Skip to main content
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2005 Aug;62(8):510–516. doi: 10.1136/oem.2004.016014

Prolonged menstrual cycles in female workers exposed to ethylene glycol ethers in the semiconductor manufacturing industry

G Hsieh 1, J Wang 1, T Cheng 1, P Chen 1
PMCID: PMC1741062  PMID: 16046602

Abstract

Background: It has been shown that female workers exposed to ethylene glycol ethers (EGEs) in the semiconductor industry have higher risks of spontaneous abortion, subfertility, and menstrual disturbances, and prolonged waiting time to pregnancy.

Aims: To examine whether EGEs or other chemicals are associated with long menstrual cycles in female workers in the semiconductor manufacturing industry.

Methods: Cross-sectional questionnaire survey during the annual health examination at a wafer manufacturing company in Taiwan in 1997. A three tiered exposure-assessment strategy was used to analyse the risk. A short menstrual cycle was defined to be a cycle less than 24 days and a long cycle to be more than 35 days.

Results: There were 606 valid questionnaires from 473 workers in fabrication jobs and 133 in non-fabrication areas. Long menstrual cycles were associated with workers in fabrication areas compared to those in non-fabrication areas. Using workers in non-fabrication areas as referents, workers in photolithography and diffusion areas had higher risks for long menstrual cycles. Workers exposed to EGEs and isopropanol, and hydrofluoric acid, isopropanol, and phosphorous compounds also showed increased risks of a long menstrual cycle.

Conclusions: Exposure to multiple chemicals, including EGEs in photolithography, might be associated with long menstrual cycles, and may play an important role in a prolonged time to pregnancy in the wafer manufacturing industry; however, the prevalence in the design, possible exposure misclassification, and chance should be considered.

