Table 2.
Geometric mean (95% CI) HE4 and CA125 by reproductive characteristics and stratified by menopausal status, NHANES 2001–02 (n=2302)
| All (n=2302) |
Premenopausal (n=1273) |
Postmenopausal (n=1029) |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| N (%)1 | Mean HE4 (95%CI)2 | Mean CA125 (95%CI)3 | N (%)1 | Mean HE4 (95%CI)2 | Mean CA125 (95%CI)3 | N (%)1 | Mean HE4 (95%CI)2 | Mean CA125 (95%CI)3 | |
| Age at menarche (years) | |||||||||
| ≤11 | 450 (21) | 17.1 (16.1–18.2) | 11.2 (10.1–12.5) | 283 (23) | 12.4 (11.4–13.5) | 12.6 (11.5–13.8) | 167 (18) | 25.2 (22.9–27.7) | 9.7 (7.9–11.8) |
| 12 | 585 (27) | 16.3 (15.4–17.3) | 10.9 (9.9–12.0) | 332 (27) | 11.5 (10.6–12.5) | 12.3 (11.2–13.6) | 253 (26) | 25.7 (23.9–27.5) | 9.5 (8.0–11.3) |
| 13 | 571 (27) | 16.8 (15.7–17.9) | 11.6 (10.6–12.8) | 315 (27) | 12.1 (11.0–13.2) | 13.2 (11.7–15.0) | 256 (26) | 25.3 (23.9–26.8) | 9.8 (8.9–10.9) |
| 14 | 281 (12) | 17.1 (15.4–18.9) | 10.8 (9.6–12.2) | 146 (12) | 12.4 (10.9–14.0) | 12.1 (10.5–14.0) | 135 (13) | 25.2 (22.0–28.9) | 9.4 (7.8–11.4) |
| ≥15 | 325 (13) | 17.4 (15.9–19.2) | 11.0 (10.2–11.9) | 144 (11) | 12.9 (11.7–14.2) | 11.9 (10.5–13.4) | 181 (16) | 25.6 (22.5–29.0) | 10.0 (8.9–11.3) |
| p-trend | 0.55 | 0.80 | 0.48 | 0.41 | 0.97 | 0.76 | |||
| Oral contraceptive use | |||||||||
| Never | 995 (37) | 17.7 (16.5–19.1) | 11.2 (10.5–12.0) | 376 (27) | 12.6 (11.5–13.7) | 12.7 (11.7–13.9) | 619 (52) | 26.8 (24.8–29.1) | 9.6 (8.5–10.8) |
| Ever | 1274 (63) | 16.5 (15.5–17.5) | 11.0 (10.1–12.1) | 867 (73) | 12.0 (11.2–12.8) | 12.4 (11.2–13.8) | 407 (48) | 24.0 (21.9–26.3) | 9.8 (8.4–11.4) |
| p-value | 0.20 | 0.63 | 0.40 | 0.73 | 0.19 | 0.76 | |||
| Duration of oral contraceptive use (months) | |||||||||
| Never users | 998 (37) | 17.7 (16.4–19.1) | 11.2 (10.5–12.0) | 379 (27) | 12.6 (11.5–13.7) | 12.7 (11.7–13.8) | 619 (52) | 26.9 (24.8–29.1) | 9.6 (8.5–10.9) |
| 1–12 | 293 (12) | 15.7 (14.1–17.4) | 10.6 (9.6–11.7) | 195 (14) | 11.6 (10.5–12.7) | 12.3 (10.6–14.4) | 98 (10) | 22.1 (18.5–26.4) | 9.0 (7.4–11.0) |
| 13–47 | 302 (15) | 16.3 (15.1–17.6) | 12.0 (10.3–13.9) | 210 (17) | 11.7 (10.6–12.8) | 13.9 (11.6–16.6) | 92 (12) | 24.5 (20.8–28.9) | 10.4 (8.7–12.6) |
| 48–96 | 392 (20) | 16.3 (14.7–18.0) | 11.3 (10.4–12.2) | 283 (25) | 11.8 (10.5–13.1) | 12.7 (11.7–13.8) | 109 (14) | 24.0 (21.5–26.7) | 9.5 (8.0–11.3) |
