Suppression of postmenopausal ovarian steroidogenesis with the luteinizing hormone-releasing hormone agonist goserelin.
Twenty-one postmenopausal women with advanced breast cancer were treated with monthly 3.6-mg sc injections of the LHRH agonist goserelin [D-Ser-(But)6, Azgly10-LHRH] to determine whether the resultant endocrine changes could provide an explanation for the clinical responses that occur during therapy with this agent. After 4 weeks, serum gonadotropin levels were less than 10% of pretreatment levels, whereas serum PRL levels did not change. A significant decrease in serum testosterone occurred in 19 of 20 patients; this fall was associated with a 22% fall in serum estradiol levels. Serum androstenedione levels also decreased, but serum estrone and dehydroepiandrosterone sulfate (DHAS) levels did not. The lack of fall in serum DHAS levels indicates that the changes in androgen levels were a result of reduced ovarian secretion, and the reduced estradiol levels were a consequence of reduced precursor (i.e. testosterone) availability. The continued dependence of ovarian androgen secretion on gonadotropin stimulation after the menopause may explain the responses of some patients to LHRH agonists and some other therapeutic agents of unknown or uncertain modes of action.
Dowsett
M
M
Department of Biochemical Endocrinology, Chelsea Hospital for Women, London, United Kingdom.
Cantwell
B
B
Lal
A
A
Jeffcoate
S L
SL
Harris
A L
AL
D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002064:Buserelin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004967:Estrogens / Q000097:blood; D005260:Female; D006065:Gonadotropins, Pituitary / Q000097:blood; D017273:Goserelin; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects*
D000728:Androgens; D004967:Estrogens; D006065:Gonadotropins, Pituitary; D017273:Goserelin; D002064:Buserelin