Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endocrine physiology of the climacteric supports a rationale for the concomitant replacement of androgen and estrogen following menopause. Clinical and research experience with estrogen-androgen hormone replacement therapy, as well as androgen-only therapy, suggests that the health benefit offered by androgen replacement exceeds the potential risk when treatment is properly managed. In this review, we concentrate on the effects of oral alkylated androgens. The virilizing effects (e.g., hirsutism, acne, voice change, and alopecia) of oral androgens are typically dose and duration dependent; androgen replacement at doses < or = 10 mg once daily administered for prolonged periods (> 6 months) produces masculinization effects that generally abate with dose reduction or discontinuation of treatment. No clinical sequelae or irreversible pathophysiologic effects have been associated with any virilization that may occur. Changes in lipoprotein metabolism associated with oral estrogen-androgen use include reduced total cholesterol levels and reduced high-density lipoprotein cholesterol levels which may reduce the long-term risk of cardiovascular disease. No clinically identifiable risk with respect to other cardiovascular variables, such as blood pressure, has been associated with the longterm administration of low doses of oral androgen. With regard to liver toxicity, reports of jaundice, peliosis hepatis, and hepatocellular carcinoma are extremely rare at the dose levels of androgen used in hormone replacement therapy, although individual sensitivity to the potential hepatotoxic effects of oral alkylated and nonalkylated androgen may vary considerably. Daily dosing with oral alkylated androgen in combination with estrogen is well tolerated. Retrospective and prospective studies involving the use of androgens alone and in combination with estrogens demonstrate that concerns about the adverse effects of androgen use associated with supraphysiologic, self-escalated doses in men do not apply to the much lower doses combined with estrogens for hormone replacement in postmenopausal women.
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PMID:Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996. 922 Feb 5

Patients with Turner syndrome (TS) are known to be at risk for excess androgen production and virilization associated with gonadoblastoma and Y chromosome mosaicism, and excess androgens are a risk factor for the development of hepatocellular carcinoma. However, virilization and hepatocellular carcinoma have not been described in a patient with TS. A 10-year-old with nonmosaic 45,X TS presented with clitoromegaly, accelerated linear growth velocity, advanced bone age, and elevated testosterone levels as well as a second occurrence of hepatocellular carcinoma. Gonadectomy was performed, and pathology revealed hilus cell hyperplasia. Immunohistochemical staining of both the original and recurrent hepatocellular carcinoma tissues was diffusely positive for androgen receptors. After gonadectomy, testosterone levels were measurable but normal, with no further virilization; however, the liver mass continued to grow. Ovarian hilus cell hyperplasia should be considered a potential etiology for virilization in the TS population. Excess endogenous testosterone exposure in girls and women with TS may be associated with hepatocellular carcinoma expressing the androgen receptor, though normalizing testosterone levels may not lead to tumor regression in these cases.
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PMID:Hepatocellular Carcinoma, Virilization, and Hilus Cell Hyperplasia in a Girl With Turner Syndrome. 2973 58