Among 1644 female survivors eligible for SJLIFE, 988 (60.1%) had a campus visit. With phenotype-specific exclusion criteria listed in the consort diagram (Supplementary Figures 1 and 2, available online), 799 remained in the analysis. PM was clinically identified in 30 (prevalence of 3.8%) participants (Table 1). Compared with non-PM survivors, PM survivors were older (mean [SD] = 37.7 [3.2] years vs mean [SD] = 31.5 [6.1] years, t test P < .001) and received higher doses of ovarian radiation (mean [SD] = 7.9 [8.9] Gy vs mean [SD] = 0.7 [3.2] Gy, t test P < .001) and cumulative CED (mean [SD] = 12.0 [8.4] g/m2 vs mean [SD] = 5.2 [6.7] g/m2, t test P < .001; data not shown).
Demographic and treatment characteristics of discovery and replication cohorts*
| Characteristics . | SJLIFE (clinically diagnosed PM) . | CCSS (self-reported PM) . | ||
|---|---|---|---|---|
| Cases (%) . | Controls (%) . | Cases (%) . | Controls (%) . | |
| Premature menopause | 30 (3.8) | 769 (96.2) | 81 (5.0) | 1543 (95.0) |
| Self-reported race/ethnicity | ||||
| Black | 4 (13.3) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| White | 26 (86.7) | 655 (81.2) | 72 (88.9) | 1373 (90.0) |
| Other | 0 (0.0) | 3 (0.3) | 7 (8.6) | 144 (9.3) |
| Genetic ancestry | ||||
| STRUCTURE European ancestry > 0.5 | 27 (90.0) | 658 (85.6) | 79 (97.5) | 1517 (98.3) |
| STRUCTURE African ancestry > 0.5 | 3 (10.0) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| Diagnosis | ||||
| Leukemia | 9 (30.0) | 297 (38.6) | 24 (29.6) | 574 (37.2) |
| Lymphoma | 8 (26.7) | 109 (14.2) | 40 (49.4) | 283 (18.3) |
| CNS tumor | 1 (3.3) | 65 (8.5) | 1 (1.2) | 101 (6.5) |
| Embryonal tumors | 2 (6.7) | 137 (17.8) | 10 (12.3) | 346 (22.6) |
| Bone and soft tissue sarcoma | 4 (13.3) | 84 (10.9) | 6 (1.7) | 263 (17.0) |
| Carcinomas | 6 (20.0) | 65 (8.5) | 0 (0.0) | 0 (0.0) |
| Other | 0 (0.0) | 11 (1.4) | 0 (0.0) | 8 (0.5) |
| Year of primary diagnosis | ||||
| <1970 | 14 (46.7) | 125 (16.3) | 0 (0.0) | 0 (0.0) |
| 1970 to 1979 | 14 (46.7) | 306 (39.8) | 51 (63.0) | 677 (43.9) |
| 1980 to 1989 | 2 (6.7) | 324 (42.1) | 30 (37.0) | 866 (56.1) |
| ≥1990 | 0 (0.0) | 14 (1.8) | 0 (0.0) | 0 (0.0) |
| Age at visit, y | ||||
| 18–25 | 0 (0.0) | 185 (24.1) | 33 (40.7) | 192 (12.4) |
| 26–35 | 6 (20.0) | 356 (46.3) | 40 (49.4) | 730 (47.3) |
| 36–40 | 24 (80.0) | 228 (29.6) | 8 (9.9) | 621 (40.2) |
| Ovarian radiation dose, cGy | ||||
| None | 7 (23.3) | 680 (88.4) | 14 (17.3) | 710 (46.0) |
| <50 | 2 (6.7) | 17 (2.2) | 32 (39.5) | 535 (34.7) |
| 50–99 | 3 (10.0) | 8 (1.0) | 8 (9.9) | 99 (6.4) |
| 100–999 | 8 (26.7) | 40 (5.2) | 20 (24.7) | 158 (10.2) |
| 1000–1999 | 7 (23.3) | 16 (2.1) | 3 (3.7) | 26 (1.7) |
| ≥2000 | 3 (10.0) | 8 (1.0) | 4 (4.9) | 15 (1.0) |
| Alkylating agents (cyclophosphamide equivalent dose), g/m2 | ||||
| 0 | 4 (13.3) | 337 (43.8) | 29 (35.8) | 908 (58.8) |
