Can oral contraceptives cause liver adenoma?

From the Guidelines

Yes, oral contraceptives can cause liver adenoma.

Evidence Summary

• The association of estrogens with hepatocellular adenomas (HCAs) is well established, and estrogen receptors have been found in up to one-third of HCAs 1.
• Cessation of estrogen-containing hormonal contraception is associated with regression of HCAs, suggesting a causal link between oral contraceptive use and liver adenoma development 1.
• The risk of HCA with hormonal contraception has significantly declined with the use of lower doses of estrogen in contemporary contraceptive methods, but the risk is still present 1.
• The US Medical Eligibility Criteria for Contraceptive Use classifies the use of combined hormonal contraceptives, including oral contraceptives, as a Category 4 for women with hepatocellular adenoma, indicating that the risk of using the method generally outweighs the benefits 1.
• The evidence suggests that oral contraceptives can cause liver adenoma, particularly in women with a history of liver disease or those taking high-dose estrogen-containing contraceptives 1.

Key Points

• Estrogen-containing oral contraceptives are associated with an increased risk of liver adenoma.
• The risk of liver adenoma is higher with high-dose estrogen-containing contraceptives.
• Cessation of estrogen-containing hormonal contraception can lead to regression of liver adenomas.
• Women with a history of liver disease or those taking oral contraceptives should be monitored for signs of liver adenoma.

From the FDA Drug Label

Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3. 3 cases/100,000 for users, a risk that increases after four or more years of use especially with oral contraceptives of higher dose (49). Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage (50,51).

Yes, oral contraceptives can cause liver adenoma, specifically benign hepatic adenomas. The risk is rare, estimated to be around 3.3 cases per 100,000 users, and increases with longer duration of use and higher dose formulations 2.

From the Research

Oral Contraceptives and Liver Adenoma

• There is evidence to suggest a possible causal relationship between the use of oral contraceptives and the development of liver adenomas 3, 4, 5, 6.
• Studies have reported cases of hepatic adenoma in women taking oral contraceptive medication, with some suggesting a strong association between the two 3, 4.
• However, other studies have found little evidence for an increased risk of hepatocellular adenoma in women using modern oral contraceptives 7.
• The association between oral contraceptive use and the risk of benign liver tumors, including hepatocellular adenoma and focal nodular hyperplasia, has been investigated in case-control studies 7.
• The use of oral contraceptives has been linked to various hepatic complications, including intrahepatic canalicular cholestasis, neoplasm formation, and vascular pathologies 4.
• Different subgroups of adenomas have been described, including inflammatory, HNF-1α-mutated, β-catenin-mutated, and unclassified, with exposure to oral contraceptive pills and estrogen having a strong association with hepatic adenomas 4.