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

J Gastroenterol. 2000;35(7):557-62.

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

Nakao A, Sakagami K, Nakata Y, Komazawa K, Amimoto T, Nakashima K, Isozaki H,
Takakura N, Tanaka N.

Department of Surgery, Shobara Red Cross Hospital, Japan.

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.

Use of growth hormone and other anabolic agents in AIDS wasting

JPEN J Parenter Enteral Nutr. 1999 Nov-Dec;23(6 Suppl):S202-9.

Use of growth hormone and other anabolic agents in AIDS wasting.

Mulligan K, Tai VW, Schambelan M.

Division of Endocrinology, San Francisco General Hospital, CA 94110, USA.

Body wasting and loss of lean body mass (LBM) have been associated with increased
mortality and disease progression, and reduced quality of life, in patients with
human immunodeficiency virus (HIV) infection. The failure of nutritional
therapies and, more recently, of effective viral suppression, to consistently
restore LBM has prompted investigation of the pharmacologic use of a number of
specific protein anabolic agents, including recombinant human growth hormone
(rhGH), insulin-like growth factor I (rhIGF-I), and synthetic testosterone
derivatives, such as nandrolone decanoate, oxandrolone, and oxymetholone. In a
placebo-controlled trial, treatment with rhGH resulted in a significant and
sustained increase in weight that was accompanied by an even greater increase in
LBM and a decrease in fat, and improvement in treadmill work output. Preliminary
data suggest that short-term rhGH treatment may be effective in mitigating weight
loss in patients with secondary infections. Open-label studies of nandrolone
decanoate suggest that this injectable agent also can increase weight and LBM.
Two oral agents, oxandrolone and oxymetholone, can increase weight, but their
effects on LBM in placebo-controlled trials have not been reported. Taken
together, these studies demonstrate that HIV-infected individuals can regain
weight and LBM under the proper therapeutic circumstances. The effects of
reversal of wasting on survival and disease progression, long-term safety, and
the potential value of these therapies in the treatment of fat redistribution
remain to be determined.

Oxymetholone: I. Evaluation in a comprehensive battery of genetic toxicology and in vitro transformation assays

Toxicol Pathol. 1999 Sep-Oct;27(5):501-6.

Comment on:
    Toxicol Pathol. 1999 Sep-Oct;27(5):507-12.

Oxymetholone: I. Evaluation in a comprehensive battery of genetic toxicology and
in vitro transformation assays.

Holden HE, Studwell D, Majeska JB.

Department of Toxicology and Safety Assessment, Boehringer Ingelheim
Pharmaceuticals, Ridgefield, Connecticut 06877, USA. heholden@midcoast.com

Oxymetholone is generally assumed to be a nongenotoxic carcinogen. This
assumption is based primarily on the results of an Ames test, existing data in
repeat-dose toxicology studies, and the predicted results of a 2-yr National
Toxicology Program (NTP) rat carcinogenicity bioassay. To provide a comprehensive
assessment of its genotoxicity in a standard battery of mutagenicity assays,
oxymetholone was tested in microbial and mammalian cell gene mutation assays, in
an in vitro cytogenetics assay (human lymphocytes), and in an in vivo
micronucleus assay. Oxymetholone was also tested in an in vitro morphologic
transformation model using Syrian hamster embryo (SHE) cells. These studies were
initiated and completed prior to the disclosure of the results of the NTP
bioassay. Oxymetholone was tested at doses up to 5,000 microg/plate in the
bacterial plate incorporation assay using 4 Salmonella strains and the WP2 uvrA
(pKM101) strain of Escherichia coil. There was no induction of revertants up to
the highest dose levels, which were insoluble as well as toxic. In the L5178Y
tk+/- mouse lymphoma assay, doses up to 30 microg/ml reduced relative survival to
approximately 30% with no increase in mutants. Male or female human lymphocytes
were exposed in vitro to oxymetholone for 24 hr without S9 or 3 hr with S9 and
evaluated for the induction of chromosomal aberrations. There was no increase in
aberration frequency over control levels and no difference between male and
female cells. Peripheral blood from Tg.AC transgenic mice treated dermally for 20
wk with 0, 1.2, 6.0, or 12.0 mg/day of oxymetholone and from p53 transgenic mice
treated orally by gavage for 26 wk with 125, 625, or 1,250 mg/kg/day of
oxymetholone was evaluated for micronuclei in polychromatic and normochromatic
erythrocytes. There was no difference in micronuclei frequency between control
and treated animals. These results confirm that oxymetholone is not genotoxic in
a comprehensive battery of mutagenicity assays. In the SHE assay, oxymetholone
produced a significant increase in morphologically transformed colonies at dose
levels of 13-18 microg/ml. The lack of genotoxicity of oxymetholone, the positive
response in the in vitro transformation assay, and the results of transgenic
mouse carcinogenicity assays will provide an interesting perspective on the
results of an on-going NTP rat carcinogenicity bioassay.

Poststeroid balance disorder--a case report in a body builder

Int J Sports Med. 1999 Aug;20(6):407-9.

Poststeroid balance disorder--a case report in a body builder.

Bochnia M, Medraś M, Pośpiech L, Jaworska M.

Clinic of Otolaryngology, Medical University in Wroclaw, Poland.

The authors describe a case of poststeroid balance disorder in a 20-year-old
athlete. Previous information of such a doping pathology among sportsmen taking
anabolics was not found. That anabolic steroids had a harm to central activities
and could be suspected especially on the basis of reported psychiatric sequels
and cerebrovascular disorders. The case described is of a patient who had been
given metandienone, oxymetholone, and nandrolone phenyloproprionate in two
courses. Vertigo appeared twice just after introducing doping and persisted in
spite of a 1.5 year break in taking anabolics. In the electronystagmography a
positional nystagmus was detected, the eye-tracking test was distempered, and
abnormal responses in the caloric tests were obtained. In the computed dynamic
posturography the number and length of body sway were increased and,
consequently, the field of the outspread area was enlarged. The moment of
appearance and long-lasting vertigo as well as the results of laboratory
examinations indicate a poststeroid permanent disorder of the central part of the
equilibrium organ. Such a diagnosis seems to be most probable here.

Analysis of 65 Turkish patients with congenital aplastic anemia (Fanconi anemia and non-Fanconi anemia): Hacettepe experience

Clin Genet. 1997 May;51(5):296-302.

Analysis of 65 Turkish patients with congenital aplastic anemia (Fanconi anemia
and non-Fanconi anemia): Hacettepe experience.

Altay C, Alikaşifoglu M, Kara A, Tunçbilek E, Ozbek N, Schroeder-Kurth TM.

Department of Pediatrics, Pediatric Hematology Unit, Ihsan Dogramaci Children's
Hospital, Hacettepe University, Ankara, Turkey.