Full Text

The Full Text of this article is available as a PDF (91.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aksel S. Hormonal characteristics of long cycles in fertile women. Fertil Steril. 1981 Oct;36(4):521–523. doi: 10.1016/s0015-0282(16)45805-x. [DOI] [PubMed] [Google Scholar]
  2. Allen B., Gentry R., Shipp A., Van Landingham C. Calculation of benchmark doses for reproductive and developmental toxicity observed after exposure to isopropanol. Regul Toxicol Pharmacol. 1998 Aug;28(1):38–44. doi: 10.1006/rtph.1998.1226. [DOI] [PubMed] [Google Scholar]
  3. Almekinder J. L., Lennard D. E., Walmer D. K., Davis B. J. Toxicity of methoxyacetic acid in cultured human luteal cells. Fundam Appl Toxicol. 1997 Aug;38(2):191–194. doi: 10.1006/faat.1997.2332. [DOI] [PubMed] [Google Scholar]
  4. Beaumont J. J., Swan S. H., Hammond S. K., Samuels S. J., Green R. S., Hallock M. F., Dominguez C., Boyd P., Schenker M. B. Historical cohort investigation of spontaneous abortion in the Semiconductor Health Study: epidemiologic methods and analyses of risk in fabrication overall and in fabrication work groups. Am J Ind Med. 1995 Dec;28(6):735–750. doi: 10.1002/ajim.4700280609. [DOI] [PubMed] [Google Scholar]
  5. Bloch M., Schmidt P. J., Rubinow D. R. Premenstrual syndrome: evidence for symptom stability across cycles. Am J Psychiatry. 1997 Dec;154(12):1741–1746. doi: 10.1176/ajp.154.12.1741. [DOI] [PubMed] [Google Scholar]
  6. Chen Pau-Chung, Hsieh Gong-Yih, Wang Jung-Der, Cheng Tsun-Jen. Prolonged time to pregnancy in female workers exposed to ethylene glycol ethers in semiconductor manufacturing. Epidemiology. 2002 Mar;13(2):191–196. doi: 10.1097/00001648-200203000-00014. [DOI] [PubMed] [Google Scholar]
  7. Cheng T. A., Williams P. The design and development of a screening questionnaire (CHQ) for use in community studies of mental disorders in Taiwan. Psychol Med. 1986 May;16(2):415–422. doi: 10.1017/s0033291700009247. [DOI] [PubMed] [Google Scholar]
  8. Chia S. E., Foo S. C., Khoo N. Y., Jeyaratnam J. Menstrual patterns of workers exposed to low levels of 2-ethoxyethylacetate (EGEEA). Am J Ind Med. 1997 Feb;31(2):148–152. doi: 10.1002/(sici)1097-0274(199702)31:2<148::aid-ajim3>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  9. Chiazze L., Jr, Brayer F. T., Macisco J. J., Jr, Parker M. P., Duffy B. J. The length and variability of the human menstrual cycle. JAMA. 1968 Feb 5;203(6):377–380. [PubMed] [Google Scholar]
  10. Clarke D. O., Elswick B. A., Welsch F., Conolly R. B. Pharmacokinetics of 2-methoxyethanol and 2-methoxyacetic acid in the pregnant mouse: a physiologically based mathematical model. Toxicol Appl Pharmacol. 1993 Aug;121(2):239–252. doi: 10.1006/taap.1993.1151. [DOI] [PubMed] [Google Scholar]
  11. Correa A., Gray R. H., Cohen R., Rothman N., Shah F., Seacat H., Corn M. Ethylene glycol ethers and risks of spontaneous abortion and subfertility. Am J Epidemiol. 1996 Apr 1;143(7):707–717. doi: 10.1093/oxfordjournals.aje.a008804. [DOI] [PubMed] [Google Scholar]
  12. Davis B. J., Almekinder J. L., Flagler N., Travlos G., Wilson R., Maronpot R. R. Ovarian luteal cell toxicity of ethylene glycol monomethyl ether and methoxy acetic acid in vivo and in vitro. Toxicol Appl Pharmacol. 1997 Feb;142(2):328–337. doi: 10.1006/taap.1996.8035. [DOI] [PubMed] [Google Scholar]
  13. Eskenazi B., Gold E. B., Lasley B. L., Samuels S. J., Hammond S. K., Wight S., O'Neill Rasor M., Hines C. J., Schenker M. B. Prospective monitoring of early fetal loss and clinical spontaneous abortion among female semiconductor workers. Am J Ind Med. 1995 Dec;28(6):833–846. doi: 10.1002/ajim.4700280615. [DOI] [PubMed] [Google Scholar]
  14. Eskenazi B., Gold E. B., Samuels S. J., Wight S., Lasley B. L., Hammond S. K., O'Neill Rasor M., Schenker M. B. Prospective assessment of fecundability of female semiconductor workers. Am J Ind Med. 1995 Dec;28(6):817–831. doi: 10.1002/ajim.4700280614. [DOI] [PubMed] [Google Scholar]
  15. Gold E. B., Eskenazi B., Hammond S. K., Lasley B. L., Samuels S. J., O'Neill Rasor M., Hines C. J., Overstreet J. W., Schenker M. B. Prospectively assessed menstrual cycle characteristics in female wafer-fabrication and nonfabrication semiconductor employees. Am J Ind Med. 1995 Dec;28(6):799–815. doi: 10.1002/ajim.4700280613. [DOI] [PubMed] [Google Scholar]
  16. Gold E. B., Eskenazi B., Lasley B. L., Samuels S. J., O'Neill Rasor M., Overstreet J. W., Schenker M. B. Epidemiologic methods for prospective assessment of menstrual cycle and reproductive characteristics in female semiconductor workers. Am J Ind Med. 1995 Dec;28(6):783–797. doi: 10.1002/ajim.4700280612. [DOI] [PubMed] [Google Scholar]
  17. Hammond S. K., Hines C. J., Hallock M. F., Woskie S. R., Abdollahzadeh S., Iden C. R., Anson E., Ramsey F., Schenker M. B. Tiered exposure-assessment strategy in the Semiconductor Health Study. Am J Ind Med. 1995 Dec;28(6):661–680. doi: 10.1002/ajim.4700280604. [DOI] [PubMed] [Google Scholar]
