Oestrogen metabolism and excretion in liver disease

Brown, J. B.; Crean, G. P.; Ginsburg, Jean

doi:10.1136/gut.5.1.56

Cited by 40 publications

(6 citation statements)

References 14 publications

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“…This is most prominent in patients with alcoholic cirrhosis (AC) (4), which is often associated with gynecomastia (5). However, in 54 patients with idiopathic hemochromatosis (IHC), including those with severe liver disease, we did not find gynecomastia (6), in agreement with other surveys (7)(8)(9). This observation suggested that IHC and AC are accompanied by different abnormalities in sex hormone metabolism.…”

supporting

confidence: 92%

Conversion of Androgens to Estrogens in Idiopathic Hemochromatosis: Comparison with Alcoholic Liver Cirrhosis*

Kley¹,

Niederau²,

Stremmel³

et al. 1985

The Journal of Clinical Endocrinology & Metabolism

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Hypogonadism is common in patients with some liver diseases, such as idiopathic hemochromatosis (IHC) and alcoholic cirrhosis (AC). However, gynecomastia, a typical feature in AC, does not occur in IHC. To determine the hormonal basis for this difference, the following parameters were determined in patients with IHC and AC as well as in normal men: plasma concentrations of androgens and estrogens, metabolic clearance and production rates of androstenedione and testosterone, and the contribution of peripheral conversion of androstenedione and testosterone to the circulating estrogens. Severe impotence in both patients with IHC and those with AC was associated with more than 50% reduction in plasma testosterone. The reduction was due to 63% and 70% decreases in testosterone production in IHC and AC, respectively. The MCRs were less affected in IHC and AC (19% and 37% reductions, respectively). In IHC, the fall in testosterone concentrations was accompanied by decreased production and plasma concentrations of androstenedione, a precursor for estrogen synthesis. In contrast, production and plasma concentrations of androstenedione were significantly increased in AC. Patients with IHC had estradiol und estrone levels similar to those in normal men (mean +/- SD, 16.2 +/- 4.6 vs. 20.3 +/- 3.7 pg/ml; P = NS), whereas in AC, estradiol and estrone were significantly elevated (38.0 +/- 5.3 and 68.5 +/- 17.2 pg/ml, respectively). In IHC, sex hormone-binding globulin levels were in the same range as in the normal men, whereas sex hormone-binding globulin was increased in AC. In IHC, the instantaneous contribution of plasma androstenedione to estrone and estradiol was normal, whereas that of plasma testosterone to plasma estrogens was decreased by about 50%. In contrast, in AC, the instantaneous contribution of plasma androstenedione to estrogens was greatly enhanced, and that of testosterone was in the normal range. Since the MCRs of androgens and the conversion ratios of androgens to estrogens indicate normal peripheral metabolism of sex hormones in IHC, decreased androgen formation implies decreased testicular synthesis. This was confirmed by a significantly decreased LH level in IHC (5.5 +/- 1.9 vs. 10.5 +/- 3.1 mU/ml in normal men), indicating pituitary failure. In AC, however, increased LH (20.0 +/- 2.7 mU/ml) may be indicative of primary testicular failure. These results confirm clinical features of hypogonadism and normal estrogenic activity in patients with IHC.(ABSTRACT TRUNCATED AT 250 WORDS)

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supporting

confidence: 92%

Conversion of Androgens to Estrogens in Idiopathic Hemochromatosis: Comparison with Alcoholic Liver Cirrhosis*

Kley¹,

Niederau²,

Stremmel³

et al. 1985

The Journal of Clinical Endocrinology & Metabolism

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“…Oestrogens could also be involved as a factor in low SM activity in cir¬ rhosis such as abnormal oestrogen metabolism in chronic liver disease (Brown et al 1964;Pentikainem et al 1975) and liver function modification following oestrogen therapy are known. Thus Wiedemann et al (1976) have described a lowering of SM activity and an increase in HGH levels after both acute and chronic oestrogen treatment.…”