| ≥0–<4 | 3 (10.0) | 63 (8.2) | 6 (7.4) | 186 (12.1) |
| 4–<8 | 3 (10.0) | 143 (18.6) | 7 (8.6) | 147 (9.5) |
| 8–<10 | 1 (3.3) | 96 (12.5) | 7 (8.6) | 63 (4.1) |
| 10–<12 | 4 (13.3) | 41 (5.3) | 10 (12.3) | 53 (3.4) |
| 12–<20 | 10 (33.3) | 58 (7.5) | 15 (18.5) | 148 (9.6) |
| ≥20 | 5 (16.7) | 31 (4.0) | 7 (8.6) | 38 (2.5) |
| Characteristics . | SJLIFE (clinically diagnosed PM) . | CCSS (self-reported PM) . | ||
|---|---|---|---|---|
| Cases (%) . | Controls (%) . | Cases (%) . | Controls (%) . | |
| Premature menopause | 30 (3.8) | 769 (96.2) | 81 (5.0) | 1543 (95.0) |
| Self-reported race/ethnicity | ||||
| Black | 4 (13.3) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| White | 26 (86.7) | 655 (81.2) | 72 (88.9) | 1373 (90.0) |
| Other | 0 (0.0) | 3 (0.3) | 7 (8.6) | 144 (9.3) |
| Genetic ancestry | ||||
| STRUCTURE European ancestry > 0.5 | 27 (90.0) | 658 (85.6) | 79 (97.5) | 1517 (98.3) |
| STRUCTURE African ancestry > 0.5 | 3 (10.0) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| Diagnosis | ||||
| Leukemia | 9 (30.0) | 297 (38.6) | 24 (29.6) | 574 (37.2) |
| Lymphoma | 8 (26.7) | 109 (14.2) | 40 (49.4) | 283 (18.3) |
| CNS tumor | 1 (3.3) | 65 (8.5) | 1 (1.2) | 101 (6.5) |
| Embryonal tumors | 2 (6.7) | 137 (17.8) | 10 (12.3) | 346 (22.6) |
| Bone and soft tissue sarcoma | 4 (13.3) | 84 (10.9) | 6 (1.7) | 263 (17.0) |
| Carcinomas | 6 (20.0) | 65 (8.5) | 0 (0.0) | 0 (0.0) |
| Other | 0 (0.0) | 11 (1.4) | 0 (0.0) | 8 (0.5) |
| Year of primary diagnosis | ||||
| <1970 | 14 (46.7) | 125 (16.3) | 0 (0.0) | 0 (0.0) |
| 1970 to 1979 | 14 (46.7) | 306 (39.8) | 51 (63.0) | 677 (43.9) |
| 1980 to 1989 | 2 (6.7) | 324 (42.1) | 30 (37.0) | 866 (56.1) |
| ≥1990 | 0 (0.0) | 14 (1.8) | 0 (0.0) | 0 (0.0) |
| Age at visit, y | ||||
| 18–25 | 0 (0.0) | 185 (24.1) | 33 (40.7) | 192 (12.4) |
| 26–35 | 6 (20.0) | 356 (46.3) | 40 (49.4) | 730 (47.3) |
| 36–40 | 24 (80.0) | 228 (29.6) | 8 (9.9) | 621 (40.2) |
| Ovarian radiation dose, cGy | ||||
| None | 7 (23.3) | 680 (88.4) | 14 (17.3) | 710 (46.0) |
| <50 | 2 (6.7) | 17 (2.2) | 32 (39.5) | 535 (34.7) |
| 50–99 | 3 (10.0) | 8 (1.0) | 8 (9.9) | 99 (6.4) |
| 100–999 | 8 (26.7) | 40 (5.2) | 20 (24.7) | 158 (10.2) |
| 1000–1999 | 7 (23.3) | 16 (2.1) | 3 (3.7) | 26 (1.7) |
| ≥2000 | 3 (10.0) | 8 (1.0) | 4 (4.9) | 15 (1.0) |
| Alkylating agents (cyclophosphamide equivalent dose), g/m2 | ||||
| 0 | 4 (13.3) | 337 (43.8) | 29 (35.8) | 908 (58.8) |
| ≥0–<4 | 3 (10.0) | 63 (8.2) | 6 (7.4) | 186 (12.1) |
| 4–<8 | 3 (10.0) | 143 (18.6) | 7 (8.6) | 147 (9.5) |
| 8–<10 | 1 (3.3) | 96 (12.5) | 7 (8.6) | 63 (4.1) |
| 10–<12 | 4 (13.3) | 41 (5.3) | 10 (12.3) | 53 (3.4) |
| 12–<20 | 10 (33.3) | 58 (7.5) | 15 (18.5) | 148 (9.6) |
| ≥20 | 5 (16.7) | 31 (4.0) | 7 (8.6) | 38 (2.5) |
CCSS = Childhood Cancer Survivor Study; PM = premature menopause; SJLIFE = St. Jude Lifetime Cohort Study.
