ESPE Abstracts (2019) 92 P1-410

Sertoli Cell Function after Chemotherapy in Boys with Hematologic Malignancies

Romina P. Grinspon1, Maria Arozarena1, Silvina Prada2, Graciela Bargman3, María Sanzone1, Marjorie Morales Bazurto1, Ana Kanneman4, Patricia Bedecarrás1, Marcela Gutiérrez2, Silvia Gottlieb1, Ariel J. Berenstein5, María Gabriela Ropelato1, Ignacio Bergadá1, Luis Aversa2, Rodolfo A. Rey1


1Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez., Buenos Aires, Argentina. 2Unidad de Hematología, Hospital de Niños Ricardo Gutiérrez., Buenos Aires, Argentina. 3División de Endocrinología, Hospital Pedro de Elizalde., Buenos Aires, Argentina. 44 División de Hemato Oncología, Hospital Pedro de Elizalde, Buenos Aires, Argentina. 5Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, Laboratorio de Biología Molecular, División Patología, Hospital de Niños Ricardo Gutiérrez., Buenos Aires, Argentina


Introduction: Gonadotoxicity associated with chemotherapy of hematologic malignancies has been described mainly in adults, focused on the sensitivity of germ cells. Little attention has been placed on Sertoli cells during childhood and puberty, even though Sertoli cell development is essential for adult spermatogenesis.

Objective: To assess function of the pituitary-testicular axis, with emphasis on Sertoli cell function, in boys and adolescents who received chemotherapy for hematologic malignancies.

Methods: We performed a retrospective analysis including 97 patients (58 treated before age 10 yr and 39 treated between 10 and 18 yr), 83 with acute lymphocytic leukaemia (ALL), 5 with acute myeloid leukemia (AML) and 9 with non-Hodgkin lymphoma (NHL). Serum LH, FSH, testosterone and AMH (as a direct marker of Sertoli cell function) were used as endpoints.

Results: Cross-sectional analysis included 61 patients with one AMH measurement between 1 to 8 years after the end of treatment. 37 were treated before age 10 yrs and evaluated at 9.4 yrs (5.7-14.9). No patient had AMH <2 SDS. One (2.7%) patient had LH > 2 SDS and 3 (8.1%) had FSH >2 SDS. Twenty-four patients were treated after age 10 and evaluated at 15.3 yrs (11.6-20.1). No patient had AMH <2 SDS. Five (20.8%) patients had LH >2 SDS and 8 (33.3%) had FSH >2 SDS. No patient had testosterone <2 SDS.

All 97 patients were included in the longitudinal analysis. During follow up 3/58 (5.2%) patients treated <10 yrs had at least one AMH <1 SDS, but none had AMH <2 SDS. Nine (15.5%) had FSH >2 SDS and 4 (6.9%) had LH >2 SDS. Of patients treated at an age>10 yrs, 10/39 (25.6%) had at least one AMH <1 SDS, but none had AMH <2 SDS. Fourteen (35.9%) had FSH >2 SDS and 11 (28.2%) had LH >2 SDS. The proportion of patients with LH and FSH >2 SDS was higher in the group of patients treated at >10 yrs (p:0.03 and 0.008 respectively).

Conclusion: Sertoli cell function is not affected by chemotherapy in boys with hematologic malignancies. During follow up high gonadotrophins are more prevalent in boys treated at pubertal age. In some patients, high FSH may be due to germ cell damage and high LH with normal testosterone may reflect a compensated Leydig dysfunction.