Section: Discussionmentioning

confidence: 99%

Somatomedin Production in Normal Adults and Cirrhotic Patients

Schimpff

Lebrec

Donnadieu

1977

Acta Endocrinologica

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The somatomedin (SM) activity was measured in blood samples withdrawn simultaneously from hepatic (HV) and peripheral (PV) veins in 10 adult patients without liver disease (control group) and in 18 alcoholic patients with cirrhosis. SM activity in the control group was 1.27 \ m=+-\0.18 U/ml (mean \ m=+-\ sem) in the HV and 1.00 \ m=+-\0.17 U/ml in the PV. In patients with cirrhosis the SM activity was respectively 0.50 \ m=+-\0.05 and 0.56 \ m=+-\0.06 U/ml. SM activity was greater in the normal subjects than in the cirrhotic patients (P < 0.001 when SM activity measured in the HV, and P < 0.01 when measured in the PV). Close examination of the means of differences of SM activity between the HV and PV, showed that the differences were significantly different from 0 in control only (P < 0.02). At least, this difference (0.275 \ m=+-\0.093 U/ml) is greater (P < 0.01) than the one observed in cirrhotic patients (0.066 \ m=+-\0.036 U/ml). In 16 subjects, the hepatic blood flow was measured, and the mean hepatic SM activity production was estimated to be 398 \ m=+-\334 U/min in 6 subjects from the control group, and 16 U/min in 10 patients with cirrhosis. The difference is significant (P < 0.01). The relationship be-

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“…This is ascribed to an increased level of transferrin protein and is not accompanied by any demonstrable change in iron absorption (Jacobi et al, 19%; Norrby et a/, 1972). Further studies are needed to establish whether the prolonged therapeutic administration of estrogens at high doses is associated with any signi&cant changes in iron handling, Or whether the high urinary excretion of estrogen in cirrhosis (Brown et al, 1964) is etiologically related to the known tendency of these patients to develop excessive storage iron deposits.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Sex Difference on Iron Exchange in the Rat

Hershko

Eilon

1974

Br J Haematol

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When compared with normal males, female Wistar rats have significantly higher serum iron levels, a higher rate of plasma iron turnover and a higher proportion of their plasma iron is diverted into non-erythroid tissues. These difference are abolished by castrationand reestablished by the supplementation of testosterone and oestrogen to castrated animals. The effect of sex hormones on iron handling is independent of their action on erythropoiesis, since in hypertransfused animals with complete inhibition of erythropoiesis the sex difference in serum iron levels and in hepatic iron uptake is maintained, The absolute rate of iron absorption is similar in both groups, but when the daily absorption of food iron is related to growth rate, it is considerably higher in females than in males (P< 0.001). The cumulative effect of a relatively higher iron absorption in females is the establishment of large iron stores which by virtue of their higher rate of exchange with transferrin contribute to their higher plasma iron turnover.In the normal state the greater part of plasma iron turnover is utilized by the erythroid marrow. Some of it is diverted to storage iron sites such as the liver and is stored in the form offerritin and haemosiderin. According to prevailing views, the major factor governing iron exchange in the body is the iron requirement of the haemopoietic tissue. Iron absorption closely follows variations in erythropoietic activity (Weintraub et ul, 1965)-Transfenin iron saturation is inversely related to the rate of erythropoiesis, and the diversion of plasm iron to storage iron sites is, in turn, a function of transferrin saturation (Cook et al, 1970). In the rat, storage irofi is greatly affected by sex differences. Significantly higher amounts of iron were found in the livers offemales than ofmales, and the rate of hepatic ferritin synthesis as well as its degradation was higher in the former group (Bjorklid & Helgeland, 1970; Lider 8i Munro, 1973). Various explanations were suggested for the observed difference. A more efficient absorption of dietary iron in females was reported, but this was not confirmed by more recent studies (Otis & Cammack Smith, 1940; Murray & Stein, 1968). Alternatively, enhancement of erythropoiesis by m& and suppression by female gonadal hormones c o d have resulted in reciprocal changes of storage iron. Finally, it has also been suggested that hepatic ferritin metabolism might directly be affected by sex hormones (Bjorklid 8r Helge land, 1970). In the present study the mechanism by which the sexdependent difference in iron exchange is established has been examined by means of gonadal hormone deprivation

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Oestrogen metabolism and excretion in liver disease

Cited by 40 publications

References 14 publications

Conversion of Androgens to Estrogens in Idiopathic Hemochromatosis: Comparison with Alcoholic Liver Cirrhosis*

Conversion of Androgens to Estrogens in Idiopathic Hemochromatosis: Comparison with Alcoholic Liver Cirrhosis*

Somatomedin Production in Normal Adults and Cirrhotic Patients

The Effect of Sex Difference on Iron Exchange in the Rat

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