Demographic and treatment characteristics of discovery and replication cohorts*
| Characteristics . | SJLIFE (clinically diagnosed PM) . | CCSS (self-reported PM) . | ||
|---|---|---|---|---|
| Cases (%) . | Controls (%) . | Cases (%) . | Controls (%) . | |
| Premature menopause | 30 (3.8) | 769 (96.2) | 81 (5.0) | 1543 (95.0) |
| Self-reported race/ethnicity | ||||
| Black | 4 (13.3) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| White | 26 (86.7) | 655 (81.2) | 72 (88.9) | 1373 (90.0) |
| Other | 0 (0.0) | 3 (0.3) | 7 (8.6) | 144 (9.3) |
| Genetic ancestry | ||||
| STRUCTURE European ancestry > 0.5 | 27 (90.0) | 658 (85.6) | 79 (97.5) | 1517 (98.3) |
| STRUCTURE African ancestry > 0.5 | 3 (10.0) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| Diagnosis | ||||
| Leukemia | 9 (30.0) | 297 (38.6) | 24 (29.6) | 574 (37.2) |
| Lymphoma | 8 (26.7) | 109 (14.2) | 40 (49.4) | 283 (18.3) |
| CNS tumor | 1 (3.3) | 65 (8.5) | 1 (1.2) | 101 (6.5) |
| Embryonal tumors | 2 (6.7) | 137 (17.8) | 10 (12.3) | 346 (22.6) |
| Bone and soft tissue sarcoma | 4 (13.3) | 84 (10.9) | 6 (1.7) | 263 (17.0) |
| Carcinomas | 6 (20.0) | 65 (8.5) | 0 (0.0) | 0 (0.0) |
| Other | 0 (0.0) | 11 (1.4) | 0 (0.0) | 8 (0.5) |
| Year of primary diagnosis | ||||
| <1970 | 14 (46.7) | 125 (16.3) | 0 (0.0) | 0 (0.0) |
| 1970 to 1979 | 14 (46.7) | 306 (39.8) | 51 (63.0) | 677 (43.9) |
| 1980 to 1989 | 2 (6.7) | 324 (42.1) | 30 (37.0) | 866 (56.1) |
| ≥1990 | 0 (0.0) | 14 (1.8) | 0 (0.0) | 0 (0.0) |
| Age at visit, y | ||||
| 18–25 | 0 (0.0) | 185 (24.1) | 33 (40.7) | 192 (12.4) |
| 26–35 | 6 (20.0) | 356 (46.3) | 40 (49.4) | 730 (47.3) |
| 36–40 | 24 (80.0) | 228 (29.6) | 8 (9.9) | 621 (40.2) |
| Ovarian radiation dose, cGy | ||||
| None | 7 (23.3) | 680 (88.4) | 14 (17.3) | 710 (46.0) |
| <50 | 2 (6.7) | 17 (2.2) | 32 (39.5) | 535 (34.7) |
| 50–99 | 3 (10.0) | 8 (1.0) | 8 (9.9) | 99 (6.4) |
| 100–999 | 8 (26.7) | 40 (5.2) | 20 (24.7) | 158 (10.2) |
| 1000–1999 | 7 (23.3) | 16 (2.1) | 3 (3.7) | 26 (1.7) |
| ≥2000 | 3 (10.0) | 8 (1.0) | 4 (4.9) | 15 (1.0) |
| Alkylating agents (cyclophosphamide equivalent dose), g/m2 | ||||
| 0 | 4 (13.3) | 337 (43.8) | 29 (35.8) | 908 (58.8) |
| ≥0–<4 | 3 (10.0) | 63 (8.2) | 6 (7.4) | 186 (12.1) |
| 4–<8 | 3 (10.0) | 143 (18.6) | 7 (8.6) | 147 (9.5) |
| 8–<10 | 1 (3.3) | 96 (12.5) | 7 (8.6) | 63 (4.1) |
| 10–<12 | 4 (13.3) | 41 (5.3) | 10 (12.3) | 53 (3.4) |
| 12–<20 | 10 (33.3) | 58 (7.5) | 15 (18.5) | 148 (9.6) |
| ≥20 | 5 (16.7) | 31 (4.0) | 7 (8.6) | 38 (2.5) |
