March 30, 2017
2 min read

Premature ovarian insufficiency tied to pelvic radiotherapy, alkylating agent exposure

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Women who had childhood cancer may have an increased risk for premature ovarian insufficiency after treatment with pelvic radiotherapy and alkylating agents, study data show.

Wassim Chemaitilly, MD, associate member and director of the division of endocrinology, at St. Jude Children’s Research Hospital in Memphis, Tennessee, and colleagues evaluated data from the St. Jude Lifetime Cohort Study on 921 female cancer survivors (median age, 31.7 years) evaluated at a median of 24 years after a childhood cancer diagnosis to determine the prevalence of premature ovarian insufficiency, its risk factors and associated long-term adverse health outcomes.

Wassim Chemaitilly
Wassim Chemaitilly

Persistent amenorrhea plus follicle-stimulating hormone level of more than 30 IU/L before age 40 years was used to define premature ovarian insufficiency.

Most participants were survivors of hematologic malignancies (61.1%), and treatment exposures included pelvic radiotherapy (13.3%) and alkylating agents (58.8%). Premature ovarian insufficiency was diagnosed in 10.9% of participants.

Ovarian radiotherapy at any dose was independently associated with premature ovarian insufficiency (< 1,000 cGy, HR = 13.85; 95% CI, 6.5-29.51; 1,000 cGy, HR = 132.34; 95% CI, 62.88-278.53) and cyclophosphamide equivalent dose of 8,000 mg/m2 or more (HR = 2.77; 95% CI, 1.18-6.51), 12,000 mg/m2 to 19,999 mg/m2 (HR = 3.9; 95% CI, 1.8-8.43) or 20,000 mg/m2 or more (HR = 4.13; 95% CI, 1.63-10.5). A diagnosis of premature ovarian insufficiency was less likely in participants with BMI 30 kg/m2 or higher at the time of evaluation (HR = 0.43; 95% CI, 0.22-0.86).

Ovarian radiotherapy exposure alone (HR = 71.7; 95% CI, 16.5-311.58) and the combination of alkylating agents and ovarian exposure to radiotherapy (HR = 95.56; 95% CI, 23.3-391.93) were significantly associated with premature ovarian insufficiency.

Participants with premature ovarian insufficiency had increased odds for low bone mineral density (OR = 5.07; 95% CI, 1.97-13.05) and frailty (OR = 3.51; 95% CI, 1.78-6.93) compared with participants without premature ovarian insufficiency.

“This study, reported on premature ovarian insufficiency in the largest cohort of clinically assessed childhood cancer survivors to date, describes the prevalence and risk factors associated with premature ovarian insufficiency as well as the potential repercussions of premature ovarian insufficiency on long-term health,” Chemaitilly told Endocrine Today. “Premature ovarian insufficiency was found to affect nearly 11% of women who survive childhood cancer and to be associated with any ovarian exposure to radiotherapy as well as to higher doses of alkylating agent chemotherapy. Premature ovarian insufficiency seemed to independently increase the risks of frail health and low bone mineral density in affected survivors and only a minority in this cohort (31%) were on sex-hormone replacement therapy. The benefits and risk of hormone replacement therapy in this population deserve further investigation; additional research is also needed in order to improve the ability to predict the risk of premature ovarian insufficiency in female childhood cancer survivors and identify among them those individuals who are the most likely to benefit from fertility preservation procedures.” – by Amber Cox

For more information:

Wassim Chemaitilly, MD, can be reached at St. Jude Children’s Research Hospital, Division of Endocrinology, 262 Danny Thomas Place – MS737, Memphis, TN 38105.

Disclosure: The researchers report no relevant financial disclosures.