Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry.

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.

Treatment of inherited bone marrow failure syndromes beyond transplantation.

Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.

Acute unilateral sensorineural hearing loss associated with anabolic steroids and polycythaemia: case report.

BACKGROUND: Unilateral sudden sensorineural hearing loss due to an infarct in the vertebrobasilar system has been widely reported. Most patients have a background of traditional coronary risk factors related to these cerebrovascular episodes. CASE REPORT: A 32-year-old male, a regular user of anabolic steroids, presented to the emergency department with unilateral sensorineural hearing loss and symptoms suggestive of an infarct of the anterior inferior cerebellar artery but in the absence of risk factors for ischaemic stroke. RESULTS: Magnetic resonance imaging confirmed the presence of infarction in the region supplied by the anterior inferior cerebellar artery. Polycythaemia was found on haematological analysis, which we believe was secondary to the use of anabolic steroids. The patient was commenced on aspirin as per the stroke management protocol. There was resolution of neurological symptomatology six weeks after the episode, but no improvement in hearing. CONCLUSION: To our knowledge, this is the first case report of unilateral sensorineural hearing loss secondary to the use of anabolic steroids causing polycythaemia. This cause should be considered in the differential diagnosis of patients presenting with sensorineural hearing loss, especially in young males, when no other risk factors can be identified.

The efficacy of oxymetholone in combination with erythropoietin on hematologic parameters and muscle mass in CAPD patients.

OBJECTIVES: To determine the efficacy of oxymetholone, an androgenic steroid, in combination with rHuEPO on hematologic and muscle mass in CAPD patients. METHODS: A double-blinded, placebo-controlled experimental study was conducted for 6 months and 24 CAPD patients were divided into two groups. The treatment group (n = 11) received rHuEPO plus oral oxymetholone (50 mg/tablet twice daily). The placebo group (n = 13) received rHuEPO plus a placebo twice daily. The evolution of the patients' hematologic parameters and the impact of the drugs on their muscle mass were evaluated. RESULTS: After 6 months of therapy, hematocrit and hemoglobin values of the treatment group were significantly different from those of the placebo group (38.1 ± 1.0% and 32.8 ± 0.9%, p = 0.001; 12.9 ± 0.3 g/dl and 11.0 ± 0.3 g/dl, p = 0.001 for hematocrit and hemoglobin, respectively). The increase in hematocrit and hemoglobin values observed in treatment group was statistically greater than those of the placebo group (p < 0.01). After 6 months, none of anthropometric parameters, albumin, protein or lean body mass levels, were significantly different from baseline in the placebo group. Conversely, most of the anthropometric parameters, albumin and lean body mass levels were significantly increased in the oxymetholone group (p < 0.05). The mean weight of subjects in the oxymetholone group changed from 63.82 ± 2.71 to 67.02 ± 3.26 kg (p = 0.001). The subjective global assessment score for 7 patients in the treatment group (63.6%) changed in a positive manner. A rise in liver enzymes was the main side effect observed in the treatment group. CONCLUSIONS: Oxymetholone significantly enhances the erythropoietic effects of rHuEPO and improves the nutritional status of CAPD patients. However, significant increases in liver enzymes need to be monitored closely.

Acute myocardial infarction and renal infarction in a bodybuilder using anabolic steroids.

A 41-year-old male bodybuilder was admitted with acute inferior myocardial infarction. The patient had been using oxymetholone and methenolone to increase his performance for 15 years and quitted smoking three years before. He underwent successful primary percutaneous coronary intervention (PCI) and bare metal stenting for total occlusion of the proximal right coronary artery. Angiography also showed a critical lesion in the left anterior descending (LAD) coronary artery. Five hours after primary PCI, the patient had severe right flank pain. Abdominal computed tomography showed a large renal infarction in the right kidney. Subcutaneous enoxaparin was added to dual antiplatelet treatment. Doppler renal ultrasound performed on the eighth day showed findings of reperfusion in the right kidney and normal-size kidneys. Transthoracic echocardiography demonstrated disappearance of previously detected thrombus remnant in the left ventricle and only mild hypokinesia around the apical and middle segments of the inferior and inferoseptal walls. The patient was discharged on the 10th day. Renal arteriography during elective LAD intervention 18 days after discharge showed complete revascularization, stent patency, and improved blood flow. This is the first case of renal infarction that developed in the early hours of primary PCI, despite effective anticoagulant and antiplatelet treatment. Intensive coronary artery and left ventricular thrombi may be explained by the use of anabolic steroids.

Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature.

Anabolic androgenic steroids (AAS) are used illicitly at high doses by bodybuilders. The misuse of these drugs is associated with serious adverse effects to the liver, including cellular adenomas and adenocarcinomas. We report two very different cases of adult male bodybuilders who developed hepatocellular adenomas following AAS abuse. The first patient was asymptomatic but had two large liver lesions which were detected by ultrasound studies after routine medical examination. The second patient was admitted to our hospital with acute renal failure and ultrasound (US) studies showed mild hepatomegaly with several very close hyperecogenic nodules in liver, concordant with adenomas at first diagnosis. In both cases the patients have evolved favourably and the tumours have shown a tendency to regress after the withdrawal of AAS. The cases presented here are rare but may well be suggestive of the natural course of AAS induced hepatocellular adenomas. In conclusion, sportsmen taking AAS should be considered as a group at risk of developing hepatic sex hormone related tumours. Consequently, they should be carefully and periodically monitored with US studies. In any case, despite the size of the tumours detected in these two cases, the possibility of spontaneous tumour regression must also be taken in account.

Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions.

The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review were as follows: (1) androgen-treated individuals who do not have FA are also at risk of liver tumors; (2) parenteral as well as oral androgens may be responsible for liver tumors; (3) FA patients develop liver tumors after smaller and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic neoplasms may depend on the specific androgen. Medline and Web of Science were searched for all cases of liver tumors associated with androgens. Information from individual cases was entered into a spreadsheet and descriptive statistical analyses were performed. Thirty-six FA cases and 97 non-FA cases with both nonhematologic disorders and acquired aplastic anemia (non-FA AA) were identified. The most common androgens were oxymetholone, methyltestosterone, and danazol. Hepatocellular carcinomas (HCC) were more often associated with oxymetholone and methyltestosterone, while adenomas were associated with danazol. Tumors were reported in six patients who received only parenteral and not oral androgens. FA patients were younger than non-FA patients when androgen use was initiated, and the FA patients developed tumors at younger ages. Non-AA patients were treated with androgens for longer periods of time, compared with FA and non-FA AA patients. All patients on anabolic androgenic steroids are at risk of liver tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be determined from currently available data, because the number of patients receiving androgens is unknown.

Littoral cell angioma of the spleen in a patient with severe aplastic anaemia.

Littoral cell angioma (LCA) is a rare benign tumour of the spleen. We describe a patient with aplastic anaemia who, following multiple treatments with rabbit and horse Anti-Thymocyte Globulin and anabolic steroids developed marked splenomegaly and hypersplenism. LCA was diagnosed post splenectomy. This is the first case of LCA associated with aplastic anaemia and its treatment.

Therapies with potential toxicity of neuro-ophthalmic interest.

PURPOSE OF REVIEW: Several therapies have potential neuro-ophthalmic or ophthalmic complications. We reviewed the recent literature for relevant therapies that affect ocular function. In this review, we discuss a variety of toxic effects of antiepileptic drugs, endocrine drugs, and miscellaneous therapies (intravitreal silicone oil and TNF-alpha inhibitors). RECENT FINDINGS: The pathogenesis of these side effects is quite heterogeneous affecting visual sensory function at the levels of the ciliary body, retina, optic nerve and chiasm, and central visual pathways. SUMMARY: Appropriate management requires prompt recognition of these associations. Practitioners should be familiar with these neuro-ophthalmic manifestations because they may present in the course of daily practice.