| > 96 | 275 (15) | 17.6 (15.9–19.6) | 10.3 (9.1–11.6) | 175 (17) | 13.0 (11.4–14.7) | 10.5 (9.6–11.5) | 100 (12) | 25.3 (22.4–28.6) | 10.4 (8.4–12.8) |
| p-trend | 0.71 | 0.10 | 0.44 | 0.0004 | 0.76 | 0.36 | |||
| Currently using OCs | |||||||||
| No | -- | -- | -- | 1096 (84) | 12.7 (12.0–13.3) | 13.2 (12.2–14.1) | -- | -- | -- |
| Yes | -- | -- | -- | 147 (16) | 9.8 (8.4–11.3) | 9.0 (8.2–9.9) | -- | -- | -- |
| p-value | -- | -- | 0.002 | <0.0001 | -- | -- | |||
| Parity | |||||||||
| Nulliparous | 358 (20) | 17.0 (15.3–19.0) | 10.0 (9.0–11.2) | 245 (26) | 12.0 (10.4–13.8) | 11.0 (9.9–12.3) | 113 (11) | 25.9 (21.4–31.5) | 10.3 (8.3–12.7) |
| Parous | 1864 (80) | 17.2 (16.7–17.8) | 11.3 (10.5–12.1) | 950 (74) | 12.3 (11.8–12.9) | 13.0 (12.1–14.1) | 914 (89) | 25.6 (24.7–26.6) | 9.6 (8.6–10.8) |
| p-value | 0.81 | 0.04 | 0.69 | 0.01 | 0.91 | 0.49 | |||
| Number of births among parous women | |||||||||
| 1 | 385 (21) | 16.9 (15.4–18.6) | 11.0 (9.9–12.3) | 272 (26) | 11.3 (9.9–12.9) | 13.9 (12.4–15.6) | 113 (14) | 26.5 (22.2–31.6) | 8.7 (7.8–9.8) |
| 2 | 549 (35) | 18.1 (17.0–19.3) | 10.9 (10.2–11.7) | 335 (41) | 13.3 (12.2–14.5) | 13.0 (11.9–14.3) | 214 (27) | 24.3 (22.4–26.4) | 8.8 (8.0–9.6) |
| 3 | 440 (24) | 17.8 (17.2–18.6) | 11.3 (10.4–12.3) | 224 (23) | 13.3 (12.2–14.5) | 12.7 (11.4–14.2) | 216 (25) | 24.2 (21.9–26.7) | 10.2 (9.0–11.6) |
| 4+ | 490 (21) | 17.3 (16.5–18.3) | 11.2 (9.9–12.5) | 119 (11) | 11.0 (9.6–12.5) | 13.6 (11.4–16.2) | 371 (34) | 26.3 (24.5–28.1) | 9.3 (8.3–10.4) |
| p-trend | 0.82 | 0.75 | 0.77 | 0.62 | 0.73 | 0.10 | |||
| Currently pregnant | |||||||||
| No | -- | -- | -- | 998 (93) | 12.2 (11.5–12.9) | 12.1 (11.3–12.9) | -- | -- | -- |
| Yes | -- | -- | -- | 275 (7) | 11.0 (8.8–13.8) | 18.3 (15.2–22.1) | -- | -- | -- |
| p-value | -- | -- | 0.44 | 0.0004 | -- | -- | |||
| Breastfeeding | |||||||||
| Never | 1138 (54) | 17.1 (16.3–18.0) | 10.6 (10.0–11.3) | 586 (53) | 12.0 (11.1–13.0) | 12.0 (11.1–13.0) | 552 (55) | 26.1 (25.0–27.2) | 9.7 (8.7–10.7) |
| Ever | 1079 (46) | 17.4 (16.5–18.3) | 11.5 (10.5–12.7) | 604 (47) | 12.6 (11.9–13.3) | 13.1 (11.9–14.3) | 475 (45) | 25.1 (23.5–26.9) | 9.6 (8.4–11.1) |
| p-value | 0.61 | 0.07 | 0.25 | 0.12 | 0.42 | 0.92 | |||
| Currently breastfeeding | |||||||||
| No | -- | -- | -- | 1223 (97) | 12.0 (11.4–12.6) | 12.6 (11.7–13.5) | -- | -- | -- |
| Yes | -- | -- | -- | 50 (3) | 15.5 (13.1–18.3) | 12.5 (8.6–18.3) | -- | -- | -- |
