Endocrine effects of aminoglutethimide plus hydrocortisone versus effects of high dose of hydrocortisone alone in postmenopausal metastatic breast cancer.
Aminoglutethimide (Ag) has been used in different dosages with and without combined treatment with glucocorticoids for the suppression of peripheral plasma levels of steroidal hormones. In the present work we have estimated changes in peripheral steroid levels after 3 days of adrenal suppression with a 'physiological' daily dose of 40 mg hydrocortisone (H). Subsequently Ag (1000 mg daily) was added or the dose of H was doubled in order to study the efficacy of the suppression of oestradiol by these conditions during a 6-week period. Sixteen postmenopausal patients with evaluable and measurable progressive breast cancer were selected for the initial treatment, thereafter Ag was added in eight patients, while the other eight patients continued on H with a double dose. Administration of 40 mg H daily during the first 3 days caused a significant decrease of plasma oestradiol (P less than 0.01), androstenedione (P less than 0.01) and DHEA-S (P less than 0.05). Basal plasma cortisol levels increased and the diurnal rhythm disappeared. These observations suggest suppression of adrenal function by the exogenous cortisol. Prolonged treatment with a higher dose of H (80 mg daily) caused further suppression of androstenedione (P less than 0.01) but not of oestradiol. The addition of 1000 mg of Ag to H had no further significant effect on plasma oestradiol levels either. The main difference between the effects of the two treatment modalities was in the levels of androgens. The group treated with H alone showed long-term significant suppression of both androstenedione and DHEA-S, while in the group treated with the combination of H + Ag a further pronounced suppression of DHEA-S and elevation of androstenedione was found. Finally, there was a significant difference between SHBG levels in the two groups at day 42. The increased levels of SHBG in the H + Ag-treated group might lower the 'free' oestradiol concentration. It is concluded that both drugs have different effects on the plasma levels of peripheral steroids. On theoretical grounds, the combination of H + Ag might be preferable, because 'free' oestradiol plasma levels may be lowest after this treatment. However, a direct correlation with clinical effects still remains to be proven.
D000368:Aged; D000616:Aminoglutethimide / Q000008:administration & dosage*; D000735:Androstenedione / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004958:Estradiol / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D006728:Hormones; D012738:Sex Hormone-Binding Globulin; D000616:Aminoglutethimide; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D013972:Thyrotropin; D013974:Thyroxine; D006854:Hydrocortisone