TABLE 3.
Associations between urinary phytoestrogen concentrations and risk of endometriosis in the ENDO study1
| Operative sample |
General sample |
|||||||||
| Quartile (range) | n | Unadjusted (n = 472) | Adjusted2 (n = 466) | Adjusted3 (n = 387) | Quartile (range) | n | Unadjusted (n =127) | Adjusted2 (n =127) | Adjusted3 (n = 117) | |
| Isoflavones, nmol/L | ||||||||||
| Genistein | Q14(0.01–22.3) | 123 | Ref | Ref | Ref | Q1(0.32–22.7) | 32 | Ref | Ref | Ref |
| Q2(22.4–77.0) | 124 | 1.18(0.78, 1.80) | 1.14(0.75, 1.74) | 1.12(0.70, 1.79) | Q2(22.8–88.8) | 33 | 1.61(0.39, 6.76) | 1.58(0.37, 6.73) | 3.49(0.57, 21.44) | |
| Q3(77.1–284) | 124 | 1.49(1.00, 2.22) | 1.39(0.93, 2.08) | 1.33(0.84, 2.10) | Q3(88.9–339) | 33 | 0.65(0.11, 3.87) | 0.63(0.10, 3.83) | 0.58(0.05, 7.00) | |
| Q4(285–76,500) | 123 | 1.06(0.69, 1.63) | 1.02(0.66, 1.57) | 0.97(0.56, 1.68) | Q4(340–21,900) | 33 | 1.29(0.29, 5.77) | 1.31(0.29, 5.88) | 4.99(0.67, 37.02) | |
| Linear5 | 1.01(0.95, 1.08) | 1.01(0.95, 1.07) | 1.02(0.93, 1.11) | 0.94(0.72, 1.22) | 0.94(0.71, 1.23) | 1.04(0.70, 1.55) | ||||
| Daidzein | Q1(0.01–44.0) | 124 | Ref | Ref | Ref | Q1(0.19–50.3) | 32 | Ref | Ref | Ref |
| Q2(45.0–138) | 123 | 1.14(0.76, 1.71) | 1.08(0.72, 1.63) | 1.17(0.75, 1.85) | Q2(50.4–178) | 33 | 1.17(0.32, 4.37) | 1.23(0.32, 4.74) | 3.37(0.50, 22.62) | |
| Q3(139–645) | 124 | 1.08(0.72, 1.62) | 1.03(0.68, 1.56) | 1.07(0.65, 1.74) | Q3(179–998) | 33 | 0.52(0.09, 2.82) | 0.54(0.10, 2.98) | 0.76(0.07, 8.73) | |
| Q4(646–13,600) | 123 | 1.04(0.69, 1.58) | 1.00(0.66, 1.52) | 1.11(0.66, 1.85) | Q4(999–39,200) | 33 | 0.70(0.16, 3.15) | 0.75(0.16, 3.45) | 2.20(0.29, 16.41) | |
| Linear | 1.00(0.94, 1.07) | 1.00(0.93, 1.06) | 1.00(0.91, 1.09) | 0.94(0.73, 1.21) | 0.95(0.73, 1.22) | 1.09(0.79, 1.51) | ||||
| O-DMA | Q1(0.003–0.33) | 123 | Ref | Ref | Ref | Q1(0.003–0.37) | 32 | Ref | Ref | Ref |
| Q2(0.34–9.25) | 124 | 0.78(0.52, 1.19) | 0.75(0.49, 1.14) | 0.82(0.51, 1.29) | Q2(0.38–14.3) | 33 | 0.68(0.15, 3.05) | 0.62(0.13, 2.96) | 0.27(0.04, 1.94) | |
| Q3(9.26–70.8) | 124 | 0.96(0.65, 1.42) | 0.90(0.61, 1.34) | 0.90(0.58, 1.41) | Q3(14.4–113) | 33 | 0.68(0.15, 3.05) | 0.68(0.15, 3.12) | 0.39(0.05, 2.89) | |
| Q4(70.9–10,700) | 123 | 0.96(0.65, 1.42) | 0.91(0.61, 1.34) | 0.94(0.58, 1.52) | Q4(114–14,300) | 33 | 0.97(0.24, 3.87) | 0.95(0.23, 3.86) | 1.47(0.22, 10.04) | |
| Linear | 0.99(0.96, 1.03) | 0.99(0.95, 1.03) | 0.99(0.95, 1.03) | 0.96(0.84, 1.10) | 0.96(0.83, 1.10) | 0.96(0.79, 1.17) | ||||
| Equol | Q1(0.003–1.24) | 124 | Ref | Ref | Ref | Q1(0.003–4.13) | 32 | Ref | Ref | Ref |
