Short answer: Yes. Estrogen labels say a 2- to 4-fold rise in gallbladder disease needing surgery has been reported in women after menopause. In the WHI trials, gallbladder events ran 78 versus 47 per 10,000 women-years on estrogen alone and 55 versus 35 on estrogen plus progestin. A large UK study found a much smaller rise with patches and gels than with pills.
Premarin, Prempro, Climara and EstroGel each carry the same sentence in section 5.4: a 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported. The highlights put it simply: estrogens increase the risk of gallbladder disease. The Premarin and Prempro Patient Information leaflets list gallbladder disease among the less common serious side effects.
Cirillo 2005 looked at gallbladder outcomes in 22,579 women aged 50 to 79 in the two WHI hormone trials who had not had their gallbladder removed. Both trials used oral conjugated estrogens (CE) 0.625 mg a day, with medroxyprogesterone 2.5 mg in the combined trial.
| Outcome | Estrogen alone (7.1 years) | Estrogen plus progestin (5.6 years) |
|---|---|---|
| Any gallbladder event, per 10,000 women-years | 78 vs 47 | 55 vs 35 |
| Any gallbladder disease or surgery | 1.67 | 1.59 |
| Gallbladder inflammation (cholecystitis) | 1.80 | 1.54 |
| Gallstones | 1.86 | 1.68 |
| Gallbladder removal | 1.93 | 1.67 |
Other bile duct surgery was not clearly raised.
The Million Women Study followed 1,001,391 women in England and Scotland, average age 56 (Liu 2008). Current hormone users were more likely to be admitted for gallbladder disease than never-users (relative risk 1.64), but the rise was much smaller with transdermal therapy (1.17) than with pills (1.74). Among pills, conjugated estrogens carried slightly more risk than estradiol, and higher doses more than lower doses. The risk fell after stopping.
Gallbladder removal per 100 women over 5 years was 1.1 in never-users, 1.3 with transdermal therapy and 2.0 with pills. This was an observational study, not a trial, and the labels make no claim that one route is safer. See transdermal patch.
MedlinePlus says many people with gallstones have no symptoms. When a stone blocks a duct, there may be pain in the right or middle upper belly lasting at least 30 minutes, fever, yellowing of the skin or eyes, clay-colored stools, nausea and vomiting. These are worth a prompt call to a clinician. GLP-1 medicines also raise gallbladder risk, covered in gallbladder problems on GLP-1 medicines; someone taking both can mention each to the prescriber.
Dose Track can log the estrogen product and any belly pain episodes with dates, which helps when talking through the route, dose and history.
Read more on Dose Track: Transdermal patch · Estradiol tablet side effects · Climara vs Vivelle-Dot · Menopause