Phthalates and risk of endometriosis

Abstract

Background Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. Objective To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. Methods We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. Results The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1–0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ΣDEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. Conclusions Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women.

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…Dioxin exposure (47,324) and exposure to the a phthalate BzBP metabolite and its metabolites MBz, P and the DEP metabolite MEP may be associated with increased risk of endometriosis (63), although BPA exposure was not linked in an epidemiological study of women with endometriosis (350). One large cross-sectional study from the United States demonstrated an association of MBP with an increased risk of endometriosis (366), and another did not confirm the associations of phthalate exposure with endometriosis and demonstrated that MEHP had an inverse association with the presence of endometriosis (351). Serum levels of the organochlorine pesticide ␤-hexachlorocyclohexane have been associated with endometriosis in a cohort of women undergoing surgical exploration for the disease (349), and dioxin and dioxin-like compounds have for many years been believed to be associated with the development of endometriosis.…”

First-trimester determination of fetal gender by ultrasound: measurement of the ano-genital distance

“…These results could be particularly relevant, as for male fetuses, to detect early sexual dysmorphism. In addition, in accordance to M a n u s c r i p t 12 previous studies [29,30] demonstrating the risk of developing endometriosis linked to exposure to phthalates and to xeno-estrogenes, abnormalities in the AGD in female foetuses might be a parameter to take into account in further studies to better understand the physiopathology of this debilating disorder.…”

Female Infertility and “Emerging” Organic Pollutants of Concern

“…The parent diesters and their metabolite monoesters possess various estrogenic and anti-estrogenic activities in vitro with ovarian and uterine toxicity in vivo [28]. In humans, urine phthalates have been associated with endometriosis [32], and higher levels around the time of conception have been associated with pregnancy loss [33].…”