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Reduced Ovarian Function in Long-Term Survivors of Radiation- and Chemotherapy-Treated Childhood Cancer

The Fertility Clinic (E.C.L., A.N.A.), the Department of Growth and Reproduction (J.M.), Pediatric Clinic II (K.S., C.R.), Late Effects Clinic (C.R.), and Department of Pediatrics (J.M.), The Juliane Marie Centre, Rigshospitalet, Copenhagen University Hospital, DK–2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Dr. Elisabeth C. Larsen, The Fertility Clinic, Section 4071, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: elisabeth.larsen{at}dadlnet.dk.

Seventy percent of children with cancer survive. Radiation and chemotherapy may, however, impair ovarian function. The aim of this population-based study was to achieve a comprehensive knowledge of the degree of ovarian damage.

Ovarian function was evaluated in 100 childhood cancer survivors and 21 controls of similar age. Menstrual cycle pattern was recorded, and strictly timed ovarian sonography and hormonal assessment were performed.

The median age of the survivors was 5.4 yr (range, 0.1–15.3) at the time of diagnosis and 25.7 yr (18.5–44.4) at study entry. Seventeen survivors with premature ovarian failure had follicle-depleted or nondetectable ovaries, elevated FSH and LH, and immeasurable inhibin B. Thirteen survivors used oral contraception. Survivors with spontaneous menstrual cycles (n = 70) had smaller ovarian volume per ovary than controls (median, 4.8 vs. 6.8 cm³; P < 0.001) and a lower number of antral follicles per ovary (median, 7.5 vs. 11; P < 0.001). Further, they had lower inhibin B levels than controls (median, 94 vs. 111 pg/ml; P = 0.03) and higher estradiol levels (median, 0.12 vs. 0.08 pM; P = 0.04). Multiple linear regression analysis was performed to predict the total antral follicle number per ovary, and it showed a reduced number with ovarian irradiation (ß = -0.40, P < 0.001), alkylating chemotherapy (ß = -0.25, P = 0.01), older age at diagnosis (ß = -0.25, P = 0.01), and longer time period off treatment (ß = -0.19, P = 0.044).

One in every six female survivors may develop premature ovarian failure. In survivors with spontaneous menstrual cycles, the results indicate a diminished ovarian reserve. Consequently, cessation of fertility may occur much earlier than anticipated. Adult survivors with spontaneous cycles should be informed hereof to plan childbearing.

This work was supported by The Danish Children Cancer Foundation.

Abbreviations: CV, Coefficient of variation; HRT, hormonal replacement therapy; OC, oral contraceptives; PRL, prolactin; r_s, correlation coefficient.

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