Phthalates and risk of endometriosis and leiomyomata 1966) and used the resulting creatinine- corrected concentrations for our primary analyses. Concentrations below the limit of detection (LOD) were replaced with the LOD divided by the square root of 2 (Hornung and Reed 1990). For any given urinary metabolite, the proportion of women in our study who had concentrations < LOD ranged from 0.2% to 20.5%. Assessment of endometriosis and uterine leiomyomata. We classified each woman’s his- tory of endometriosis and uterine leiomyomata according to her response to two questions: a) “Has a doctor or other health professional ever told you that you had endometriosis?” b) “Has a doctor or other health professional ever told you that you had uterine fibroids?” Women who answered positively to either of these questions were further queried regarding their age at first diagnosis (open-ended ques- tion) (CDC 2009). Assessment of covariates. Data on age at menarche, gravidity, parity, current pregnancy status, breast-feeding, use of hormonal contra- ception, menopausal status, and gynecologic surgeries were obtained from the NHANES reproductive health questionnaire. We obtained data on age and race/ethnicity from the NHANES home interview. Statistical analysis. We conducted all sta- tistical analyses using SAS-callable SUDAAN, release 9.0.2 (RTI International, Research Triangle Park, NC). Unless specified, our analyses accounted for the complex sampling design of and nonresponse to the NHANES through use of sampling weights and sam- ple design variables. Sampling errors were estimated using the Taylor series linearized method (CDC 2005). We computed geometric mean phthalate metabolite concentrations within diagnosis groups, testing differences by case status using linear regression models of log-transformed phthalate concentrations. Within quartiles of each phthalate metabolite and within case sta- tus for each of the two outcomes, we deter- mined means and frequencies of various characteristics, testing differences using linear and logistic regression models. To evaluate the association between exposure to phthalates and the two outcomes, we used multiple logistic regression to derive adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) across quartiles of each phthalate metabolite concen- tration in relation to endometriosis and uterine leiomyomata. Tests for trend were calculated by including in the regression model a single variable coded as the median of each exposure quartile (Breslow and Day 1987). We con- ducted separate analyses for each phthalate metabolite and for each outcome, comparing women who reported a history of the outcome with those who did not. Because endometriosis and uterine leiomyomata share some common hormonal characteristics, we also analyzed a combined end point defined as having a his- tory of one or both conditions, allowing for increased statistical power, the caveat being that associations could be diluted if the phthalate- related etiologies differ by outcome. Because the distributions of the urinary phthalate con- centrations were strongly right-skewed, we also conducted analyses in which we compared women in the highest quartile of each metabo- lite with those in the lowest three quartiles. As potential confounders, we examined variables that were associated with urinary phthalate concentrations in our study popula- tion and are also considered well-established risk factors for the outcomes of interest. Final models were adjusted for age (years) at time of NHANES urine sample collection, race/ ethnicity (African American, white, other), age at menarche (years), and both current preg- nancy and breast-feeding status. Because of the possibility that hysterectomy, nulliparity, and oral contraceptive use could be consequences of the outcomes, we did not adjust for these vari- ables. For models involving only 2001–2004 data, we did not adjust for breast-feeding sta- tus, because very few women in this popula- tion (n = 28) reported breast-feeding. We were unable to consider infertility history, because these data were not publicly available. The exposure interval directly reflected by urinary phthalate concentrations is quite short. To evaluate the associations between phthalate exposures and the two outcomes in a manner that better reflected the exposures that were actually measured, we conducted secondary analyses that excluded women who had the diagnosis of interest or a hysterectomy > 10 years before their NHANES evaluation [leaving n = 1,146 (47 cases) and 1,134 (96 cases) for analyses of endometriosis and uter- ine leiomyomata, respectively] and > 7 years before [leaving n = 1,128 (38 cases) and 1,112 (79 cases) for endometriosis and leiomyomata, respectively]. For the analyses of uterine leio- myomata and the combined end point, we had sufficient cases to additionally make these exclu- sions on the basis of a 5-year interval [leaving n = 1,096 (67 cases) for leiomyomata analyses]. We performed several sensitivity analyses. In parallel to our primary analyses of creati- nine-corrected urinary phthalate metabolite concentrations, we conducted analyses using raw phthalate metabolite concentrations as the measures of exposure and then included urinary creatinine as an additional term in the logistic regression models. We also reanalyzed the data, allowing for the inclusion of the 127 women with very low (< 30 mg/dL) or very high (> 300 mg/dL) urinary creatinine concentrations. Finally, although our analy- ses of MEHHP and MEOHP constitute a sensitivity analysis of the MEHP analyses, for enhanced comparability, we evaluated MEHP Environmental Health Perspectives • volume 118 | number 6 | June 2010 over the same period in which the oxidative metabolites were assessed (2001–2004). We considered a p-value < 0.05 to be statis- tically significant. For all analyses, we used cre- atinine-corrected urinary concentrations of the phthalate metabolites, unless stated otherwise. Results Among the 1,227 women included in our analysis, the unweighted percentages of those 20–29, 30–39, 40–49, and 50–54 years of age were, respectively, 33.8%, 27.1%, 27.8% and 11.3%. Eighty-seven women (7%) reported a previous diagnosis of endometriosis, 151 (12%) reported a previous diagnosis of uterine leiomyomata, and 201 (16%) reported a pre- vious diagnosis of either condition [34 (3%) had both conditions]. Women with a history of endometriosis reported that their diagno- ses occurred < 1 year to 34 years before their NHANES evaluation (median, 9 years). For uterine leiomyomata, this range was < 1 to 36 years (median, 7 years). Table 1 lists the geometric mean urinary concentrations of the phthalate metabo- lites. Urinary concentrations of MBP were somewhat higher among women with endo- metriosis, and women with endometriosis or leiomyomata had significantly lower concen- trations of MEHP than did women without these conditions (p = 0.03). Women in the highest quartiles of urinary MEP were significantly more likely to be non- Hispanic black or Mexican American than were women in the lowest quartiles (Table 2). Women in the lowest MEP quartile were more likely to be currently breast-feeding than were women in the higher quartiles. Women in the highest quartile of urinary MBzP were sig- nificantly younger, less likely to be Mexican- American, and more likely to be pregnant than were women in the lower quartiles. None of the characteristics varied significantly across quartiles of urinary MEHP, but some patterns emerged in data on the DEHP oxidative metabolites (data not shown). For example, compared with the lowest quartiles of urinary MEOHP, women in the highest quartile were more likely to be non-Hispanic white (p = 0.02). Women who reported a history of endo- metriosis were significantly older, more likely to be non-Hispanic white, and less likely to be non-Hispanic black or Mexican American than were noncases (Table 2). They were also significantly less likely to have been currently breast-feeding. Women who reported a his- tory of uterine leiomyomata were also signifi- cantly older than noncases, but in contrast to the race/ethnicity pattern for endometriosis, leiomyomata cases were significantly more likely than noncases to be non-Hispanic black. Nulliparity and current use of oral contracep- tives were significantly less common among leiomyomata cases than among noncases. 827