Can birth control cause cholelithiasis (gallstones)?

Can Birth Control Cause Gallstones?

Yes, hormonal birth control can increase the risk of gallstones, though the magnitude of risk varies significantly by formulation, with modern low-dose combined oral contraceptives appearing safer than older high-dose formulations, while medroxyprogesterone acetate injections and levonorgestrel intrauterine devices show increased risk.

Risk by Contraceptive Type

Combined Oral Contraceptives (COCs)

• Modern low-dose estrogen formulations do not appear to significantly increase gallstone risk 1
• The effect of estrogen on gallstone formation is dose-dependent, and newer oral contraceptives with low estrogen doses do not seem to increase the rate of gallstone formation 1
• Older studies showed age-dependent effects: increased risk in younger women but decreased risk in older women using oral contraceptives 2
• One large cohort study found no increased risk of cholecystectomy with standard levonorgestrel/ethinyl estradiol combined oral contraceptives compared to other formulations 3

Injectable Contraceptives

• Medroxyprogesterone acetate (Depo-Provera) carries a 22% increased risk of cholecystectomy (HR: 1.22,95% CI: 1.07-1.40) compared to combined oral contraceptives 3
• This represents one of the higher-risk hormonal contraceptive options for gallbladder disease 3

Intrauterine Devices

• Levonorgestrel IUDs used for at least 1 year show a 74% increased risk of cholecystectomy (HR: 1.74,95% CI: 1.19-2.54) compared to combined oral contraceptives 3
• This finding is particularly important given the widespread use of hormonal IUDs 3

Mechanism of Increased Risk

• Estrogen increases biliary cholesterol secretion, causing cholesterol supersaturation of bile, which is the primary mechanism for gallstone formation 1
• Female sex hormones are causally related to cholesterol gallstone disease, explaining why rates are 2-3 times higher in women than men during childbearing years 1
• The hormonal effects are similar to those seen in pregnancy, where hormonal changes lead to decreased gallbladder motility and lithogenic bile 4

Clinical Context and Monitoring

Risk Stratification

• Women with baseline risk factors (obesity, high prepregnancy BMI, elevated serum leptin) face compounded risk when using hormonal contraceptives 4, 5
• The estimated incidence of gallstone-related disease is 0.5-0.8% in the general pregnant population, providing context for baseline risk 4, 5
• Oral contraceptives can be used in patients with non-advanced liver disease (including primary sclerosing cholangitis), but regular monitoring of serum liver tests every 6 months is advisable 4

Postmenopausal Hormone Therapy (Different Context)

• The U.S. Preventive Services Task Force concluded there is fair evidence that postmenopausal hormone replacement therapy increases risk for cholecystitis 4
• Current HRT users show 1.8-fold increased risk (RR: 1.8,95% CI: 1.6-2.0), and long-term users (>5 years) show 2.5-fold increased risk (RR: 2.5,95% CI: 2.0-2.9) compared to nonusers 4
• Combined estrogen-progestin therapy increased biliary tract surgery risk by 48% (RR: 1.48,95% CI: 1.12-1.95) over 6.8 years of follow-up 4
• Postmenopausal hormone therapy also increases risk for cholelithiasis (HR: 1.61-1.79) 4

Clinical Recommendations

For Women Considering Contraception

• Choose modern low-dose combined oral contraceptives over medroxyprogesterone acetate injections or levonorgestrel IUDs if gallstone risk is a concern 1, 3
• Women with symptomatic cholelithiasis should undergo laparoscopic cholecystectomy before pregnancy to prevent recurrent symptoms and complications 6
• Multidisciplinary counseling should be provided for all women of reproductive age with cholelithiasis who are planning pregnancy 6

For Women with Existing Gallstones

• Women harboring asymptomatic gallstones should not receive estrogens (particularly postmenopausal HRT) because of the possibility of developing cholecystitis 7
• However, oral contraceptives can be used in patients with non-advanced liver disease with regular monitoring 4

Common Pitfalls to Avoid

• Do not assume all hormonal contraceptives carry equal gallstone risk—the formulation and delivery method matter significantly 3
• Do not dismiss gallbladder symptoms in women using hormonal contraceptives, as the risk is real and clinically significant 4, 3
• Do not confuse the risk profile of modern low-dose oral contraceptives with older high-dose formulations or with postmenopausal hormone therapy 1, 7