During the last 14 years, 65 unrelated patients were diagnosed as having
constitutional aplastic anemia (CAA). In 52 of 65 patients the diepoxybutane
(DEB) test was positive. Comparison of several hematological and clinical
parameters in Fanconi anemia (FA) (DEB+) and non-Fanconi anemia (non-FA)(DEB )
patients disclosed no statistically significant differences. The study indicated
that in Turkey there were no peculiarities in associated congenital abnormalities
in FA and non-FA. The rate of consanguinity was 78% in FA and 46% in non-FA,
suggesting that also among the non-FA group recessively inherited disorders are
hidden. The mean age at diagnosis in FA was 7.7+/-4.4 (1.8-12) and in non-FA
7.8+/-3.8 (2-15) years. Nine out of 52 FA and five out of 13 non-FA patients died
during the follow-up period. Five of the 52 FA patients developed malignancies,
three of them had acute myeloblastic leukemia (AML), one a squamous cell
carcinoma of the gingiva, and another a hepatocellular carcinoma. Peliosis
hepatica occurred in three of the FA and one of the non-FA patients. A total of
seven patients stayed in remission without any medication. The remaining 58
patients were given 2-5 mg/kg of oxymetholone and 5 mg prednisolone treatment.
Because of sustained remission, oxymetholone therapy was terminated in four of
the 45 FA and two of the 13 non-FA patients. Detailed examination of the
pedigrees of all of patients indicated the presence of multiple congenital
anomalies. In seven of 52 FA and one of 13 non-FA patients there was increased
risk for AML and/or other cancers among family members.

Treatment results of 23 cases of severe aplastic anemia with lymphocytapheresis

Arch Med Res. 1997 Spring;28(1):85-90.

Treatment results of 23 cases of severe aplastic anemia with lymphocytapheresis.

Morales-Polanco MR, Sánchez-Valle E, Guerrero-Rivera S, Gutiérrez-Alamillo L,
Delgado-Márquez B.

Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F.

We report the results of 23 patients with aplastic anemia (AA) treated with a
program of 14 lymphocytapheresis (LC). Treatments were performed with apheresis
machines, models Haemonetics 30-S and Baxter CS3000, using the standard program.
This procedure was done because AA in many cases appears as a result of the
action of a T cell population that inhibits hematopoiesis. Theoretically, removal
of this clonal population would produce hematopoietic recovery. Of the total of
23 patients, 9 were excluded for final evaluation of treatment results because 7
died during or shortly after treatment (0.7-3 months); one patient abandoned
treatment after three LC and another died 7 months later because of
transformation to acute leukemia. The remaining 14 patients were included in the
final evaluation of treatment; seven females and seven males, average age 46.1
years (range 22-69); 13 with severe, and one with moderate AA; 11 with recently
diagnosed, and 3 with chronic AA; 12 without previous treatment and two treated
before with antilymphocyte globulin + oxymetholone (OXM) + cyclosporine A (CsA)
with transient partial remission (PR). Besides lymphocytapheresis, 13 patients
received OXM; 4 of them GM-CSF and one low dose CsA. Four patients had complete
remission lasting > 59.5 months (range 42-78); eight PR (average duration of >
38.6 months), and two minimal remission (> 37 and 29 months). Platelet,
reticulocyte and granulocyte counts increased on average at 48.7, 73.3 and 91.4
days, respectively. In conclusion, 14 (60.8%) of 23 patients with AA showed an
improvement related to LC treatment, with a survival probability of 63% from the
fourth month, the latter with an added beneficial effect of the other therapies
used. Larger numbers of patients have to be treated with LC to determine its real
usefulness, mechanism of action and the best conditions for its use.

Hepatocellular carcinoma associated with anabolic steroid therapy: report of a case and review of the Japanese literature

J Gastroenterol. 1996 Jun;31(3):450-4.

Hepatocellular carcinoma associated with anabolic steroid therapy: report of a
case and review of the Japanese literature.

Kosaka A, Takahashi H, Yajima Y, Tanaka M, Okamura K, Mizumoto R, Katsuta K.

Department of Surgery, Matsusaka City Hospital, Mie, Japan.

We report herein the case of a 35-year-old woman with aplastic anemia who
developed hepatocellular carcinoma after long-term therapy with oxymetholone. She
was treated with 60 mg/day of oxymetholone for 3 years (total dose 64.8 g).
Alpha-fetoprotein, hepatitis B surface antigen, and hepatitis C antibody were all
negative, but serum titers of carcinoembryonic antigen and carbohydrate antigen
were elevated. Lateral segmentectomy of the liver was performed. The
histopathological findings were compatible with those of multiple hepatocellular
carcinoma without liver cirrhosis. Three years since the operation, the patient
is doing well and no signs of tumor recurrence have been detected. According to
our review of Japanese cases of hepatocellular carcinoma associated with anabolic
steroid therapy, in all instances the tumors developed after long-term
administration of anabolic steroids for hematologic diseases. In patients under
long-term anabolic steroid therapy, routine screening of the liver by
ultrasonography and computed tomography should be performed to detect liver
tumors in the early stages.

Oxymetholone promotes weight gain in patients with advanced human immunodeficiency virus (HIV-1) infection

Br J Nutr. 1996 Jan;75(1):129-38.

Oxymetholone promotes weight gain in patients with advanced human
immunodeficiency virus (HIV-1) infection.

Hengge UR, Baumann M, Maleba R, Brockmeyer NH, Goos M.

Department of Dermatology, University of Essen, Germany.

The effect of the testosterone derivative oxymetholone alone or in combination
with the H1-receptor antagonist ketotifen, which has recently been shown to block
tumour necrosis factor alpha (TNF alpha), on weight gain and performance status
in human immunodeficiency virus (HIV) patients with chronic cachexia was
evaluated in a 30-week prospective pilot study. Thirty patients were randomly
assigned to either oxymetholone monotherapy (n 14) or oxymetholone plus ketotifen
(n 16). Patients receiving treatment were compared with a group of thirty
untreated matched controls, who met the same inclusion criteria. Body weight and
the Karnofsky index, which assesses the ability to perform activities of daily
life, and several quality-of-life variables were measured to evaluate response to
therapy. The average weight gain at peak was 8.2 (SD 6.2) kg (+ 14.5% of body
weight at study entry) in the oxymetholone group (P < 0.001), and 6.1 (SD 4.6) kg
(+10.9%) in the combination group (P < 0.005), compared with an average weight
loss of 1.8 (SD 0.7) kg in the untreated controls. The mean time to peak weight
was 19.6 weeks in the monotherapy group and 20.8 weeks in the combination group.
The Karnofsky index improved equally in both groups from 56% before to 67% after
20 weeks of treatment (P < 0.05). The quality of life variables (activities of
daily life, and appetite/nutrition) improved in 68% (P < 0.05) and 91% (P < 0.01)
of the treated patients respectively. Oxymetholone was safe and promoted weight
gain in cachectic patients with advanced HIV-1 infection. The addition of
ketotifen did not further support weight gain. These results suggest the need for
a randomized, double-blind, placebo-controlled multicentre trial.

Other therapies for wasting

GMHC Treat Issues. 1995 May;9(5):7-8, 12.

Other therapies for wasting.

Smart T.

