The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients.
The influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA) given intramuscularly on the peripheral aromatisation of androstenedione into oestrone was investigated in postmenopausal women with breast cancer and compared with the suppression of plasma oestradiol (E2). 7 patients were investigated before and during treatment on day 7, i.e. midway between two weekly injections. After an intravenous injection of [3H] androstenedione and [14C] oestrone, urine was collected for 96 h and the isotope ratio determined in the urinary oestrogen metabolites after isolation with high performance liquid chromatography. At 250 mg, 4OHA inhibited aromatisation to [mean (S.D.)] 15.2 (5)% of baseline (P < 0.002). There was significantly greater inhibition to 8.1 (2.7)% at 4OHA 500 mg (P < 0.01). Plasma E2 was reduced to 41.2 (14.1)% of baseline at 4OHA 250 mg with a further reduction to 32.7 (19.8)% at 500 mg (P < 0.05). These results confirm the dose-response relation previously established with plasma oestrogen measurements alone.
Jones
A L
AL
Section of Medicine, Royal Marsden Hospital, Sutton, Surrey.
MacNeill
F
F
Jacobs
S
S
Lonning
P E
PE
Dowsett
M
M
Powles
T J
TJ
D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000652:urine; D004964:Estriol / Q000652:urine; D004970:Estrone / Q000652:urine; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004970:Estrone; D000735:Androstenedione; D004958:Estradiol; D004964:Estriol; C014594:formestane