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

Abstract

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)

Testosterone treatment of men with idiopathic hemochromatosis

“…Before treatment, the estradiol levels were even less than in normal subjects (Table 2), and they were much lower than in patients with alcoholic liver cirrhosis, as has been demonstrated before [16]. The reason for the low estradiol concentrations in patients with IHC is a decreased aromatization rate of androgens to estrogens, as already demonstrated [19]. The low estrogen formation in patients with IHC is also found when stimulation tests for steroid production are performed by the application of adrenocorticotropic hormone or human chocionic gonador [15,18].…”

“…One reason for decreased testosterone and estradiol levels in IHC may be pituitary failure [19], as the LH levels were low despite substantially decreased plasma testosterone concentrations. This hypothesis is supported by other investigations demonstrating multiple pituitary failure [1,24,27].…”

“…However, side-effects of this treatment relevant to both metabolic and clinical findings have to be expected, since increased estrogen formation and elevated estrogenic effects have been shown to occur [2,16]. In patients with IHC, however, the conversion of androgens to estrogens was found to be normal [19] and consequently, the gynecomastia usually seen in patients with alcoholic liver cirrhosis was not found [23]. Therefore, we investigated whether or not testosterone may be given to patients with IHC.…”

Hereditäre Hämochromatose

“…In der Hypophyse sieht man hingegen ausgeprägte Eisenablagerungen in den gonadotrophen Zellen, wäh-rend in den thyreotrophen, kortikotrophen und somatotrophen Zellen kaum Eisen gefunden wird. Funktionelle Untersuchungen haben bestätigt, dass bei der Hämo-chromatose ein sekundärer Hypogonadismus vorliegt [16]. In anderen endokrinen Organen wie Schilddrüse und Nebenniere werden nur diskrete Eisenablagerungen gefunden.…”

Hypothalamic Hypogonadism in Hemochromatosis: A Case Report

“…Typically, patients are middleaged men who present with u nexplained cirrhosis accompanied by diabetes mell1tus and abnormally pigmented skin (l,3). Hypogonadocropic hypogonadism occurs 111 up to 64% of all individuals with advanced disease (2,3). Primary testicular dysfunction, although less frequent, also may occur (4,5).…”