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Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Author(s) -
Levine Jennifer M,
Whitton John A.,
Ginsberg Jill P.,
Green Daniel M.,
Leisenring Wendy M.,
Stovall Marilyn,
Robison Leslie L.,
Armstrong Gregory T.,
Sklar Charles A.
Publication year - 2018
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31121
Subject(s) - medicine , odds ratio , pregnancy , confidence interval , premature menopause , menarche , obstetrics , cancer , pediatrics , gynecology , menopause , biology , genetics
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. © 2018 American Cancer Society .