Moderate adverse effects hepatobiliary complications

Severe   hepatobiliary   complications   secondary   to   the   use   of   hormonal contraceptives are rares.  Vascular symptomatology attribuitable to pill use includes the Budd-Chiari syndrome and Hepatic Peliose, which may be reversed in some   cases   on   discontinuation   of   pill   use   (1,2,3,4).

Combined   hormonal contraceptives (HCs) are inducers of certain hepatic enzyme systems and their use may alter the parameters of substances such as alpha 1-antitrypsine or gamma glutamy l transferase, with little clinical effect. HCs favor the formation of delta-aminolevulinic acid and should be avoided in case of Porphyrie(5).

Reversible intra-hepatic cholestasis as estrogend ependent effect,  in women with genetic predisposition may induce pruritus,anorexia,  asthenia,  vomiting and weight loss without fever, rash or abdominal pain. 

Termination of HCs clears the condition without sequelae within 1-3 months, sometimes after a temporary aggravation. In this condition,abdominal pain and fever are most common(6). This condition is not related to duration of use and disappears 5-15 days after HC use is terminated.

Moreover, estrogen-containing contraceptive methods may induce the impairement or the relief of cholestasis in liver disease such as primitive biliary cirrosis(5). Despite causing a reduction of biliary excretion, HCs may provoke jaundice   which   is   rare   and   apparently   due   to   the   estrogen   and   the progestagen, both. Jaundice-HCs related, usually appears within the first six months of pill use and disappears, without sequelae 1 or 2 months after termination of pill use.  Half of these women developing jaundice with HCs had experienced intrahepatic cholestasis of pregnancy.

These women should be closely monitored while taking birth-control pill (7).  Women with familial defect of biliary excretion,including   Dubin-Johnson   syndrome, Rotor’s   syndrome, and   benign intrahepatic recurrent cholestasis should not take oral contraceptives(7).

Asymptomatic biliary lithiases is another possible clinical effect and is twice as common in pill users as in the control population. Therefore women taking HCs,  almost always have elevated cholesterol levels in their bile which probably explains the increased frequency of complications leading to cholecystectomy, in women receiving longterm estrogen treatment. It is important to know that the anomalies in the composition of bile, almost always disappear when HCs use is stopped(8). Cholestasis induced by estrogens seems to be dose-dependet but few clinical data are available on this point. An asymptomatic lithiasis in a young HC user does not necessarily require termination of HCs (7,8,9).

The role of estrogens in the genesis of hepatic adenomas is well established,but is more controversial with focal nodular hyperplasia(10,11)

Rosa Sabatini
Dept.Obstetrics and Gynecology,
General Hospital Policlinico-University of Bari, Italy


[1] Hung, N.R., Chantrain, L., Dechambre, S. (2004). Peliosis hepatis revealed by   biliary   colic   in   a   patient   with   oral   contraceptive   use.  Acta Chir.Belg,104(6), 727-9. 
[2] Eugene,  M., Chong, M.F., Genin,  R., Amat,  D.  (1985). Peliosis hepatis and oral contraceptives: a case report. Mediterr.Med, 13(343),21-24. 
[3] Akbas,  T.,  Imeryuz,  N.,  Bayalan,  F.,  Baltacroglu,  F.,  Atagunduz,  P., Mulazimoglu,  L.,  Direskenell H.  (2007). A case of Budd-Chiari syndrome with Behcet’s disease and oral contraceptive usage.  Rheumatol.Int,  28(1), 83-86.
[4] Tong, H.K., Fai, G.L., Ann, L.T., Hock, O.B. (1981). Budd-Chiari syndrome and hepatic adenomas associated with oral contraceptives. A case report. Singapore Med, J, 22(3), 168-72.
[5] Bianchetti,  J.,  Lipniaxka,  A.,  Szlendak,  U.,  Gregor,  A.  (2006).  Acute intermittent porphyria and oral contraception.  Case report. Ginekol. Pol, Mar,77(3), 223-6
[6] Hecht,  Y.  (1991).  Hepatic and biliary repercussions of estrogens:dose or duration of treatment effect.Contracept.Fertil.Sex(Paris),19(5), 403-8.6) 
[7] Lindberg, M.C. (1992). Hepatobiliary complications of oral contraceptives. J. Gen. Intern. Med, 7(2),199-209. 
[8] Saint-Marc   Girardin,  M.F.  (1984). Hepatic   complications   of   oral contraceptives Contracept. Fertil. Sex (Paris), 12(1),13-6.
[9] Leclere,  J.,  Meot-Rossinot,  B.,  Rauber,  G.  (1983). The pill and the liver. Lyon Mediterr. Med. Med. Sud Est, 19(2),7075-80). 
[10] Shortell,C.K.,  Schwartz,  S.I.  (1991).  Hepatic adenoma and focal nodular hyperplasia. Surg. Gynecol. Obstet, 173(5), 426-31.
[11] Tajada M, Nerin J, Ruiz MM, Sanchez-Dehesa M.,Fabre E.  (2001).  Liver adenoma and focal nodular hyperplasia associated with oral contraceptives. Eur.J.Contracept.Reprod.Health Care, 6(4), 227-30.

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