1 Hex-Tox 논문초독회 이 장 우
2 1. Introduction Short-lived chemicals and persistent compounds might be associated with gynecologic disorders such as endometriosis - But, spot urine may not reflect the timing of disease onset and/or progression In contrast, limited study exists on environmental chemicals and uterine leiomyoma, an estrogen sensitivity tumor of the myometrium Non-persistant chemicals : BPA, Phthalate, Benzophenone-type UV filter - BPA : polycarbonate plastics and epoxy resin - Phthalate : cosmetics and other consumer products - UV filter : dermal exposure to sunscreen products - Health effects : estrogen activity, anti-androgenic effect
3 1. Introduction Previous studies PhthalateLuisi et al., 2006 and Huang et al., 2010 Small clinical samples with 36 cases or less, lower DEHP serum level in fibroid cases (Luisi et al., 2006), MEHP level were higher in fibroid cases (Huang et al., 2010) Weuve et al., 2010 MEHP (negative association), MBP (positive association) Wise et al., 2012 Hair relaxer use and leimyoma Colon et al., 2000 Other gynecologic disease (premature breast development)
4 1. Introduction Previous studies BPAItoh et al., 2007 and Kandaraki et al., 2011 Not associated with endometriosis and associated with polycystic ovary syndrome (PCOS) Buck Louis et al., 2013 and Li et al., 2011 Not associated with endometriosis and polycystic ovary syndrome (PCOS) But, experimental studies have identified disturbances of the hypothalamic-pituitary gonadotropin axis following exposure to BPA and phthalates
5 1. Introduction Objectives- We are unaware of any studies focusing on BPA ,a potent estrogen, or UV filters, particularly those with estrogenic properties, and fibroids. In response to this data gap, we assessed BPA, 14 phthalate metabolites, and 5UV filters in relation to a fibroids diagnosis.
6 2. Methods Study population Data collection Assessment of exposure- Endometriosis, Natural history, Diagnosis, and Outcomes (ENDO) study - 14 clinical centers in 4 states (Salt Lake, Utah, San Francisco, California, N=494) in - Age (18-44) - Without history of endometriosis and cancer - No breastfeeding for > 6months - No use of injectable hormones for the past 2 years Data collection - Computer assisted personal interview questionnaires Assessment of exposure - HPLC-MS/MS (API 2000), Zhang et al., 2011 and Guo et al., 2011
7 2. Methods Assessment outcome Statistical analysis- Uterine leiomyoma denoted a postoperative surgical diagnosis of fibroids. Statistical analysis - Geometric mean chemical concentrations (95% CI) - Women with and without fibroids were compared by various characteristics with using the Chi-square statistics or nonparametric Wilcoxon rank sum test - Logistic regression was used to estimate the odds of fibroids along with 95% CIs - Chemicals were log(x+1) transformed and rescaled by their standard deviations before analysis to aid the interpretation of point and interval estimates - Potential confounders : creatinine, age, race, BMI, serum cotinine, research site
8 3. Results
9 3. Results
10 3. Results
11 4. Discussion We did not find that BPA, phthalate metabolites, or UV filter metabolites were associated with surgically visualized fibroids - Previous studies 문헌 물질 질환 결과 비고 Huang et al., 2010 MEHP fibroids Increased odds Small cases (n=36), not consider possible confounding factor Weuve et al., 2010 MBP No association Kunisue et al., 2012 2,4OH-BP endometriosis Significant trend in odds Upon et al., 2014 BPA
12 4. Discussion Toxicological research (evidences)BPA exposure early in pregnancy led to fibroid development in offspring (Newbold et al., 2009) Benzophenon-type UV filters act as endocrine disruptors in fish and rats (Coronado et al., 2008; Nakagawa and Tayama, 2001) Utero exposures to chemicals may alter reproductive tract development and function, leading to uterine fibroids (McLachlan et al., 1980)
13 4. Discussion Strengths Limitations Surgical visualization of fibroidsBiomarker measurement in urine (Wise et al., 2012; Luisi et al., 2006) Limitations Chemical levels measured at the time of diagnosis may reflect a relevant period at least for their short- term growth Fibroids are generally detected upon the onset of symptoms among women in the 4th and 5th decade of life The exposures are not persistent but evidence demonstrates that single measurements may reflect chronic exposure if daily exposure is consistent High intraclass correlation coefficients But, a period of several weeks is too narrow for the onset of fibroids.