| Characteristics . | SJLIFE (clinically diagnosed PM) . | CCSS (self-reported PM) . | ||
|---|---|---|---|---|
| Cases (%) . | Controls (%) . | Cases (%) . | Controls (%) . | |
| Premature menopause | 30 (3.8) | 769 (96.2) | 81 (5.0) | 1543 (95.0) |
| Self-reported race/ethnicity | ||||
| Black | 4 (13.3) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| White | 26 (86.7) | 655 (81.2) | 72 (88.9) | 1373 (90.0) |
| Other | 0 (0.0) | 3 (0.3) | 7 (8.6) | 144 (9.3) |
| Genetic ancestry | ||||
| STRUCTURE European ancestry > 0.5 | 27 (90.0) | 658 (85.6) | 79 (97.5) | 1517 (98.3) |
| STRUCTURE African ancestry > 0.5 | 3 (10.0) | 111 (14.4) | 2 (2.5) | 26 (1.7) |
| Diagnosis | ||||
| Leukemia | 9 (30.0) | 297 (38.6) | 24 (29.6) | 574 (37.2) |
| Lymphoma | 8 (26.7) | 109 (14.2) | 40 (49.4) | 283 (18.3) |
| CNS tumor | 1 (3.3) | 65 (8.5) | 1 (1.2) | 101 (6.5) |
| Embryonal tumors | 2 (6.7) | 137 (17.8) | 10 (12.3) | 346 (22.6) |
| Bone and soft tissue sarcoma | 4 (13.3) | 84 (10.9) | 6 (1.7) | 263 (17.0) |
| Carcinomas | 6 (20.0) | 65 (8.5) | 0 (0.0) | 0 (0.0) |
| Other | 0 (0.0) | 11 (1.4) | 0 (0.0) | 8 (0.5) |
| Year of primary diagnosis | ||||
| <1970 | 14 (46.7) | 125 (16.3) | 0 (0.0) | 0 (0.0) |
| 1970 to 1979 | 14 (46.7) | 306 (39.8) | 51 (63.0) | 677 (43.9) |
| 1980 to 1989 | 2 (6.7) | 324 (42.1) | 30 (37.0) | 866 (56.1) |
| ≥1990 | 0 (0.0) | 14 (1.8) | 0 (0.0) | 0 (0.0) |
| Age at visit, y | ||||
| 18–25 | 0 (0.0) | 185 (24.1) | 33 (40.7) | 192 (12.4) |
| 26–35 | 6 (20.0) | 356 (46.3) | 40 (49.4) | 730 (47.3) |
| 36–40 | 24 (80.0) | 228 (29.6) | 8 (9.9) | 621 (40.2) |
| Ovarian radiation dose, cGy | ||||
| None | 7 (23.3) | 680 (88.4) | 14 (17.3) | 710 (46.0) |
| <50 | 2 (6.7) | 17 (2.2) | 32 (39.5) | 535 (34.7) |
| 50–99 | 3 (10.0) | 8 (1.0) | 8 (9.9) | 99 (6.4) |
| 100–999 | 8 (26.7) | 40 (5.2) | 20 (24.7) | 158 (10.2) |
| 1000–1999 | 7 (23.3) | 16 (2.1) | 3 (3.7) | 26 (1.7) |
| ≥2000 | 3 (10.0) | 8 (1.0) | 4 (4.9) | 15 (1.0) |
| Alkylating agents (cyclophosphamide equivalent dose), g/m2 | ||||
| 0 | 4 (13.3) | 337 (43.8) | 29 (35.8) | 908 (58.8) |
| ≥0–<4 | 3 (10.0) | 63 (8.2) | 6 (7.4) | 186 (12.1) |
| 4–<8 | 3 (10.0) | 143 (18.6) | 7 (8.6) | 147 (9.5) |
| 8–<10 | 1 (3.3) | 96 (12.5) | 7 (8.6) | 63 (4.1) |
| 10–<12 | 4 (13.3) | 41 (5.3) | 10 (12.3) | 53 (3.4) |
| 12–<20 | 10 (33.3) | 58 (7.5) | 15 (18.5) | 148 (9.6) |
| ≥20 | 5 (16.7) | 31 (4.0) | 7 (8.6) | 38 (2.5) |
CCSS = Childhood Cancer Survivor Study; PM = premature menopause; SJLIFE = St. Jude Lifetime Cohort Study.
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