Hepatotoxicity Complicating Flutamide Treatment of Hirsutism

Wallace, Clarissa

doi:10.7326/0003-4819-119-11-199312010-00020

Cited by 38 publications

(10 citation statements)

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“…Flutamide can cause hepatotoxic effects [32,33]. In our study, two patients had slight impairment of liver function tests that normalized after the discontinuation of flutamide.…”

Section: Discussionmentioning

confidence: 46%

Androgen-Receptor Blockade Does Not Impair Bone Mineral Density in Adolescent Females

et al. 1997

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The effect of peripheral androgen hypersensitivity on bone mineral density (BMD) was investigated in a group of adolescent women with idiopathic hirsutism (n = 17; mean age 17.0 +/- 1.7 years). The effect of long-term androgen-receptor blockade with flutamide (500 mg daily in two divided doses for 12 months) on BMD was assessed too. BMD was measured at lumbar spine (L2-L4) by a dual energy X-ray densitometer. Before flutamide treatment, patient BMD (1.14 +/- 0.07 g/cm2) was not significantly different from that of the control group (1.16 +/- 0.12 g/cm2, n = 22), and was normal for age and sex (BMD 0.14 +/- 0.69 SDS, P = NS vs. 0). After 12 months of treatment, absolute BMD in patients increased (1.18 +/- 0.08 g/cm2, P < 0.002), but SDS BMD did not change (0.21 +/- 0.72, P = NS vs. baseline). Flutamide treatment determined a clinical, marked improvement of androgen hypersensitivity (Ferriman-Gallwey score: before 22.0 +/- 6.2; 6 months: 13.2 +/- 6.4, P < 0.003; 12 months; 7.6 +/- 4.1, P < 0. 001; acne score: before 3.8 +/- 0.8; 3 months 0.8 +/- 0.5, P < 0. 001; later disappeared). The serum levels of 3alpha-androstenediol-glucoronide decreased (before: 8.6 +/- 1.1 microg/liter; 12 months: 7.2 +/- 1.0 microg/liter, P < 0.02), whereas the other endocrinological parameters did not change. No relationship was found between BMD and clinical or biochemical parameters of hyperandrogenism. We concluded that in adolescent women, peripheral hyperandrogenism is not associated with abnormal BMD; long-term treatment with flutamide, which blocks the androgen receptor, does not alter their BMD.

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“…Flutamide can cause hepatotoxic effects [32,33]. In our study, two patients had slight impairment of liver function tests that normalized after the discontinuation of flutamide.…”

Section: Discussionmentioning

confidence: 46%

Androgen-Receptor Blockade Does Not Impair Bone Mineral Density in Adolescent Females

et al. 1997

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“…Some patients diagnosed with prostate cancer were simultaneously taking other hepatotoxic drugs to control concomitant diseases, and this could have played a role in these particular cases. However, there are also reports of young women taking low doses of cyproterone acetate or fl utamide, either alone or in combination with estradiol, who developed fatal fulminant hepatitis [30,45,58,60,70]. Therefore it is clear Review that antiandrogens alone are capable of inducing hepatotoxicity in subjects with a previously healthy liver.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity Induced by Antiandrogens: A Review of the Literature

Thole

Manso²,

Salgueiro³

et al. 2004

Urol Int

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Introduction: Hepatotoxicity is a serious adverse reaction potentially induced by all antiandrogens. We have reviewed here the published cases of hepatotoxicity induced by steroidal and nonsteroidal antiandrogens, and compared the type and characteristics of liver damage. Methods: Using two different databases: MEDLINE and IDIS (Iowa Drug Information Service), we searched for published cases of liver injury induced by antiandrogens. Analysis was made of the type of hepatotoxicity, therapeutic indication, other pharmacological treatments and evolution. Mean values of latency and recovery periods of the adverse reactions and liver function tests were also evaluated. Results: Hepatitis was the most common type of hepatotoxicity reported, and was associated with all antiandrogens. This adverse reaction does not seem to be dependent on the patients age, therapeutic indication or the dose prescribed. Hepatitis showed a longer latency period for cyproterone acetate than for flutamide. Some transaminase levels were significantly higher for flutamide than for cyproterone acetate, although the evolution was no worse in the cases reported for flutamide. We also found occasional reports of hepatocellular carcinoma and hepatic cirrhosis suspected of being induced by cyproterone acetate. Conclusion: Although there are differences in the clinical features of hepatotoxicity induced by steroidal and nonsteroidal antiandrogens, these do not predict which patients will develop hepatotoxicity during treatment or evolution. Serial liver function tests are required for early detection of liver damage.

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“…Most cases of severe hepatotoxicity have been observed when flutamide was given in a dose ranging 750-1500 mg/d (11)(12)(13)(14)(15). Some cases of hepatotoxicity also have been documented with doses as low as 250-375 mg/ d (7,10).…”

Section: Discussionmentioning

confidence: 99%

“…Some cases of hepatotoxicity also have been documented with doses as low as 250-375 mg/ d (7,10). In the majority of cases, hepatotoxicity occurs as a mild liver involvement, characterized by an increase in transaminase levels without clinical consequence, but unfortunately cases of evolution in fatal or fulminant hepatitis has been described (11,14).…”

Section: Discussionmentioning

confidence: 99%

“…Flutamide alone or in combination with other drugs has been used successfully at doses of 250 or 500 mg daily in the treatment of hyperandrogenism (4)(5)(6)(7). The most debated aspect of flutamide administration is an increased risk of treatment-induced hepatotoxicity, which is a rare but potentially fatal side effect, reported by many investigators at different dosages (8)(9)(10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

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