| Q2(1.25–8.09) | 123 | 0.71(0.46, 1.10) | 0.74(0.48, 1.15) | 0.69(0.43, 1.10) | Q2(4.14–8.80) | 33 | 0.70(0.16, 3.15) | 0.74(0.17, 3.34) | 1.05(0.17, 6.48) | |
| Q3(8.10–19.0) | 124 | 1.33(0.92, 1.94) | 1.32(0.90, 1.92) | 1.14(0.75, 1.75) | Q3(8.81–15.0) | 33 | 0.25(0.03, 2.24) | 0.24(0.03, 2.18) | 0.53(0.05, 5.70) | |
| Q4(19.1–11,800) | 123 | 0.93(0.62, 1.40) | 0.92(0.61, 1.39) | 0.76(0.45, 1.27) | Q4(15.1–8240) | 33 | 1.45(0.41, 5.15) | 1.61(0.45, 5.82) | 4.51(0.70, 29.13) | |
| Linear | 1.01(0.96, 1.07) | 1.01(0.95, 1.06) | 0.97(0.91, 1.04) | 0.99(0.80, 1.24) | 1.00(0.80, 1.25) | 1.08(0.82, 1.42) | ||||
| Total isoflavones | Q1(0.05–87.1) | 123 | Ref | Ref | Ref | Q1(14.6–95.8) | 32 | Ref | Ref | Ref |
| Q2(87.2–287) | 124 | 1.11(0.74, 1.67) | 1.08(0.72, 1.63) | 1.08(0.69, 1.71) | Q2(95.9–307) | 33 | 1.17(0.32, 4.37) | 1.22(0.32, 4.65) | 3.06(0.49, 19.29) | |
| Q3(288–1290) | 124 | 1.10(0.74, 1.66) | 1.03(0.68, 1.56) | 0.99(0.61, 1.61) | Q3(308–1870) | 33 | 0.52 0.09, 2.82) | 0.54(0.10, 3.01) | 0.70(0.06, 7.70) | |
| Q4(1300–18,400) | 123 | 1.08(0.71, 1.63) | 1.06(0.70, 1.60) | 1.06(0.64, 1.74) | Q4(1880–61,700) | 33 | 0.70(0.16, 3.15) | 0.74(0.16, 3.36) | 2.08(0.32, 13.62) | |
| Linear | 1.00(0.93, 1.08) | 1.00(0.93, 1.07) | 0.98(0.89, 1.07) | 0.89(0.67, 1.19) | 0.90(0.67, 1.20) | 1.06(0.75, 1.51) | ||||
| Lignan metabolites, nmol/L | ||||||||||
| Enterodiol | Q1(0.003–20.6) | 123 | Ref | Ref | Ref | Q1(0.004–17.0) | 32 | Ref | Ref | Ref |
| Q2(20.7–60.2) | 124 | 1.14(0.76, 1.73) | 1.05(0.69, 1.60) | 0.88(0.56, 1.40) | Q2(17.1–65.5) | 33 | 1.94(0.49, 7.75) | 1.90(0.47, 7.67) | 1.92(0.42, 8.75) | |
| Q3(60.3–166) | 123 | 1.11(0.73, 1.68) | 1.06(0.70, 1.61) | 0.93(0.58, 1.47) | Q3(65.6–206) | 33 | 0.3(0.03, 3.20) | 0.33(0.03, 3.19) | 0.59(0.05, 6.77) | |
| Q4(167–25,300) | 124 | 1.25(0.83, 1.88) | 1.19(0.79, 1.79) | 1.19(0.74, 1.92) | Q4(207–2360) | 33 | 1.25(0.28, 5.60) | 1.31(0.29, 6.01) | 1.47(0.20, 10.68) | |
| Linear | 1.01(0.96, 1.06) | 1.00(0.96, 1.05) | 1.00(0.95, 1.06) | 1.02(0.86, 1.21) | 1.02(0.86, 1.22) | 1.03(0.84, 1.28) | ||||
| Enterolactone | Q1(0.15–108) | 123 | Ref | Ref | Ref | Q1(1.62–170) | 32 | Ref | Ref | Ref |
| Q2(109–516) | 123 | 1.03(0.67, 1.58) | 1.03(0.67, 1.59) | 1.01(0.61, 1.67) | Q2(171–559) | 33 | 1.52(0.36, 6.34) | 1.39(0.32, 6.00) | 1.71(0.27, 10.77) | |
| Q3(517–1380) | 125 | 1.32(0.88, 1.98) | 1.22(0.81, 1.85) | 1.25(0.80, 1.96) | Q3(560–1490) | 33 | 0.32(0.03, 3.10) | 0.29(0.03, 2.90) | 0.54(0.04, 6.65) | |
