Impact of chemotherapy on gonadal function in pubertal children with Hodgkin lymphoma.

Abstract

e22001 Background: Hodgkin lymphoma (HL) in pubertal children carries a high risk of reproductive dysfunction, both due to the disease itself and the gonadotoxic effects of chemotherapy (CT), which is especially critical during puberty. The objective was to determine the concentration of sex hormones (estrone – E1, estradiol – E2, estriol – E3, progesterone – P4, total and free testosterone – T, FT) and their receptors (ERα, ERβ, AR) in the blood of adolescents with HL before and after CT. Methods: The study included 20 boys and 20 girls aged 13–17 years with a verified diagnosis of stage II-IV HL. Hormone and receptor levels were measured using an enzyme immunoassay before treatment and 14 days after completion of all CT courses. A comparison group consisted of 40 healthy adolescents of similar age. Statistical analysis was performed using Statistica 10; differences were considered significant at p < 0.05. Results: In girls before treatment, significant decreases were found in levels of E1 (2.4-fold), P4 (3.7-fold), T and FT (more than 2-fold), and AR (3-fold), while E3 concentration was increased 27.5-fold (p < 0.05). Levels of E2, ERα, and ERβ were normal. In boys before treatment, decreases were found in blood levels of E1 (1.9-fold), E2 (2.7-fold), P4 (1.7-fold), FT (1.4-fold), and AR (4.7-fold; p < 0.05). The T level was elevated 1.8-fold in 50% of boys and decreased 42.0-fold in the others (p < 0.05). E3, ERα, and ERβ levels were normal. In girls 14 days after CT, compared to baseline, E1 decreased 3.4-fold and remained 8.0-fold below normal; E3 decreased 3.8-fold but remained 7.3-fold above normal (p < 0.05); ERα decreased 8.3-fold; and P4 decreased 2.0-fold from baseline and was 7.5-fold below normal (p < 0.05). T and FT remained 1.9- and 2.0-fold below normal, respectively (p < 0.05); AR increased 2.2-fold but remained 1.3-fold below normal (p < 0.05). In boys 14 days after CT, E2 decreased 1.7-fold; P4 decreased 2.6-fold from baseline and was 4.5-fold below normal (p < 0.05). T remained 1.7-fold above normal in 50% of patients; in the others, it increased 10.2-fold but remained 4.1-fold below normal (p < 0.05). FT decreased 1.6-fold and was 2.2-fold below normal (p < 0.05). AR increased 3.0-fold but remained 1.6-fold below normal (p < 0.05). Conclusions: Children with HL exhibit persistent hormonal disturbances even before treatment: a progesterone deficiency and sex-specific imbalances (estriol excess with androgen deficiency in girls, and a heterogeneous androgen status with estrogen deficiency in boys), which makes pre-therapeutic gonadal tissue harvesting impractical. These imbalances persist after chemotherapy, forming the basis for a high risk of hypogonadism and infertility. This necessitates mandatory hormonal monitoring and preemptive measures to preserve reproductive health.