Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer

A report from the Childhood Cancer Survivor Study

Jennifer M. Levine, John A. Whitton, Jill P. Ginsberg, Daniel M. Green, Wendy M. Leisenring, Marilyn Stovall, Leslie L. Robison, Gregory Armstrong, Charles A. Sklar

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact on reproduction remain poorly defined. METHODS: The menopausal status of 2930 survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20 years]) who were aged > 18 years at the time of the current study (median age, 35 years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as the cessation of menses ≥6 months in duration occurring 5 years after diagnosis and before age 40 that was not due to pregnancy, surgery, or medications. Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years [range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3) compared with siblings. Independent risk factors included exposure to a procarbazine dose ≥4000 mg/m 2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT ≥ 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (rate ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95% CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood cancer are at risk of NSPM associated with lower rates of live birth in their 30s. Those at risk should consider fertility preservation if they anticipate delaying childbearing. Cancer 2018;124:1044-52.

Original languageEnglish (US)
Pages (from-to)1044-1052
Number of pages9
JournalCancer
Volume124
Issue number5
DOIs
StatePublished - Mar 1 2018

Fingerprint

Premature Menopause
Survivors
Confidence Intervals
Neoplasms
Odds Ratio
Live Birth
Radiation
Siblings
Fertility Preservation
Procarbazine
Menstruation
Birth Rate
Stem Cell Transplantation
Pregnancy Rate
Reproduction
Logistic Models
Parturition

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Levine, J. M., Whitton, J. A., Ginsberg, J. P., Green, D. M., Leisenring, W. M., Stovall, M., ... Sklar, C. A. (2018). Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer, 124(5), 1044-1052. https://doi.org/10.1002/cncr.31121

Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer : A report from the Childhood Cancer Survivor Study. / Levine, Jennifer M.; Whitton, John A.; Ginsberg, Jill P.; Green, Daniel M.; Leisenring, Wendy M.; Stovall, Marilyn; Robison, Leslie L.; Armstrong, Gregory; Sklar, Charles A.

In: Cancer, Vol. 124, No. 5, 01.03.2018, p. 1044-1052.

Research output: Contribution to journalArticle

Levine, JM, Whitton, JA, Ginsberg, JP, Green, DM, Leisenring, WM, Stovall, M, Robison, LL, Armstrong, G & Sklar, CA 2018, 'Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study', Cancer, vol. 124, no. 5, pp. 1044-1052. https://doi.org/10.1002/cncr.31121
Levine, Jennifer M. ; Whitton, John A. ; Ginsberg, Jill P. ; Green, Daniel M. ; Leisenring, Wendy M. ; Stovall, Marilyn ; Robison, Leslie L. ; Armstrong, Gregory ; Sklar, Charles A. / Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer : A report from the Childhood Cancer Survivor Study. In: Cancer. 2018 ; Vol. 124, No. 5. pp. 1044-1052.
@article{3a4a26faa78c4899bbfc6a5f2da80d42,
title = "Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study",
abstract = "BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact on reproduction remain poorly defined. METHODS: The menopausal status of 2930 survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20 years]) who were aged > 18 years at the time of the current study (median age, 35 years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as the cessation of menses ≥6 months in duration occurring 5 years after diagnosis and before age 40 that was not due to pregnancy, surgery, or medications. Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years [range, 16-40 years]), with a prevalence at age 40 years of 9.1{\%} (95{\%} confidence interval [95{\%} CI], 4.9{\%}-17.2{\%}); the odds ratio (OR) was 10.5 (95{\%} CI, 4.2-26.3) compared with siblings. Independent risk factors included exposure to a procarbazine dose ≥4000 mg/m 2 (OR, 8.96 [95{\%} CI, 5.02-16.00]), any dose of ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95{\%} CI, 1.33-5.61] and OvRT ≥ 500 cGy: OR, 8.02 [95{\%} CI, 2.81-22.85]; referent RT, 0), and receipt of a stem cell transplantation (OR, 6.35; 95{\%} CI, 1.19-33.93). Compared with survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (rate ratio, 0.49; 95{\%} CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95{\%} CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood cancer are at risk of NSPM associated with lower rates of live birth in their 30s. Those at risk should consider fertility preservation if they anticipate delaying childbearing. Cancer 2018;124:1044-52.",
author = "Levine, {Jennifer M.} and Whitton, {John A.} and Ginsberg, {Jill P.} and Green, {Daniel M.} and Leisenring, {Wendy M.} and Marilyn Stovall and Robison, {Leslie L.} and Gregory Armstrong and Sklar, {Charles A.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1002/cncr.31121",
language = "English (US)",
volume = "124",
pages = "1044--1052",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer

T2 - A report from the Childhood Cancer Survivor Study

AU - Levine, Jennifer M.

AU - Whitton, John A.

AU - Ginsberg, Jill P.

AU - Green, Daniel M.

AU - Leisenring, Wendy M.

AU - Stovall, Marilyn

AU - Robison, Leslie L.

AU - Armstrong, Gregory

AU - Sklar, Charles A.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact on reproduction remain poorly defined. METHODS: The menopausal status of 2930 survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20 years]) who were aged > 18 years at the time of the current study (median age, 35 years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as the cessation of menses ≥6 months in duration occurring 5 years after diagnosis and before age 40 that was not due to pregnancy, surgery, or medications. Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years [range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3) compared with siblings. Independent risk factors included exposure to a procarbazine dose ≥4000 mg/m 2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT ≥ 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (rate ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95% CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood cancer are at risk of NSPM associated with lower rates of live birth in their 30s. Those at risk should consider fertility preservation if they anticipate delaying childbearing. Cancer 2018;124:1044-52.

AB - BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact on reproduction remain poorly defined. METHODS: The menopausal status of 2930 survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20 years]) who were aged > 18 years at the time of the current study (median age, 35 years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as the cessation of menses ≥6 months in duration occurring 5 years after diagnosis and before age 40 that was not due to pregnancy, surgery, or medications. Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years [range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3) compared with siblings. Independent risk factors included exposure to a procarbazine dose ≥4000 mg/m 2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT ≥ 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (rate ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95% CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood cancer are at risk of NSPM associated with lower rates of live birth in their 30s. Those at risk should consider fertility preservation if they anticipate delaying childbearing. Cancer 2018;124:1044-52.

UR - http://www.scopus.com/inward/record.url?scp=85042348454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042348454&partnerID=8YFLogxK

U2 - 10.1002/cncr.31121

DO - 10.1002/cncr.31121

M3 - Article

VL - 124

SP - 1044

EP - 1052

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 5

ER -