結論與建議

4-7 鄰苯二甲酸酯暴露、雙酚 A 及壬基酚與良性攝護腺增生

鑑於 Scarano 等人研究結果顯示暴露 PAEs 時，大鼠攝護腺組織切片中上皮及基質細胞的 增生比例顯著高於控制組 (P-value < 0.05) (Scarano et al. 2009)，本研究將進一步討論 PAEs 對於 攝護腺疾病的直接影響，將校正影響因子後再進一步與攝護腺體積及 PSA 進行複迴歸結果如表 4-8 所示，MiBP、MEHP、MEOHP、MECPP、BPA 分別與 PSA 及攝護腺體積呈正相關，PAEs 代謝物與 PSA 迴歸之 β 值分別為 1.19 (95% CI：1.02~1.38, P-value < 0.05)、1.37 (95% CI：

1.16~1.61, P-value < 0.01)、1.27 (95% CI：1.06~1.52, P-value < 0.05) 、1.33 (95% CI：1.12~1.58, P-value < 0.01)、1.34 (95% CI：1.12~1.60, P-value < 0.01)及 1.24 (95% CI：1.02~1.50, P-value < 0.01)，

而MiBP、MEHP、MEOHP、MECPP、%MEHP、BPA 與攝護腺體積迴歸之 β 值分別為 1.12 (95%

CI：1.03~1.21, P-value < 0.01)、1.19 (95% CI：1.09~1.29, P-value < 0.01)、1.12 (95% CI：1.02~1.23, P-value < 0.05)、1.15 (95% CI：1.05~1.25, P-value < 0.01)、1.18 (95% CI：1.01~1.37, P-value < 0.05) 及1.14 (95% CI：1.04~1.26, P-value < 0.05)，由上述結果可知 PAEs 及雙酚 A 暴露可能與攝護腺 疾病相關，但兩者之間的更詳細之關係仍需更多研究探討。

第五章 結論與建議 

5-1 結論

由本研究調查攝護腺疾患之男性成人族群尿液中鄰苯二甲酸酯代謝物、雙酚A 及壬基酚濃 度、生殖荷爾蒙及臨床指標資料，獲得下述結論：

1. 尿液中鄰苯二甲酸酯代謝物除 MIDP、MINP 及 MBzP 外，檢出率皆高過 87%。BPA 檢出 率為 83.1%，NP 為 79.2%。 

2. 輕、中、重度攝護腺肥大患者生殖荷爾蒙濃度分析結果，以 E2、the E₂: E₁ ratio 及 the E₂: TT ratio 於三組間具統計上顯著差異（P-value < 0.05）；FSH、E₂、the E₂: E₁ ratio 及 the E₂: TT ratio 於三組間具統計上顯著趨勢性增加（P-trend < 0.05）。 

3. 輕、中、重度攝護腺肥大患者 PAEs 代謝物、雙酚A及壬基酚濃度分析結果，經 creatinine 校正後 MEHP、MECPP 及 BPA於三組間具統計上顯著差異（P-value < 0.05）；MiBP、

MnBP、MEHP、MEHHP、MEOHP、MECPP、BPA、NP於三組間具統計上顯著趨勢性增 加（P-trend< 0.05）。 

4. 經校正干擾因子後之複迴歸結果指出，PAEs（特別是 DEHP、DBP）及BPA暴露對於攝 護腺發展之敏感生殖荷爾蒙（E2 及 DHT）具顯著正相關（P-trend < 0.05）。 

5. 經校正過干擾因子後之複迴歸結果指出，PAEs（特別是 DEHP、DiBP）及BPA暴露對於 攝護腺體積及攝護腺特異性抗原具顯著正相關（P-trend < 0.05）。 

5-2 建議

1. PAEs、BPA 及 NP 雖然於人體內半衰期短，但其對於人體影響為長時間累積所造成，本研 究結果觀察到 PAEs、BPA 及 NP 之暴露可能會干擾荷爾蒙調控，因此建議民眾於飲食及 生活習慣上應減少使用塑膠製品、聚碳酸酯製品及清潔劑等，以避免 PAEs、BPA 及 NP 之暴露。

2. 本研究為第一篇探討暴露 PAEs、BPA 及 NP 對攝護腺疾病之影響研究，目前已初步建立

20

PAEs 、BPA 及 NP 暴露與生殖荷爾蒙調控對攝護腺疾病影響之相關性，但因本研究為橫 斷式研究，對於疾病因果關係可能無法完整解釋，建議未來若要進一步確認 PAEs、BPA 及NP 暴露對攝護腺疾病之影響可進行時間較長之世代追蹤研究。

21

Age (year) 59.4±1.73^d 63.4±1.07 65.2±1.17 0.020*

Height (cm) 167±0.67 167±0.71 166±0.75 0.258

Weight（kg） 70.1±1.37 67.7±1.21 70.2±1.45 0.667

BMI（kg/m²） 25.2±1.06 24.4±0.41 25.5±0.50 0.214

Chest measurement (cm) 95.7±1.00 91.5±1.51 96.2±0.96 0.934 Waist measurement (cm) 93.0±1.15 89.1±1.81 92.3±1.28 0.512 Hip measurement (cm) 101±0.96 96.3±1.88 100±0.95 0.970 Smoking（cigarettes/day） 17.0±9.60 16.7±15.9 13.1±9.26 0.417 Drinking（ml/week） 54.3±85.4 89.2±62.1 85.1±96.4 0.064 Coffee（ml/week） 1265±1120 1120±994 790±749.2 0.614

