ESPE Abstracts (2019) 92 LB-7

Long-Term Evaluation of Ovarian Function and Follicular Reserve in Patients with Malignant Diseases Treated with Chemotherapy in Prepubertal or Pubertal Age

Andrea Josefina Arcari, Analía Verónica Freire, Romina Paula Grinspon, Patricia Bedecarrás, María Eugenia Escobar, María Gabriela Ropelato, Ignacio Bergadá, Rodolfo Rey, Mirta Graciela Gryngarten

Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

The survival rate of young patients with cancer has greatly improved in the last decades, in part due to the introduction of new therapeutic agents and protocols.

Chemotherapy may be associated with risk of ovarian dysfunction, permanent or transient amenorrhea, symptoms of ovarian insufficiency and infertility.

It has been suggested that prepubertal ovary is less susceptible to deleterious effect of chemotherapy.

Pre-clinical studies suggested that hormonal suppression of the hypothalamic-pituitary-ovarian axis could minimize the impact of cytotoxic agents on the ovary. The effectiveness of gonadotropin-releasing hormone agonists (GnRHa) in preventing the impairment of ovarian function due to exposure to cytotoxic agents in pubertal girl is still controversial.

AMH is expressed by the ovarian granulosa cells of primary, preantral and small follicles. It is independent of gonadotropins, representing an ideal surrogate for ovarian reserve.

Objective: To evaluate long-term ovarian function in female adolescents with history of malignant diseases treated with chemotherapy at prepubertal or pubertal stage.

Material and Methods: Female adolescent patients with history of malignancy who required chemotherapy were analyzed at least two years after menarche. A transversal study was conducted to evaluate gonadal function measuring gonadotropins (ECLIA) and AMH (ELISA) levels after at least two-year treatment withdrawal.

Patients were divided into two groups, group A: patients treated at pubertal stage who received chemotherapy concomitant with GnRHa; group B: patients treated at prepubertal stage only with chemotherapy.

Results: Thirty-nine patients were enrolled.

Group A (n=21) Group B (n=18)P value
Chronological age at diagnosis (years)14.3 (9.2-18.1)6 (0.5-10.5)<0.001
Age of evaluation (years)17.5 (17-30)17 (13.6-22.9)ns
Menarcheal age (years)12.4 (10-15)12.0 (10.2-14.7)ns
Regular menses (n)20/2118/18ns
Hot flushes (n)1/210/18ns
LH mUI/ml5.7 (1.23-65.7)6.4 (6.8-14.8)ns
FSH mUI/ml6.5 (0.11-200)5.7 (3.6-9.4)ns
AMH (pmol/L)16.2 (1.2-57.6)26.0 (9.1-76)0.02

Median and range.

Serum LH and FSH were within normal levels in both group except in one patient from group A, who had hypergonadotropic hypogonadism. AMH levels were significantly lower in group A. Two patients from group A achieved fertility.

Conclusion: In this long term follow up study prepubertal girls who received chemotherapy and pubertal girls who received chemotherapy concomitantly with GnRHa showed low rates of ovarian dysfunction. However, the decline of AMH levels in patients who received chemotherapy in pubertal stage could indicate a decreased follicular reserve, although the effect of age cannot be ruled out.