The 2017 Hormone Therapy Position Statement of The North American Menopause Society

The North American Menopause Society 2017 Hormone Therapy Position Statement Advisory Panel


The North American Menopause Society (NAMS). 2018;24(7):728-753. 

In This Article

Gallbladder and Liver

Cholelithiasis, cholecystitis, and cholecystectomy occur more frequently in women who take oral estrogen, presumably because of the first-pass hepatic effect after oral ingestion. Estrogens increase biliary cholesterol secretion and saturation, promote precipitation of cholesterol in the bile, and reduce gallbladder motility, with increased bile crystallization.[141,142]

The transdermal route of administration bypasses involvement of the liver, with less risk of gallbladder disease seen in observational studies.[143] The attributable risk for gallbladder disease as self-reported in the WHI was an additional 47 cases per 10,000 women per year for CEE + MPA and 58 cases per 10,000 women per year for CEE alone, both statistically significant (P < 0.001).[14]

Preclinical and observational studies suggest possible benefits of HT on liver fibrosis and fatty liver,[144] but research is needed before definitive recommendations can be made.

Key Points

  • Risk of gallstones, cholecystitis, and cholecystectomy is increased with oral estrogen-alone and combination HT.

  • Observational studies report lower risk with transdermal HT than with oral and with oral estradiol compared with CEE, but neither observation is confirmed in RCTs.

  • An association of HT with slower fibrosis progression in hepatitis C and with fatty liver has been observed, but randomized trials are needed to establish any potential benefits and risks of HT in postmenopausal women with liver disease.