ESPE Yearbook of Paediatric Endocrinology

Brief summary: This single-centre retrospective study analysed gonadal function in 62 patients (41 males) with medulloblastoma, treated between 1987 and 2021. The aim of the study was to characterize gonadal function and identify risk factors for gonadal failure.

Survival rates of patients with medulloblastoma have significantly improved with the combination of many therapeutic approaches, such as adjuvant chemotherapy, craniospinal irradiation (CSI), surgery, and proton-therapy, together with risk-stratified and molecular-matched targeted treatments. However, a concomitant increase in long-term sequelae of treatment has been observed. Long-term adverse effects on the hypothalamic–pituitary–gonadal axis (HPGA) and gonads may manifest as precocious puberty (PP), hypogonadotrophic hypogonadism (HypoH), hypergonadotrophic hypogonadism (HyperH), or transient impairment of gonadal function.

This study, with a mean follow-up of 9.2 and 12 years for males and females, respectively, reported a significant higher frequency of clinical or biochemical gonadal dysfunction in females than in males (76% vs 34%). A higher mean cyclophosphamide-equivalent dose (CED) was positively correlated with HPGA impairment in females but not in males. Males experienced PP and HypoH, while females showed indirect signs of HypoH, or a combination of HypoH and HyperH, as suggested by inappropriately normal FSH associated with other signs of ovarian insufficiency (low AMH levels and/or menstrual cycle abnormalities). Four successful pregnancies, all achieved by in vitrofertilization, were reported in females, while none was reported in males.

It is notable that the evaluation of the extent of fertility impairment cannot be reduced to a pregnancy and/or offspring count, because comorbidities, such as cognitive damage or other endocrinopathies, can affect the desire and opportunity to conceive. Comparison between the current results and previous data is not easy, due to the heterogenous sample characteristics (sex, age at diagnosis and at follow-up, pubertal stage at evaluation), inclusion and exclusion criteria, follow-up duration, treatment protocols, time and modality of endocrine evaluation, and definition of HPGA dysfunction.

Although the sample size of this study is not small, the work has some limitations that might partially explain the discordances with previous studies. Most patients were treated in the 1990s and 2000s, the recruitment period (1987–2021) is very long and reflects the evolution in treatment regimens. Clinical parameters were extracted from medical records up to the last visit and patients >18 years were invited to fill in questionnaires regarding hormone replacement therapy, fertility wishes and attempts to conceive, but only a small number of questionnaires was collected, probably reflecting a cognitive impairment secondary to the disease and/or its treatment. Finally, males were older than females at the last visit (range 9–40 vs 7–28 years), so the evaluation of gonadal function, fertility, and family planning, could have been limited especially in females.