Female Gonadal Toxicity

Most females treated with contemporary risk-adapted therapy will have menarche (if prepubertal at treatment) or regain normal menses (if pubertal at treatment) unless pelvic radiation therapy is given without oophoropexy. Current regimens used in pediatric oncology are tailored to minimize the risk of ovarian failure. Data presented below related to pediatric treatment before 1987 [15,16] or adult trials in Europe (European Organisation for Research and Treatment of Cancer H1–H9 trials) [17] are not likely reflective of the expected reproductive outcomes in the current era.

Ovarian transposition to a lateral or medial region from the planned radiation volume may preserve ovarian function in young and adolescent girls who require pelvic radiation therapy for lymphoma.[18] Ovarian transposition did not appear to modify risk of premature ovarian insufficiency in a cohort of 49 long-term survivors of Hodgkin lymphoma enrolled in the St. Jude Lifetime Cohort Study who were treated with gonadotoxic therapy and underwent ovarian transposition before pelvic radiation therapy.[19]

The risk of acute ovarian failure and premature menopause is substantial if treatment includes combined-modality therapy with alkylating agent chemotherapy and abdominal or pelvic radiation or dose-intensive alkylating agents for myeloablative conditioning before HSCT.[15,16] The risk of ovarian failure after treatment with contemporary regimens using lower cumulative doses of cyclophosphamide without procarbazine is anticipated to be lower.

In the CCSS, investigators observed that Hodgkin lymphoma survivors were among the highest risk groups for acute ovarian failure and early menopause. In this cohort, the cumulative incidence of nonsurgical premature menopause among survivors treated with alkylating agents and abdominal or pelvic radiation approached 30%.[15,16] These patients were treated before 1986, usually with substantially higher doses of alkylating agents than are used in current regimens in the Children's Oncology Group (COG), EuroNet, or other consortiums.

A German study demonstrated that parenthood for female survivors of Hodgkin lymphoma was similar to that of the general population, although parenthood was lower for survivors who received pelvic radiation therapy.[20]