Influence of toremifene on the endocrine regulation in breast cancer patients.
In a combined phase I-II study, the hormonal effects of toremifene (TOR) were investigated in 30 patients. Half of the patients received continuous therapy of TOR 60 mg and half 300 mg of TOR orally daily. Serum concentrations of oestradiol (E2), progesterone (PROG), testosterone (TE), follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL), human growth hormone (hGH) and sex hormone binding globulin (SHBG) were monitored prior to the treatment and at the second, sixth, eighth and twelfth weeks. The influence of TOR upon the hypothalamo-hypophyseal axis was investigated by the TRH (thyroid-stimulating hormone releasing hormone) functional test using 400 micrograms intravenous injection of TRH for stimulation of PRL secretion. The concentration of E2 decreased during the TOR therapy with 60 mg and 300 mg causing 82 and 71% decreases, respectively (non-significant). PRL was significantly (P < 0.001) suppressed. Both these effects reflect the anti-oestrogenic action of TOR. SHBG increased significantly at both doses of TOR, probably due to a direct oestrogen-like effect of TOR in the liver. TE decreased as a consequence of the elevated SHBG. The TRH-induced PRL release was suppressed by both doses of TOR. There were 17 and 27% reductions at 12 weeks in the 60 and 300 mg groups, respectively. Other hormones measured were not significantly affected by TOR. The hormonal effects of 60 and 300 mg doses of TOR did not differ significantly. Anti-oestrogenic (i.e. decrease of E2), and partially oestrogenic (i.e. increase of SHBG) properties as well as the antiprolactinic effects of TOR may have an overall beneficial effect in the clinical management of breast cancer patients.
Számel
I
I
National Institute of Oncology, Budapest, Hungary.
Hindy
I
I
Vincze
B
B
Eckhardt
S
S
Kangas
L
L
Hajba
A
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D006065:Gonadotropins, Pituitary / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008875:Middle Aged; D011374:Progesterone / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D017312:Toremifene / Q000627:therapeutic use*
D006065:Gonadotropins, Pituitary; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D017312:Toremifene; D013006:Growth Hormone