Tea（ml/week） 2414±2770 2106±2414 2084±2988 0.196

Educational attainment 0.913

High/Partial High School 33 (50.0)^c 36 (53.7) 43 (62.3) College/Partial College 23 (34.8) 22 (32.8) 19 (27.5) Graduate school 10 (15.2) 9 (13.4) 7 (10.1)

Race 0.598

Taiwanese 60 (90.1) 59 (88.1) 64 (92.8)

Mainland Chinese 4 (6.06) 7 (10.4) 3 (4.25)

Hakkanese 2 (3.03) 1 (1.49) 2 (3.00)

Social status 0.489

Low 18 (27.3) 23 (34.3) 27 (39.1)

Medium 18 (27.3) 17 (25.4) 19 (27.5)

High 30 (45.5) 27 (40.3) 22 (31.9)

Occupational group 0.124

Agriculture, forestry, fishery and animal Husbandry 5 (8.0) 5 (7.0) 9 (13.0) Mining and Quarrying 1 (2.0) 1 (1.0) 1 (1.0)

Manufacturing 8 12.0 13 (19.0) 4 (6.0)

Electricity, Gas and Water 3 (5.0) 1 (1.0) 0 (0.0)

Construction 4 (6.0) 2 (3.0) 1 (1.0)

Wholesale and retail trade 2 (3.0) 0 (0.0) 2 (3.0) Accommodation and food service activities 3 (5.0) 0 (0.0) 0 (0.0) Transportation, Storage and Communication 6 (9.0) 7 (10.0) 6 (9.0) Financial and insurance activities 0 (0.0) 2 (3.0) 3 (4.0) Real estate activities and leasing industry 1 (2.0) 0 (0.0) 0 (0.0) Professional, scientific and technical Activities 3 (5.0) 2 (3.0) 4 (6.0)

Education 6 (9.0) 4 (6.0) 2 (3.0)

Medical and health care 3 (5.0) 2 (3.0) 2 (3.0) Arts, entertainment and recreation 0 (0.0) 1 (1.0) 4 (6.0) Other service activities 11 (17.0) 5 (7.0) 4 (6.0) Public administration 1 (2.0) 1 (1.0) 1 (1.0) Unemployed 9 (14.0) 21 (31.0) 26 (38.0)

Occupational phthalate exposure (yes, %) 0 (0.00) 2 (0.99) 2 (0.99) 0.549

a The patients were divided into three subgroups according to the tertiles of prostate volume: small-sized prostate group (< 29.5 mL), medium-sized prostate group (29.5-43.7 mL), large-sized prostate group (>

43.7 mL).

b Continuous variables between three groups were compared using One-way ANOVA test or Kruskal Wallis

22

test.^.

c Categorical variables were compared with Chi-Square test or Fisher’s exact test.

d Expressed as Mean ± SD

PSA (ng/ml) 1.37±0.55^d 2.70±0.32 6.42±0.55 <0.001**

DRE^d Intravesical protruding (yes, %) 5 (9.03) 19 (28.4) 43 (62.3) <0.001**

Prostate volume (ml) 23.5±0.73 35.9±0.50 72.0±3.01 <0.001**

IPSS 14.1±8.84 13.8±7.82 16.6±7.61 0.061

Uroflowmetry (ml/s)

Voided Volume (ml) 261±23.1 213±21.3 226±17.3 0.020*

Max. Flow rate 15.4±1.16 10.7±1.13 11.5±0.75 0.028*

Mean Flow rate 7.45±0.60 4.90±0.54 4.67±0.40 0.001**

PSA, prostatic specific antigen; DRE, Digital Rectal examination; IPSS, International prostate symptoms score

a Patients were divided into three subgroups according to the tertiles of prostate volume:

small-sized prostate group (< 29.5 mL), medium-sized prostate group (29.5-43.7 mL), large-sized prostate group (> 43.7 mL).

b Continuous variables between three groups were compared using One-way ANOVA test.

c Categorical variables were compared with Chi-Square test or Fisher’s exact test.

d Expressed as GM ± GSD

e n（%）

* P<0.05; ** P <0.01

23

表4- 3 生殖荷爾蒙濃度之分析結果

BPH/BPE patient

P-value^b P-trend 項目 Small-sized

prostate group ^a (n = 69)

Medium-sized prostate group

(n = 69)

Large-sized prostate group

(n = 69)

LH (mIU/mL) 5.67±0.49^c 5.63±0.43 6.35±0.48 0.421 0.318 FSH (mIU/mL) 9.04±0.74 9.44±0.77 11.2±0.94 0.184 0.034*

InhibinB 162±13.3 166±15.9 172±12.6 0.915 0.550 SHBG (nmol/L) 45.4±2.63 45.8±2.16 49.7±3.21 0.431 0.146