| p-value | -- | -- | 0.008 | 0.99 | -- | -- | |||
| Age at first live birth among parous women (years) | |||||||||
| <20 | 596 (29) | 18.3 (17.2–19.4) | 11.2 (10.4–12.2) | 318 (30) | 13.1 (11.9–14.3) | 13.2 (11.8–14.8) | 278 (28) | 25.9 (23.9–28.2) | 9.9 (9.0–10.9) |
| 20–24 | 741 (40) | 17.8 (16.8–18.9) | 11.0 (10.1–12.0) | 353 (36) | 12.8 (11.7–14.0) | 13.2 (12.3–14.2) | 388 (45) | 25.3 (23.6–27.1) | 9.4 (8.4–10.6) |
| 25–29 | 361 (22) | 17.3 (16.0–18.6) | 11.0 (9.9–12.2) | 184 (22) | 12.4 (11.4–13.4) | 13.7 (12.4–15.0) | 177 (21) | 24.4 (21.7–27.5) | 8.5 (7.5–9.7) |
| 30+ | 162 (10) | 15.1 (13.0–17.6) | 11.4 (9.6–13.6) | 95 (12) | 10.1 (8.2–12.5) | 12.7 (10.3–15.8) | 67 (7) | 24.0 (20.3–28.3) | 10.1 (7.7–13.2) |
| p-trend | 0.006 | 0.96 | 0.002 | 0.89 | 0.33 | 0.41 | |||
| Endometriosis4 | |||||||||
| No | 1310 (91) | 12.4 (11.9–13.0) | 12.1 (11.2–13.1) | 1169 (93) | 12.0 (11.4–12.6) | 12.5 (11.6–13.5) | 141 (78) | 15.5 (13.6–17.5) | 10.3 (8.5–12.4) |
| Yes | 102 (9) | 14.1 (12.2–16.3) | 12.1 (10.2–14.3) | 65 (7) | 14.0 (11.2–17.6) | 13.9 (11.5–17.0) | 37 (22) | 16.1 (12.5–20.7) | 10.6 (8.0–14.0) |
| p-value | 0.08 | 0.96 | 0.16 | 0.30 | 0.74 | 0.81 | |||
| Fibroids4 | |||||||||
| No | 1246 (87) | 12.6 (12.0–13.2) | 12.2 (11.3–13.0) | 1114 (89) | 12.2 (11.6–12.8) | 12.6 (11.7–13.5) | 132 (74) | 14.9 (13.2–17.0) | 10.2 (8.5–12.3) |
| Yes | 165 (13) | 12.3 (10.7–14.1) | 11.9 (9.5–14.9) | 120 (11) | 11.1 (9.7–12.8) | 12.4 (9.7–15.9) | 45 (26) | 17.5 (14.3–21.5) | 11.3 (8.1–15.7) |
| p-value | 0.76 | 0.85 | 0.23 | 0.90 | 0.13 | 0.50 | |||
| Hysterectomy and oophorectomy | |||||||||
| Neither | 1554 (75) | 17.6 (16.9–18.3) | 11.9 (11.0–12.8) | 1034 (91) | 12.1 (11.5–12.8) | 13.1 (12.2–13.9) | 520 (52) | 26.8 (25.4–28.2) | 10.0 (8.6–11.7) |
| Hysterectomy only | 202 (9) | 16.5 (14.7–18.5) | 9.4 (8.2–10.9) | 47 (5) | 12.0 (10.5–13.8) | 8.3 (6.4–10.8) | 155 (14) | 24.4 (21.4–27.9) | 9.5 (8.1–11.1) |
| Unilateral | 38 (2) | 17.4 (13.6–22.3) | 12.8 (9.5–17.3) | 18 (2) | 13.5 (11.0–16.6) | 16.3 (11.2–23.7) | 20 (2) | 21.4 (13.3–34.3) | 8.7 (7.1–10.8) |
| oophorectomy only | |||||||||
| Oophorectomy and | 328 (14) | 16.2 (14.5–18.0) | 9.2 (8.3–10.3) | 15 (2) | 9.7 (6.5–14.5) | 9.1 (6.3–13.2) | 313 (32) | 24.3 (22.4–26.3) | 9.2 (8.4–10.0) |
| hysterectomy | |||||||||
| p-value | 0.48 | <0.0001 | 0.47 | 0.009 | 0.35 | 0.37 | |||
| Hormone replacement therapy | |||||||||
