Androgen and Estrogen Response to Adrenal and Gonadal Stimulation in Idiopathic Hemochromatosis: Evidence for Decreased Estrogen Formation

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Abstract
Gonadal function in idiopathic hemochromatosis (IHC) was evaluated by comparing clinical features and levels of sex hormones in 10 male patients with IHC (cirrhosis, 4; fibrosis, 6), 6 male patients with alcoholic cirrhosis (AC) and 10 healthy, age–matched controls. Impotence was present in 9 IHC and all AC patients and was associated with decreased plasma testosterone levels. However, gynecomastia, a feature in all patients with AC, was not present in IHC, and plasma sex hormone binding globulin was normal. Patients with IHC showed significantly lower basal estradiol levels (17.7 ± 6.3 pg per ml) than did controls (28.5 ± 8.5 pg per ml), and low LH levels (p < 0.01), which were insufficiently stimulated by luteinizing hormone releasing hormone (n = 8) as well as a decrease in prolactin concentration (2.9 ± 1.4 vs. 5.9 ± 1.9 ng per ml in the controls) suggesting pituitary failure. Synthesizing capacity of sex hormones was determined by adrenocorticotropic hormone and human chorionic gonadotropin administration. Basal and stimulated levels of andro–stenedione and cortisol indicated normal function of the adrenals in IHC. However after adrenocorticotropic hormone, estrone levels increased to only 16.2 ± 8.4 pg per ml (controls, 27.3 ± 4.7 pg per ml; p < 0.01). Increments of estrone (12.5 ± 9.2 pg per ml) and estradiol (17.9 ± 11.6 pg per ml) were also lower in IHC following human chorionic gonadotropin administration than in controls (26.0 ± 7.2 and 37.5 ± 11.4 pg per ml, respectively). In contrast, plasma human chorionic gonadotropin raised testosterone levels 3.3–fold in IHC and 2.2–fold in controls. Basal and stimulated levels of testosterone, estrone and estradiol were lower in IHC patients with cirrhosis than fibrosis. Normal estrogen levels in IHC may be due to “normal” conversion from androgens to estrogens, as occurred for androstenedione in four patients with IHC. In patients with AC, reduced levels of plasma testosterone were associated with increased luteinizing hormone; androstenedione and estrogens were elevated and rose higher after adrenocorticotropic hormone or human chorionic gonadotropin stimulation. High estrogen activity was paralleled by elevated sex hormone binding globulin, and an increase in plasma prolactin. These findings suggest low estrogen activity in IHC, which appears to correlate with the severity of liver damage. These features are in contrast to AC, where increased conversion of androgens to estrogens was established previously.