E1 (pg/mL) 62.3±2.44 63.2±2.59 67.3±3.36 0.320 0.077 E2 (pg/mL) 26.3±2.16 26.5±1.77 38.1±2.73 0.002** <0.001**

E₂/E₁ 0.42±0.03 0.42±0.42 0.57±0.05 0.032* 0.005**

TT (ng/mL) 4.10±0.18 3.86±0.21 3.83±3.40 0.454 0.500 FT (pg/mL) 60.8±3.64 61.3±2.85 61.6±2.60 0.931 0.391 DHT (pg/mL) 386±21.1 406±19.8 440±25.5 0.392 0.090

DHEA(ng/mL) 1.12±0.21 1.79±0.25 1.72±0.24 0.225 0.272 DHEAs (μg/dL) 144±12.4 122±11.6 108±12.1 0.201 0.190 AD (ng/mL) 0.87±0.05 0.80±0.05 0.76±0.05 0.476 0.298 E2/TT 6.36±0.56 6.85±0.05 10.1±0.94 0.008** <0.001**

LH, luteinizing hormone; FAI, free androgen index;
 FSH, follicle-stimulating hormone; SHBG, sex hormone-binding globulin; E1, estrogen; E2, estradiol; TT, total testosterone; DHT, dihydrotestosterone; FT, free testosterone; DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulfate; AD, androstenedione.

a Patients were divided into three subgroups according to the tertiles of prostate volume:

small-sized prostate group (< 29.5 mL), medium-sized prostate group (29.5-43.7 mL), large-sized prostate group (> 43.7 mL).

b Continuous variables between three groups were compared using Kruskal Wallis test.

c Expressed as GM ± GSD

* P<0.05; ** P<0.0

24

表4- 4 尿液中鄰苯二甲酸酯代謝物、雙酚 A 及壬基酚濃度分佈

GM Min 10 th 25 th 50 th 75 th 95 th Max Unadjusted-Creatinine (ng/ml)

Phthalates metabolites

MMP 2.81 0.04 1.02 1.57 2.82 5.60 12.4 34.5 MEP 6.55 0.08 1.18 2.89 6.28 14.6 60.2 413 MiBP 3.35 0.50 0.50 1.87 3.18 6.65 23.2 168 MnBP 7.03 0.50 1.96 3.56 6.96 12.2 40.0 235 MBzP 0.20 0.05 0.05 0.05 0.50 0.50 1.70 5.71 MEHP 2.60 0.50 0.50 1.45 2.74 4.35 14.0 50.4 MEHHP 6.10 0.07 1.76 3.10 5.97 12.5 36.9 380 MEOHP 4.29 0.50 1.36 2.35 4.24 8.26 20.5 170 MECPP 8.66 0.50 2.53 4.53 8.22 15.8 47.1 480 MiNP 0.19 0.05 0.05 0.05 0.50 0.50 0.50 3.70 MiDP 0.27 0.07 0.07 0.07 0.50 0.50 0.50 0.50 BPA 1.58 0.33 0.63 0.93 1.60 2.35 6.05 10.2 NP 1.34 0.33 0.73 0.96 1.27 1.89 3.33 4.55 Adjusted-Creatinine (ng/mg-cre)

Phthalates metabolites

MMP 3.67 0.20 1.49 2.35 3.99 5.77 10.5 35.8 MEP 8.55 0.10 2.23 4.13 7.10 17.8 85.3 657 MIBP 4.37 0.49 1.42 2.41 3.91 7.23 21.1 139 MNBP 9.17 1.72 3.71 5.98 8.77 12.8 35.8 192 MBZP 0.27 0.02 0.04 0.06 0.39 0.85 2.36 5.83 MEHP 3.39 0.61 1.27 1.85 3.12 5.33 11.8 131 MEHHP 7.96 0.13 2.97 4.94 7.90 14.0 30.2 509 MEOHP 5.60 1.04 2.15 3.43 5.55 8.08 19.4 260 MECPP 11.3 1.56 4.59 7.08 11.0 16.8 39.7 626 BPA 2.16 0.22 0.73 1.16 2.02 3.89 11.0 29.9 NP 1.81 0.22 0.64 1.04 1.82 2.95 7.11 20.6

25

MMP 2.96±0.34^c 2.73±0.28 2.76±0.35 0.966 0.601 MEP 7.09±1.16 5.61±0.93 7.06±1.20 0.384 0.941 MiBP 2.88±0.33 3.09±0.43 4.20±0.57 0.159 0.041*

MnBP 6.63±0.66 6.51±0.73 8.00±1.20 0.737 0.013*

MBzP 0.19±0.03 0.25±0.04 0.18±0.03 0.393 0.278 MEHP 2.20±0.24 2.30±0.24 3.42±0.44 0.061 0.002**

MEHHP 6.06±0.69 5.52±0.63 6.76±1.21 0.367 0.039*

MEOHP 3.94±0.44 4.09±0.43 4.87±0.62 0.543 0.087 MECPP 7.83±0.86 7.80±0.77 10.6±1.49 0.186 0.041*

MiNP 0.18±0.03 0.20±0.03 0.18±0.03 0.623 0.606 MiDP 0.26±0.03 0.27±0.03 0.29±0.03 0.689 0.616 BPA 1.40±0.36 1.43±0.25 2.03±1.72 0.006* <0.001**