| Never | -- | -- | -- | -- | -- | -- | 527 (45) | 26.9 (25.4–28.6) | 9.9 (8.6–11.3) |
| Former | -- | -- | -- | -- | -- | -- | 193 (21) | 25.1 (22.6–27.8) | 8.9 (7.7–10.3) |
| Current5 | -- | -- | -- | -- | -- | -- | 270 (34) | 23.7 (21.8–25.8) | 9.1 (8.1–10.1) |
| p-value | -- | -- | 0.08 | 0.26 | |||||
| Age at natural menopause (years) | |||||||||
| <46 | -- | -- | -- | -- | -- | -- | 136 (22) | 25.6 (22.8–28.7) | 9.2 (7.5–11.3) |
| 46 to 49 | -- | -- | -- | -- | -- | -- | 123 (24) | 28.6 (25.7–31.9) | 9.5 (7.6–11.8) |
| 50 to 52 | -- | -- | -- | -- | -- | -- | 195 (35) | 26.1 (23.7–28.7) | 10.5 (8.9–12.4) |
| 52+ | -- | -- | -- | -- | -- | -- | 116 (19) | 28.5 (25.8–31.6) | 10.3 (8.7–12.2) |
| p-trend | -- | -- | 0.28 | 0.11 | |||||
| Genital powder use6 | |||||||||
| No | 1208 (97) | 11.9 (11.3–12.6) | 12.6 (11.7–13.7) | 1150 (97) | 11.8 (11.2–12.5) | 12.7 (11.7–13.8) | 58 (92) | 14.6 (11.1–19.1) | 9.7 (8.4–11.3) |
| Yes | 45 (3) | 13.1 (9.4–18.3) | 11.1 (9.4–13.1) | 40 (3) | 11.9 (8.8–16.3) | 11.4 (9.3–13.9) | 5 (8) | 36.5 (25.9–51.5) | 7.7 (6.1–9.6) |
| p-value | 0.60 | 0.16 | 0.95 | 0.32 | 0.003 | 0.12 | |||
1
Unweighted number and weighted percentage
2
Geometric least squares means calculated from linear regression models with log transformed HE4 as the dependent variable. Each model included the characteristic of interest, age (continuous), age-squared (continuous), and smoking status (never, former, current). P-values from Wald’s F test.
3
Geometric least squares means calculated from linear regression models with log transformed CA125 as the dependent variable. Each model included the characteristic of interest, age (continuous), BMI (<18.5, 18.5–24.9, 25–29.9, 30–34.9, 35–39.9, and ≥40 kg/m2), and race/ethnicity (Mexican American, other Hispanic, non-Hispanic white, non-Hispanic Black, and other races). P- values from Wald’s F test.
4
Information on endometriosis and fibroids was only collected on women age 20–54.
5
HE4 among current estrogen only HRT users, 23.5 (21.0–26.5) was borderline significantly lower than mean HE4 among never/former HRT users, 27.1 (25.5–28.7), p=0.05.
6
Genital powder use in the past month among women ages 20–49. When restricted to women age 40 years and older, the geometric mean (95% CI) HE4 among 12 powder users was 28.0 (18.9– 41.3) compared to 12.7 (11.4–14.1) among 368 non-users, p=0.002.