Norethisterone-induced hepatic adenomas can cause life-threatening bleeding in girls with inherited platelet disorders

Fertil Steril. 2010 Nov;94(6):2329.e1-3. doi: 10.1016/j.fertnstert.2010.03.045. Epub 2010 Apr 24.

Abstract

Objective: To describe four cases of hepatic adenoma in adolescents and women with severe inherited bleeding disorders treated with norethisterone.

Design: Case reports.

Setting: Necker-Enfants Malades University Hospital, Paris, Department of Pediatric Endocrinology, Gynecology and Diabetes.

Patient(s): Two adolescents and two young women with inherited platelet disorders, treated with high-dose norethisterone (10 to 20 mg/day) to induce amenorrhea.

Intervention(s): Immediate cessation of norethisterone.

Main outcome measure(s): Spontaneous regression of hepatic adenoma.

Result(s): 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.

Conclusion(s): 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.

Publication types

  • Case Reports

MeSH terms

  • Adenoma / chemically induced*
  • Adenoma / complications
  • Adolescent
  • Blood Coagulation Disorders, Inherited / complications*
  • Blood Platelet Disorders / complications*
  • Blood Platelet Disorders / genetics
  • Contraceptives, Oral, Synthetic / adverse effects
  • Contraceptives, Oral, Synthetic / therapeutic use
  • Female
  • Hemorrhage / etiology*
  • Humans
  • Liver Neoplasms / chemically induced*
  • Liver Neoplasms / complications
  • Norethindrone / adverse effects*
  • Norethindrone / therapeutic use
  • Withholding Treatment
  • Young Adult

Substances

  • Contraceptives, Oral, Synthetic
  • Norethindrone