NP 1.28±1.12 1.33±0.84 1.56±0.94 0.046 0.002*

Adjusted-Creatinine

MMP 3.76±0.33^c 3.48±0.29 3.77±0.38 0.511 0.714 MEP 9.01±1.40 7.14±0.98 9.67±1.51 0.227 0.817 MiBP 3.66±0.33 3.94±0.44 5.72±0.71 0.050 0.005**

MnBP 8.43±0.60 8.29±0.66 11.0±1.31 0.544 0.002**

MBzP 0.25±0.05 0.31±0.05 0.25±0.04 0.632 0.618 MEHP 2.81±0.23 2.93±0.28 4.70±0.59 0.002** 0.004**

MEHHP 7.71±0.57 7.02±0.66 9.27±1.51 0.097 0.024*

MEOHP 5.02±0.36 5.21±0.46 6.67±0.77 0.157 0.037*

MECPP 9.96±0.74 9.93±0.84 14.5±1.89 0.030* 0.016*

MiNP 0.22±0.04 0.26±0.04 0.25±0.04 0.817 0.494 MiDP 0.33±0.05 0.35±0.05 0.40±0.06 0.477 0.950 BPA 1.75±0.27 2.02±1.70 2.82±1.61 0.026* 0.002*

NP 1.58±0.89 1.87±1.93 2.16±0.96 0.165 0.029*

a The patients were divided into three subgroups according to the tertiles of prostate volume:

small-sized prostate group (< 29.5 mL), medium-sized prostate group (29.5-43.7 mL), large-sized prostate group (> 43.7 mL).

b Continuous variables between three groups were compared using Kruskal Wallis test.

c Expressed as GM ± GSD

* P<0.05; ** P<0.01

26

表4- 6 荷爾蒙及氧化壓力與攝護腺臨床診斷指標之迴歸結果^{a, c}

PSA^b Prostate volume

Reproductive hormone

LH^b 1.07(0.83, 1.38) 1.03(0.90, 1.17) FSH 1.10(0.86, 1.40) 1.07(0.95, 1.22) SHBG 1.32(0.94, 1.85) 1.02(0.86, 1.21) Inhibin B 0.98(0.78, 1.22) 1.07(0.96, 1.20) E₁ 1.78(1.11, 2.87)* 1.34(1.05, 1.70)*

E2 1.53(1.22, 1.94)** 1.31(1.17, 1.47)**

E2/E1 1.29(1.00, 1.66)* 1.19(1.05, 1.36)**

TT 0.74(0.53, 1.04) 0.89(0.75, 1.06) FT 0.79(0.54, 1.14) 1.07(0.89, 1.30) DHT 1.60(1.15, 2.23)** 1.29(1.09, 1.52)**

DHEA 1.20(1.06, 1.38)** 1.06(0.99, 1.14) DHEA-S 1.04(0.85, 1.28) 0.95(0.86, 1.05) AD 1.06(0.80, 1.47) 0.97(0.84, 1.05) E₂/TT 1.55(1.27, 1.89)** 1.28(1.16, 1.42)**

Oxidative stress

MDA 1.56(1.04, 2.35)* 1.22(0.99, 1.50) 8-OHdG 1.33(1.13, 1.57)** 1.14(1.05, 1.24)**

iNOS 1.05(0.98, 1.13) 1.04(1.00, 1.08)*

a All models are adjusted for age, body mass index (modeled continuously).

b In all models, ln-transformations of hormone, oxidative stress leveland clinical diagnosis data level were used.


c Coefficient represents a multiplicative change in clinical diagnosis data for an IQR change in hormone or oxidative stress level concentration after back-transformation of both hormone or oxidative stress level and clinical diagnosis data.

* P< 0.05; ** P< 0.01

27

表4- 7 鄰苯二甲酸酯代謝物、雙酚 A、壬基酚與荷爾蒙之迴歸結果^{a, c}

LH ^b FSH SHBG InhibinB E₁ E₂ E₂/E₁

MMP ^b 0.96(0.86, 1.07) 1.03(0.92, 1.16) 1.08(0.99, 1.17) 0.93(0.82, 1.05) 1.00(0.94, 1.06) 1.03(0.92, 1.16) 1.03(0.91, 1.17) MEP 1.00(0.94, 1.07) 0.99(0.92, 1.06) 1.05(1.00, 1.10) 1.08(1.00, 1.16)* 1.02(0.99, 1.06) 1.01(0.94, 1.09) 0.99(0.92, 1.06) MiBP 0.96(0.88, 1.05) 0.98(0.90, 1.08) 1.05(0.99, 1.13) 1.07(0.97, 1.18) 1.03(0.98, 1.09) 1.07(0.97, 1.17) 1.03(0.93, 1.14) MnBP 0.97(0.87, 1.08) 1.04(0.93, 1.17) 1.03(0.95, 1.12) 1.08(0.96, 1.22) 1.00(0.94, 1.06) 1.04(0.92, 1.17) 1.04(0.92, 1.18) MBzP 0.89(0.84, 0.95)** 0.93(0.87, 0.99) 0.98(0.94, 1.03) 0.92(0.85, 0.98)* 1.02(0.99, 1.06) 0.98(0.92, 1.05) 0.96(0.89, 1.03) MEHP 1.02(0.92, 1.12) 1.05(0.95, 1.16) 1.05(0.97, 1.12) 1.07(0.96, 1.19) 1.04(0.99,1.10) 1.22(1.11, 1.35)** 1.17(1.05, 1.31)**

