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Nonsurgical premature menopause affects fertility in female childhood cancer survivors

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February 8, 2018

Women who survived childhood cancer faced an increased risk for nonsurgical premature menopause, resulting in lower rates of live birth for female survivors in their 30s, according to findings from the ongoing Childhood Cancer Survivor Study.

“Previous Childhood Cancer Survivor Study investigations have demonstrated acute ovarian failure in 6.3% of female survivors and a cumulative incidence of nonsurgical premature menopause in 8% of female survivors,” Jennifer M. Levine, MD, MSW, of Weill Cornell Medical College, and colleagues wrote. “Treatment-related risk factors including higher doses of alkylating agents and increasing doses of radiotherapy to the ovaries have been implicated in premature menopause.”

The researchers compared the menopausal status of 2,930 women who survived childhood cancer with that of 1,399 siblings. All patients were aged 18 years or older (median age, 35 years) at the time of the study, and were diagnosed between 1970 and 1986.

The researchers used multivariable logistic regression to identify risk factors for nonsurgical premature menopause, defined as cessation of menses for six months or longer and occurring 5 years after diagnosis before patient age of 40 years.

Overall, 110 survivors experienced nonsurgical premature menopause, resulting in a prevalence of 9.1% at age 40 years (95% CI, 4.9-17.2). Patients were aged a median of 32 years at the time of menopause.

Compared with siblings, the patients’ OR for developing nonsurgical premature menopause was 10.5 (95% CI, 4.2-26.3).

Therapies associated with menopause included a procarbazine dose of 4000 mg/m2 or greater (OR = 8.96; 95% CI, 5.02-16), any dose of radiation to the ovaries (less than 500 cGy, OR = 2.73; 95% CI, 1.33-5.61; 500 cGy or greater, OR = 8.02; 95% CI, 2.81-22.85) and stem cell transplantation (OR = 6.35; 95% CI, 1.19-33.93).

Women aged 31 to 40 years who had experienced nonsurgical premature menopause appeared less likely to have a pregnancy (RR = 0.49; 95% CI, 0.27-0.8) or a live birth (RR = 0.42; 95% CI, 0.19-0.79) compared with women who had not.

“Clinicians should incorporate this information as they counsel female patients with childhood cancer and their families at the time of cancer diagnosis and in the years after the completion of cancer-directed treatment,” the researchers wrote. – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures.