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Causes of ICP: hormones

In all pregnancies the levels of the hormones estrogen and progesterone in the blood increase. Like many substances, they are metabolised (broken down) by the liver.

In ICP the levels of estrogen and progesterone are not higher than normal, but the level of some progesterone breakdown products (called sulfated metabolites) is higher in women with ICP. Some researchers think that it is these substances that affect the liver’s ability to cope with bile acids, leading to cholestasis. Similarly, experimental studies of high estrogen levels show that they affect the transportation of bile salts across liver cells. These theories are supported by the observation that ICP is more common in twin and triplet pregnancies, where the levels of estrogen and progesterone are naturally higher.

Women with ICP have also reported developing cholestasis following the use of oral contraceptives, and we know that progesterone preparations used to prevent preterm labour may also increase the risk of developing ICP. This does not mean that you should never be prescribed progesterone in pregnancy if the benefits outweigh the risks. This could either be to prevent preterm labour or as a treatment to maintain pregnancy after IVF.

Women with ICP are usually advised to avoid the combined oral contraceptive pill (which contains both estrogen and progesterone). However, contraception may be used on a ‘try and see’ basis if you feel that you have no other acceptable alternative. You must not start this until you have normal liver function and your bile acids are at normal levels. You will need to let your doctor know if the pruritus (itching) returns so that a decision can be made about whether you can continue with the contraception you are using. We know that some women can tolerate the combined oral contraceptive pill, but others have reported problems on the progesterone-only pill. Why this happens is not fully understood. However, most progesterone-only contraception does not commonly cause problems in women with previous ICP. There has been little research in this area, so the long-term implications of using hormones as contraceptives are not known, and it’s important that you know this before making a decision.

References

Abu-Hayyeh S et al. Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum Hepatology; 2015 doi:10.1002/hep.28265 (epub ahead of print) | PDF

Song X et al. Transcriptional dynamics of bile salt export pump during pregnancy: mechanisms and implications in intrahepatic cholestasis of pregnancy. Hepatology; 2014 60(6): 1993–2007