Oral contraceptives have been used for many years and a number of adverse effects have been recognized e. Tumour-like lesions of the liver have also been reported. The presentation of such tumours, their management and pathologic features are reviewed. The biochemical effects of the oral contraceptive on the liver, with particular reference to jaundice, are discussed in detail. PIP: This paper discusses the hepatic and biochemical effects of OCs oral contraceptives based on a review of current literature on the subject.
Schaffner F. Perarnau JM, Bacq Y. Kay S. Medical Research Council. Textbook of pharmacology and therapeutics. Hepatocellular contrace;tives and oral contraceptives. The popularity of hormonal replacement therapy decreased in the late s when prospective studies demonstrated excess morbidity and mortality associated with replacement therapy in post-menopausal women. Valla D, Benhamou JP.
Asian shit dvd. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].
Have a blood test for liver function done Medium sex 12 months and if you have any abdominal discomfort ask for an ultrasound scan of your liver. Liver cell adenomas associated with use of oral contraceptives. Abnormal liver function and synthetic estrogens. Related information. The ratio of ALT to alkaline phosphatase elevations suggested that Connection between liver disease and contraceptives injury was "mixed," but the liver biopsy showed bland intrahepatic cholestasis with little hepatocyte necrosis or inflammation, and the symptoms were decidedly cholestatic with a prominence of conttraceptives that only slowly resolved. Budd-Chiari syndrome associated with oral contraceptive steroids: review of treatment of 47 cases. Ugeskr Laeger ; 45 My solo orgasm Kay S. Oral contraceptives and primary liver cancer: temporal trends in three countries. You may also like December 17, A population-based study in northern Sweden. Liver hamartomas in patients on oral contraceptives.
- Victor Wynn was one of the first physicians to testify about the effects of hormonal birth control on the liver.
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- Many women choose oral contraception because it effectively prevents unplanned conceptions and otherwise fits well with their lives.
Oral contraceptives have been used for many years and a number of adverse effects have been recognized e. Tumour-like lesions of the liver have also been reported. The presentation of such tumours, their management and pathologic features are reviewed. The biochemical effects of the oral contraceptive on the liver, with particular reference to jaundice, are discussed in detail.
PIP: This paper discusses the hepatic and biochemical effects of OCs oral contraceptives based on a review of current literature on the subject. The histological and pathologic features of liver tumors are described, as are the different etiological agents diethylstilbestrol and androgenic anabolic steroids and methods used in the management of liver tumors laparotomy; normal tissue excision; liver scanning and ultrasonography; clinical surveillance; further pregnancies are not recommended.
Estrogens and progesterones were found not to be highly cytolitic to liver cells, with estrogen being more cholestatic than progesterone. When given alone, neither is capable of producing high transaminasemia.
When progestogens are given simultaneously, the cholestatic effect of estrogens is enhanced. Contraindications to OC use are cholestasis of pregnancy; constitutional hyperbilirubinemia; primary biliary cirrhosis within 6 months after infectious hepatitis and preexisting chronic liver disease.
Development of jaundice or an increase in serum glutamic pyruvic transaminase concentration and retention of bromsulfalein are not considered contraindications to OC use. The lowest possible dose of estrogens should be used to achieve contraceptive effect. During the 1st 2 months of OC use, the pill user should have her blood tested for bilirubin weekly. Darkening of urine necessitates further examination.
Possibility of liver tumors in pill users should be considered. Any fertile-aged OC user may experience spontaneous rupture of liver with evidence of hemoperitoneum. Benign tumor as a cause of hemoperitoneum should be excised together with the smallest amount of normal liver tissue necessary to achieve hemostasis.
She was taking no other medications and had no risk factors for viral hepatitis. In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none of the 96 were attributed to estrogens or OCCs. J Clin Gastroenterol ; Hepatic impairment during the intake of contraceptive pills: clinical trial with postmenopausal women. Expert review of effects of estrogens and birth control pills on the liver. Chronic use of oral contraceptives is associated with sinusoidal dilatation, a finding on liver biopsy of uncertain significance.
Connection between liver disease and contraceptives. About the Author:
She had been taking the oral contraceptive pill for over 20 years without a break and this was a big factor in the development of her liver tumors.
I recommended that she stop the OCP and avoid taking any oral forms of hormones. To shrink her liver tumors I recommended that she take selenium in the form of Selenomune which contains three forms of selenium that have been shown to exert anti-cancer effects. This is a powerful formula to boost the strength of the immune system and increase energy levels.
It is interesting that so many women take the oral contraceptive pill for years without having checks on their liver such as a blood test for liver function or an ultrasound scan of their liver. This is because no one warns them that prolonged use of the oral contraceptive pill can cause liver problems.
