What is the significance of elevated estrogen and progesterone levels with elevated Liver Function Tests (LFTs)?

From the Guidelines

Elevated estrogen and progesterone levels are not typically a direct cause of elevated Liver Function Tests (LFTs), but rather, the liver's role in metabolizing these hormones can be affected in certain liver diseases.

Key Points

• Hormonal contraceptives containing estrogen and progestin can be used safely in patients with non-advanced liver disease, but regular monitoring of serum liver tests is recommended 1.
• Estrogen is metabolized in the liver, and high doses may cause cholestatic liver injury, but current formulations of hormonal contraceptives do not carry an increased risk of elevated serum liver tests 1.
• Progesterone-only contraceptives, such as implants and IUDs, should be avoided in certain liver conditions like acute hepatic porphyrias, as they can achieve significant systemic levels and liver exposure 1.
• Liver disease severity is not typically affected by the use of hormonal contraceptives, although evidence is limited and caution is advised in advanced liver disease or cirrhosis 1.

Clinical Considerations

• Patients with polycystic liver disease (PLD) should avoid exogenous estrogen use, as it may aggravate hepatic cyst growth, and alternative contraceptive options like levonorgestrel-releasing intrauterine devices may be considered 1.
• Women with acute hepatic porphyrias should exercise caution when using estrogen-progestin combinations, as they may exacerbate the condition, and barrier methods or IUDs without progesterone are recommended 1.

From the Research

Significance of Elevated Estrogen and Progesterone Levels

Elevated estrogen and progesterone levels have been associated with various effects on liver function, as indicated by Liver Function Tests (LFTs). The significance of these effects can be understood by examining the relationship between estrogen, progesterone, and liver function.

Effects of Estrogen on Liver Function

• Estrogen plays a crucial role in maintaining homeostasis and making the liver less susceptible to chronic liver diseases in healthy premenopausal individuals 2.
• However, increased estrogen levels have also been implicated in chronic liver diseases, suggesting a complex relationship between estrogen and liver function 2.
• Estrogen receptors are expressed in the liver, and their impaired expression and function are associated with obesity and liver-associated metabolic dysfunctions 2.

Effects of Progesterone on Liver Function

• Elevated progesterone levels have been associated with liver dysfunction, as seen in a case report of moderate ovarian hyperstimulation syndrome (OHSS) 3.
• Progesterone levels were higher than the upper limit of normal for a third-trimester gestation, suggesting a potential link between progesterone and liver function 3.

Relationship Between Estrogen, Progesterone, and LFTs

• The use of oral contraceptives containing estrogen and progestin has been associated with changes in LFTs, including decreases in bilirubin and alkaline phosphatase levels 4.
• However, the effects of estrogen and progestin on LFTs can be complex and may depend on the specific composition and dosage of the oral contraceptive 4.
• Elevated LFTs can be a common problem in emergency medicine, and an algorithmic approach can be used to interpret abnormalities and narrow the differential diagnosis 5.

Clinical Implications

• Liver function should be analyzed even in moderate cases of OHSS, as hepatic dysfunction is not limited to severe forms of the syndrome 3.
• The effects of estrogen and progestin on liver function should be considered when evaluating patients with elevated LFTs, particularly in the context of oral contraceptive use or hormonal therapies 4.