| Q4(1390–116,000) | 123 | 1.30(0.87, 1.96) | 1.15(0.76, 1.74) | 1.11(0.98, 1.81) | Q4(1500–23,100) | 33 | 1.52(0.36, 6.34) | 1.52(0.35, 6.57) | 4.39(0.60, 32.29) | |
| Linear | 1.04(0.97, 1.13) | 1.02(0.94, 1.10) | 1.01(0.92, 1.10) | 1.08(0.80, 1.47) | 1.09(0.80, 1.49) | 1.29(0.87, 1.91) | ||||
| Total | Q1(0.16–159) | 123 | Ref | Ref | Ref | Q1(1.63–208) | 32 | Ref | Ref | Ref |
| Q2(160–30) | 124 | 0.97(0.63, 1.49) | 0.95(0.62, 1.47) | 0.88(0.54, 1.44) | Q2(209–734) | 33 | 0.91(0.23, 3.63) | 0.86(0.21, 3.52) | 0.51(0.08, 3.21) | |
| Q3(631–1610) | 124 | 1.29(0.86, 1.92) | 1.18(0.79, 1.78) | 1.16(0.74, 1.81) | Q3(735–1630) | 33 | 0.73(0.16, 3.24) | 0.70(0.15, 3.18) | 1.05(0.19, 5.75) | |
| Q4(1620–128,000) | 123 | 1.28(0.86, 1.92) | 1.13(0.75, 1.70) | 1.13(0.70, 1.82) | Q4(1640–24,100) | 33 | 0.68(0.15, 3.05) | 0.68(0.15, 3.18) | 1.17(0.17, 7.86) | |
| Linear | 1.05(0.96, 1.13) | 1.02(0.94, 1.11) | 1.01(0.92, 1.12) | 1.08(0.79, 1.49) | 1.09(0.79, 1.51) | 1.29(0.85, 1.94) | ||||
| Total phytoestrogens, nmol/L | Q1(6.58–435) | 123 | Ref | Ref | Ref | Q1(51.2–574) | 32 | Ref | Ref | Ref |
| Q2(436–1310) | 124 | 1.21(0.79, 1.85) | 1.17(0.76, 1.79) | 1.26(0.78, 2.02) | Q2(575–1280) | 33 | 0.58(0.14, 2.43) | 0.56(0.13, 2.39) | 0.75(0.11, 4.84) | |
| Q3(1320–3670) | 124 | 1.38(0.91, 2.07) | 1.23(0.81, 1.86) | 1.24(0.78, 1.98) | Q3 (1290–4490) | 33 | 0.40(0.08, 2.06) | 0.40(0.08, 2.06) | 0.65(0.09, 4.44) | |
| Q4(3680–184,000) | 123 | 1.22(0.80, 1.86) | 1.14(0.74, 1.74) | 1.12(0.67, 1.90) | Q4 (4500–62,600) | 33 | 0.75(0.20, 2.80) | 0.76(0.20, 2.86) | 2.53(0.39, 16.36) | |
| Linear | 1.03(0.94, 1.12) | 1.01(0.92, 1.10) | 1.00(0.89, 1.12) | 0.87(0.62, 1.23) | 0.87(0.62, 1.24) | 1.06(0.68, 1.66) | ||||
1
Values are RRs (95% CIs) unless otherwise indicated. ENDO, Endometriosis, Natural History, Diagnosis, and Outcomes; O-DMA, O-desmethylangolensin; Q, quartile; Ref, reference.
2
Adjusted for age and BMI (in kg/m2).
3
Adjusted for age, BMI, race, site, supplement use, use of soy products, physical activity, creatinine, caffeine consumption, and the sum of the remaining individual phytoestrogens.
4
Poisson regression with robust error variance was used to estimate the RRs of being diagnosed with endometriosis comparing quartiles of urinary phytoestrogen concentrations (the first quartile is the reference group).
5
Poisson regression with robust error variance was used to estimate the RRs of being diagnosed with endometriosis by individual urinary phytoestrogen concentrations (per log-unit increase in phytoestrogens).