The influence of different intensity of treatment on hormonal markers of gonadal function in acute lymphoblastic leukemia survivors

Abstract

Anti‐cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti‐Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed‐up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.

Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

“…For males, elevated levels of FSH and LH and decreased inhibin B levels, as indicators of lower spermatogenesis, characterized the survivors, with more predominant changes in the HR-ALL group. Only lower AMH levels in the HR-ALL group were reported in females, reflecting lower ovarian reserve (109).…”

“…Male gonads are usually more prone to cancer therapy effects than females. Oligospermia and harmful changes in the sperms' quality are commonly reported, matched to fewer reports on induced ovarian insufficiency, and oocyte number depletion in females (109).…”

“…Moreover, harmful gonadal effects are reported with cytarabine and doxorubicin, but to less extent. However, ALL patients usually suffer less gonadal toxicity than other types of tumors (109). To determine the effect of different ALL treatment modalities on gonadal function, Krawczuck-Rybak and colleagues analyzed multiple parameters in a group of pediatric ALL survivors of both sexes.…”