Authors
S. L. Farr, G. S. Cooper, J. Cai, D. A. Savitz, D. P. Sandler.

Title:
Pesticide use and menstrual cycle characteristics among premenopausal women in the agricultural health study.

Journal:
American Journal of Epidemiology 160:1194-1204, 2004.

Summary:
Disturbances in menstrual cycle can be reflective of underlying reproductive dysfunction. Prior studies have demonstrated adverse reproductive effects following exposure to pesticides, producing both hormonal disruption and impaired oocyte quality in humans and laboratory animals; however pesticide-related disruption to the menstrual cycle has not been well addressed.

The present study determined the effects of exposure to pesticides (other than DDT) on menstrual cycle characteristics. The study was based on the cross-sectional data obtained from 3,103 premenopausal women, between 21-40 years from the Agricultural Health Study, a prospective cohort study of commercial and private pesticide applicators and spouses of pesticide applicators, in Iowa and North Carolina for the years 1993-1997. Details about the preparation and application of a variety of pesticides, farming practices, and demographic characteristics, including information on general and reproductive health, were obtained from questionnaires designed to examine pesticide use and reproductive health. Women who were pregnant or breastfeeding and those with extreme values of body mass index or using oral contraceptives were excluded from the analysis, in addition to the women with missing information on exposure, outcome and other factors such as smoking, body mass index.

Effects of personally mixing and applying pesticides on menstrual cycle characteristics were evaluated. Menstrual cycles were characterized as follows: long cycles (36 days or more), short cycles (24 days or less), irregular cycles, missed period (not experiencing a period for more than 6 weeks in last 12 months) and intermenstrual bleeding (bleeding between menstrual periods in last 12 months). The analyses were limited to 40 pesticides present in the market at the time of study. Pesticides were classified as probable or possible hormonally active or ovotoxic pesticides, based on a literature review using PubMed and other toxicological databases. Details on ever use of pesticide of specific functional groups and chemical classes including the number of days of exposure per year (0, 1-9, 10 or more days) were obtained from the questionnaire responses of female applicators and female spouses of applicators.

Ever mixing or applying pesticides groups were associated with increased odds of missed periods (OR=1.6, 95% confidence interval (CI): 1.3-2.0) and increased menstrual cycle length (p<0.02) but a decreased odds of irregular cycles (OR=0.55, 95% CI: 0.41-0.75). Increasing trends were observed for long cycles (p=0.08) and missed periods (p<0.001) with increased duration of pesticide use. Furthermore, limiting the analysis to women exposed to probable or possible hormonally active or ovotoxic pesticides strengthened the associations with long cycle length (OR=1.6), missed periods (OR=1.7) and intermenstrual bleeding (OR=1.3). Limiting the analysis to women exposed to probable hormonally active pesticides (lindane, atrazine, and manozeb or maneb) further strengthened the above results. Three separate analyses were performed to control for physical activity and the healthy worker effect by adjusting number of days worked in the field, limiting the reference group to women who worked in fields, and limiting the reference group to women who used other pesticides (excluding probable of possible hormonally active pesticides). The associations for probable hormonally active pesticides remained after controlling for occupational physical activity except for the attenuation of odds ratios for short and irregular periods.

In this study, an increase in cycle length and increased odds of missed periods were observed in women mixing or applying pesticides (compared with never users). However, the mechanism behind such an association was unexplained. A large study population and consistency of results with current literature contribute to the strengths of this study. The limited information on pesticide exposure is a limitation of this study. Further, the use of pesticides as mixtures limits the classification of pesticides as hormonally active, and limits the attribution of menstrual cycle dysfunction to a specific pesticide. Misclassification of outcomes due to faulty recall of menstrual history, or misclassification of exposure status could not be ruled out. Although the results are similar for long cycles, missed periods and intermenstrual bleeding after controlling for physical activity, the attenuated associations for short and irregular periods were unexplained. Overall, this study suggests that menstrual cycle characteristics may be altered by women exposed to pesticides.