Effect of oestrogen/gestagen replacement therapy on liver enzymes in patients with Ullrich-Turner Syndrome

Abstract

The absence of breast development and the prevention of osteoporosis in Ullrich-Turner syndrome (UTS) require oestrogen/gestagen substitution therapy. In 8 out of 35 (23%) patients with UTS treated with conjugated equine oestrogens and cyclically with norethisterone acetate, the serum liver enzymes increased to conspicuous levels (AST 35; 20-73 U/l, ALT 92; 37-141 U/l, GGT 77; 25-227 U/l, [median; min-max]). These findings were compared with those in 41 tall girls who received a six-fold larger dose of conjugated equine oestrogens for the reduction of final height. None of these 41 girls showed abnormal serum liver enzyme levels. The conspicuous rise in serum liver enzyme levels occurred in the majority of the UTS patients before norethistherone acetate was added to the oestrogen replacement therapy. No essential morphological equivalent was found in liver sonography and biopsy studies. During the follow up the elevated serum liver enzyme levels showed reversibility when medication was temporarily discontinued and either a slow decrease or a steady state after therapy was continued. CONCLUSION. Patients with UTS on oral oestrogen replacement therapy are more susceptible to develop increased serum liver enzyme levels as compared with eukaryotic females treated with the same oestrogen preparation for other disorders. As the underlying pathomechanism is unknown and adverse long-term effects cannot be ruled out, avoiding the portal vein and using the transdermal application of oestrogen may represent a viable solution to the problem.

Serum liver enzymes in Turner syndrome

“…Excluding the three patients positive for HCV serological markers, we found that 28% of Turner patients had transient or persistent elevation of liver enzymes of unknown cause. Our results agree with those of Wemme [24], who observed high enzyme values in 23% of patients with the same age range as our case series. In a study on 49 middle-aged Turner women [21], this characteristic was found in 80% of cases, suggesting that in TS the elevation of liver enzyme levels becomes more frequent with aging.…”

“…In a recent paper [24], the increase in serum liver enzymes observed in 8/35 girls with TS was ascribed to oestrogen/gestagen treatment.…”

Hepatic Enzyme Abnormalities in Turner Syndrome: A Case Report

“…Estrogens are thought to influence the metabolic activity of the liver, and some investigators associate estrogen therapy in TS with abnormal liver function [3]. However, others have noticed that estrogens should not be considered an important cause of hepatic enzyme elevations in TS [4,7,8,9] and the findings in the case described here are in agreement with this view.…”

“…The prevalence of these abnormalities ranges from 20 to 80%, depending on the patient’s age [1,3,4,5,6] inasmuch as these abnormalities become more frequent with advancing age.…”

Adulthood in Women with Turner Syndrome

“…The suggestion that the abnormalities found in TS may be due to oestrogen deficiency is based on the finding that oestrogen improves the disturbance [37, 95]; but others have documented a deterioration in liver function with oestrogen therapy [98]. The optimal type of oestrogen replacement is therefore still in question.…”