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

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Abstract
Hypogonadism is common in patients with some liver diseases, such as idiopathic hemochromatosis (IHC) and alcoholic cirrhosis (AC). 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 MCR [metabolic clearance rate] 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. Production and plasma concentrations of androstenedione were significantly increased in AC. Patients wth 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 [not significant]; 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; sex hormone-binding globulin was increased in AC. In IHC, the instantaneous contribution of plasma androstenedione to estrone was estradiol and normal; 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 MCR 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 [luteinizing hormone] level in IHC (5.5 .+-. 1.9 vs. 10.5 .+-. 3.1 mU/ml in normal men), indicating pituitary failure. In AC, increased LH (20.0 .+-. 2.7 mU/ml) may be indicative of primary testicular failure. Clinical features of hypogonadism and normal estrogenic activity were confirmed in patients with IHC. The differences in sex hormone production and metabolism in IHC and AC also may have important clinical implications with respect to substitution therapy with androgens.