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Perturbations of the human menstrual cycle by oxymetholone.

The luteolytic activity of oxymetholone, and anabolic steroid, has been evaluated in 10 women. Administration early in the follicular phase of the cycle inhibited ovulation and prolonged the duration of the cycles in 2 of 3 subjects, but treatment beginning on Day 10 (3 subjects) did not prevent ovulation, although subsequent plasma progesterone concentrations were reduced. Treatment after ovulation (4 subjects) suppressed progesterone levels by 50 to 80 per cent and shortened cycle length by 6 to 8 days. Side effects were weight gain and bromosulfophthalein retention. The most likely mechanisms producing these perturbations are the inhibition of luteinizing hormone release early in the cycle and, later, inhibition of progesterone biosynthesis.

Administration, Oral↗

Studies on anabolic steroids. 10. Synthesis and identification of acidic urinary metabolites of oxymetholone in a human.

Two major unconjugated acidic metabolites of oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one, 1), namely, 17 beta-hydroxy-17 alpha-methyl-2,3-seco-5 alpha-androstane-2,3-dioic acid (2) and 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 beta-carboxylic acid (6a), were detected by gas chromatography/mass spectrometry in urine samples collected after oral administration of 1 to a human volunteer. Reference steroid 2 was synthesized and identified. The identification of urinary metabolite 6a was based on the synthesis of its stereoisomers and the isomerization of the methyl ester 6b to its 2-epimer, 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 alpha-carboxylic acid methyl ester (9b). The mechanisms accounting for the formation of these acidic metabolites are discussed.

Acids↗

Enhancing effect of oxymetholone, an anabolic steroid, on development of liver cell foci in rats initiated with N-diethylnitrosamine.

The promoting potential of oxymetholone (OXM) administration on development of liver cell foci was investigated in male F344 rats previously treated with N-diethylnitrosamine (DEN). One week after a single injection of DEN (100 mg/kg, i.p.), rats were given OXM at a dietary level of 0.2% for the first 4 weeks and then at a concentration of 0.1% for an additional 35 weeks. All rats were killed at week 40 for histopathological and immunohistopathological examination of liver tissue. The numbers and areas of both clear cell and glutathione S-transferase placental form (GST-P) positive foci were significantly increased in the group treated with DEN and OXM as compared with the respective values for the DEN alone group. The results thus suggested that OXM possesses promoting potential for rat liver carcinogenesis.

Animals↗

Effect of oxymetholone on human cyclic haematopoiesis.

A 62-year-old woman had recurrent fluctuations of neutrophil, monocyte, reticulocyte and platelet counts with a cycling time of 38.5 d. Periodic fluctuations of granulo-, erythro- and megakaryopoiesis were also demonstrated in her bone-marrow. Oxymetholone reduced the magnitude of the profound cyclic fluctuations in all these cell lines. During treatment a reduced number of in vitro CFU-C of the progenitor myeloid series from the bone marrow was observed. Using the patient leucocytes as feeders for normal control marrow cells, indication was found for a fluctuation in colony stimulating activity in vitro, rising above normal at the nadir of the WBC.

Blood Cell Count↗

Aplastic anaemia, acute myeloblastic leukaemia, and oxymetholone.

Four patients developed acute myeloblastic leukaemia after treatment of aplastic anaemia with oxymetholone. Two had previously shown an excellent clinical response to the drug and a third some improvement. Though no definite causal relationship between therapy and the onset of leukaemia has been established, the number of cases is greater than might have been expected by chance. The association of the two diseases is discussed.

Adult↗

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

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.

Adolescent↗