title: Restoration of ovarian function after chemotherapy for osteosarcoma.
abstract: OBJECTIVE
  To evaluate ovarian function after modern intensive multi-agent chemotherapy for osteosarcoma given during childhood or adolescence.
  
  
  METHODS
  After discontinuation of treatment, 10 female osteosarcoma survivors were followed up for 1.5-14 (median 4.6) years. Their age at diagnosis was a median of 12.9 (range 6-15) years and at the last follow up 18.6 (range 16-22). The main follow up included recording of their pubertal and menstrual status and of sex hormone determinations.
  
  
  RESULTS
  Prior to diagnosis, 5/10 had had their menarche, and one had it while on therapy. At discontinuation of chemotherapy, ovarian function had severely deteriorated; none of the girls experienced regular menstrual cycles. However, during follow up, significant restoration of ovarian function was evident. At the last follow up, 9/10 patients were menstruating spontaneously. During follow up, four patients, three of whom had received high doses of alkylating agents, presented with clear hypergonadotrophism with high FSH levels (14.4-132 IU/l). Three of these four patients initiated menstruation after their gonadotrophin levels normalised.
  
  
  CONCLUSIONS
  The modern multi-agent chemotherapy applied for osteosarcoma impairs ovarian function. Normalisation of ovarian function is common, even in cases with severe hypergonadotrophic hypogonadism, but may only occur after several years off chemotherapy. Regular assessment of ovarian function and cautious use of hormone replacement therapy are important in patients with chemotherapy induced gonadal damage.
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. anne.wikstrom@fimnet.fi
authors.forename: A M
authors.initials: AM
authors.lastname: Wikström
authors.forename: L
authors.initials: L
authors.lastname: Hovi
authors.forename: L
authors.initials: L
authors.lastname: Dunkel
authors.forename: U M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D015331:Cohort Studies; D004958:Estradiol / Q000032:analysis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D008572:Menarche / Q000502:physiology; D012516:Osteosarcoma / Q000188:drug therapy*; D010053:Ovary / Q000503:physiopathology*; D011627:Puberty / Q000502:physiology; D012189:Retrospective Studies
chemical_list: D004958:Estradiol; D005640:Follicle Stimulating Hormone