Summary:Conditioning for bone marrow transplantation (BMT) may alter viability of germ cells and production of gonadal hormones. We analyzed the risk factors for gonadal failure after 12 Gy total body irradiation (TBI) given as six fractions (n = 31, group 1), 10 Gy (one dose) TBI (n = 20, group 2), 6 Gy (one dose) total lymphoid irradiation (TLI, n = 17, group 3) and chemotherapy alone (n = 7, group 4), given at 7.7 ± 0.4 (0.6-13.6) years. Among the 34 girls, seven (20.6%) had normal ovarian function with regular spontaneous menstruation and normal plasma follicle-stimulating (FSH) and luteinizing (LH) hormones, five (14.7%) had partial ovarian failure with regular menstruation but increased FSH and/or LH, and 22 (64.7%) had complete ovarian failure. The 24 girls with chronological and bone ages Ͼ13 years included similar percentages, with increased FSH or LH in all four groups. There was a positive correlation between age at BMT and FSH (r = 0.54, P Ͻ 0.01), but not with LH, and between FSH and LH (r = 0.8, P = 0.0003). Plasma FSH concentrations had returned to normal spontaneously in six cases, and those of LH in two cases. Among the 41 boys, 16 (39%) had normal testicular function and 25 (61%) had tubular failure and increased FSH. Of these, 10 also had Leydig cell failure (three complete and seven partial). The 18 boys with chronological and bone ages Ͼ15 years included similar percentages with increased FSH or LH in groups 1 to 3, and testicular volume was significantly lower in group 2 than in group 3 (P = 0.008). There was no correlation between age at BMT and FSH, LH or testosterone, but there was a negative correlation between FSH and inhibin B (rho = −0.87, P Ͻ 0.003). We conclude that girls are more likely to suffer ovarian failure the older they are at BMT, and that early ovarian recovery is possible. Keywords: bone marrow transplantation; fertility; inhibin; irradiation; ovary; testis Conditioning for bone marrow transplantation (BMT) may alter the production of gonadal hormones (estradiol and progesterone in girls, testosterone in boys) and the viability of germ cells. 1-3 Gonadal failure results in incomplete sexual development and growth at puberty, and sterility in adulthood. Gonadal hormones are required for the development of secondary sexual characteristics, and for the growth acceleration which normally occurs at puberty.The risk factors for gonadal failure in patients undergoing BMT are difficult to analyze because of the variety of conditioning regimens used, and the possibility of gonadal recovery. 4 This study analyzes the expression and frequency of gonadal failure in both sexes according to the conditioning protocol, and the significance of the age during childhood at which BMT is carried out. We also measured plasma inhibin B concentrations as an additional marker of tubular function in these young patients where semen analysis is not possible.
PatientsThe gonadal function of 75 patients (34 girls and 41 boys) who received a BMT during childhood, and who were aged more than 10 years ...