MEHHP 1.00(0.92, 1.09) 1.01(0.92, 1.10) 0.97(0.91, 1.03) 0.98(0.89, 1.08) 1.01(0.96, 1.06) 1.15(1.06, 1.26)** 1.14(1.04, 1.26)**

MEOHP 0.99(0.89, 1.10) 1.04(0.93, 1.16) 0.99(0.91, 1.07) 1.04(0.93, 1.18) 1.05(1.00, 1.12) 1.16(1.04, 1.30)** 1.10(0.98, 1.24) MECPP 1.01(0.91, 1.11) 1.06(0.95, 1.17) 0.99(0.92, 1.07) 1.04(0.93, 1.16) 1.05(0.97, 1.11) 1.19(1.07, 1.32)** 1.14(1.02, 1.27)*

MiNP 0.93(0.87, 0.99)* 0.91(0.85, 0.98)** 0.97(0.93, 1.03) 0.90(0.83, 0.97)** 1.01(0.97, 1.05) 1.01(0.94, 1.09) 1.00(0.93, 1.08) MiDP 0.89(0.81, 0.98)* 0.90(0.82, 0.99)* 0.94(0.88, 1.01) 0.88(0.80, 0.97)* 0.99(0.94, 1.04) 1.06(0.96, 1.17) 1.08(0.97, 1.19) MEHP % 1.05(0.89, 1.25) 1.03(0.86, 1.23) 1.18(1.04, 1.34)* 1.12(0.92, 1.35) 1.01(0.92, 1.11) 1.08(0.89, 1.30) 1.11(0.90, 1.35) BPA 1.01(0.91, 1.14) 0.99(0.88, 1.10) 1.09(0.99, 1.19) 1.15(1.02, 1.29)* 1.13(1.07, 1.19)** 1.13(1.03, 1.25)* 1.02(0.92, 1.13) NP 0.96(0.85, 1.09) 0.98(0.87, 1.11) 1.04(0.95, 1.15) 1.03(0.91, 1.17) 1.10(1.04, 1.17)* 1.07(0.96, 1.19) 0.99(0.88, 1.10)

TT FT DHT DHEA DHEAs AD E₂/TT

MMP 1.01(0.93, 1.08) 0.96(0.89, 1.04) 1.00(0.92, 1.08) 1.17(0.94, 1.46) 1.11(0.97, 1.27) 0.95(0.86, 1.04) 1.03(0.90, 1.17) MEP 1.05(1.03, 1.09)* 1.04(1.00, 1.09) 1.03(0.98, 1.08) 1.11(0.97, 1.26) 1.01(0.93, 1.10) 1.01(0.96, 1.07) 0.97(0.89, 1.04) MiBP 0.99(0.93, 1.05) 1.00(0.94, 1.06) 1.00(0.93, 1.07) 1.00(0.84, 1.20) 0.97(0.87, 1.09) 0.98(0.90, 1.05) 1.07(0.97, 1.19) MnBP 0.98(0.93, 1.05) 0.97(0.90, 1.04) 1.08(1.00, 1.18) 0.82(0.66, 1.03) 1.03(0.89, 1.18) 0.96(0.88, 1.06) 1.06(0.93, 1.21) MBzP 1.00(0.93, 1.04) 1.02(0.97, 1.06) 1.06(1.01, 1.11)* 1.48(1.31, 1.66)** 1.06(0.98, 1.14) 0.99(0.93, 1.04) 0.98(0.91, 1.05) MEHP 0.98(0.93, 1.04) 0.99(0.93, 1.06) 1.12(1.04, 1.20)** 0.97(0.80, 1.18) 1.00(0.89, 1.13) 0.98(0.90, 1.06) 1.24(1.12, 1.39)**

MEHHP 0.98(0.93, 1.04) 0.99(0.93, 1.05) 1.11(1.04, 1.18)** 1.05(0.89, 1.25) 1.00(0.90, 1.11) 0.99(0.92, 1.06) 1.17(1.06, 1.29)**

MEOHP 1.00(0.93, 1.06) 1.03(0.96, 1.11) 1.13(1.04, 1.22)** 1.12(0.91, 1.39) 0.99(0.87, 1.13) 0.96(0.88, 1.05) 1.17(1.04, 1.32)*

MECPP 0.98(0.93, 1.04) 1.01(0.95, 1.08) 1.12(1.04, 1.21)** 1.03(0.84, 1.26) 0.97(0.86, 1.10) 0.95(0.87, 1.03) 1.21(1.08, 1.36)*

