Authors:
Gerhard I, Monga B, Krahe J, Runnebaum B.

Title:
Chlorinated Hydrocarbons in Infertile Women

Journal:
Environmental Research Section A. 80:299-310, 1999.

Summary:
There is some evidence to suggest that exposure to chlorinated hydrocarbons (CHC) can have detrimental effects on fertility. Many chemicals labeled as chlorinated hydrocarbons share a number of important properties. In particular, they are generally fairly toxic, they are persistent in the environment, and they are bioaccumulated. Many of these compounds are estrogenic and disrupt progestational events, and/or partial or weak estrogen antagonists, and thus disrupt estrogen-dependent events. The present study was conducted to investigate peripheral blood PCP (pentachlorophenol), PCB (polychlorinated biphenyls), DDT and DDT-metabolites, HCH (hexachlorocyclohexane), and HCB (hexachlorobenzene) levels in 489 infertile women living in Germany in order to evaluate possible associations between environmental toxicant exposure and fertility.

Ninety percent of the subjects were German, and the foreigners were mainly Turkish. Multivariate regression analysis was used to correlate CHC concentrations to specific reproductive variables (i.e. endometriosis, uterine fibroids, miscarriage, primary infertility) and general factors (age, body mass index (BMI), nationality and smoking). At least one CHC level was elevated in 47% of the subjects, two in 30%, three in 10%, four in 5%, and five in 0.5% subjects, which were considered 'contaminated'. The concentrations of ß- and total HCH, DDT, HCB, and PCB increased significantly with increasing age as expected, however, CHC levels were not significantly correlated with occupation, smoking, or alcohol intake. Bioaccumulation of pollutants with increasing age is one factor suggested to increase risk of miscarriage and reduce pregnancy rate. Significantly greater levels of DDT, ß-HCH, and total HCH were measured in foreign women, whereas German women had significantly higher concentrations of HCB and PCB. ß-HCH was positively correlated to body weight with PCB levels highest in women with a low BMI. High HCH levels were observed in women with a history of previous miscarriages, positive thyroid or antinuclear antibodies, and uterine fibroids.

PCP concentrations were significantly elevated in women with a higher rate of miscarriage, positive antinuclear antibodies or alopecia. The association between high PCP levels and increased risk of miscarriage has also been confirmed in a related study in women exposed to wood preservatives (PCP source) compared to age-matched controls. PCB concentrations were significantly greater in women with endometriosis, positive auto- and thyroid antibodies. The immunotoxicity of PCB may contribute to the immunopathy of endometriosis. Elevated DDT concentrations were detected in women with presumed immunological infertility and lower conception rates. Finally, HCB levels were significantly higher in women with hyperprolactinemia and significantly lower in women with hyperandrogenemia.

Animal studies (rats, dogs, seals, monkeys) have demonstrated that CHC exposure causes adverse reproductive and developmental effects. In this study, the authors attempted to measure a wide range of CHC compounds examining a large number of reproductive and developmental endpoints. The authors first examined each reproductive endpoint and its association with CHC concentration independently. Although this form of analysis did reveal that PCP concentrations were elevated in women under certain conditions, this analysis does not take into account confounding variables such as age, nationality, smoking, body mass index. Using a more complicated test, multivariate regression, there did not appear to be an association between CHC concentration and reproductive endpoints (endometriosis, uterine fibroids, miscarriage etc.) when other variables were taken into account. The results of the cross-sectional analysis suggest that long-term exposure to low levels of CHCs may adversely affect human reproduction.

Interpretation of the importance of elevated levels of CHC compounds in this population is extremely difficult for several reasons. First, no control population was used. It is possible that serum levels of CHC compounds are also elevated in fertile women. Second, the sample size in many of the diagnostic categories is extremely low (endometriosis n=28; uterine fibroids n=17) and some women were diagnosed with a combination of reproductive disorders. Third, the authors attempt to associate nationality with increased CHC levels, however, this study is poorly designed to examine this question. No attempt was made to match Germans and 'foreigners' on the basis of chemical exposure due to occupation, diet, agriculture and other factors. Again, as 90% of the study population was German the sample size of the 'foreign' population was too small for comparison. While the findings of elevated CHC levels in infertile women are interesting, it is unclear how these compounds might contribute to the etiology of infertility. Several different reproductive disorders were examined, some of which are hormonally dependent, whereas others have no clear etiology. The authors did not attempt to propose a mechanism(s) of action for these compounds with respect to infertility. Future controlled or cohort studies are necessary to investigate the possible association between environmental CHC exposure and the development of human reproductive disorders. It would be advisable to limit the scope of such studies to defined biological endpoints (ie. endometriosis) rather than general infertility (ie. primary infertility, hormonal disorders).