Estrogens and oral contraceptives are associated with several liver problems including sluggish bile flow intrahepatic cholestasis , dilatation of spaces in the liver sinusoidal dilatation liver adenomas, liver cancer hepatocellular carcinoma , clotting of the veins in the liver hepatic venous thrombosis and an increased risk of gallstones. These side effects are more common with higher doses of estrogens, as were used in the early high dose estrogen formulation of oral contraceptives, but they have also been described with use of more modern birth control pills and with low dose, estrogen hormonal replacement therapy.
Estrogens and OCPs can cause mild inhibition of bilirubin excretion, leading to jaundice in patients with inherited forms of bilirubin metabolism. Estrogens and OCPs can induce bile stasis cholestatic liver injury which usually starts during the first few cycles of OCP use.
The onset is typically insidious with fatigue and itching skin pruritus , followed by nausea, dark urine and jaundice.
Estrogens and OCPs have also been linked to hepatic tumors, both benign and malignant. Numerous reports of hepatic adenomas have been linked to estrogen and OCP use, typically arising after several years of use and presenting either with pain or a liver mass. The risk of developing hepatic adenomas on OCPs is estimated to be 0.
In some instances, malignant transformation and liver cancer hepatocellular carcinoma have been found. Benign tumors may shrink to some extent with stopping estrogens, but others require treatment. Estrogens may also promote the growth of other benign liver tumors, such as focal nodular hyperplasia, hemangiomas, and hamartomas.
Hepatocellular carcinoma has been linked to use of oral contraceptives in several case reports and case controlled studies. However, in larger studies and population based analyses, oral contraceptives have not been clearly linked to liver cancer. Hepatocellular carcinoma is extremely rare in young women without other liver diseases, and even if oral contraceptives increase the risk of this cancer by 2- to 3-fold, it remains very rare.
Long term use of oral contraceptives is associated with dilatation of the spaces in the liver sinusoidal dilatation a finding on liver biopsy of uncertain significance. Extreme sinusoidal dilatation associated with venous lakes and liver rupture is referred to as peliosis hepatis, which can be associated with pain and hepatic rupture. Oral contraceptive pill use has been associated with rare instances of peliosis hepatis. This ability to sustain and recover from damage is fortunate.
Among its over known essential-to-life functions, the liver filters the body's blood supply in order to clear and metabolize many different compounds it perceives as poisonous, including medications.
The liver metabolizes most drugs, including oral contraceptives. Thus it can be vulnerable to various kinds of DILIs, or drug-induced liver injuries. The liver is also the site of many drug interactions. One drug may speed up or slow down the rate at which the liver metabolizes another drug, intensifying or hindering its clinical effects. Many drug interactions with oral contraceptives can be explained by metabolic events within the liver. Drug interactions may worsen if DILI is present.
Liver function is often assessed through blood tests of certain enzymes from the liver. Some of these test results, especially for alkaline phosphatase, or ALP, and total bilirubin, may be higher than normal in some oral contraceptive users. Elevated liver enzymes may result from liver inflammation or damage.
If you are on the pill and have elevated liver enzymes, ask your doctor what these test results mean in your case; whether you need further tests and treatments; and whether you should switch birth control methods. Because of liver-based drug interactions, this manual also recommends that women on certain antiseizure medications, the anti-tuberculosis drug rifampicin and the anti-HIV drug ritonavir not take COCs or POPs.
NCBI Bookshelf. Estrogens and oral contraceptives are both associated with several liver related complications including intrahepatic cholestasis, sinusoidal dilatation, peliosis hepatis, hepatic adenomas, hepatocellular carcinoma, hepatic venous thrombosis and an increase risk of gallstones. These side effects are more common with higher doses of estrogens, as were used in the early high dose estrogen formulation of oral contraceptives, but they have also been described with use of more modern birth control pills and with low dose, estrogen hormonal replacement therapy.
Synthetic estrogens for regulation of menstrual cycles and hormonal replacement therapy were developed in the early s and came into increasing use in thereafter. Hormonal replacement therapy became increasing popular in the s and s. Both estrogen only and combination forms of hormonal replacement therapy were used.
In women with a uterus, combination hormonal replacement therapy was recommended usually combining a conjugated equine estrogen with medroxyprogesterone. The estrogen doses used in hormonal replacement therapy were 5 to 6 times lower than the equivalent ethinylestradiol doses used in OCCs.