MiNP 1.01(0.93, 1.05) 1.03(0.99, 1.08) 1.05(1.00, 1.11) 1.58(1.40, 1.79)** 1.02(0.94, 1.11) 0.99(0.93, 1.05) 1.00(0.92, 1.09) MiDP 1.00(0.93, 1.06) 1.02(0.96, 1.09) 1.06(0.99, 1.14) 1.64(1.38, 1.95)** 1.01(0.90, 1.13) 0.94(0.86, 1.01) 1.05(0.95, 1.18) MEHP % 0.98(0.83, 1.09) 0.91(0.81, 1.03) 0.99(0.87, 1.12) 0.83(0.58, 1.17) 0.99(0.80, 1.24) 1.04(0.90, 1.21) 1.10(0.89, 1.35) BPA 0.96(0.90, 1.03) 0.97(0.90, 1.03) 1.15(1.07, 1.23)** 1.27(1.07, 1.51)* 0.84(0.74, 0.96)* 1.01(0.92, 1.10) 1.18(1.04, 1.34)*

NP 0.97(0.90, 1.05) 0.97(0.90, 1.05) 1.13(1.04, 1.23)* 1.32(1.09, 1.58)* 0.87(0.75, 1.01) 0.96(0.87, 1.06) 1.10(0.96, 1.26)

a All models are adjusted for age, body mass index (modeled continuously),smoking, drinking, level of urinary creatinine and the time and season during which the blood was collected for hormone analysis.

Total testosterone, estradiol, ratio of total testosterone and estradiol and ratio of total testosterone were additionally adjusted for SHBG.


b In all models, ln-transformations of urinary phthalate metabolites and reproductive hormones level were used.


c Coefficient represents a multiplicative change in hormone level for an IQR change in phthalate metabolites concentration after back-transformation of both hormone and phthalate metabolites concentration.

* P< 0.05; ** P< 0.01

28

表4- 8 鄰苯二甲酸酯代謝物與氧化壓力及攝護腺診斷指標之迴歸結果^a,c

PSA Prostate volume

MMP ^b 1.02(0.84, 1.24) 0.98(0.89, 1.08) MEP 0.96(0.86, 1.08) 1.04(0.98, 1.10) MiBP 1.19(1.02, 1.38)* 1.12(1.03, 1.21)**

MnBP 1.19(0.98, 1.43) 1.07(0.98, 1.18) MBzP 0.99(0.89, 1.10) 0.98(0.92, 1.03) MEHP 1.37(1.16, 1.61)** 1.19(1.09, 1.29)**

MEHHP 1.15(0.99, 1.34) 1.06(0.99, 1.15) MEOHP 1.27(1.06, 1.52)* 1.12(1.02, 1.23)*

MECPP 1.33(1.12, 1.58)** 1.15(1.05, 1.25)**

MiNP 0.98(0.87, 1.11) 0.99(0.93, 1.05) MiDP 0.99(0.84, 1.16) 1.00(0.92, 1.08) MEHP % 1.28(0.94, 1.74) 1.18(1.01, 1.37)*

BPA 1.10(0.99, 1.22) 1.14(1.04, 1.26)*

NP 0.94(0.71, 1.11) 1.06(0.88, 1.27)

a All models are adjusted for age, body mass index (modeled continuously), level of urinary creatinine.

Oxidative stress markers were additionally adjusted hypertension.

b In all models, ln-transformations of urinary phthalate metabolites, oxidative stress level and clinical diagnosis data were used.


c Coefficient represents a multiplicative change in Oxidative stress level and clinical diagnosis data for an IQR change in phthalate metabolites concentration after back-transformation of both hormone and phthalate metabolites concentration.

* P<0.05; ** P< 0.01

29

REFERENCE

Ademollo N, Ferrara F, Delise M, Fabietti F, Funari E. 2008. Nonylphenol and octylphenol in human breast milk. Environment international 34:984-987.

Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, Jacek R, et al. 2003. Prenatal exposures to phthalates among women in new york city and krakow, poland. Environmental Health

Perspectives 111:1719.

Albert O, Jégou B. 2013. A critical assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood. Human reproduction update:dmt050.

Aydogan Ahbab M, Barlas N. 2013. Developmental effects of prenatal di-n-hexyl phthalate and dicyclohexyl phthalate exposure on reproductive tract of male rats: Postnatal outcomes. Food Chem Toxicol 51:123-136.

Baade PD, Youlden DR, Cramb SM, Dunn J, Gardiner RA. 2013. Epidemiology of prostate cancer in the asia-pacific region. Prostate international 1:47-58.

Barrett-Connor E, Garland C, McPhillips JB, Khaw K-T, Wingard DL. 1990. A prospective, population-based study of androstenedione, estrogens, and prostatic cancer. Cancer research 50:169-173.

Becker K, Güen T, Seiwert M, Conrad A, Pick-Fuß H, Müller J, et al. 2009. Geres iv: Phthalate metabolites and bisphenol a in urine of german children. International journal of hygiene and environmental health 212:685-692.

Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL. 2004. Urinary

concentrations of bisphenol a and 4-nonylphenol in a human reference population. Environmental Health Perspectives 113:391-395.

Calafat AM, McKee RH. 2006. Integrating biomonitoring exposure data into the risk assessment process: Phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study. Environmental health perspectives 114:1783-1789.

Chang WH, Li SS, Wu MH, Pan HA, Lee CC. 2015. Phthalates might interfere with testicular function by reducing testosterone and insulin-like factor 3 levels. Hum Reprod 30:2658-2670.

Chapin RE, Adams J, Boekelheide K, Gray LE, Jr., Hayward SW, Lees PS, et al. 2008. Ntp-cerhr expert panel report on the reproductive and developmental toxicity of bisphenol a. Birth defects research Part B, Developmental and reproductive toxicology 83:157-395.

Chen G-W, Ding W-H, Ku H-Y, Chao H-R, Chen H-Y, Huang M-C, et al. 2010. Alkylphenols in human milk and their relations to dietary habits in central taiwan. Food and Chemical Toxicology 48:1939-1944.

Chitra K, Latchoumycandane C, Mathur P. 2003. Induction of oxidative stress by bisphenol a in the epididymal sperm of rats. Toxicology 185:119-127.

Chute C, Panser L, Girman C, Oesterling J, Guess H, Jacobsen S, et al. 1993. The prevalence of prostatism: A population-based survey of urinary symptoms. The Journal of urology 150:85-89.

Denis LJ, Griffiths K. Endocrine treatment in prostate cancer. In: Proceedings of the Seminars in surgical oncology, 2000, Vol. 18Wiley Online Library, 52-74.

Doyle TJ, Bowman JL, Windell VL, McLean DJ, Kim KH. 2013. Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice. Biology of reproduction 88:112.

30

Drake AJ, van den Driesche S, Scott HM, Hutchison GR, Seckl JR, Sharpe RM. 2009.

Glucocorticoids amplify dibutyl phthalate-induced disruption of testosterone production and male reproductive development. Endocrinology 150:5055-5064.

Duty SM, Calafat AM, Silva MJ, Ryan L, Hauser R. 2005. Phthalate exposure and reproductive hormones in adult men. Hum Reprod 20:604-610.

Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. 2002. Age trends in the level of serum testosterone and other hormones in middle-aged men: Longitudinal results from the massachusetts male aging study. Journal of Clinical Endocrinology & Metabolism 87:589-598.

Galloway T, Cipelli R, Guralnik J, Ferrucci L, Bandinelli S, Corsi AM, et al. 2010. Daily bisphenol a excretion and associations with sex hormone concentrations: Results from the inchianti adult population study. Environ Health Perspect 118:1603-1608.

Girman CJ, Jacobsen SJ, Guess HA, Oesterling JE, Chute CG, Panser LA, et al. 1995. Natural history of prostatism: Relationship among symptoms, prostate volume and peak urinary flow rate.

The Journal of urology 153:1510-1515.

Gong Y, Han X-D. 2006. Effect of nonylphenol on steroidogenesis of rat leydig cells. Journal of Environmental Science and Health Part B 41:705-715.

Gray A, FELDMAN HA, MCKINLAY JB, LONGCOPE C. 1991. Age, disease, and changing sex hormone levels in middle-aged men: Results of the massachusetts male aging study. Journal of Clinical Endocrinology & Metabolism 73:1016-1025.

Gray LE, Barlow NJ, Howdeshell KL, Ostby JS, Furr JR, Gray CL. 2009. Transgenerational effects of di (2-ethylhexyl) phthalate in the male crl: Cd (sd) rat: Added value of assessing multiple

offspring per litter. Toxicological sciences 110:411-425.

Guenther K, Heinke V, Thiele B, Kleist E, Prast H, Raecker T. 2002. Endocrine disrupting nonylphenols are ubiquitous in food. Environmental science & technology 36:1676-1680.

Gupta C. 2000. Reproductive malformation of the male offspring following maternal exposure to estrogenic chemicals. Proceedings of the Society for Experimental Biology and Medicine

224:61-68.

Han X, Cui Z, Zhou N, Ma M, Li L, Li Y, et al. 2013. Urinary phthalate metabolites and male reproductive function parameters in chongqing general population, china. International journal of hygiene and environmental health.

Hanaoka T, Kawamura N, Hara K, Tsugane S. 2002. Urinary bisphenol a and plasma hormone concentrations in male workers exposed to bisphenol a diglycidyl ether and mixed organic solvents.

Occupational and environmental medicine 59:625-628.

Hauser R, Calafat AM. 2005. Phthalates and human health. Occup Environ Med 62:806-818.

Heudorf U, Mersch-Sundermann V, Angerer J. 2007. Phthalates: Toxicology and exposure.

International journal of hygiene and environmental health 210:623-634.

Ho S-M, Tang W-Y, de Frausto JB, Prins GS. 2006. Developmental exposure to estradiol and bisphenol a increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer research 66:5624-5632.

Huang PC, Kuo PL, Chou YY, Lin SJ, Lee CC. 2009. Association between prenatal exposure to phthalates and the health of newborns. Environ Int 35:14-20.

