title: Norethisterone-induced hepatic adenomas can cause life-threatening bleeding in girls with inherited platelet disorders.
abstract: OBJECTIVE
  To describe four cases of hepatic adenoma in adolescents and women with severe inherited bleeding disorders treated with norethisterone.
  
  
  METHODS
  Case reports.
  
  
  METHODS
  Necker-Enfants Malades University Hospital, Paris, Department of Pediatric Endocrinology, Gynecology and Diabetes.
  
  
  METHODS
  Two adolescents and two young women with inherited platelet disorders, treated with high-dose norethisterone (10 to 20 mg/day) to induce amenorrhea.
  
  
  METHODS
  Immediate cessation of norethisterone.
  
  
  METHODS
  Spontaneous regression of hepatic adenoma.
  
  
  RESULTS
  In four patients with inherited platelet disorders, hepatic adenoma developed at 14, 18, 22, and 24 years of age, respectively, during continuous norethisterone therapy started at 1.5, 2.5, 10.0, and 13.0 years of age, respectively. Life-threatening bleeding occurred in two patients. Immediate norethisterone discontinuation was followed by complete or nearly complete tumor regression within a few months.
  
  
  CONCLUSIONS
  Our four cases strongly support a causal link between norethisterone treatment and hepatic adenoma. Continuous high-dose (10 to 20 mg/day) continuous norethisterone to treat menorrhagia in adolescents and young women with bleeding disorders is inadvisable. If other nortestosterone derivatives are needed, the patient should be closely monitored for the development of hepatic adenoma.
authors.affiliation: Centre de Référence des Maladies Gynécologiques Rares, Necker-Enfants Malades University Hospital, AP-HP, Université Paris-Descartes, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Crosnier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Thibaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Duflos
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
mesh_terms: D000236:Adenoma / Q000139:chemically induced* / Q000150:complications; D000293:Adolescent; D025861:Blood Coagulation Disorders, Inherited / Q000150:complications*; D001791:Blood Platelet Disorders / Q000150:complications* / Q000235:genetics; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000150:complications; D009640:Norethindrone / Q000009:adverse effects* / Q000627:therapeutic use; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D003280:Contraceptives, Oral, Synthetic; D009640:Norethindrone