AIDS: Individuals with wasting syndrome lose muscle or lean body mass rather than
body fat. Several possible alternatives to the approved drugs for AIDS-related
wasting are discussed. Ketotifen, an antihistamine approved in Europe, is a TNF
inhibitor. Anabolic steroids are testosterone derivatives designed to increase
strength and muscle. Although there are anecdotal reports of success with these
steroids, their long-term safety and efficacy have yet to be established in
placebo-controlled studies. An ongoing study at Mt. Sinai shows a statistically
significant effect on lean body mass in the first twelve men to complete the
study. Dehydroepiandrosterone (DHEA) is a hormone produced by the adrenal gland.
Although its role in the body is poorly understood; it may have immunologic
effects, and appears to influence metabolism. There have been no studies of
DHEA's effect on weight or body composition in people with AIDS-related wasting.
A study combining ketotifen and oxymetholone, the oral anabolic steroid, was
presented at the Ninth International AIDS Conference. Preliminary data from a
study combining ketotifen and oxymetholone showed that 18 out of 22 patients
gained an average of 11.4 pounds after treatment of an average of 3.9 weeks.
Finally, a trial of smoked marijuana versus the oral drug marinol for
AIDS-related wasting syndrome may be canceled. The Drug Enforcement
Administration (DEA) and the National Institute of Drug Abuse (NIDA) rejected the
Community Consortium of San Francisco's proposal to obtain officially sanctioned
cannabis.

Assessment of attentional bias and mood in users and non-users of anabolic-androgenic steroids

Drug Alcohol Depend. 1995 Mar;37(3):241-5.

Assessment of attentional bias and mood in users and non-users of
anabolic-androgenic steroids.

Bond AJ, Choi PY, Pope HG Jr.

Department of Psychiatry, Institute of Psychiatry, University of London, UK.

Forty-six male strength athletes took part in a study to measure the effects of
anabolic-androgenic steroids on attentional bias to aggressive cues. They were 16
current users of anabolic steroids, 16 former users and 14 non-users.
Testosterone, deca-durabolin and anadrol were the three most commonly taken
steroids during the last cycle. Users generally took 2-3 drugs during each cycle;
the average cycle lasted 8-11 weeks and they had completed 3-4 cycles. The
subjects completed visual analogue scales of current feelings and were presented
with a modified Stroop Colour Word Conflict Task containing sets of neutral,
verbally aggressive and physically aggressive words. Current users tended to rate
themselves more negatively. Users took longer than former users to name the
colours of all word sets but there were no significant differences between word
sets. Therefore, attentional bias did not differ between groups but current
steroid use produced subtle mood changes and slowed performance compared to users
not currently taking steroids.

Rupture of the triceps tendon associated with steroid injections.

Am J Sports Med. 1993 May-Jun;21(3):482-5.

Comment in:
    Am J Sports Med. 1995 Nov-Dec;23(6):778.

Rupture of the triceps tendon associated with steroid injections.

Stannard JP, Bucknell AL.

Orthopaedic Surgery Service, Brook Army Medical Center, Fort Sam Houston, Texas.

Rupture of the triceps mechanism is an uncommon injury that has been recognized
with increasing frequency in recent years. It has been proposed that such
injuries commonly accompany fractures of the radial head and must be actively
evaluated in the presence of such a fracture. We present a unique case of
isolated rupture of the triceps tendon in an athlete who was lifting weights.
This case was complicated by a history of olecranon bursitis that had been
treated with numerous local steroid injections, as well as a history of anabolic
steroid abuse. Both systemic steroids and local injections may predispose tendons
to rupture. Triceps tendon ruptures may result in uniformly good to excellent
results if recognized and treated surgically. This case also serves as a reminder
of the risks of treating inflamed tissues with local steroid injections,
especially in strength athletes who place high demands on their musculoskeletal
structures. Finally, this case documents a second case of triceps mechanism
rupture in an athlete who has abused anabolic steroids. A study by Hunter et al.
suggests that oral steroid abuse may be associated with detrimental effects on
the mechanical properties of connective tissue, demonstrating another negative
effect of anabolic steroid use in athletes.

A familial case of hereditary angioneurotic edema in Japan

Intern Med. 1992 Mar;31(3):353-6.

A familial case of hereditary angioneurotic edema in Japan.

Yamato H, Nakashima Y, Ninomiya K, Sakurai S, Kuroiwa A.

Second Department of Internal Medicine, University of Occupational and
Environmental Health, School of Medicine, Kitakyushu, Japan.

A 53-year-old man was admitted with impairment of breathing following laryngeal
edema. Serum levels of CH50 (22 U/ml), C4 (3 mg/dl), C1-INH protein (10.6 mg/dl)
and C1-INH activity (LT 25%) were low. Complement study of the patient's family
members revealed that he was one of 5 patients in 3 generations with hereditary
angioneurotic edema (HANE). Administration of the androgen derivatives Danazol
(600 mg/day) and Oxymetholone (30 mg/day) effectively increased serum levels of
C1-INH activity and C4. Though eruption and hepatic dysfunction attributable to
administration of the drugs appeared, these side effects improved after
withdrawal of the drugs. Subsequently, the treatment with Danazol at a low dose
(100 mg/day) was resumed, and the patient has had no episodes of edema for the
past 3 years. Regarding the familial cases of HANE, fewer than 20 have been
reported in Japan.

A clinico-haematologic profile of paroxysmal nocturnal haemoglobinuria

J Assoc Physicians India. 1991 Oct;39(10):741-3.

Comment in:
    J Assoc Physicians India. 1991 Oct;39(10):735-6.

A clinico-haematologic profile of paroxysmal nocturnal haemoglobinuria.

Saxena R, Malhotra OP, Saraya AK.

Department of Medicine, All India Institute of Medical Sciences, New Delhi.

Clinico-haematological parameters in sixteen patients of paroxysmal nocturnal
haemoglobinuria (PNH) are presented. Their modes of presentation included
recurrent episodes of cola-coloured urine (6/16), refractory anaemia (9/16) and
predominant thrombotic manifestations (1/16). Laboratory investigations revealed
the presence of anaemia (16/16), reticulocytosis (14/16), thrombocytopenia
(11/16), leucopenia (5/16) and cellular bone marrow (14/16). Two patients had
hypoplastic bone marrow initially but subsequently developed PNH. The patients
were treated with haematinics, prednisolone (16/16) and oxymethalone (2).
Prednisone was effective in suppressing haemolytic episodes. Oxymethalone given
to the 2 patients with hypoplastic bone marrow resulted in amelioration of
anaemia in one but no effect in the other patient.

Hepatocellular carcinoma and squamous cell carcinoma in a patient with Fanconi's anemia

Ann Hematol. 1991 Jul;63(1):54-5.

Hepatocellular carcinoma and squamous cell carcinoma in a patient with Fanconi's
anemia.

Linares M, Pastor E, Gomez A, Grau E.

Department of Hematology, Hospital de Xátiva Lluis Alcanyis, Valencia, Spain.

Acute leukemia, hepatocellular carcinoma, and squamous cell carcinoma have been
reported in patients with Fanconi's anemia. We report on a 31-year-old woman who
developed squamous cell carcinoma of the esophagus and hepatocellular carcinoma.
Jaundice and hepatic tumor developed in 1981, after she had received oxymetholone
for 10 years. Liver biopsy revealed peliosis hepatis. Androgenic therapy was
stopped and the jaundice resolved. However, the hepatic tumor was observed to be
unchanged. The patient died of disseminated squamous cell carcinoma, but no
metastatic lesions from hepatocellular carcinoma were detected in the autopsy.
The association of Fanconi's anemia and squamous cell carcinoma is reviewed, and
the malignant potential of androgen-related hepatic tumors is discussed.

