title: Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: A systematic review.
abstract: BACKGROUND
  Anti-cancer treatment may reduce the fertile life span and induce premature menopause. This review aims to provide an overview of the available literature on effects of chemotherapy only on the incidence of ovarian dysfunction and to evaluate the relationship between dose of chemotherapy, age at time of treatment, and time since treatment in female survivors of childhood and young adult cancer.
  
  
  METHODS
  A comprehensive search of electronic databases was performed (search date December 2015).
  
  
  RESULTS
  45 studies were included, describing, in total, 5607 female survivors. Median age at menopause was earlier in cancer survivors than in the general population. The prevalence of amenorrhoea varied from 0% to 83%. Those exposed to MVPP protocols were at highest risk for amenorrhoea (39-79%), as were breast cancer survivors receiving cyclophosphamide-containing regimens, in whom the prevalence of amenorrhoea was 40-80%. The most important risk factors for ovarian dysfunction were: (1) alkylating agents, specifically procarbazine and busulfan, (2) older age at treatment.
  
  
  CONCLUSIONS
  Breast cancer survivors, those treated with procarbazine or other alkylating agents and those with a higher age at diagnosis are at highest risk of diminished ovarian function. However, all studies included in this review showed methodological limitations. It is imperative that nation-wide registries guarantee long term follow-up during the adult life of cancer survivors.
authors.affiliation: Department of Pediatrics, Division of Pediatric Oncology/Haematology, VU University Medical Center, Amsterdam, Netherlands; Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, Netherlands. Electronic address: a.overbeek@vumc.nl.
authors.forename: Annelies
authors.initials: A
authors.lastname: Overbeek
authors.affiliation: Department of Pediatrics, Division of Pediatric Oncology/Haematology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Marleen H
authors.initials: MH
authors.lastname: van den Berg
authors.affiliation: Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Department of Pediatrics, Division of Pediatric Oncology/Haematology, VU University Medical Center, Amsterdam, Netherlands; Princess Máxima Center of Pediatric Oncology, Utrecht, Netherlands.
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.affiliation: Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Cornelis B
authors.initials: CB
authors.lastname: Lambalk
authors.affiliation: Department of Pediatrics, Division of Pediatric Oncology/Haematology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Eline
authors.initials: E
authors.lastname: van Dulmen-den Broeder
mesh_terms: D000367:Age Factors; D000568:Amenorrhea / Q000453:epidemiology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002066:Busulfan / Q000009:adverse effects; D005260:Female; D006801:Humans; D008593:Menopause; D009369:Neoplasms / Q000188:drug therapy*; D010053:Ovary / Q000187:drug effects* / Q000502:physiology*; D011344:Procarbazine / Q000009:adverse effects; D017741:Survivors
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D011344:Procarbazine; D002066:Busulfan
keywords: Chemotherapy; Childhood cancer; Fertility; Late effects; Ovarian function; Reproduction