Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang, Korea
Copyright © 2023 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
Ethics approval and consent to participation: This study was reviewed and approved by the Institutional Review Board (IRB) of the National Cancer Center, Goyang, Korea (approval number NCC 2022-0226). The requirement of informed consent was waived by the IRB due to the retrospective nature of this study and anonymity of clinical data.
Author Contributions
Conceived and designed the analysis: Jin HY, Park HJ.
Collected the data: Jin HY.
Contributed data or analysis tools: Jin HY, Lee JA, Park M.
Performed the analysis: Jin HY.
Wrote the paper: Jin HY.
Conflicts of Interest
Conflicts of interest relevant to this article was not reported.
Baseline characteristics
No. (%) (n=69) | |
---|---|
Diagnosis | |
Leukemia | 18 (26.1) |
Lymphoma | 4 (5.8) |
CNS tumor | 6 (8.7) |
Embryonal tumor | 1 (1.5) |
Bone and soft tissue sarcoma | 19 (27.5) |
Ovarian tumor | 21 (30.4) |
Age at diagnosis (yr) | |
Mean±SD | 12.4±4.4 |
Median (min–max) | 13.1 (0.4–19.8) |
Follow-up period (yr) | |
Median (min–max) | 10.8 (1–16.5) |
BMI (kg/m2) | |
Mean±SD | 22.02±3.49 |
Median (min–max) | 21.6 (14.9–31.3) |
CED (mg/m2) | |
≤ 8,000 | 31 (44.9) |
> 8,000 | 38 (55.1) |
GnRH agonist | |
No | 38 (55.1) |
Yes | 31 (44.9) |
Surgery | |
No | 22 (31.9) |
Yes | 47 (68.1) |
Radiotherapy | |
No | 48 (69.6) |
Yes | 21 (30.4) |
Pelvis or total body irradiation | 9 (13.0) |
SCT | |
No | 53 (76.8) |
Yes | 16 (23.2) |
Allo(total body irradiation)/Auto | 9 (5)/7 |
LH (IU/L) | |
Median (min–max) | 10.1 (1.4–88) |
FSH (IU/L) | |
Median (min–max) | 8.5 (1.4–138.5) |
AMH (ng/mL) | |
Median (min–max) | 1.65 (0.02–12.5) |
AMH, anti-müllerian hormone; BMI, body mass index; CED, cyclophosphamide equivalent dose; CNS, central nervous system; FSH, follicular stimulation hormone; GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; SCT, stem cell transplantation; SD, standard deviation.
Clinical characteristics and the AMH concentrations according to gonadal function
FSH < 12 IU/L (n=41) | 12 ≤ FSH < 40 IU/L (n=14) | FSH ≥ 40 IU/L (n=14) | p-value | |
---|---|---|---|---|
Age at diagnosis (yr) | 12.0±4.3 | 13.9±4.8 | 12.0±4.2 | 0.336 |
Age at diagnosis (yr) | 12.0±4.3 | 13.9±4.8 | 12.0±4.2 | 0.336 |
Follow-up period (yr) | 9.9±4.2 | 10.5±4.8 | 9.0±5.3 | 0.689 |
BMI (kg/m2) | 21.8±3.6 | 22.9±3.4 | 21.9±3.2 | 0.576 |
CED (≥ 8,000 mg/m2) | 23 (56.1) | 3 (21.4) | 5 (35.7) | 0.054 |
GnRH agonist | 18 (43.9) | 10 (71.4) | 3 (21.4) | 0.037 |
Surgery | 30 (73.2) | 9 (64.3) | 8 (57.1) | 0.454 |
Oophorectomy | 16 (39.0) | 3 (21.4) | 2 (14.3) | 0.180 |
Radiotherapy (pelvis or TBI) | 1 (0.02) | 2 (14.3) | 6 (42.9) | 0.001 |
Stem cell transplantation | 2 (0.05) | 3 (21.4) | 11 (78.6) | < 0.001 |
Low AMH (< 1 ng/mL) | 3 (7.3) | 11 (78.6) | 14 (100) | < 0.001 |
LH (IU/L) | 7.9±5.4 | 10.5±5.4 | 52.7±20.3 | < 0.001 |
FSH (IU/L) | 6.8±2.2 | 20.7±7.9 | 88.7±26.3 | < 0.001 |
AMH (ng/mL) | 4.1±3.0 | 0.48±0.58 | 0.03±0.03 | < 0.001 |
Age of AMH measurement (yr) | 20.7±4.0 | 22.6±3.9 | 20.4±5.3 | 0.301 |
Amenorrhea or sex hormone replacement | 0 | 3 | 14 | < 0.001 |
Values are presented as mean±SD or number (%). AMH, anti-müllerian hormone; BMI, body mass index; CED, cyclophosphamide equivalent dose; FSH, follicular stimulating hormone; GnRH, gonadotropin; LH, luteinizing hormone; SD, standard deviation; TBI, total body irradiation.
Risk factors associated with low AMH levels
Low AMH level (< 1 ng/mL) | Univariable | Multivariable | ||||
---|---|---|---|---|---|---|
No (n=41) | Yes (n=28) | OR (95% CI) | p-value | OR (95% CI) | p-value | |
Age at diagnosis (yr) | 12.19±4.39 | 12.67±4.48 | 1.026 (0.918–1.147) | 0.650 | - | - |
BMI (kg/m2) | 21.7±3.72 | 22.5±3.12 | 1.070 (0.930–1.230) | 0.345 | - | - |
CED (mg/m2) | ||||||
≤ 8,000 | 25 (61.0) | 6 (21.4) | 1 | 1 | ||
> 8,000 | 16 (39.0) | 22 (78.6) | 5.729 (1.908–17.200) | 0.002 | 10.160 (2.054–50.268) | 0.005 |
GnRH agonist | ||||||
No | 21 (51.2) | 17 (60.7) | 1 | - | ||
Yes | 20 (48.8) | 11 (39.3) | 0.679 (0.256–1.801) | 0.437 | - | - |
Radiotherapy | ||||||
No | 40 (97.6) | 20 (71.4) | 1 | 1 | ||
Yes | 1 (2.4) | 8 (28.6) | 16.000 (1.869–136.951) | 0.011 | 3.042 (0.272–34.040) | 0.367 |
SCT | ||||||
No | 39 (95.1) | 14 (50.0) | 1 | 1 | ||
Yes | 2 (4.9) | 14 (50.0) | 19.500 (3.927–96.826) | < 0.001 | 26.604 (3.392–208.642) | 0.002 |
Values are presented as mean±SD or number (%). AMH, anti-müllerian hormone; BMI, body mass index; CED, cyclophosphamide equivalent dose; CI, confidence interval; GnRH, gonadotropin; OR, odds ratio; SCT, stem cell transplantation; SD, standard deviation.
Associated health problem in terms of bone mineral density and lipid profile according to gonadal function
FSH < 12 IU/L (n=41) | 12 ≤ FSH < 40 IU/L (n=14) | FSH ≥ 40 IU/L (n=14) | p-value | |
---|---|---|---|---|
BMI (kg/m2) | 21.8±3.6 | 22.9±3.4 | 21.9±3.2 | 0.576 |
Glucose (mg/dL) | 89.7±8.05 | 92.3±14.78 | 88.8±6.76 | 0.601 |
Total cholesterol (mg/dL) | 180.1±33.64 | 206.7±33.49 | 187.0±35.00 | 0.047 |
HDL cholesterol (mg/dL) | 50.2±26.79 | 55.1±19.79 | 55.2±25.71 | 0.735 |
LDL cholesterol (mg/dL) | 87.5±47.01 | 123.1±23.53 | 99.23±41.54 | 0.030 |
Triglyceride (mg/dL) | 73.0±53.95 | 115.4±100.01 | 122.1±89.20 | 0.045 |
L-spine Z-score | −0.13±1.13 | −0.23±0.75 | −0.89±0.97 | 0.081 |
Femur neck Z-score | −0.13±1.22 | −0.33±1.04 | −1.28±1.05 | 0.011 |
Values are presented as mean±SD. BMI, body mass index; FSH, follicular stimulating hormone; HDL, high-density lipoprotein; LDL, low-density lipoprotein; L-spine, lumbar spine; SD, standard deviation.
AMH, anti-müllerian hormone; BMI, body mass index; CED, cyclophosphamide equivalent dose; CNS, central nervous system; FSH, follicular stimulation hormone; GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; SCT, stem cell transplantation; SD, standard deviation.
Values are presented as mean±SD or number (%). AMH, anti-müllerian hormone; BMI, body mass index; CED, cyclophosphamide equivalent dose; FSH, follicular stimulating hormone; GnRH, gonadotropin; LH, luteinizing hormone; SD, standard deviation; TBI, total body irradiation.
Values are presented as mean±SD or number (%). AMH, anti-müllerian hormone; BMI, body mass index; CED, cyclophosphamide equivalent dose; CI, confidence interval; GnRH, gonadotropin; OR, odds ratio; SCT, stem cell transplantation; SD, standard deviation.
Values are presented as mean±SD. BMI, body mass index; FSH, follicular stimulating hormone; HDL, high-density lipoprotein; LDL, low-density lipoprotein; L-spine, lumbar spine; SD, standard deviation.