title: Chemotherapy-induced ovarian failure as a prototype for acute vascular toxicity.
abstract: BACKGROUND
  Chemotherapy-related amenorrhea is a frequent side effect observed in young breast cancer patients. Studies in mice revealed that chemotherapy-induced gonadal toxicity may result from vascular damage. We prospectively evaluated ovarian blood flow and function in young breast cancer patients following chemotherapy.
  
  
  METHODS
  Young female patients with localized breast cancer undergoing adjuvant or neoadjuvant anthracycline- or taxane-based chemotherapy were evaluated using transvaginal ultrasound prior to initiation of and immediately after cessation of chemotherapy. Doppler-flow velocity indices of the ovarian vasculature-resistance index (RI), pulsatility index (PI)-and size measurements were visualized. Hormonal profiles, anti-Müllerian hormone (AMH) levels, and menopausal symptoms were assessed at the same time points.
  
  
  RESULTS
  Twenty breast cancer patients were enrolled in the study. The median age was 34 ± 5.24 years. Ovarian blood flow was significantly reduced shortly following chemotherapy: RI decreased by 52.5% and PI decreased by 24.2%. The mean ovarian size declined by 19.08%. Patients who were treated with sequential chemotherapy experienced further reductions in ovarian blood flow and ovarian size after the second sequence. AMH levels dropped dramatically in all patients following treatment. Hormonal profiles after treatment depicted a postmenopausal profile for most patients, accompanied by related symptoms.
  
  
  CONCLUSIONS
  Our results may imply a mechanism of chemotherapy-induced ovarian toxicity manifested by decreased ovarian blood flow accompanied by a reduction in ovarian size and diminished post-treatment AMH levels. Based upon our former preclinical studies, we assume that this may derive from an acute insult to the ovarian vasculature and may represent an initial event triggering a generalized phenomenon of end-organ toxicity.
authors.affiliation: Institute of Oncology, Davidoff Center, Rabin Medical Center, Petah-Tiqva, Israel. iritbenaharon@gmail.com
authors.forename: Irit
authors.initials: I
authors.lastname: Ben-Aharon
authors.forename: Israel
authors.initials: I
authors.lastname: Meizner
authors.forename: Tal
authors.initials: T
authors.lastname: Granot
authors.forename: Shiri
authors.initials: S
authors.lastname: Uri
authors.forename: Noa
authors.initials: N
authors.lastname: Hasky
authors.forename: Shulamith
authors.initials: S
authors.lastname: Rizel
authors.forename: Rinat
authors.initials: R
authors.lastname: Yerushalmi
authors.forename: Aaron
authors.initials: A
authors.lastname: Sulkes
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced*; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008594:Menopause, Premature / Q000187:drug effects; D010053:Ovary / Q000098:blood supply* / Q000187:drug effects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced*; D012039:Regional Blood Flow / Q000187:drug effects; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids