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J Intern Med. 1993 Sep;234(3):287-92.

Liver damage from low-dose oral contraceptives.

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Medical Clinic, Sahlgrenska University Hospital, Göteborg, Sweden.



To study whether the decrease in the content of oestrogen and gestagen in modern low-dose oral contraceptives (OC) has yielded a lower incidence of adverse liver reactions, and to describe the biochemical pattern of the adverse liver reactions from low-dose OC.


We surveyed all liver reactions from OC reported to SADRAC (Swedish Adverse Drug Reactions Advisory Committee) from 1966 to 1989.


Incidence of reported adverse liver reactions (number of reported adverse reactions/OC sales in defined daily dose [DDD]).


There was a sharp decline in the number of reports during the studied period, suggesting changes in reporting habits. However, there was also a significantly lower incidence of reports for medium-compared to high-oestrogen dose OC, and a further decrease, albeit non-significant, in incidence with low-oestrogen dose OC. Furthermore, in three comparisons of pairs of OC that differed only in the gestagen dose, there was a strong trend towards a higher reporting rate with higher gestagen dose. Cholestatic and hepatocellular liver enzyme patterns were equally frequent in patients with adverse reactions from low-dose oestrogen OC. There was no report of liver tumours related to use of low-oestrogen dose OC.


There seems to be a decrease in the incidence of adverse liver reactions related to lower contents of both oestrogen and gestagens in OC of the combined-preparation type.


Between 1966 and 1975, the Swedish Adverse Drug Reactions Advisory Committee received a decline in reports of liver reactions from high and medium dose oral contraceptives (OCs) (25-30/1 million treatment cycles vs. 1/1 million treatment cycles; P = 0.0373). (Incidence of reported OC-related liver reactions = number of reported reactions/OC sales in defined daily dose.) During 1975-1990, the incidence hovered around 1/1 million treatment cycles. Physicians at Sahlgrenska University Hospital in Goteborg, Sweden, compared the reporting rates for pairs of OCs (A = 0.05 mg ethinyl estradiol + 3-4 mg/norethisterone acetate, B = 0.1 mg mestranol + 1-2 mg norethisterone, C = 0.05 mg ethinyl estradiol + 0.25-0.5 mg norgestrel) to determine whether the decrease in the dose of the estrogen and gestagen components contributed to the lower incidence of adverse liver reactions. A much greater incidence of reported adverse liver reactions occurred with the higher estrogen dose OCs than with the medium estrogen dose OCs (P = 0.0373). No significant difference existed between the medium and low estrogen dose OCs, however, Medium estrogen dose OCs tended to have a higher incidence of reports than the low estrogen dose OCs, however. The incidence of OC-related hepatic side effects with high-dose gestagen (OC-A) was greater than it was with a low-dose gestagen and estrogen comparable OC (P = 0.0003). Neither OC-B nor OC-C had a significantly higher incidence than did their low dose, estrogen comparable OC counterpart (P = 0.1211 and 0.2609, respectively), but the tendency was for a higher incidence in OC-B and OC-C. Hepatocellular liver enzyme and cholestatic patterns occurred at the same rate in women using low dose estrogen OCs. No report of liver tumors existed in these women. Duration between treatment and reported hepatic reaction ranged from 3 to 360 days (median = 60 days). The lower doses of estrogens and gestagens were associated with a decrease in the incidence of adverse liver reactions.

[Indexed for MEDLINE]

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