Oxymetholone for the treatment of HIV-wasting: a double-blind, randomized, placebo-controlled phase III trial in eugonadal men and women.

BACKGROUND: Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients due to various alterations in energy metabolism and endocrine regulation. Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of lean body mass (LBM), but these treatments have largely not been sufficiently studied in eugonadal individuals. METHOD: A double-blind, randomized, placebo-controlled trial of 89 HIV-positive eugonadal women and men with wasting assigned to the anabolic steroid oxymetholone (50 mg bid or tid) or placebo for 16 weeks was performed. Body weight, bioimpedance measurements, quality of life parameters, and appetite were analyzed. RESULTS: Oxymetholone led to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the tid and bid groups, respectively (p <.05 for each treatment versus placebo), while individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell mass (BCM) increased in the oxymetholone bid group (3.8 +/- 0.4 kg; p <.0001) and in the oxymetholone tid group (2.1 +/- 0.6 kg; p <.005). Significant improvements were noted in appetite and food intake, increased wellbeing, and reduced weakness by self-examination. The most important adverse event was liver-associated toxicity. Overall, 43% of patients in the tid group, 25% of patients in the bid oxymetholone group, and 8% in the placebo group had a greater than 5 times baseline increase for ALT, AST, or gamma GT, while other adverse events were not increased over placebo. CONCLUSION: Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting. The bid (100 mg/day) regimen appeared to be equally effective to the tid (150 mg/day) regimen in terms of weight gain, LBM, and BCM and was associated with less liver toxicity.

Double-blind, randomized, placebo-controlled phase III trial of oxymetholone for the treatment of HIV wasting.

BACKGROUND: Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients. Various alterations in energy metabolism and endocrine regulation have been found to cause loss of lean body mass (LBM) and body cell mass (BCM). Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of LBM, but these treatments have largely been ineffective in eugonadal individuals. STUDY DESIGN: Double-blind, randomized, placebo-controlled trial of 89 HIV-positive women and men with wasting assigned to the anabolic steroid oxymetholone [50 mg twice (BID) or three times daily (TID)] or placebo for 16 weeks followed by open-label treatment. STUDY ENDPOINTS: Body weight, bioimpedance measurements, quality of life parameters and appetite. RESULTS: Oxymetholone led to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the TID and BID groups, respectively (P < 0.05 for each treatment versus placebo), whereas individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell mass increased in the oxymetholone BID group (3.8 +/- 0.4 kg; P < 0.0001) and in the oxymetholone TID group (2.1 +/- 0.6 kg; P < 0.005), corresponding to 12.4 and 7.4% of baseline BCM, respectively. Significant improvements were noted in appetite and food intake, increased well-being and reduced weakness by self-examination. The most important adverse event was liver-associated toxicity. Overall, 35% of patients in the TID, 27% of patients in the BID oxymetholone group and no patients in the placebo group had a greater than five times baseline increase for alanine aminotransferase during the double-blind phase of the study. CONCLUSIONS: Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting. The BID (100 mg/day) regimen appeared to be equally effective as the TID (150 mg/day) regimen in terms of weight gain, LBM and BCM and was associated with less, but still significant liver toxicity.

Review of oxymetholone: a 17alpha-alkylated anabolic-androgenic steroid.