Effect of extended use of single anabolic steroids on urinary steroid excretion and metabolism

J Chromatogr. 1989 Apr 7;489(1):121-6.

Effect of extended use of single anabolic steroids on urinary steroid excretion
and metabolism.

Harrison LM, Martin D, Gotlin RW, Fennessey PV.

Department of Pediatrics, University of Colorado, Denver 80262.

Long-term use of single anabolic steroids by weightlifters and body builders at
dosages greater than or equal to 25 mg per 24 h resulted in reduced excretion of
urinary androgen metabolites, androsterone and etiocholanolone, compared to
values prior to anabolic use. The excretion of major urinary metabolites of
glucocorticoids was not affected by anabolic use. Urinary excretion of anabolic
steroids or anabolic metabolites averaged 20-25% of total anabolic steroid
administered. The major excreted metabolites of methandrostenolone, nandrolone,
oxandrolone and oxymetholone were identified by gas chromatography-mass
spectrometry based on the major mass spectral ion peaks.

Oxymetholone therapy in patients with familial antithrombin III deficiency

Thromb Haemost. 1988 Dec 22;60(3):495-7.

Oxymetholone therapy in patients with familial antithrombin III deficiency.

Shibuya A, Ninomiya H, Nakazawa M, Nagasawa T, Yoda Y, Abe T.

Division of Hematology, University of Tsukuba, Ibaraki, Japan.

Three patients with familial antithrombin III (ATIII) deficiency, who also have
histories of thromboembolism, were treated with oxymetholone in combination with
warfarin. Thrombolysis was observed in one patient with acute thrombosis of
inferior vena cava during the oxymetholone and warfarin therapy. No further
thromboembolic episodes occurred in these patients after initiation of warfarin
with or without oxymetholone. The levels of plasma ATIII, alpha 1-antitrypsin,
plasminogen and Cl-inactivator were significantly increased in all patients after
the introduction of oxymetholone therapy. This suggests that oxymetholone
augments anticoagulant and fibinolytic activity. Hence we consider that
oxymetholone in combination with warfarin may be possible thrombolytic therapy in

Cerebral hemorrhagic infarction associated with anabolic steroid therapy for hypoplastic anemia

Angiology. 1986 Oct;37(10):725-30.

Cerebral hemorrhagic infarction associated with anabolic steroid therapy for
hypoplastic anemia.

Shiozawa Z, Tsunoda S, Noda A, Saito M, Yamada H.

A twenty-two-year-old student with hypoplastic anemia was treated with large
doses of anabolic steroid hormone preparations for two months. Cerebral
hemorrhagic infarction shown by CAT scan developed when his hematologic
conditions were improving. In treating hypoplastic anemia with anabolic steroid
hormone preparations, one should be aware of the possible development of cerebral
hemorrhagic infarction at the time of hematologic improvement.

Long-term survival with tumor regression in androgen-induced liver tumors

Cancer. 1985 Dec 1;56(11):2622-6.

Long-term survival with tumor regression in androgen-induced liver tumors.

McCaughan GW, Bilous MJ, Gallagher ND.

Two patients with androgen-induced liver tumors, one of whom had been partially
treated by a liver resection, are reported. Hepatocellular carcinoma was
diagnosed on histologic grounds. The patients had been receiving androgen therapy
for primary diagnoses of either hypopituitarism or paroxysmal nocturnal
hemoglobinuria. After androgen withdrawal, both are alive and well with no
evidence of residual tumor 10 and 14 years after diagnosis, respectively.

Regression of androgen-related hepatic tumors in patients with Fanconi's anemia following marrow transplantation

Transplantation. 1984 May;37(5):452-5.

Regression of androgen-related hepatic tumors in patients with Fanconi's anemia
following marrow transplantation.

Schmidt E, Deeg HJ, Storb R.

Two patients with Fanconi's anemia treated for 5 years with oxymetholone
developed hepatic function abnormalities in association with hepatic tumors
demonstrated by isotope liver-spleen scan or abdominal echogram. The lesions
resolved over a period of 26 months after allogeneic marrow transplantation, and
the patients are alive and well 3 and 4 years following transplantation. The
course of these patients indicates that marrow transplantation for Fanconi's
anemia allows the withdrawal of androgens and subsequent regression of
androgen-related hepatic tumors in patients who might otherwise have a fatal
outcome.

Hepatic lesions in patients on anabolic androgenic therapy.

Isr J Med Sci. 1983 Apr;19(4):332-7.

Hepatic lesions in patients on anabolic androgenic therapy.

Turani H, Levi J, Zevin D, Kessler E.

The histopathological changes in the livers of 11 patients treated with alkylated
and nonalkylated anabolic androgenic steroids are presented. The histological
changes in the liver included: proliferation of the bile ducts with or without
cystic dilatation (9/11), peliosis (8/11), atypical hyperplasia of liver cells
(2/11), and tumors (3/11). The latter included one case of cholangiocarcinoma,
one of hepatocellular carcinoma, and one of combined cholangiocellular and
hepatocellular carcinoma. The pathological changes in the liver in this series
suggest a possible relationship between anabolic androgenic steroids and bile
duct proliferation and/or cholangiocarcinoma.

Superior sagittal sinus thrombosis associated with androgen therapy for hypoplastic anemia

Ann Neurol. 1982 Dec;12(6):578-80.

Superior sagittal sinus thrombosis associated with androgen therapy for
hypoplastic anemia.

Shiozawa Z, Yamada H, Mabuchi C, Hotta T, Saito M, Sobue I, Huang YP.

Of 27 patients with hypoplastic anemia treated between 1971 and 1974 with male
hormone and protein-assimilating hormone, 3 developed superior sagittal sinus
thrombosis (SSST). The clinical symptoms and signs and angiographic findings of
SST were characteristic enough to allow an early diagnosis. Signs related to SST
were seizures, hemiplegia, facial palsy, stupor, and coma, with the most
important prodrome and consistent subjective complaint being headache. Following
discontinuation of the hormone therapy, neurological signs and symptoms related
to SSST gradually subsided. In all cases, the hematological picture improved with
discontinuation of the hormone therapies. It appears that administration of male
hormone can be associated with the development of SSST. If neurological symptoms
and signs of SSST appear, administration of the hormones should be discontinued.

A case of leukemic reticuloendotheliosis responding to oxymetholone

Cancer. 1982 Aug 1;50(3):396-400.

A case of leukemic reticuloendotheliosis responding to oxymetholone.

Feffer SE, Westring DW, Lee AC, Lin JH.

A 63-year-old man presented with fever, easy bruisability, splenomegaly and
pancytopenia. Bone marrow aspiration was unsuccessful, and marrow biopsy revealed
crowding by sheets of mononuclear cells; a diagnosis of leukemic
reticuloendotheliosis (LRE) was made and the patient underwent splenectomy. There
was no hematologic improvement, and the patient continued to have a significant
requirement for erythrocytes and platelet transfusions. Within two months of
beginning oxymetholone therapy (50 mg orally three times a day) the patient's
platelet count had normalized, followed by improved erythrocyte and leukocyte
counts. When the drug was discontinued, the peripheral blood counts deteriorated
drastically; he again demonstrated hematologic improvement when oxymetholone
therapy was reinstated. We feel that by demonstrating a hematologic response to
oxymetholone, relapse when it was withdrawn, and another remission upon
readministration, that we have provided stronger evidence than previously
reported for the efficacy of this drug in LRE.

Prognostic factors and evolution of acquired aplastic anemia in childhood. A prospective analysis of 48 androgen-treated cases

Am J Pediatr Hematol Oncol. 1982 Fall;4(3):273-83.

Prognostic factors and evolution of acquired aplastic anemia in childhood. A
prospective analysis of 48 androgen-treated cases.

Najean Y, Girot R, Baumelou E.

Forty-eight cases of acquired aplastic anemia in children were analyzed in
comparison to 26 cases of genetic aplastic anemia and 483 cases of aplastic
anemia in adults. All were gathered from similar institutions and all were
similarly followed and treated with androgens. The following conclusions were
drawn: 1) Initial severity is greater in children than in adults, and is greater
in acquired than in genetic aplastic anemia; 2) even in cases of similar initial
severity, the early death rate is higher in children than in adults; 3) a
multiparametric index allows the correct prediction of short-term evolution in
70% of the cases and thus aids in providing an indication for bone marrow graft;
its sensitivity is similar to that of the classical parameters proposed by
Camitta, et al., but its specificity significantly higher; 4) most deaths
occurred during the first 3-4 months and the chance for long-term improvement
appears similar in the more severe than in the less severe cases if they survive
this delay; 5) some data (relapse after androgen withdrawal and
androgen-dependence and failure of corticoid therapy alone) suggest that androgen
therapy in children is useful, as it is in adults, and that corticosteroids do
not modify the course of the disease at its usual dosage (1 mg/kg/day); and 6)
very few side effects, particularly concerning height, of androgens were noted in
the survivors at adult age after long-term androgen therapy prescribed before
puberty.

Glucose intolerance and insulin resistance in aplastic anemia treated with oxymetholone

J Clin Endocrinol Metab. 1981 Nov;53(5):905-8.

Glucose intolerance and insulin resistance in aplastic anemia treated with
oxymetholone.

Woodard TL, Burghen GA, Kitabchi AE, Wilimas JA.

Because of a suspected association between the drug oxymetholone and abnormal
glucose metabolism, we determined immunoreactive insulin (IRI) and plasma glucose
during oral glucose tolerance testing in seven patients with aplastic anemia, six
of whom received oxymetholone therapy. All patients receiving oxymetholone
therapy had abnormal glucose and/or IRI values. This finding was independent of
GH, cortisol, and glucagon. In one patient, glucose and IRI levels were normal
before oxymetholone but became abnormally elevated after the use of this drug.
Furthermore, normal glucose and IRI values were present in the single patient not
receiving oxymetholone. Thus, a positive relationship was demonstrated between
oxymetholone administration and the presence of glucose intolerance and insulin
resistance.

A comparison of androgens for anemia in patients on hemodialysis

N Engl J Med. 1981 Apr 9;304(15):871-5.

A comparison of androgens for anemia in patients on hemodialysis.

Neff MS, Goldberg J, Slifkin RF, Eiser AR, Calamia V, Kaplan M, Baez A, Gupta S,
Mattoo N.

To compare the erythropoietic effects of nandrolone decanoate, testosterone
enanthate, oxymetholone, and fluoxymesterone, we performed a randomized clinical
trial in patients with anemia who were receiving maintenance hemodialysis (the
women were not given testosterone enanthate). After a control period of at least
two months, patients received one of the drugs for six months and then returned
to control status; a second and third drug were administered in a similar
fashion. Seventy-seven patients completed the first drug period, 56 the second,
and 35 the third. The response to nandrolone and testosterone enanthate, the two
drugs given by injection, was clearly superior to the response to oxymetholone or
fluoxymesterone, given by mouth, in terms of the percentage of patients
responding and the mean rise in hematocrit. Approximately half the patients had
an increase of at least 5 percentage points in hematocrit after an injectable
androgen was given; more than half the women responded. Patients who required
transfusions regularly and those who had bilateral nephrectomies did not respond.

Fanconi anemia. Oxymetholone hepatic tumors, and chromosome aberrations associated with leukemic transition

Cancer. 1980 Sep 15;46(6):1401-4.

Fanconi anemia. Oxymetholone hepatic tumors, and chromosome aberrations
associated with leukemic transition.

Obeid DA, Hill FG, Harnden D, Mann JR, Wood BS.

Jaundice and hepatomegaly developed in a boy with Fanconi anemia after he had
undergone treatment with oxymetholone for nine years. A liver scan showed patchy
uptake consistent with the presence of space-occupying lesions. After
oxymetholone treatment was stopped, the jaundice resolved, the liver size
decreased, and the filling defects were no longer detectable on the liver scan. A
year later, 5% of his white blood cells showed a consistent chromosomal
abnormality. His leukocyte count increased and 85% of these cells showed the same
chromosomal abnormality. The rapid replication of this abnormal clone suggests
that it was leukemic. The significance of oxymetholone therapy and the occurrence
of hepatic tumors and leukemia is discussed.

Regression on oxymetholone-induced hepatic tumors after bone marrow transplantation in aplastic anemia

Transplantation. 1980 Aug;30(2):90-6.

Regression on oxymetholone-induced hepatic tumors after bone marrow
transplantation in aplastic anemia.

Montgomery RR, Ducore JM, Githens JH, August CS, Johnson ML.

Treatment of acquired aplastic anemia with androgens has been occasionally
associated with the development of hepatic tumors. We have studied a 13-year-old
boy with idiopathic aplastic anemia in whom oxymetholone treatment was associated
with a partial hematological remission. Thirty-four months later, however, the
patient developed multiple hepatic tumors. When oxymetholone therapy was
discontinued, the aplastic anemia relapsed. He then underwent bone marrow
transplantation from his HLA-A, B, and D-compatible sibling. This was followed by
hematological and immunological reconstitution. The hepatic tumors underwent
progressive regression after bone marrow transplantation. The patient is now 3
years post-bone marrow transplantation and is in complete remission of his
aplastic anemia with no evidence of detectable liver tumors.

Cytotoxicity of oxymetholone to endothelial cells in vitro

Arch Pathol Lab Med. 1980 Aug;104(8):405-8.

Cytotoxicity of oxymetholone to endothelial cells in vitro.

Kosek JC, Smith DL.

Morphologic and chromium release studies demonstrated degeneration in monolayer
cultures of endothelial cells exposed to the anabolic steroidal hormone
oxymetholone. The concentrations approximated those occurring transiently in the
hepatic sinusoidal blood after oral administration of the drug during treatment
for aplastic anemia. It is suggested that damage to sinusoidal endothelium, with
impairment of its ability to maintain sinusoidal collagenous reticulin, is a
mechanism by which oxymetholone can cause peliosis hepatis in these patients.

Clinical and biochemical effects of impeded androgen (oxymetholone) therapy of hereditary angioedema

J Allergy Clin Immunol. 1979 Oct;64(4):275-80.

Clinical and biochemical effects of impeded androgen (oxymetholone) therapy of
hereditary angioedema.

Sheffer AL, Fearon DT, Austen KF.

Daily therapy and alternate-day therapy with the attenuated androgen oxymetholone
were compared in patients with hereditary angioedema (HAE). Fifteen of 16
patients who experienced at least monthly attacks of HAE without treatment were
asymptomatic on administration of 5 mg oxymetholene daily. When 13 of the
patients who had been maintained asymptomatically on 5 mg oxymetholone daily were
advanced to a treatment schedule of 5 mg every other day, seven attacks occurred
during a cummulative 50 mo of therapy. The adverse effects that occurred with
daily oxymetholone therapy largely subsided when the patients received
alternate-day therapy, while a significant mean rise in C4 protein and function
occurred only on daily therapy. Statistically significant mean increases in serum
levels of C1INH occurred with daily therapy and were maintained with
alternate-day therapy. Clinical benefit can be obtained with a treatment program
that does not produce a statistically significant rise in C4 protein or function
and does not raise C1INH to the lower limit of normal. The finding that
alternate-day therapy diminished the side effects of the drug while affording a
substantial reduction in the incidence and severity of attacks indicates the
feasibility of this therapeutic approach.

Immunosuppression, bone marrow infusion and low dose androgens, successful therapy of severe aplastic anemia

Schweiz Med Wochenschr. 1979 Sep 29;109(37):1384-5.

[Immunosuppression, bone marrow infusion and low dose androgens, successful
therapy of severe aplastic anemia]

[Article in German]

Cornu P, Speck B, Gratwohl A, Nissen C, Sartorius J, Jeannet M.

18 patients with severe aplastic anemia (SAA) but without an HLA-identical
sibling were treated by antilymphocyte globulin (ALG) followed by infusion of
marrow cells from a semi-compatible family donor. 13 of these received low dose
androgens after ALG: 11 (85%) achieved stable remission without transfusion
requirement. One patient relapsed after 4 months, one patient with only partial
remission died from infection. None of the 4 patients who did not receive
androgens after ALG achieved remission. ALG, marrow and low-dose androgens
represent a promising therapy for SAA and can be favorably compared with
allogeneic bone marrow transplantation.

Androgen therapy of aplastic anaemia--a prospective study of 352 cases

Scand J Haematol. 1979 Apr 4;22(4):343-56.

Androgen therapy of aplastic anaemia--a prospective study of 352 cases.

[No authors listed]

A prospective study of 352 patients with aplastic anaemia on androgen therapy has
been performed. The following main observations have been obtained: The actuarial
mortality rate at the 20th month is 52%, half the deaths being observed during
the first 3 months; these figures are similar to those previously published, from
smaller series of androgen-treated patients, and lower than those of
non-androgen-treated cases. Differences in survival and improvement were observed
between groups of patients treated for more than 3 months with either alkylated
or non-alkylated drugs. Signs of liver damage were observed no matter which was
the drug used. Continous improvement can be observed even in the 2nd year of
treatment indicating that full-dose androgen therapy should be continued up to 20
months in not fully improved patients. The degree of initial disease activity is
a clear prognostic parameter for the mortality in the first quarter of the
course. In case of survival of severe cases, improvement can be obtained to the
same extent as in milder cases. This stress the need for adequate maintenance
therapy in all types of patients. Addition of glucocorticoids harms the
prognosis, mainly in most granulocytopenic patients. Glucocorticoids have no
effect upon the liver damage induced by androgens.

Clinical course in 28 unselected patients with aplastic anaemia treated with anabolic steroids

Br J Haematol. 1979 Mar;41(3):323-33.

Clinical course in 28 unselected patients with aplastic anaemia treated with
anabolic steroids.

Van Hengstum M, Steenbergen J, Haanen C.

Twenty-eight unselected patients with histologically proven aplastic anaemia were
electively treated with anabolic steroids (75-150 mg orally q.d.) Additional
supportive treatment with blood cell components and antibiotics was given if
indicated. Response to therapy was defined as favourable if after 3 months of
anabolic therapy overt bleeding tendency had disappeared, there was no need for
transfusion therapy, a spontaneous increase of haemoglobin had occurred of
greater than 3 g/dl above the initial level, and a platelet rise of twofold the
initial count (up to at least greater than 30 x 10(9) /L) had occurred. Of 22
patients evaluable for the results of long-term (greater than 3 months) anabolic
treatment, six showed a partial response and eleven responded favourably. These
11 are all alive at the end of the study. Five of these patients proved to be
anabolic steroid-dependent. The 50% actuarial survival is approximately 4 years
after diagnosis, which compares favourably with the best published results from
bone marrow transplantation for aplastic anaemia. It is concluded that anabolic
therapy in aplastic anaemia should be tried for 2-3 months before the bone marrow
transplantation or immunosuppressive therapy is taken into consideration.

Peliosis hepatis due to oxymetholone--a clinically benign disorder

Am J Gastroenterol. 1979 Feb;71(2):213-6.

Peliosis hepatis due to oxymetholone--a clinically benign disorder.

Arnold GL, Kaplan MM.

Peliosis hepatis is a rare hepatic disorder mainly diagnosed at surgery or
autopsy. Clinical outcome is thus frequently poor. We report a patient in whom
the diagnosis was established by percutaneous needly biopsy. Withdrawal of the
steroid medication was followed by a prompt clinical improvement. Although
histologic proof of regression is not available, this experience suggests a more
favorable prognosis than previously thought possible.

Anabolic steroid therapy and intrahepatic cholangiocarcinoma

Cancer. 1979 Feb;43(2):440-3.

Anabolic steroid therapy and intrahepatic cholangiocarcinoma.

Stromeyer FW, Smith DH, Ishak KG.

A 47-year-old man who had been treated with an anabolic steroid for refractory
anemia developed an intrahepatic cholangiocarcinoma with metastases to abdominal
lymph nodes and lungs. Microscopically, the tumor showed mucin production and was
devoid of hepatocellular elements. Previous reports have suggested a possible
relationship between anabolic steroid therapy and hepatocellular carcinoma. In
many such cases, there are doubts about the histological diagnosis, malignant
potential, and the nature of the association between the steroids and the tumors.
The presence of distant metastases attests to the malignant nature of the tumor
in the present case. Despite the apparent temporal eligibility of the steroid as
an etiologic agent, a causative relationship between therapy and tumor is not
established.

Effect of a single oral dose of oxymetholone on the metabolism of human erythrocytes.

Exp Hematol. 1978 Sep;6(8):648-54.

Effect of a single oral dose of oxymetholone on the metabolism of human
erythrocytes.

Molinari PF, Neri LL.