IARC. 2012. Globocan 2012: Estimated incidence, mortality and prevalence worldwide in 2012

31

Ito Y, Yokota H, Wang R, Yamanoshita O, Ichihara G, Wang H, et al. 2005. Species differences in the metabolism of di(2-ethylhexyl) phthalate (dehp) in several organs of mice, rats, and marmosets.

Archives of toxicology 79:147-154.

Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. 2003. Cancer statistics, 2003. CA: a cancer journal for clinicians 53:5-26.

Joensen UN, Frederiksen H, Jensen MB, Lauritsen MP, Olesen IA, Lassen TH, et al. 2012.

Phthalate excretion pattern and testicular function: A study of 881 healthy danish men.

Environmental health perspectives 120:1397.

Jurewicz J, Radwan M, Sobala W, Ligocka D, Radwan P, Bochenek M, et al. 2013. Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm

aneuploidy and reproductive hormones. Reproductive Toxicology 42:232-241.

Kendig EL, Buesing DR, Christie SM, Cookman CJ, Gear RB, Hugo ER, et al. 2012. Estrogen-like disruptive effects of dietary exposure to bisphenol a or 17alpha-ethinyl estradiol in cd1 mice.

International journal of toxicology 31:537-550.

Kim TS, Jung KK, Kim SS, Kang IH, Baek JH, Nam H-S, et al. 2010. Effects of in utero exposure to di (n-butyl) phthalate on development of male reproductive tracts in sprague-dawley rats. Journal of Toxicology and Environmental Health, Part A 73:1544-1559.

Koch HM, Rossbach B, Drexler H, Angerer J. 2003. Internal exposure of the general population to dehp and other phthalates—determination of secondary and primary phthalate monoester

metabolites in urine. Environmental research 93:177-185.

Kuklenyik, John Ekong, Caroline D. Cutchins, Larry L. Needham, Calafat AM. 2003. Simultaneous measurement of urinary bisphenol a and alkylphenols by automated solid-phase extractive

derivatization gas chromatography-mass spectrometry.

Laurenzana EM, Balasubramanian G, Weis C, Blaydes B, Newbold RR, Delclos KB. 2002. Effect of nonylphenol on serum testosterone levels and testicular steroidogenic enzyme activity in neonatal, pubertal, and adult rats. Chemico-biological interactions 139:23-41.

Lee BM, Koo HJ. 2007. Hershberger assay for antiandrogenic effects of phthalates. Journal of Toxicology and Environmental Health, Part A 70:1365-1370.

Li J, Ma M, Wang Z. 2010. In vitro profiling of endocrine disrupting effects of phenols. Toxicology in vitro 24:201-207.

Liao C, Kannan K. 2012. Determination of free and conjugated forms of bisphenol a in human urine and serum by liquid chromatography-tandem mass spectrometry. Environ Sci Technol

46:5003-5009.

Maffini MV, Rubin BS, Sonnenschein C, Soto AM. 2006. Endocrine disruptors and reproductive health: The case of bisphenol-a. Molecular and cellular endocrinology 254:179-186.

Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK. 2013. Plastics derived endocrine disruptors (bpa, dehp and dbp) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PloS one 8:e55387.

Meeker JD, Calafat AM, Hauser R. 2009. Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. Journal of andrology 30:287-297.

Meeker JD, Calafat AM, Hauser R. 2009. Urinary bisphenol a concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic. Environmental science &

technology 44:1458-1463.

32

Mendiola J, Jørgensen N, Andersson A-M, Calafat AM, Ye X, Redmon JB, et al. 2010. Are environmental levels of bisphenol a associated with reproductive function in fertile men?

Environmental health perspectives 118:1286.

Mendiola J, Jørgensen N, Andersson AM, Calafat A, Silva M, Redmon J, et al. 2011. Associations between urinary metabolites of di (2­ethylhexyl) phthalate and reproductive hormones in fertile men.

International journal of andrology 34:369-378.

Nagel SC, vom Saal FS, Thayer KA, Dhar MG, Boechler M, Welshons WV. 1997. Relative binding affinity-serum modified access (rba-sma) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol a and octylphenol. Environmental health perspectives 105:70.

Parkin DM, Muir CS, Whelan S, Gao Y, Ferlay J, Powell J. 1992. Cancer incidence in five continents, volume vi:International Agency for Research on Cancer.

Roddam AW, Allen NE, Appleby P, Key TJ. 2008. Endogenous sex hormones and prostate cancer: A collaborative analysis of 18 prospective studies. Journal of the National Cancer Institute

100:170-183.

Rove KO, Debruyne FM, Djavan B, Gomella LG, Koul HK, Lucia MS, et al. 2012. Role of testosterone in managing advanced prostate cancer. Urology 80:754-762.

Rudel RA, Camann DE, Spengler JD, Korn LR, Brody JG. 2003. Phthalates, alkylphenols,

pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air

pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air

在文檔中 內分泌干擾物質多重暴露與攝護腺疾病之相關性及機制探討研究---鄰苯二甲酸酯、壬基酚、雙酚A共同暴露與攝護腺疾病之相關性及機制探討研究 (頁 19-33)