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. 2022 Nov 29;18(2):122–132. doi: 10.17925/EE.2022.18.2.122

Table 3: Hypothalamic–pituitary–ovarian axis function in girls with cancer.

Study reference Inclusion criteria Exclusion criteria Study design, treatment and follow-up Main results
Crofton et al. (2003)66 Prepubertal girls, haematological or solid malignancies Germ cell tumours Longitudinal, chemotherapy, lumbar radiotherapy, analysis from diagnosis to 1–6 months after end of treatment

  • Analysis not distinguishing between malignancy types (n=9)

  • Inhibin B: pretreatment normal, declined to undetectable during chemotherapy, variable recovery

  • FSH and LH: pretreatment normal, no significant changes during or after treatment
Cuny et al. (2011)71 Age <11 years, medulloblastoma or ependymoma NA Longitudinal, surgery, cranial irradiation, spinal irradiation, chemotherapy, analysis 75–166 months after end of treatment

  • Analysis only after pubertal age, 13–16 years (n=22)

  • Early puberty requiring gonadotropin hormone-releasing hormone analogue treatment associated with radiotherapy (n=10)

  • Clinical progression of puberty normal in 15 girls: normal FSH and LH in 14 and high in 1, normal AMH and inhibin B in 11, low in 4

  • Abnormal progression of puberty in 7 girls: 2 with central hypogonadism (low FSH and LH), 4 with primary hypogonadism (low AMH and inhibin B, high FSH and LH), and 1 with combined (central and ovarian) hypogonadism (low AMH and inhibin B with inadequately normal FSH and LH)
Brougham et al. (2012)67 Age <18 years, haematological or solid malignancies ALL, brain tumours, gonadal tumours and primary gonadal dysgenesis Longitudinal, chemotherapy, spinal or abdominal radiotherapy for 5–39 months, analysis 4–43 months after end of treatment

  • Analysis not distinguishing between malignancy types in prepubertal (n=17) and pubertal (n=5)

  • AMH: pretreatment normal/low, positive correlation with age, declined during first 6 treatment cycles

  • Inhibin B: pretreatment normal/undetectable, declined during first 4 treatment cycles

  • FSH: pretreatment normal, no significant changes during treatment
Mörse et al. (2013)68 Age <18 years, haematological or solid malignancies Brain tumours, death shortly after diagnosis, ovarian cancer, contraceptives, Down syndrome Longitudinal, chemotherapy, abdominal radiotherapy, HSCT, analysis at diagnosis and 0–36 months after end of treatment

  • Analysis not distinguishing premenarche (n=23) and postmenarche (n=11), or between solid (n=23) and haematological (n=11) malignancies

  • AMH: pretreatment normal/low, positive correlation with age, declined during first 3 months of treatment, normalized in low-dose chemotherapy, undetectable in radiotherapy and HSCT

  • Inhibin B: pretreatment normal/undetectable, declined during first 3 months of treatment, normalized in low-dose chemotherapy, undetectable in radiotherapy and HSCT

  • FSH, LH and E2: pre-treatment normal, increase in FSH and LH, and variable changes in E2 at 3 months. No further changes thereafter
van Dorp et al. (2014)70 Age <18 years, haematological or solid malignancies Brain tumours, germ cell tumours Cross-sectional study at diagnosis (no follow-up)

  • 114 haematological malignancies, 94 solid tumours

  • AMH: pretreatment lower than in normal age-matched controls, associated with impaired general health status. No relation with age or malignancy type
Wędrychowicz et al. (2017)72 Patients requiring HSCT for haematological or solid malignancies Cross-sectional, HSCT (including TBI), abdominal radiotherapy, analysis 6–132 months after end of treatment

  • 6 ALL, 4 neuroblastoma, 1 NHL, 1 HD. HSCT: 6 auto, 6 allo

  • AMH: undetectable or extremely low in all

  • Auto: 1 eugonadism (normal FSH, LH and inhibin B), 1 central hypogonadism (low FSH, LH and inhibin B), 2 primary hypogonadism (high FSH and LH, low/normal inhibin B), 2 combined hypogonadism (low inhibin B, inadequately normal FSH and LH)
van der Kooi et al. (2019)69 Age <18 years, haematological or solid malignancies NA Longitudinal, chemotherapy, cranial, chest, abdominal radiotherapy, analysis from diagnosis to 10 months after end of treatment

  • Analysis not distinguishing between haematological (n=31) and solid (n=18) malignancies

  • AMH: pretreatment normal/low in premenarche and postmenarche. No changes during treatment and increased after treatment in premenarche standard risk; declined with no recovery in premenarche high risk. Decreased after 1 month of treatment with no recovery after treatment in postmenarche

ALL = acute lymphoblastic leukaemia; AMH = anti-Müllerian hormone; E2 = oestradiol; FSH = follicle-stimulating hormone; HD = Hodgkin disease; HSCT = haematopoietic stem cell transplantation; LH = luteinizing hormone; NA = data not available; NHL = non-Hodgkin lymphoma; TBI = total body irradiation.