Norethisterone-induced hepatic adenomas can cause life-threatening bleeding in girls with inherited platelet disorders.
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.
Crosnier
Hélène
H
Centre de Référence des Maladies Gynécologiques Rares, Necker-Enfants Malades University Hospital, AP-HP, Université Paris-Descartes, Paris, France.
Thibaud
Elisabeth
E
Duflos
Catherine
C
Polak
Michel
M
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
D003280:Contraceptives, Oral, Synthetic; D009640:Norethindrone