Gonadal Function in Patients Treated for Leukemia in Childhood

Abstract

Ovarian and testicular function were assessed in 67 long-term survivors (37 females, 30 males) treated for leukemia between 1973 and 1992. At diagnosis they were 1-16 (median 5) years old and had evaluation of gonadal function 4-25 (median 13) years later at the age of 13-31 (median 19). All had been treated with various combinations of chemotherapy (ChT) (including cyclophosphamide (CYC) and cytarabine in 32 patients), 62 patients had received prophylactic cranial irradiation with 12-49 (median 18) Gy, 2 patients had had craniospinal irradiation with 24 and 10 Gy respectively. Nine patients were treated for relapse; 2 boys had testicular irradiation (RT) with 12 Gy in 3 fractions and 1 girl whole-abdomen RT with 20 Gy as a part of this treatment. Three patients were treated for second malignancies. Gonadal function was assessed by clinical examination and measurement of serum concentrations of estradiol and testosterone. Serum levels of LH and FSH were determined in basal state and after stimulation. Primary hypogonadism was found in 6 (9%) patients. Five (16,5%) males had primary hypogonadism with evidence of damage to the germinal epithelium, 2 of them, treated with testicular RT, had evidence of damage to the Leydig cells and 2 had evidence of dysfunction of Leydig cells as well. Primary hypogonadism was found in 1 female, who was heavily treated for relapse (ChT containing CYC, abdominal RT and craniospinal RT). She was amenorrhoic and needed substitutional estrogen therapy but delivered a child anyway. Five females had early puberty after cranial RT. One female had secondary hypogonadism and hyposomatotropism after cranial RT with 30 Gy, one male had hyposomatotropism after receiving cranial RT twice (49 Gy total). Primary treatment for leukemia does not produce primary hypogonadism in girls, but it does in boys. Alkylating agents and gonadal RT are the most damaging factors. Not only RT to gonads but also alkylating agents alone cause dysfunction of Leydig cells.

Changes in body composition after childhood cancer treatment: Impact on future health status—A review

“…One study showed a relationship between ovarian dysfunction and increased serum lipid levels [58] and another one showed that survivors of testicular cancer with a hypogonadism had a higher waist-to-hip ratio (p = 0.045) and higher diastolic blood pressure (p = 0.014) than survivors without hypogonadism [59]. Because development of gonadal dysfunction after childhood cancer treatment has been widely described [60][61][62][63][64], we need to elucidate the possible relationship between gonadal dysfunction and abnormal changes in body composition, also in childhood cancer survivors.…”

Late somatic sequelae after treatment of childhood cancer in Slovenia

“…Slovene Ministry of Science has been financing the program for “Late effects of childhood cancer treatment” since 1993. Survivors included in the program have been evaluated and analyzed as to their late somatic sequelae including neurological deficits [17], endocrine function deficits [18], renal function damage [19], secondary tumors [20,21], cardiac damage [22], and psychosocial consequences [23]. …”

Gonadal function in patients treated for Hodgkin's disease in childhood

“…Endocrine glands, gonads in particular, are very susceptible to damaging effects of anticancer therapy 5. The damaging effect of both ChT and radiotherapy (RT) on gonads is well known 6. In a study of 2283 long-term survivors of childhood cancer Byrne and colleagues found that RT below the diaphragm depressed fertility in both sexes for about 25%, ChT with alkylating agents with or without RT below the diaphragm depressed fertility by 60% in men, but in women alkylating agents therapy administered alone had no apparent effect on fertility 7…”