Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

Cicardi, Marco; Bergamaschini, Luigi; Tucci, Antonietta; Agostoni, A; Tornaghi, G; Coggi, G; Colombi, R.; Viale, G.

doi:10.1016/0091-6749(83)90034-9

Cited by 44 publications

(19 citation statements)

References 17 publications

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“…The results are in agreement with the findings from cross-sectional studies conducted by other researchers, that is, danazol does not cause clinically significant alteration of liver function parameters when administered at the lowest effective dose [12,13,32,33].…”

Section: Discussionsupporting

confidence: 83%

The effect of long-term danazol prophylaxis on liver function in hereditary angioedema—a longitudinal study

Farkas

Czaller

Csuka

et al. 2009

Eur J Clin Pharmacol

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Background Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients. Methods Characteristic parameters of liver function (including bilirubin, GOT, GPT, γGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively.Results From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study. Conclusions Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients.

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Section: Discussionsupporting

confidence: 83%

The effect of long-term danazol prophylaxis on liver function in hereditary angioedema—a longitudinal study

Farkas

Czaller

Csuka

et al. 2009

Eur J Clin Pharmacol

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“…Danazol, stanozolol and oxandrolone are most commonly used. Their side effects, which are dosedependent, include weight gain, virilization, muscle pains and cramps, headaches, depression, fatigue, nausea, consti-pation, menstrual irregularities and liver function derangement [46,61,62] (evidence level 3). Decreased growth rate in children [63][64][65] is the main contraindication for their use in this age group.…”

Section: Attenuated Androgensmentioning

confidence: 99%

C1 inhibitor deficiency: consensus document

Gompels

Lock

Abinun

et al. 2005

Clinical and Experimental Immunology

380

460

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SummaryWe present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification.

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“…Symptoms may appear to be related to large doses, as morphological evaluation of the liver in hereditary angioedema patients receiving long-term low to moderate doses of stanozolol or danazol did not induce signi¢cant hepatic damage as assessed by laboratory tests or biopsy. 52 Caution must be exercised in the interpretation of results from liver function tests as exercise can also increase alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as lactate dehydrogenase and creatine kinase (CK). Although the aminotransferase levels increase initially with steroid treatment, they can return to normal often while the steroids are still being used.…”

Section: Effects On the Livermentioning

confidence: 99%

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

2003

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International Olympic Committee accredited laboratories play a key role in upholding the principle of fair play and innate ability, as desired by the majority of sports competitors and spectators. Not only does doping damage the image of sport, but it can also be harmful to the individual. The great majority of samples test negative but, when an adverse nding is declared, the analytical data must be of a suf ciently high standard to withstand legal challenges by third parties. The most widely misused performance-enhancing drugs are the anabolic-androgenic steroids, commonly referred to as 'anabolic steroids'. This review attempts to address the complex issues concerning anabolic steroids in sport by considering the clinical, biochemical and analytical perspectives. Fifty years of anabolic steroids and sport: an overviewThe discovery of a process for synthesizing the steroid testosterone (T) from cholesterol in 1935 1 greatly accelerated scienti¢c investigations into the e¡ects of this endogenous androgen. T rapidly became noted for its anabolic properties in increasing muscle size and strength and in its androgenic properties of increasing virilization and aggression. In a comprehensive review of the history of the use of anabolic steroids in sport, Todd 2 noted that, as early as 1945, the science writer Paul de Kreuf had speculated that`it would be interesting to watch the productive power of [a] . . . professional group [of athletes] that would try a systematic supercharge with testosterone . . .'.In the early 1950s, the ¢rst suspicion that T was actually being administered to improve sporting performance came with the allegation that Soviet weightlifters were administering T to gain strength. 2 Also, around that time, pharmaceutical companies were developing synthetic analogues of T with the aim of treating patients in a`catabolic state', the objective being to enhance the anabolic e¡ects of T and to dissociate the unwanted androgenic e¡ects (particularly to minimize the viriliz ing e¡ects). Nandrolone (19-nortestosterone) was the ¢rst synthetic analogue of T to show enough anabolic-androgenic dissociation in animal experiments 3 to justify its introduction as a therapeutic agent. 4 Subsequently, numerous analogues of T [and also its 5a-reduced metabolite, 5a-dihydrotestosterone (DHT)] were developed (see Fig. 1), such as methandienone (methandrostenolone), oxymesterone and stanozolol (for dates of patent awards see Ref. 5). With the growing availability of these licensed compounds, competitors began to experiment with them in an attempt to gain improvements in sporting performance without imparting the full androgenic e¡ects associated with T. During the 1960s, a number of deaths occurred in sports competitors from the use of stimulants and, as a result, in 1967 the International Olympic Committee (IOC) reestablished a medical commission (an IOC Medical Commission was rst established in Athens in 1961; see Ref. 6) which banned the practice of doping in sport, the banned classes including stimula...

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Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

Cited by 44 publications

References 17 publications

The effect of long-term danazol prophylaxis on liver function in hereditary angioedema—a longitudinal study

The effect of long-term danazol prophylaxis on liver function in hereditary angioedema—a longitudinal study

C1 inhibitor deficiency: consensus document

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

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