14 4. Discussion Future researchneed for longitudinal designs and measurement of exposures including during sensitive windows of disease onset and/or progression include a methodologic component to empirically delineate the variability
15 가임기 여성 과제
16 Table 2. Median (IQR) comparison of chemicals by myoma status.Chemicals (ng/mL) Above LOQ (n) myoma (n=95) no myoma (n=411) no adjusted SG-adjusted Phthalates MMP 501/506 2.13 ( ) 2.53 ( ) 1.69 ( ) 2.10 ( )* MEP 505/506 4.43 ( ) 6.47 ( ) 6.09 ( ) 6.86 ( ) MiBP 480/506 2.36 ( ) 3.05 ( ) 2.06 ( ) 2.60 ( ) MBP 500/506 5.16 ( ) 6.04 ( ) 5.03 ( ) 5.83 ( ) MECPP 507/506 11.2 ( ) 15.2 ( ) 10.9 ( ) 12.9 ( )* MEHHP 2.31 ( ) 3.23 ( ) 2.64 ( ) 2.95 ( ) MEOHP 504/506 1.34 ( ) 1.66 ( ) 1.25 ( ) 1.40 ( ) MCMHP 506/506 3.86 ( ) 4.81 ( ) 3.99 ( ) 4.73 ( ) MBzP 494/506 0.46 ( ) 0.63 ( ) 0.49 ( ) 0.60 ( ) DEHP 23.8 ( ) 27.7 ( ) 21.9 ( ) 24.4 ( )* Bisphenols BPS 510/509 3.61 ( ) 3.78 ( ) 3.29 ( ) 3.87 ( ) BPA 0.59 ( ) 0.65 ( ) 0.50 ( ) 0.60 ( ) *DEHP는 대사산물의 농도 합
17 Chemicals (ng/mL) Above LOQ (n) myoma (n=95) no myoma (n=411) no adjusted SG-adjusted Parabens Mepr 510/509 39.1 ( ) 49.5 ( ) 45.3 ( ) 56.2 ( ) EtP 501/509 17.7 ( ) 23.5 ( ) 17.5 ( ) 22.2 ( ) PrP 478/509 2.20 ( ) 3.17 ( ) 2.35 ( ) 2.99 ( ) BuP 323/509 0.10 ( ) 0.24 ( ) 0.10 ( ) 0.11 ( ) OH-MeP 489/509 2.10 ( ) 2.68 ( ) 1.70 ( ) 1.99 ( ) DHB 407/509 25.0 ( ) 26.9 ( ) 21.2 ( ) 26.9 ( ) HB 710 ( ) 769 ( ) 676 ( ) 762 ( ) Benzophenone derivatives BP1 1.34 ( ) 1.57 ( ) 1.21 ( ) 1.52 ( ) BP3 378/509 0.49 ( ) 0.48 ( ) 0.43 ( ) 0.44 ( ) OHBP 502/509 1.56 ( ) 1.98 ( ) 1.90 ( ) 2.31 ( ) Triclosan 457/509 0.30 ( ) 0.38 ( ) 0.30 ( ) 0.40 ( ) Nonparametric Wilcoxon ranksumt est was used to compare chemical concentrations between those with and without myoma *p<0.05, **p<0.01
18 bisphenols, parabens, benzophenone derivates and triclosanTable3. The odds of myoma by concentration of SG corrected urianry phthalate metabolites, bisphenols, parabens, benzophenone derivates and triclosan Chemicals OR (95% CI) aOR (95% CI) Phthalates MMP 1.76 (1.09, 2.85)* 2.10 (1.24, 6.54)** MEP 1.05 (0.63, 1.76) 1.07 (0.62, 1.84) MiBP 1.64 (1.01, 2.65)* 1.45 (0.87, 2.41) MBP 1.49 (0.92, 2.43) 1.37 (0.81, 2.29) MECPP 0.99 (1.24, 3.20)** 1.77 (1.07, 2.93)* MEHHP 1.00 (0.60, 1.66) 0.98 (0.57, 1.69) MEOHP 1.10 (0.66, 1.81) 1.13 (0.67, 1.92) MCMHP 1.68 (1.04, 2.73)* 1.46 (0.88, 2.44) MBzP 1.13 (0.69, 1.85) 1.00 (0.59, 1.69) DEHP 1.65 (0.99, 2.76)* Bisphenols BPS 0.83 (0.49, 1.41) 0.90 (0.51, 1.58) BPA 1.32 (0.80, 2.71) 1.09 (0.65, 1.85) Parabens Mepr 1.23 (0.75, 2.03) 1.11 (0.66, 1.88) EtP 1.38 (0.85, 2.26) 1.40 (0.83, 2.37) PrP 0.94 (0.56, 1.58) 0.82 (0.48, 1.43) BuP 1.40 (0.86, 2.29) 1.21 (0.71, 2.06) OH-MeP 1.08 (0.65, 1.80) 0.97 (0.57, 1.67) DHB 1.80 (1.05, 3.09)* HB 0.82 (0.48, 1.39) 0.88 (0.51, 1.54) Benzophenone derivatives BP1 1.17 (0.71, 1.94) 1.07 (0.63, 1.82) BP3 0.92 (0.54, 1.59) OHBP 0.87 (0.51, 1.46) 0.71 (0.41, 1.24) Triclosan 1.22 (0.71, 2.08) aOR, adjusted for age and bmi *p<0.05, **p<0.01