BACKGROUND: Oxymetholone (17beta-hydroxy-2-[hydroxymethylene]-17-methyl-5alpha-androstan-3-one) is a 17alpha-alkylated anabolic-androgenic steroid and a synthetic derivative of testosterone. It has been approved by the US Food and Drug Administration for the treatment of anemias caused by deficient red cell production. OBJECTIVES: This review summarizes the pharmacokinetics, current and future clinical applications, and adverse effects of oxymetholone. Relevant studies were identified using a search of MEDLINE through March 2001, supplemented by conference abstracts and presentations. RESULTS: Because of its anabolic properties, oxymetholone has been studied for the treatment of HIV-associated wasting, antithrombin III deficiency, pediatric growth impairment, and damaged myocardium, with varying degrees of success. Hepatotoxicity is a major adverse effect associated with the use of oxymetholone, with cholestatic jaundice the most important hepatic side effect. Less common hepatic side effects associated with the use of anabolic-androgenic steroids include peliosis hepatis and formation of hepatic tumors. All anabolic-androgenic steroids can cause androgenic side effects, including acne, hirsutism, hair loss, clitoral/phallic enlargement, vocal changes, erectile tissue stimulation, gynecomastia, amenorrhea, and changes in libido and sexual potency. CONCLUSIONS: As is the case with many anabolic-androgenic steroids, few pharmacokinetic and tolerability studies were performed before oxymetholone's approval in the 1960s. It has proved, however, to be an appropriate treatment choice for selected patients with anemia, if carefully monitored.

Ampullary carcinoma developing after androgenic steroid therapy for aplastic anemia: Report of a case.

Sex steroids influence the development and course of human genital carcinomas including breast, testis, prostata, and ovarian cancers. (1) Other carcinomas such as hepatoma, cholangioma, and pancreatic cancer have also been reported to be related to sex hormones. (2-4) The existence of sex hormone receptors has been demonstrated immunohistochemically in specimens of these diseases. We recently encountered a patient in whom an ampullary carcinoma developed 39 months after the start of androgenic steroid therapy for aplastic anemia. Immunohistochemic analysis of resected tumor specimens of the patient suggested a possible hormonal effect on the tumor oncology.

Cerebral venous thrombosis associated with tentorial subdural hematoma during oxymetholone therapy.

Androgen was reported to cause cerebral venous thrombosis (CVT) during replacement therapy for aplastic anemia. Oxymetholone, a synthetic androgen analogue, has been widely used in the treatment of aplastic anemia. A 40-year-old woman with aplastic anemia visited our hospital because of severe headache, nausea, vomiting, blurred vision and diplopia for a period of 1 month. She had taken oxymetholone for 2 years. Neurological examination revealed bilateral papilledema and bilateral sixth nerve palsies. Brain magnetic resonance imaging (MRI), performed at the time of admission, demonstrated left-sided tentorial SDH, and focal cerebral thrombosis of the left superficial sylvian vein and sigmoid sinus. MR venography revealed multiple irregularities in the superior sagittal sinus and left transverse sinus. CVT with tentorial subdural hematoma (SDH) caused by oxymetholone was strongly suggested. Oxymetholone was immediately discontinued, and her symptoms and signs disappeared. Because of the thrombocytopenia, anticoagulation was not started. She was discharged and visited the outpatient clinic without neurological symptoms for 6 months. This report supports the cautions given about the risk of CVT with oxymetholone supplementation in aplastic anemia. To the best of our knowledge, this is the first report of CVT associated with tentorial SDH that was probably caused by oxymetholone.

Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis.

We report a rare case of hepatic adenomas (HA), in a 20-year-old Japanese girl treated for 6 years with anabolic androgens for aplastic anemia. In a review of the world literature using computer MEDLINE search, we found only 17 cases of androgen-induced HA published between 1975 and 1998 in the English-language literature. The patient was referred to us because of liver lesions detected during a follow-up examination for familial adenomatous polyposis. After being diagnosed with aplastic anemia at 14 years of age, she had been treated with oxymetholone (30 mg/day) for 6 years. Laboratory evaluation revealed normal liver function. Ultrasonography (US) and computed tomography (CT) demonstrated multiple liver lesions. Histopathological examinations of biopsied specimens from the liver tumor showed HA. After the patient was diagnosed with HA, oxymetholone was tapered off. Patients taking androgenic-anabolic steroids should be carefully monitored with US and CT and tumor markers should be measured. This report may be helpful in identifying the population who is at risk of developing hepatic sex hormone-related tumors.