  18. Harlow S. D., Matanoski G. M. The association between weight, physical activity, and stress and variation in the length of the menstrual cycle. Am J Epidemiol. 1991 Jan;133(1):38–49. doi: 10.1093/oxfordjournals.aje.a115800. [DOI] [PubMed] [Google Scholar]
  19. Hornsby P. P., Wilcox A. J., Weinberg C. R. Cigarette smoking and disturbance of menstrual function. Epidemiology. 1998 Mar;9(2):193–198. [PubMed] [Google Scholar]
  20. Joffe M. Biases in research on reproduction and women's work. Int J Epidemiol. 1985 Mar;14(1):118–123. doi: 10.1093/ije/14.1.118. [DOI] [PubMed] [Google Scholar]
  21. Kesner J. S., Wright D. M., Schrader S. M., Chin N. W., Krieg E. F., Jr Methods of monitoring menstrual function in field studies: efficacy of methods. Reprod Toxicol. 1992;6(5):385–400. doi: 10.1016/0890-6238(92)90002-b. [DOI] [PubMed] [Google Scholar]
  22. Lenton E. A., Landgren B. M., Sexton L., Harper R. Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age. Br J Obstet Gynaecol. 1984 Jul;91(7):681–684. doi: 10.1111/j.1471-0528.1984.tb04830.x. [DOI] [PubMed] [Google Scholar]
  23. Lohstroh Pete N., Chen Jiangang, Ba Jianming, Ryan Louise M., Xu Xiping, Overstreet James W., Lasley Bill L. Bone resorption is affected by follicular phase length in female rotating shift workers. Environ Health Perspect. 2003 Apr;111(4):618–622. doi: 10.1289/ehp.5878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matsumoto S., Tamada T., Konuma S. Endocrinological analysis of environmental menstrual disorders. Int J Fertil. 1979;24(4):233–239. [PubMed] [Google Scholar]
  25. Pastides H., Calabrese E. J., Hosmer D. W., Jr, Harris D. R., Jr Spontaneous abortion and general illness symptoms among semiconductor manufacturers. J Occup Med. 1988 Jul;30(7):543–551. [PubMed] [Google Scholar]
  26. Rowland Andrew S., Baird Donna Day, Long Stuart, Wegienka Ganesa, Harlow Siobán D., Alavanja Michael, Sandler Dale P. Influence of medical conditions and lifestyle factors on the menstrual cycle. Epidemiology. 2002 Nov;13(6):668–674. doi: 10.1097/00001648-200211000-00011. [DOI] [PubMed] [Google Scholar]
  27. Rubinow D. R., Roy-Byrne P. Premenstrual syndromes: overview from a methodologic perspective. Am J Psychiatry. 1984 Feb;141(2):163–172. doi: 10.1176/ajp.141.2.163. [DOI] [PubMed] [Google Scholar]
  28. Scott W. J., Fradkin R., Wittfoht W., Nau H. Teratologic potential of 2-methoxyethanol and transplacental distribution of its metabolite, 2-methoxyacetic acid, in non-human primates. Teratology. 1989 Apr;39(4):363–373. doi: 10.1002/tera.1420390408. [DOI] [PubMed] [Google Scholar]
  29. Sternfeld Barbara, Jacobs Marlena K., Quesenberry Charles P., Jr, Gold Ellen B., Sowers MaryFran. Physical activity and menstrual cycle characteristics in two prospective cohorts. Am J Epidemiol. 2002 Sep 1;156(5):402–409. doi: 10.1093/aje/kwf060. [DOI] [PubMed] [Google Scholar]
  30. Swan S. H., Beaumont J. J., Hammond S. K., VonBehren J., Green R. S., Hallock M. F., Woskie S. R., Hines C. J., Schenker M. B. Historical cohort study of spontaneous abortion among fabrication workers in the Semiconductor Health Study: agent-level analysis. Am J Ind Med. 1995 Dec;28(6):751–769. doi: 10.1002/ajim.4700280610. [DOI] [PubMed] [Google Scholar]
  31. Thompson M. L., Myers J. E., Kriebel D. Prevalence odds ratio or prevalence ratio in the analysis of cross sectional data: what is to be done? Occup Environ Med. 1998 Apr;55(4):272–277. doi: 10.1136/oem.55.4.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Treloar A. E., Boynton R. E., Behn B. G., Brown B. W. Variation of the human menstrual cycle through reproductive life. Int J Fertil. 1967 Jan-Mar;12(1 Pt 2):77–126. [PubMed] [Google Scholar]
  33. VOLLMAN R. F. The degree of variability of the length of the menstrual cycle in correlation with age of woman. Gynaecologia. 1956 Nov;142(5):310–314. doi: 10.1159/000307655. [DOI] [PubMed] [Google Scholar]
  34. Waller K., Swan S. H., Windham G. C., Fenster L., Elkin E. P., Lasley B. L. Use of urine biomarkers to evaluate menstrual function in healthy premenopausal women. Am J Epidemiol. 1998 Jun 1;147(11):1071–1080. doi: 10.1093/oxfordjournals.aje.a009401. [DOI] [PubMed] [Google Scholar]
  35. Zeleznik A. J., Hutchison J. S., Schuler H. M. Interference with the gonadotropin-suppressing actions of estradiol in macaques overrides the selection of a single preovulatory follicle. Endocrinology. 1985 Sep;117(3):991–999. doi: 10.1210/endo-117-3-991. [DOI] [PubMed] [Google Scholar]
  36. Zeleznik A. J. Premature elevation of systemic estradiol reduces serum levels of follicle-stimulating hormone and lengthens the follicular phase of the menstrual cycle in rhesus monkeys. Endocrinology. 1981 Aug;109(2):352–355. doi: 10.1210/endo-109-2-352. [DOI] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES