Heart lesions associated with anabolic steroid abuse: comparison of post-mortem findings in athletes and norethandrolone-induced lesions in rabbits.

Among 15,000 forensic post-mortem examinations performed on the coroner's order over a 24-year period (January 1981-December 2004) in the area of Lyon, France (population: 2,000,000), 2250 cases of unexpected cardiac sudden death were identified retrospectively according to WHO criteria. Of these, 108 occurred during recreational sport and 12 occurred in athletes. In the latter category, a history of anabolic steroid abuse was found in 6 cases, whereas pre-existing ordinary cardiac lesions were observed in the 6 remaining cases. To shed light on the possible role of anabolic steroids in the induction of cardiac lesions, an experimental study was conducted in rabbits that were treated orally with norethandrolone 8mg/kg/day for 60 days, and sacrificed at day 90. The histopathological examination of the heart from treated animals showed coronary thrombosis associated with left ventricle hypertrophy in 3 cases, and lesions analogous to toxic or adrenergic myocarditis in all other treated animals. These findings were very similar to those observed after cardiac sudden death in the 6 athletes with a history of anabolic steroid abuse. In addition, elevated caspase-3 activity in the heart of treated rabbits as compared to controls suggests that apoptosis is involved in the induction of norethandrolone-induced cardiac lesions. These results confirm the cardiotoxic potential of anabolic steroid abuse.

Exposure to anabolic-androgenic steroids shortens life span of male mice.

Adult male laboratory mice were exposed for 6 months to a combination of four anabolic-androgenic steroids of the kinds and at the relative levels to which human athletes and body builders expose themselves. The four steroids included testosterone, two 17-alkylated steroids, and an ester, and they were given at doses that totaled either 5 or 20 times normal androgenic maintenance levels for mice. By the time the survivors were 20 months old (1 yr after the termination of steroid exposure), 52% of the mice given the high dose of steroids had died compared with 35% of the mice given the low dose and only 12% of the control mice given no exogenous hormones (P < 0.001). Autopsy of the steroid-treated mice typically revealed tumors in the liver or kidney, other kinds of damage to these two organs, broadly invase lymphosarcomas, or heart damage, and usually more than one of these conditions. It can be concluded that the life span of male mice is decreased dramatically by exposing them for 6 months to the kinds and relative levels of anabolic steroids used by many athletes and body builders.

Hepatic tumours during androgen therapy in Fanconi anaemia.

The occurrence of liver tumours in the course of Fanconi anaemia (FA) has been well documented. We present a case, review the literature and conclude that androgen therapy would increase the risk of developing tumours, most of which appear to be benign (adenomas or peliosis) and androgen-dependent, generally decreasing in size after cessation of treatment. Survival of patients is poor, mostly because of the rapid evolution of the tumour. In the absence of an allogenic bone marrow transplantation, administration of haematopoietic growth factors might be effective. As a preventive measure, other types of unsubstituted androgens may be used.

Norethandrolone produces temporary loss of the ability to escape from salt-retaining steroids.

Patients with diseases characterized by salt retention manifest a loss of the normal ability of healthy persons to escape from repeat injections of aldosterone or other salt-retaining steroids. This phenomenon may be a clue to the pathophysiological mechanisms of salt retention. Administration of norethandrolone to a subject who had demonstrated the ability to escape from the salt-retaining effect of corticosteroid administration temporarily and reversibly deleted his ability to escape. Thus norethandrolone administration provides the basis for a model system for exploring the mechanisms of escape (and therefore of salt retention).

[Tumors of the liver secondary to androgen therapy. Apropos of 2 cases in children]. / Tumeurs du foie secondaires à l'androgénothérapie. A propos de 2 cas chez l'enfant.

