Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study

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/m2 (OR, 8.96 [95% CI, 5.02‐16.00]), any dose of ovarian radiation (OvRT) (OvRT