Androgenic steroids have been shown to enhance erythrocyte 2,3-DPG production in
vivo and in vitro, and to stimulate the pentose shunt oxidative reactions in
vitro. Furthermore, a 3 beta- and a 17 beta-hydroxysteroid dehydrogenase have
been identified in red cells. The present study was carried out to explore a
cumulative effect of androgens on glycolysis and androgen reduction in human
erythrocytes in vivo following a single 50 mg oral dose of 17 beta-hydroxy-2
(hydroxymethylene)-17 methyl-5 alpha-androstan-3-one (oxymetholone). The rate of
erythrocyte glycolysis was measured by quantitative determination of:
fructose-1,6-diphosphate (FDP); dehydroxyacetone phosphate (DAP);
2,3-diphosphoglycerate (2,3-DPG); adenosine triphosphate (ATP); and lactate.
Serum and erythrocyte steroids were separated by thin layer chromatography. The
reduction of 5 alpha-androstan-17 beta-ol-3-one by red cell hemolysate was
measured in the presence of NADPH as an index of 3(17)beta-hydroxysteroid
dehydrogenase activity. Our results show that oxymetholone administration is
followed by the appearance of an unidentified steroid fraction in chromatograms
of serum and erythrocytes, simultaneously with the enhancement of glycolysis and
of hydroxysteroid dehydrogenase activity in erythrocytes. A direct effect of
androgen on erythrocyte metabolism, which is independent of the hormone
erythropoietic effect, is discussed.

Peliosis: a morphologic curiosity becomes an iatrogenic problem.

Hum Pathol. 1978 May;9(3):331-40.

Peliosis: a morphologic curiosity becomes an iatrogenic problem.

Taxy JB.

Peliosis is a morphologic entity describing a condition of blood filled spaces,
most frequently occurring in the liver. In recent years it has evolved from an
anatomic curiosity seen at autopsy to a potential clinical problem in view of its
association with the administration of anabolic steroid hormones. The
pathogenesis and predilection of peliosis for the liver remain unexplained. This
article reports five patients with peliosis, four with splenic involvement, all
but one of whom received an anabolic steroid preparation. One patient died as a
result of rupture of the splenic peliotic spaces. The diagnosis in three cases
was established on the basis of surgical material, i.e., liver biopsy or
splenectomy. An increased awareness of peliosis in patients at risk, as well as
an appreciation for the histopathologic changes in less advanced cases, may
become an important issue for the surgical pathologist.

Effect of sodium fluoride, inorganic phosphate, and oxymetholone therapies in osteoporosis: a six-year progress report

J Gerontol. 1978 Mar;33(2):204-12.

Effect of sodium fluoride, inorganic phosphate, and oxymetholone therapies in
osteoporosis: a six-year progress report.

Vose GP, Keele DK, Milner AM, Rawley R, Roach TL, Sprinkle EE 3rd.

Elderly osteoporotic males treated with sodium fluoride or inorganic phosphate
for 4 years plus 2 years of follow-up observations exhibited a mean but not
significant decrease in the rate of bone mass loss in comparison with those
receiving oxymetholone or a placebo. No hip fractures occurred in the patients
who received fluoride, while 11 hip fractures occurred in the patients in the
phosphate, oxymetholone, and control groups. Because the densitometric trends and
fracture incidence are impressive, the progress of all subjects will be followed
for an additional 4 years.

Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with androgens

Am J Dis Child. 1977 Oct;131(10):1104-6.

Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with
androgens.

Shapiro P, Ikeda RM, Ruebner BH, Connors MH, Halsted CC, Abildgaard CF.

We report the case of a 13-year-old boy who was known to have Fanconi's anemia
for five years. For treatment of this condition he was given androgens and
corticosteroids. Two months before his death, severe varicella developed
complicated by pneumonia, jaundice, and prolonged fever; all of which resolved
during a five-week hospitalization. Three weeks later he died of Clostridium
septicum sepsis caused by necrotizing enterocolitis. At autopsy he was found to
have multiple hepatocellular neoplasms. A striking feature of the neoplasms was
cholestasis. The liver also showed peliosis hepatis. The association of the use
of certain androgenic steroids with hepatic neoplasms histologically resembling
hepatocarcinomas, but characterized by lack of metastases and apparent
reversibility, suggests the desirability of a new nomenclature for these
hepatocellular lesions.

Androgen dependency in acquired aplastic anemia.

Am J Med. 1977 Aug;63(2):320-4.

Androgen dependency in acquired aplastic anemia.

Azen EA, Shahidi NT.

We describe three patients with acquired aplastic anemia showing dependency on
androgens, with blood counts that correlated directly with variation in
oxymetholone dosage. In two of the patients, red cells, neutrophils and platelets
showed parallel fluctuations, whereas in one patient the red cells and white
cells, but not the platelets, fluctuated in relationship to oxymetholone therapy.
There was no hematologic response to dromostanolone in two patients. These
results support the benefit of androgen therapy in some patients with acquired
aplastic anemia.

Peliosis hepatis. Twelve cases associated with oral androgen therapy.

Arch Pathol Lab Med. 1977 Aug;101(8):405-10.

Peliosis hepatis. Twelve cases associated with oral androgen therapy.

Nadell J, Kosek J.

Peliosis hepatis was encountered in 12 patients treated with high-dose
oxymetholone or fluoxymesterone therapy. In three cases liver failure was the
primary cause of death. In one case, the diagnosis was established by biopsy, the
androgen therapy was discontinued, and the lesion was absent at autopsy two years
later. In eight cases peliosis hepatis was an incidental finding at postmortem
examination. The clinical and anatomic features of these cases are described, and
previously reported cases of peliosis are briefly reviewed. A hypothesis is
offered to explain the association of this peculiar lesion with anabolic androgen
therapy.

Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma

Aust N Z J Med. 1977 Feb;7(1):47-51.

Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma.

Young GP, Bhathal PS, Sullivan JR, Wall AJ, Fone DJ, Hurley TH.

Two patients with multiple myeloma died in acute liver failure. Both had been
treated with the anabolic steroid oxymetholone and both subsequently developed
severe cholestatic hepatitis. In one the histological lesion progressed despite
cessation of oxymetholone therapy. Myeloma infiltration of the liver and peliosis
hepatis were not seen. As a fatal outcome from cholestatic hepatitis due to
oxymetholone is rare it is possible that an unknown potentiating factor is
present in multiple myeloma that can lead to a fatal outcome. If oxymetholone
therapy is to be used in such patients then close clinical and laboratory
assessment of liver function should be carried out in an attempt to prevent this
unusual and fatal complication.

Acquired aplastic anaemia in adults. II. Conventional treatment: retrospective study in 40 patients

Acta Haematol. 1977;58(6):339-52.

Acquired aplastic anaemia in adults. II. Conventional treatment: retrospective
study in 40 patients.

Haak HL, Hartgrink-Groeneveld CA, Guiot HF, Speck B, Eernisse JG, von Rood JJ.

The effect of conservative treatment of aplastic anaemia was evaluated
retrospectively in 40 patients. No significant beneficial effect was provided by
long-term high-dose oxymethalone in 20 patients or by metenolone, adrenstonolone,
or testosterone in 14 patients. Splenectomy gave no improvement in the majority
of cases, although in some it decreased the transfusion requirement.
Immunosuppressive treatment was successful in 1 patient with a positive LE
phenomenon. Until a specific treatment becomes available, the possibility offered
by alternative treatment, e.g. bone marrow transplantation, in cases with poor

Liver lesions due to long-term use of anabolic steroids and oral contraceptives

Ned Tijdschr Geneeskd. 1976 Dec 11;120(50):2214-20.

[Liver lesions due to long-term use of anabolic steroids and oral contraceptives]

[Article in Dutch]

Bakker K, Brouwers TM, Houthoff HJ, Postma A.

PIP: Multiple liver tumors were observed in 2 women, 14 and 30 years of age, who
had taken anabolic steroids over a period of years. In one case peliosis hepatis
was found. 2 patients, 24 and 34 years of age, who had used oral contraceptives
(o.c.s) for 9-10 years, were also examined for liver tumors. In one patient an
increased uptake of the left hepatic lobe was observed, which corrected itself
after discontinuation of o.c. use. Focal nodular hyperplasia was found in the
other patient. 3 types of liver tumors are distinguished: focal nodular
hyperplasia, hepaticellular carcinoma, and peliosis hepatis. They can be
associated with long-term o.c. use, usually in younger women. Pain and swelling
are the first symptoms of such tumors, and tests show slightly elevated liver
enzyme values. A diagnosis can be reached using scintigram, angiogram, or
angiography. Surgery to remove the tumor is indicated in the event of bleeding.

Bone marrow insufficiency in the child and androgen therapy. Preliminary results of a prospective schedule of examination and treatment

Arch Fr Pediatr. 1976 Oct;33(8):761-9.

[Bone marrow insufficiency in the child and androgen therapy. Preliminary results
of a prospective schedule of examination and treatment]

[Article in French]

Girot R, Pecking A, Najean Y.

The preliminary results of a prospective study of androgen therapy in the
treatment of bone marrow insufficiency in children are reported. This study
includes 11 children with the Fanconi syndrome, 21 idiopathic and 3 with toxic
aplastic anaemia. Nine patients died early in the course of treatment. Impaired
liver function was observed in 28% of patients and virilization in 37% of
patients.

Hyperlipidemia due to oxymetholone therapy. Occurrence in a long-term hemodialysis patient.

JAMA. 1976 Aug 2;236(5):469-72.

Hyperlipidemia due to oxymetholone therapy. Occurrence in a long-term
hemodialysis patient.

Reeves RD, Morris MD, Barbour GL.

Marked hypertriglyceridemia and hypercholesterolemia accompanied by angina and a
left cerebral thrombosis occurred in a long-term hemodialysis patient following 5
1/2 weeks of oral treatment with oxymetholone, 100 mg/day, a synthetic androgen.
After androgen therapy was discontinued, over a three-month period, plasma lipid
values progressively decreased below pretreatment values, and clinical symptoms
disappeared. During rechallenge with oxymetholone, serum lipid values increased
substantially, and the lipoprotein pattern changed from a type IV to a type V.
Detailed lipid studies showed subnormal postheparin lipolytic activity and a
fast-migrating pre-beta-lipoprotein in a very-low-density lipoproteins (VLDL)
fraction. Because of the data linking lipid abnormalities to atherosclerosis and
the acceleration of atherosclerosis in long-term hemodialysis patients, great
caution should be exercised in administering androgenic steroids to these
patients.

Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids.

S Afr Med J. 1976 Jul 24;50(32):1233-7.

Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment
with androgenic steroids.

Kew MC, Van Coller B, Prowse CM, Skikne B, Wolfsdorf JI, Isdale J, Krawitz S,
Altman H, Levin SE, Bothwell TH.

Three patients are reported in whom treatment of Fanconi's anaemia with
androgenic steroids was complicated by the development of either primary
hepatocellular cancer (PHC) or peliosis hepatis. The first, a White woman aged 34
years, was found to have PHC after receiving first methyltestosterone and then
oxymetholone for a total period of 7 years. She died 4 months after the diagnosis
was made. The other 2 patients were White children who presented with peliosis
hepatis after receiving methyltestosterone and oxymetholone for 8 years and
oxymetholone for 5 years, respectively. Both died from their primary diseases
shortly after oxymetholone treatment was discontinued. Possible pathogenic
mechanisms involved in the development of these serious complications are
discussed and the therapeutic dilemma raised by their occurrence is emphasised.

Oxymetholone treatment in aregenerative anaemia. II. Remission and survival--a prospective study.

Scand J Haematol. 1976 Feb;16(2):90-100.

Oxymetholone treatment in aregenerative anaemia. II. Remission and survival--a
prospective study.

Hast R, Skårberg KO, Engstedt L, Jameson S, Killander A, Lundh B, Reizenstein P,
Udén AM, Wadman B.

This is a prospective multi-center study in which patients with aregenerative
anaemia were treated with a standardized high dosage regime of an anabolic
steroid (oxymetholone, Anasteron). 53 patients were included and divided into two
groups according to bone marrow cellularity. Furthermore the hypocellular group
was subdivided in order to make comparison with earlier studies possible. In the
hypocellular group, the frequency of remission was 56% and the 2-year-survival
from the onset of symptoms was 75%. This is longer than in some earlier studies,
perhaps because of possible differences in etiology and/or because of the effect
of systematic high dosage, long term androgen therapy. Patient selection was
minimized and was not considered to be of major importance. Patients with
hypercellular marrows, on the other hand, responded poorly to androgens. In this
group 63% died of acute leukaemia, which confirms earlier suggestions that this
form of aregenerative anaemia, frequently is of a preleukaemic nature.

Fanconi's familial hypoplastic anaemia with some unusual features.

Med J Aust. 1976 Jan 31;1(5):116-8.

Fanconi's familial hypoplastic anaemia with some unusual features.

Farrell GC.

A case of Fanconi's familial hypoplastic anaemia is described in a 48-year-old
woman who had the usual haematological and constitutional abnormalities of this
condition. Chromosomal studies on peripheral blood lymphocytes and direct marrow
preparations demonstrated the chromosomal breaks previously described. The age of
the patient and a congenital abnormality of breast development were unusual
features, while the discovery of a benign liver tumour at necropsy is of
interest, as the patient had received therapy with oxymetholone.

Hereditary angioedema: modification of clinical manifestations with androgens.

Birth Defects Orig Artic Ser. 1976;12(6):283-7.

Hereditary angioedema: modification of clinical manifestations with androgens.

Davis PJ, Davis FB, Charache P.

HAE is an autosomal dominant trait of decreased levels or function of circulating
and tissue C'1 esterase inhibitor. The clinical illness is characterized by
disabling episodes of peripheral, oropharyngeal and gut-wall edema. Long-term
fluoxymesterone treatment of 5 affected males (393 patient-months) and
oxymetholone treatment of 6 affected females (204 patient-months) has
significantly decreased the frequency of attacks of edema without substantive
side effects.

Peliosis hepatis, complicating treatment with anabolic steroids

Med Klin. 1975 Oct 3;70(40):1602-7.

[Peliosis hepatis, complicating treatment with anabolic steroids (author's
transl)]

[Article in German]

Kühböck J, Radaszkiewicz T, Walek H.

The clinical and pathological findings of peliosis hepatis are reported,
complicating a long-term treatment with an anabolic steroid in a 19 year old male
patient suffering from chronic aplastic anemia. Following a 15 months course of
oxymetholone (Anapolon) a cholestatic jaundice developed without regression
despite discontinuing the drug. 4 months later the patient expired as a
consequence of his hematologic disease. At autopsy the liver showed a parenchymal
type of peliosis hepatis with multiple blood filled cavities and focal liver cell
necroses. The pathogenesis of this rare condition is discussed by means of
literature demonstrating the hepatotoxic effect of C17-alkylated androgens.