The authors report 2 cases of hepatocellular tumour in children treated with anabolic androgens for aplastic anemia. In both cases, the presentation was by a picture of acute abdomen due to hemoperitoneum caused by tumour rupture. In the first case, there was multiple hepatic adenomas necessitating right hepatic lobectomy. The second infant had a single tumour of segment IV treated by simple excision of the tumour. It was a hepatocellular-carcinoma. Follow-up for one year after the initial operation showed no signs of recurrence in both infants. The review of the literature permitted us to find 48 other cases of hepatocellular tumour secondary to androgen therapy. In order of frequency, the hepatocellular-carcinoma is the most frequent and it is usually single; followed by the adenoma which is usually multiple. The other types of tumours are rare: focal nodular hyperplasia, angiosarcoma and cholangiocarcinoma. The hepatocellular-carcinoma and adenoma have some characteristic features: spontaneous regression may occur after withdrawing of androgens; the risk of rupture is important; their evolution is almost always favorable despite of a severe histopathological picture; the alpha-foeto-protein is nearly always negative; and the metastasis are exceptional. The hepatocellular-carcinomas associated with androgen therapy are probably just adenomas with marked dysplasia, but their long term malignant potential remain unknown. Except in case of rupture, surgical intervention should be postponed until the effect of discontinuing the hormonal therapy is assessed, because of the potential for spontaneous regression. The administration of antineoplastic chemotherapeutic agents should be reserved for the tumours showing evidence of malignancy.

Hepatocellular carcinoma and focal nodular hyperplasia associated with norethandrolone-therapy: a case report.

A 33-year-old woman was treated for severe aplastic anemia with norethandrolone over a period of four years, with a cumulative dose of 25 g. In the fifth year of therapy two intrahepatic tumors were detected and were classified as hepatocellular carcinoma and as focal nodular hyperplasia, respectively.

[Effects of weakly androgenic anabolic steroids on growth in Turner's syndrome]. / Effets des stéroïdes anabolisants faiblement androgéniques sur la croissance dans le syndrome de Turner.

The effects of weakly androgenic steroids at minimal doses (norethandrolone 2.5 to 10 mg/day or methandienone 1 mg/day, administered 2 months every trimester) have been studied in 67 patients with Turner syndrome: 37 with 45 XO karyotype and 30 with mosaicism or partial X deletion. Mean bone age at the onset of treatment was 10 4/12 +/- 1 8/12 years, and the mean height retardation, adjusted to parents' height, was 3.7 +/- 1.2 standard deviations. Growth velocity was very significantly increased during the first 3 semesters of treatment. The ratio of bone age to height age, evaluated after 2 years of treatment, did not increase. The adult height reached by 37 treated patients was at the average 1.96 cm higher than that of a control group of 25 adult untreated Turner cases, this difference being not significant. The results varied greatly between individuals, without relation to the type of chromosomal abnormality or the kind and dose of steroid received. The psychological evolution of the treated patients was studied accordingly to their school and/or professional accomplishments. It was satisfactory in most of them. The anabolic treatment and/or the gain in growth velocity during treatment seemed to have positive psychological effect. No side-effects were noticed.

Veno-occlusive disease of the liver associated with oral contraceptives: case report and review of literature.

This report concerns a young woman who, after taking a contraceptive preparation orally for three years, developed the Budd-Chiari syndrome as the result of a widespread chronic obliterative process involving the intrahepatic efferent venous system. Her prolonged course, which failed to respond to an end-to-side portacaval shunt procedure, mimicked chronic hepatitis evolving to cirrhosis. Additional noteworthy features were the presence of two small benign hepatic adenomas, observed both at biopsy and at necropsy, a lesion recently recognized as a complication of anovulatory drugs, and widespread hepatic calcifications found at autopsy.

[Association of Fanconi's disease and hepatic tumor in a patient undergoing long-term androgen treatment]. / Association d'une maladie de Fanconi de d'une tumeur hepatique chez une malade soumise a un traitement androgénique au long cours

A Fanconi's disease was discovered in a 9 1/2 year old girl. She received androgens daily and died with a severe aplastic attack after 4 years of evolution. Hepatic involvement of treatment with androgens was regularly checked. Autopsy however, showed a multinodular adenoma of the liver without any malignant manifestation. Relationships between aplastic anemia, long-term treatment with androgens and tumour of the liver are discussed. The difficulty of in vivo diagnosis is emphasized.