Endocrine mechanism of action of toremifene at the level of the central nervous system in advanced breast cancer patients.
OBJECTIVE
To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial.


METHODS
In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormone (FSH) and LH release--induced by an LHRH agonist (Suprefact injection, 0.5 mg s.c.)--was monitored during a 16-week period of toremifene treatment (60 mg/day p.o.). Prolactin, estradiol, and sex hormone-binding globulin (SHBG) levels were also measured. The functional test was carried out prior to toremifene therapy and then 4, 8, 12, and 16 weeks afterward.


RESULTS
The drug sensitized the pituitary to the action of the gonadotrophins; the LHRH-induced FSH and LH release showed a considerably increasing tendency during the toremifene therapy. Estradiol levels decreased statistically significantly and SHBG levels showed a statistically significant increase. A decreased level of prolactin is the sign of an antiestrogenic effect of toremifene on the hypophysis and, as a result, provides evidence for a direct influence of toremifene upon the pituitary. An increase in LH and prolactin release in response to the LHRH test was characteristic in the responders.


CONCLUSIONS
According to the LHRH test, the antagonistic effect of toremifene seems to be more dominant than the concomitantly existing agonistic property. Neither clinical nor endocrinological side effects could be observed at the level of the CNS during a prolonged period of toremifene administration.
Clinical Research Department, National Institute of Oncology, Budapest, Hungary.
I
I
Számel
I
I
Hindy
B
B
Budai
L
L
Kangas
A
A
Hajba
R
R
Lammintausta
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D017698:Postmenopause / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D017312:Toremifene / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D017312:Toremifene; D005640:Follicle Stimulating Hormone