uterine leiomyomata. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997;90(6):967–73.CrossRefPubMedGoogle Scholar
  25. 25.
    Maggiore ULR, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update. 2016;22(1):70–103. Scholar
  26. 26.
    Signorile PG, Baldi F, Bussani R, Viceconte R, Bulzomi P, D'Armiento M, et al. Embryologic origin of endometriosis: analysis of 101 human female fetuses. J Cell Physiol. 2012;227(4):1653–6. Scholar
  27. 27.
    •• Mahalingaiah S, Hart JE, Laden F, Aschengrau A, Missmer SA. Air pollution exposures during adulthood and risk of endometriosis in the Nurses' Health Study II. Environ Health Perspect. 2014;122(1):58–64. First study to prospectively examine ambient air pollution exposures and incidence of laparoscopically confirmed endometriosis. The authors discuss a null association due to wide confidence intervals, but point estimates suggest a lower incidence of endometriosis in those with higher air pollution exposures measured in the 2-year, 4-year, and cumulative study windows. PubMedCrossRefGoogle Scholar
  28. 28.
    Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol. 2004;160(8):784–96. Scholar
  29. 29.
    Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, et al. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation. 2004;109(21):2655–71.CrossRefPubMedGoogle Scholar
  30. 30.
    Salvi S, Blomberg A, Rudell B, Kelly F, Sandstrom T, Holgate ST, et al. Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers. Am J Respir Crit Care Med. 1999;159(3):702–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836–43.CrossRefPubMedGoogle Scholar
  32. 32.
    Peters A, Dockery DW, Muller JE, Mittleman MA. Increased particulate air pollution and the triggering of myocardial infarction. Circulation. 2001;103(23):2810–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Mine Safety and Health Administration, Department of Labor. Underground coal miners; proposed rule Federal Register 1998; 30 CFR Part 72 and 751998.Google Scholar
  34. 34.
    Blake GJ, Ridker PM. Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med. 2002;252(4):283–94.CrossRefPubMedGoogle Scholar
  35. 35.
    Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004;350(14):1387–97.CrossRefPubMedGoogle Scholar
  36. 36.
    van Eeden SF, Tan W, Suwa T, Mukae H, Terashima T, Fujii T, et al. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). Am J Respir Crit Care Med. 2001;164(5):826–30.CrossRefPubMedGoogle Scholar
  37. 37.
    Andrade AZ, Rodrigues JK, Dib LA, Romao GS, Ferriani RA, Jordao Junior AA et al. Serum markers of oxidative stress in infertile women with endometriosis. Rev Bras Ginecol Obstet32(6):279–85.Google Scholar
  38. 38.
    Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Vet Med Int. 2010; [doi].
  39. 39.
    Maybin JA, Critchley HO, Jabbour HN. Inflammatory pathways in endometrial disorders. Mol Cell Endocrinol. 2011;335:42–51. Scholar
  40. 40.
    Miyamoto K, Sato EF, Kasahara E, Jikumaru M, Hiramoto K, Tabata H et al. Effect of oxidative stress during repeated ovulation on the structure and functions of the ovary, oocytes, and their mitochondria. Free Radic Biol Med.49(4):674–81. doi:
  41. 41.
    Motejlek K, Palluch F, Neulen J, Grummer R. Smoking impairs angiogenesis during maturation of human oocytes. Fertil Steril. 2006;86(1):186–91. Scholar
  42. 42.
    Whyatt RM, Jedrychowski W, Hemminki K, Santella RM, Tsai WY, Yang K, et al. Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility. Cancer Epidemiol Biomark Prev. 2001;10(6):581–8.Google Scholar
  43. 43.
    Whyatt RM, Santella RM, Jedrychowski W, Garte SJ, Bell DA, Ottman R, et al. Relationship between ambient air pollution and DNA damage in Polish mothers and newborns. Environ Health Perspect. 1998;106(Suppl 3):821–6.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Younglai EV, Foster WG, Hughes EG, Trim K, Jarrell JF. Levels of environmental contaminants in human follicular fluid, serum, and seminal plasma of couples undergoing in vitro fertilization. Arch Environ Contam Toxicol. 2002;43(1):121–6. [doi].
  45. 45.
    Al-Saleh I, El-Doush I, Arif J, Coskun S, Jaroudi K, Al-Shahrani A et al. Levels of DNA adducts in the blood and follicular fluid of women undergoing in vitro fertilization treatment and its correlation with the pregnancy outcome. Bull Environ Contam Toxicol84(1):23–8. doi: [doi].
  46. 46.
    Misaki K, Suzuki M, Nakamura M, Handa H, Iida M, Kato T, et al. Aryl hydrocarbon receptor and estrogen receptor ligand activity of organic extracts from road dust and diesel exhaust particulates. Arch Environ Contam Toxicol. 2008;55(2):199–209. Scholar
  47. 47.
    Oh SM, Ryu BT, Chung KH. Identification of estrogenic and antiestrogenic activities of respirable diesel exhaust particles by bioassay-directed fractionation. Arch Pharm Res. 2008;31(1):75–82.CrossRefPubMedGoogle Scholar
  48. 48.
    Sidlova T, Novak J, Janosek J, Andel P, Giesy JP, Hilscherova K. Dioxin-like and endocrine disruptive activity of traffic-contaminated soil samples. Arch Environ Contam Toxicol. 2009;57(4):639–50. Scholar
  49. 49.
    Wang J, Xie P, Kettrup A, Schramm KW. Inhibition of progesterone receptor activity in recombinant yeast by soot from fossil fuel combustion emissions and air particulate materials. Sci Total Environ. 2005;349(1–3):120–8. Scholar
  50. 50.
    Martens D, Cox B, Janssen B, Clemente D, Gasparrini A, Vanpoucke C, et al. Prenatal air pollution and newborns’ predisposition to accelerated biological aging. JAMA Pediatr. 2017;
  51. 51.
    Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, et al. Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics. 2015;16(3):493–508. Scholar
  52. 52.
    Rubin DB. Bayesian-inference for causal effects—role of randomization. Ann Stat. 1978;6(1):34–58. Scholar
  53. 53.
    VanderWeele TJ. Causal mediation analysis with survival data. Epidemiology. 2011;22(4):582–5. Scholar
  54. 54.
    Tchetgen EJT. Inverse odds ratio-weighted estimation for causal mediation analysis. Stat Med. 2013;32(26):4567–80. Scholar
  55. 55.
    Wang W, Albert JM. Causal mediation analysis for the Cox proportional hazards model with a smooth baseline hazard estimator. J R Stat Soc C-Appl. 2017;66(4):741–57. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Shruthi Mahalingaiah
    • 1
    • 2
    • 3
    Email author
  • Kevin J. Lane
    • 4
  • Chanmin Kim
    • 5
  • J. Jojo Cheng
    • 1
  • Jaime E. Hart
    • 6
    • 7
  1. 1.Department of Obstetrics and GynecologyBoston University School of MedicineBostonUSA
  2. 2.Department of Epidemiology, TalbotBoston University School of Public HealthBostonUSA
  3. 3.Department of Obstetrics & GynecologyBoston University Medical CampusBostonUSA
  4. 4.Department of Environmental Health, TalbotBoston University School of Public HealthBostonUSA
  5. 5.Department of Biostatistics, TalbotBoston University School of Public HealthBostonUSA
  6. 6.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  7. 7.Exposure, Epidemiology, and Risk Program, Department of Environmental HealthHarvard TH Chan School of Public HealthBostonUSA

Personalised recommendations