The popularity of hormonal replacement therapy decreased in the late s when prospective studies demonstrated excess morbidity and mortality associated with replacement therapy in post-menopausal women. Commercially available OCCs include monophasic, biphasic, triphasic, extended cycle and progestin only formulations.
Hormonal replacement therapy usually employs conjugated equine estrogen in doses of 1. While early formulations of OCCs were associated with frequent serum enzyme elevations, current formulations and hormonal replacement therapy have not been linked to ALT or alkaline phosphatase elevations at rates any higher than occur with placebo.
Estrogens and OCCs can cause mild inhibition of bilirubin excretion, leading to jaundice in patients with inherited forms of bilirubin metabolism such as the Dubin Johnson syndrome. More importantly, estrogens and OCCs can induce a clinically apparent cholestatic liver injury which typically arises during the first few cycles of therapy, and rarely after the six months Case 1. The onset is typically insidious with fatigue and pruritus, followed by nausea, dark urine and jaundice.
Serum enzyme elevations are usually mixed or cholestatic, although very early during the injury, ALT levels can be markedly elevated 5- to fold. The characteristic pattern, however, is bland intrahepatic cholestasis and liver biopsy shows little inflammation or hepatocyte necrosis. Resolution may be delayed Case 2 , but estrogens have not been definitely linked to chronic injury, vanishing bile duct syndrome or acute liver failure.
Women with OCC induced cholestasis often have a history of idiopathic cholestasis of pregnancy and there is likely a genetic component, most commonly with variants in the bile salt export pump BSEP, ABC B Estrogens and OCCs have also been linked to hepatic tumors, both benign and malignant. Numerous reports of hepatic adenomas have been linked to estrogen and OCC use, typically arising after several years of use and presenting either with pain, liver mass or rupture with hemoperitoneum Case 3.
In population based surveys, the risk of developing hepatic adenomas on OCCs is estimated to be 0. In some instances, malignant transformation and hepatocellular carcinoma have been found. Benign tumors may regress to some extent with stopping estrogens, but others require intervention.
Estrogens may also promote the growth of other benign liver tumors, such as focal nodular hyperplasia, hemangiomas, and hamartomas. Hepatocellular carcinoma has been linked to use of oral contraceptives in several case reports and case controlled studies.
However, in larger studies and population based analyses, oral contraceptives have not been clearly linked to liver cancer. Hepatocellular carcinoma is extremely rare in young women without accompanying liver disease, and even if oral contraceptives increase the risk of this cancer by 2- to 3-fold, it remains extremely rare. Use of oral contraceptives has also been linked to an increase in venous thrombosis and cases of hepatic venous thrombosis or Budd Chiari syndrome Case 4.
Women who develop this complication are often found to have other risk factors for venous thromboses such as Protein C or Protein S deficiency or Factor V Leiden. Portal vein thrombosis has also been reported with oral contraceptive use.
Chronic use of oral contraceptives is associated with sinusoidal dilatation, a finding on liver biopsy of uncertain significance. Extreme sinusoidal dilatation associated with venous lakes and propensity for hepatic rupture is referred to as peliosis hepatis, which can be associated with symptoms and hepatic rupture. Oral contraceptive use has been associated with rare instances of peliosis hepatis, but the association a striking dilation of sinusoids with venous lakes has been rarely reported with oral contraceptive use.
Stopping oral contraceptives has occasionally been associated with regression in the severity of peliosis. Both oral contraceptives and chronic hormonal replacement therapy are also associated with a slight increased rate of gallbladder disease, typically occurring during the first few years of estrogen use. Cholestasis due to estrogens and OCCs appears to be related to inhibition of bilirubin and bile acid secretion related to effects of estrogens on the orphan nuclear receptors that modulate bile acid and bilirubin metabolism.
In addition, women who develop hepatic adenomas on OCCs are often heterozygous for gene variations associated with multiple hepatic adenomas such as in hepatic nuclear factor 1 alpha HNF1-alpha.
The cholestasis associated with OCCs is typically mild and resolves rapidly with stopping. Some cases, however, are protracted and associated with severe pruritus with or without marked jaundice.
Corticosteroids should not be used. Recurrence of cholestasis with restarting OCCs is typical, although lower dose formulations may be found that do not trigger the response. Management of hepatic tumors related to OCCs is complex. In many instances, merely stopping oral contraceptives is followed by regression in the tumor size, but surgery may be required for larger tumors and those in which malignant transformation is believed to a risk.
Intrahepatic cholestatic jaundice of pregnancy followed by Enovid-induced cholestatic jaundice. Ann Intern Med ; PubMed Citation ]. A 28 year old woman developed pruritus within 4 days of starting oral contraceptives and stopped them after a week.
