The Link Between
Estrogen and
Gallbladder Disease
Kelly Butler
Advisor: Dr. Grimes
April 18, 2008
The Gallbladder
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Storage and
concentrating unit for
bile
Contracts to release bile
in response to food,
especially fatty foods
Dysfunction occurring to
slow or obstruct the flow
of bile from the
gallbladder results in
gallbladder disease
Epidemiology
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Common around the world
Higher rates of gallstone formation in
western Caucasian, Hispanic, and Native
American populations
Lower rates in eastern European countries,
African Americans, and Japanese
Eastern Kentucky, there is an abnormally
high incidence of gallbladder disease with
gallstone formation.
Female > male
Pathophysiology
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Includes inflammation, infection,
stones, sludge, or obstruction of the
gallbladder or its duct
Cholesterol gallstone formation is
thought to rely on three factors,
which include: (1) supersaturation of
biliary cholesterol from liver
oversecretion, (2) nucleation of
cholesterol monohydrate crystals, and
(3) gallbladder hypomotility
Estrogen
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Primary female sex
hormones
Regulating the
development of
secondary sex
characteristics
Regulate the
menstrual cycle
Stimulate the uterine
lining to thicken
Estrogen Receptors
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The liver, which produces bile, has estrogen
receptors present. Endogenous estrogens act on
these receptors to cause cholesterol saturation in
the bile. Exogenous estrogens have been shown
to affect physiologic markers in a pattern that
favors gallstone formation. Progestin’s, which are
often given in combination with estrogen for
therapy, inhibit gallbladder contraction which
increases bile stasis and can decrease the
gallbladders response to cholecystokinin
Pregnancy Induced
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Alterations in cholesterol
metabolism and decreased
gallbladder motility
Increasing # pregnancies
= increased risk of
developing gallstones
Ireland study
Usually asymptomatic
after delivery
Levels of estrogen return
to normal cycling after
delivery
Oral Contraceptives
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Accelerate the
development of
cholesterol gallstones in
women who are already
susceptible because
cholesterol saturation is
higher in persons using
oral contraceptives as
compared to nonusers
Medical University in
Bangladesh
Post-menopausal Women
and HRT
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Women’s Health Initiative
– Estrogen alone (with hysterectomy) or E+P
group (without hystectomy)
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Risk for gallstones or cholecystectomy is
increased by a factor of 2-3 in
postmenopausal women receiving estrogen
Causal relationship between estrogen
therapy and gallstones and risk of surgical
procedure among women using estrogen
alone or a combination of estrogen and
progestin
Prostate Carcinoma
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Study in Sweden looked at the development of gallstones in
men with prostate cancer who received estrogen therapy vs.
orchidectomy
Before treatment, gallbladder disease affected a quarter of
the patients equally distributed between the groups
Five patients previously without gallstones before treatment in
the estrogen group developed new gallstones
Four patients in the estrogen group with previous gallstones
had an increase in the number or size of gallstones and
increasing symptomatic pain
Biliary lipids analysis showed an increase in the concentration
of cholesterol and cholesterol saturation of bile during
estrogen treatment
Male-to-Female
Transsexuals
Change to Expect
Traits That Will Not Change
*Softer skin and body
appearance
*Voice
*Breast growth and lessening of
body hair
*Height
*Loss of strength
*Size of hands and feet
*Increased emotional sensitivity,
especially to stress –
depression is not
uncommon
*Presence of facial hair (may
grow finer.)
*Diminished ability to achieve
erections and to ejaculate
*Hair loss stops, but what has
been lost will not grow
back
*Redistibution of body fat from
stomach to breasts, hips,
and thighs
*Adam’s apple
•One known health risk seen is
that estrogen can cause maleto-female transsexual patients
to be at a higher risk for
gallbladder disease
•Hospital in Germany, over 800
patients, elevated liver
enzymes and symptomatic
gallstones
Conclusions
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OC’s should be used with caution in those
women who have a pre-existing or
predisposition to gallbladder disease
Further Research: Women’s International
Study of Long Duration Estrogen after
Menopause in 14 countries, results expected
in 2012
The risks for males is shown to be the same
as in females
Estrogen is probably a contributing factor in
the development of gallstones
References
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Scragg, R.K.R., A.J. McMichael, and R.F. Searmark. 1984. Oral Contraceptives, Pregnancy, and
Endogenous Oestrogen in Gall Stone Disease - A Case Control Study. British Medical Joural. Vol. 288,
p. 1795-1800
Richardson, J. David, F.Douglas Scutchfield, Warren H. Proudfoot, and Abram S. Benenson. 1973.
Epidemiology of Gallbladder Disease in an Appalachian Community: Comparisons with the Framingham
and Pima Indian Studies. Health Services Reports. Vol. 88, No. 3.
Oriel, Kathleen A. 2000. Medical Care of Transsexual Patients: Clinical Update. Journal of the Gay and
Lesbian Medical Association. Vol. 4, No. 4.
Medline Plus Medical Encyclopedia. Gallbladder Disease.
http://www.nlm.nih.gov/medlineplus/print/ency/article/001138.htm Accessed: November, 2007.
McCollum, Basso L., M.R. Darling, A. Tocchi, and W.A. Tanner. 1992. A Study of Cholelithiasis During
Pregnancy and Its Relationship with Age, Parity, Menarche, Breast-feeding, Dysmenorrhea, Oral
Contraception, and a Maternal History of Cholelithiasis. Surgical Gynecology and Obstetrics. Vol. 175,
No. 1: 41-46.
Henriksson, Peter, Kurt Einarsson, Ambjörn Eriksson, Ulrike Kelter, and Bo Angelin. 1989. EstrogenInduced Gallstone Formation in Males: Relation to Changes in Serum and Biliary Lipids during
Hormonal Treatment of Prostatic Carcinoma. Journal of Clinical Investigation. Vol. 84, p. 811-816.
Everson, Gregory T., Carol McKinley, and Fred Kern, Jr. 1991. Mechanisms of Gallstone Formation in
Women: Effects of Exogenous Estrogen (Premarin) and Dietary Cholesterol on Hepatic Lipid
Metabolism. Journal of Clinical Investigation. Vol. 87, p. 237-246.
Bateson, Malcolm C. 1999. Gallbladder Disease: Fortnightly Review. British Medical Journal. Vol.
318: 1745-1748.