One week later 14 days after starting , she had darkening of the urine and 4 weeks later was found to the jaundiced. She was taking no other medications and had no risk factors for viral hepatitis.
Important in her past medical history were episodes of jaundice and pruritus during two pregnancies. The jaundice arose during the fifth month of her second and the sixth week of her third pregnancies with peak bilirubin values of 3.
The cause of jaundice during her pregnancies was not identified despite extensive evaluation including laparotomy and cholecystectomy the gallbladder was normal without stones. Thereafter, she was well until she started birth control pills.
On examination, she was jaundiced but had no fever or rash. Serum bilirubin was 4. A liver biopsy showed intrahepatic cholestasis with minimal inflammation. Upon stopping the contraceptive pills, serum laboratory tests improved and jaundice cleared within 2 weeks. However, she continued to have pruritus for 3 months after stopping the medication.
Ultimately, all symptoms and itching resolved and laboratory tests except for alkaline phosphatase were normal 6 months later. View in own window. A woman with a history of idiopathic cholestasis of pregnancy developed pruritus a few days after starting birth control pills, and dark urine followed by jaundice several weeks later. The ratio of ALT to alkaline phosphatase elevations suggested that the injury was "mixed," but the liver biopsy showed bland intrahepatic cholestasis with little hepatocyte necrosis or inflammation, and the symptoms were decidedly cholestatic with a prominence of pruritus that only slowly resolved.
Severe and prolonged oral contraceptive jaundice. J Clin Gastroenterol ; 6: A 22 year old woman developed jaundice and pruritus after a single 28 day cycle of oral contraceptives L-Ovral: orgestrel 0. Over the next several months, she developed worsening pruritus, anorexia, nausea, fatigue and weight loss. She had no previous history of liver disease or risk factors for viral hepatitis.
Her only medications were birth control pills and rarely acetaminophen for pain. Examination showed marked jaundice and multiple excoriations. The liver was enlarged and somewhat tender to palpation. Laboratory results showed bilirubin of 7. Because of persistent jaundice, she underwent endoscopic retrograde cholangiopancreatography which was normal.
A liver biopsy showed intrahepatic cholestasis with minimal inflammation and bile duct proliferation. She eventually began to improve and all laboratory values were normal or near normal 6 months later. Oral contraceptive induced jaundice usually arises during the first cycle of birth control pills and is typically cholestatic with mild jaundice and pruritus, resolving in 1 to 2 months.
In this instance, jaundice and pruritus were prolonged and laboratory values did not return to normal or near normal for 6 months. While oral contraceptives can cause prolonged jaundice, they have not been definitely associated with vanishing bile duct syndrome or fatal liver disease.
Complete regression of hepatocellular adenoma after withdrawal of oral contraceptive use. Dig Dis Sci ; A 28 year old woman who had been on oral contraceptives 0. She had no other significant medical problems and took no medications except occasional aspirin. She rarely drank alcohol and had no risk factors for viral hepatitis or liver disease.
Physical examination revealed an obvious mass in the epigastrium and right upper quadrant that appeared to involve the liver. There was no tenderness, ascites, wasting or jaundice. A technitium colloid liver-spleen scan showed a large liver, but no obvious masses whereas a HIDA scan showed a large hypofunctioning mass in the liver. A liver biopsy showed hepatic adenoma with sinusoidal dilatation.
A hepatic arteriogram showed a large vascular tumor occupying most of the right and central lobes. Resection was not considered technically possible. Oral contraceptives were stopped and she underwent tubal ligation. During the ensuing 12 months she remained well and repeat scans showed return of liver to normal size. Alkaline phosphatase also fell to normal.
Hepatic adenomas are a rare, but well defined complication of long term use of oral contraceptives.
They can present in three manners: 1 with sudden acute right upper quadrant pain and rupture, 2 as a abdominal mass with or without mild degrees of pain, or 3 as an incidental finding on physical examination, during unrelated abdominal surgery or on routine radiological imaging. The association of contraceptive use and hepatic adenomas has been made both epidemiologically and clinically, the clinical evidence being supported by the rarity of this tumor before the introduction of oral contraceptives, and the spontaneous resolution or shrinkage of the tumors upon withdrawal of the pill as in this case.
Serum alkaline phosphatase levels are raised in some, but certainly not all women with this tumor and liver tests are typically normal.
In this instance, the high alkaline phosphatase levels were probably related to the size of the tumor and its encroachment on the normal liver and biliary system. This case also demonstrates that the tumor can be managed by stopping the oral contraceptives and careful follow up.
In rare instances, hepatic adenomas have later been found to show malignant transformation.